[Federal Register Volume 59, Number 8 (Wednesday, January 12, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-753]
[[Page Unknown]]
[Federal Register: January 12, 1994]
_______________________________________________________________________
Part IV
Environmental Protection Agency
_______________________________________________________________________
40 CFR Part 372
Addition of Certain Chemicals; Toxic Chemical Release Reporting;
Community Right-to-Know; Proposed Rule
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 372
[OPPTS-400082; FRL-4645-6]
RIN 2070-AC47
Addition of Certain Chemicals; Toxic Chemical Release Reporting;
Community Right-to-Know
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
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SUMMARY: EPA is proposing to add 313 chemicals and chemical categories
to the list of toxic chemicals required to be reported on under section
313 of the Emergency Planning and Community Right-to-Know Act of 1986
and section 6607 of the Pollution Prevention Act of 1990. The proposed
addition of these chemicals and chemical categories is based on their
acute human health effects, carcinogenicity or other chronic human
health effects, and/or their environmental effects. EPA believes that
these chemicals and chemical categories meet the EPCRA section
313(d)(2) criteria for addition to the list of toxic chemicals.
DATES: Written comment on this proposed rule must be received on or
before April 12, 1994. The public meeting will take place on March 2,
1994, at 1 p.m. and adjourn by 5 p.m.
ADDRESSES: Written comments should be submitted in triplicate to: OPPT
Docket Clerk, TSCA Document Receipt Office (7407), Office of Pollution
Prevention and Toxics, Environmental Protection Agency, Rm. E-G99, 401
M St., SW., Washington, DC 20460. Comments containing information
claimed as confidential must be clearly marked as confidential business
information (CBI). If CBI is claimed, three additional sanitized copies
must also be submitted. Nonconfidential versions of comments on this
proposed rule will be placed in the rulemaking record and will be
available for public inspection. Comments should include the docket
control number for this proposal, OPPTS-400082. Unit VI. of this
preamble contains additional information on submitting comments
containing information claimed as CBI.
The public meeting will be held at the: Environmental Protection
Agency, Auditorium, Education Center, 401 M St., SW., Washington, DC.
FOR FURTHER INFORMATION CONTACT: Maria J. Doa, Emergency Planning and
Community Right-to-Know Information Hotline, Environmental Protection
Agency, Mail Stop 5101, 401 M St., SW., Washington, DC 20460, Toll
free: 800-535-0202 or Toll free TDD: 800-553-7672, Attention: Docket
Number OPPTS-400082.
SUPPLEMENTARY INFORMATION:
I. Introduction
A. Statutory Authority
This proposed rule is issued under sections 313(d) and (e)(1) of
the Emergency Planning and Community Right-to-Know Act of 1986 (EPCRA),
42 U.S.C. 11023. EPCRA is also referred to as Title III of the
Superfund Amendments and Reauthorization Act of 1986.
B. Background
Section 313 of EPCRA requires certain facilities manufacturing,
processing, or otherwise using listed toxic chemicals to report their
environmental releases of such chemicals annually. Beginning with the
1991 reporting year, such facilities also must report pollution
prevention and recycling data for such chemicals, pursuant to section
6607 of the Pollution Prevention Act, 42 U.S.C. 13106. When enacted,
section 313 established an initial list of toxic chemicals that was
comprised of more than 300 chemicals and 20 chemical categories.
Section 313(d) authorizes EPA to add chemicals to or delete chemicals
from the list, and sets forth criteria for these actions. Under section
313(e), any person may petition EPA to add chemicals to or delete
chemicals from the list. EPA has added to and deleted chemicals from
the original statutory list.
EPA issued a statement of petition policy and guidance in the
Federal Register of February 4, 1987 (52 FR 3479), to provide guidance
regarding the recommended content and format for submitting petitions.
EPA must respond to petitions within 180 days either by initiating a
rulemaking or by publishing an explanation of why the petition is
denied. On May 23, 1991 (56 FR 23703), EPA issued guidance regarding
the recommended content of petitions to delete individual members of
the section 313 metal compound categories.
II. Explanation for Expansion of the EPCRA Section 313 Chemical
List
A. General Rationale
The Toxics Release Inventory (TRI), through the public access
provisions of EPCRA, has proven to be one of the most powerful forces
in empowering the Federal government, State governments, industry,
environmental groups, and the general public, to fully participate in
an informed dialogue about the environmental impacts of toxic chemicals
in the United States.
A major section of EPCRA, which Congress passed in 1986, resulted
in the creation of the Toxics Release Inventory. TRI is a publicly
available data base that provides quantitative information on toxic
chemical releases, transfers, recycling, and disposal. With the
collection of this information for the first time in 1987, came the
ability for the public, government, and the regulated community to
understand the magnitude of chemical emissions in the United States; to
compare chemical releases and transfers of chemical wastes among
States, industries, facilities, and environmental media; and perhaps
most importantly, to assess the need to reduce and where possible,
eliminate these releases and transfers. TRI enables all interested in
environmental progress to establish credible baselines, to set
realistic goals, and to measure progress over time, in meeting those
goals. The TRI system has become a neutral yardstick by which progress
can be measured by all interested parties.
The original list of chemicals for which reporting was required
consisted of 320 chemicals and chemical categories. The list was a
combination of the Maryland Chemical Inventory Report List of Toxic or
Hazardous Substances and the New Jersey Environmental Hazardous
Substance List. The combination of these two lists provided a sound and
logical starting point for the national TRI program. Recognizing
however that the list would need to be a dynamic one, EPCRA
specifically authorizes additions to and deletions from the list. To
date, EPA has added 16 chemicals to the list and has deleted 12
chemicals from the list.
With 5 years experience behind the program, EPA, other federal
agencies, Congress, and the public have recognized the need to expand
the TRI list beyond the original chemicals and chemical categories and
beyond the relatively limited reporting universe. (Currently reporting
is only required from facilities that fall within the manufacturing
Standard Industrial Classification (SIC) codes 20 through 39 that meet
certain thresholds).
While the data on the chemicals that are covered have allowed the
public and private sectors to be informed and involved in environmental
decisionmaking as they never were before, it has become increasingly
evident to those same constituents that they have access to information
on a relatively small number of important chemicals. Congress has
echoed this recognition in the Right-to-Know More bills that were put
forward in the 102nd Congress. EPA and State regulatory agencies have
integrated TRI information as a critical component in their
environmental decisionmaking and in many cases are constrained by the
lack of similar information on chemicals of concern not covered by the
TRI. While the TRI has been successful in focusing attention on the
initial list of chemicals and in many cases fostering emissions
reductions and prevention activities, that same focus has highlighted
the need to expand beyond that initial list and to include additional
chemicals that exhibit similar toxicity characteristics. This proposal
is one of the first in a series of actions that EPA plans to use to
expand the coverage of the TRI. This first phase will focus on adding
chemicals, followed by a second phase that will identify additional
facilities for inclusion. EPA is considering a third phase, which would
look at modification of the data elements currently required by TRI.
In conjunction with these expansion activities EPA has been
considering whether other adjustments are needed in the scope of the
TRI program. EPA received petitions from the Small Business
Administration and the American Feed Industry Association seeking an
exemption for ``small sources'' (i.e, those facilities that file TRI
forms with zero or small release estimates). EPA previously put those
petitions out for public comment and, on review, believes there is
substantial merit to the general concerns raised in the petitions.
The Agency's plan for proceeding on the small source issue would
include the following steps. EPA is examining four options for
establishing a small release exemption from the TRI reporting
obligation: Cutoffs at zero, 500 pounds, 1,000 pounds, and 5,000
pounds. EPA will provide the public with a report on these four options
by the end of January. This analysis will consider what data might not
be available at both the national and community level, and the cost
savings to the government and to industry of the four exemption levels.
EPA plans to hold a public meeting in February for discussion of the
report. Based on this feedback, EPA will then design a regulatory
strategy that will align the small source issue with final action on
today's proposal. The Agency's objective will be to minimize
unnecessary data collection and reporting by facilities, including for
the chemicals identified in today's proposal.
B. Development of the Chemical Addition Candidates
As a starting point for screening candidates for addition to the
toxic chemical list under EPCRA section 313, EPA chose to examine the
lists of chemicals regulated or identified, as of concern, under
various environmental statutes including: (1) Section 112(b) of the
Clean Air Act (CAA) as amended in 1990 (Hazardous Air Pollutants); (2)
section 602(b) of the CAA (Class II ozone depleting substances); (3)
section 307(a) of the Clean Water Act (CWA) (Priority Pollutant List);
(4) Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Active
Ingredients, including Special Review, Canceled/Denied or Suspended,
and Restricted Use Pesticides; (5) section 302 of EPCRA (Extremely
Hazardous Substances); (6) section 102 of the Comprehensive
Environmental Response, Compensation, and Liability Act (CERCLA); (7)
section 3001 of the Resource Conservation and Recovery Act (RCRA) and
chemicals listed at 40 CFR 261.33(e) and (f) and Appendix VIII; (8)
section 1412 of the Safe Drinking Water Act as amended; (9) certain
chemicals subject to the Toxics Substance Control Act (Existing
Chemicals); and (10) the State of California Safe Drinking Water and
Toxic Enforcement Act of 1986 (Proposition 65) (List of Chemicals Known
to the State to Cause Reproductive Toxicity).
In addition, EPA considered chemicals designated as possible,
probable, or known carcinogens in the Monographs of the International
Agency for Research on Cancer (IARC) and the 6th Annual Report on
Carcinogens of the National Toxicology Program (NTP), U.S. Department
of Health and Human Services (DHHS).
From this initial group of substances, EPA excluded chemicals that
are already listed on section 313 or are already reportable under one
of the EPCRA section 313 categories. For example, ``cyanide, total'' is
listed under section 307(a) of the CWA. This listing is considered to
be a subset of the EPCRA section 313 cyanide compounds category and the
hydrogen cyanide listing. EPA decided not to propose listing these
types of chemicals separately because they are already reportable under
one of the existing section 313 categories. To prioritize chemicals for
possible addition to EPCRA section 313, EPA applied a human health and
ecotoxicity screen and a production volume screen, which are described
below. The results of the toxicity screen for a subset of these
chemicals were presented at a public meeting on May 29, 1992 (Ref. 4).
Other chemicals were also removed from consideration for this
rulemaking because they are the subjects of two recently published
EPCRA petition responses. On March 4, 1992, EPA received a petition
from Governor Mario M. Cuomo of New York and the Natural Resources
Defense Council (NRDC) to add 80 chemicals and 2 chemical categories to
the list of toxic chemicals under section 313 of EPCRA. All of these
chemicals and chemical categories appear on the RCRA list of hazardous
wastes under 40 CFR 261.33(f) and as such are a subset of the chemicals
screened by EPA. EPA responded to the petition in a proposed rulemaking
on September 8, 1992 (57 FR 41020) and in a final rule adding 22
chemicals on November 30, 1993 (58 FR 63500).
On December 3, 1991, EPA received a petition from the NRDC, Friends
of the Earth, and the Environmental Defense Fund to add
hydrochlorofluorocarbons (HCFCs) to the list of toxic chemicals under
section 313 of EPCRA. The HCFCs are listed under section 602(b) of the
CAA as Class II ozone depleting substances and as such are a subset of
the chemicals screened by EPA. EPA responded to the petition in a
proposed rulemaking on June 24, 1992 (57 FR 28159) and in a final rule
adding 11 HCFCs on November 30, 1993 (58 FR 63496). An additional 16
HCFCs not added to the TRI list by the November 30, 1993 final rule are
proposed for addition in this rulemaking (See Unit IV.B.135. of this
preamble).
1. Toxicity screen. A toxicity screen is a limited review of
readily available toxicity data (e.g., information in data bases and
other secondary sources) that is used for a preliminary categorization
of a chemical during the process of selecting candidates for possible
listing under EPCRA section 313. The toxicity screen is used to
identify chemicals for further consideration and does not reflect a
final determination for listing a chemical under EPCRA section 313.
Such a determination can only be made after a hazard assessment is
conducted (See Unit II.B.3. of this preamble). The chemicals identified
above were screened for four general effect categories: Acute human
health effects, cancer, other chronic human health effects, and
ecological effects.
The screening criteria associated with each of the effect areas
used in the toxicity screen are discussed in detail in the Revised
Draft Hazard Assessment Guidelines for Listing Chemicals on the Toxic
Release Inventory (Draft Hazard Assessment Guidelines), (Ref. 6). The
numerical screening values reflected in the Draft Hazard Assessment
Guidelines were developed to capture, in the ``sufficient for listing''
screening category, the majority of chemicals already listed on various
CERCLA and EPCRA lists, and thus known or suspected to be toxic and/or
hazardous. These Draft Hazard Assessment Guidelines contain guidance
for both the screening and hazard assessments of chemicals and are
available for review in the docket associated with this rulemaking.
This draft document was distributed at a public meeting on May 29,
1992. A final version of these guidelines has not yet been developed.
Requests for further information about these draft guidelines should be
addressed to the person identified under ``FOR FURTHER INFORMATION
CONTACT.''
Based on the results of this screen, the chemicals were
preliminarily placed in one of three screening categories defined in
the Draft Hazard Assessment Guidelines: ``sufficient;'' ``may be
sufficient;'' or ``insufficient.'' EPA received comment in response to
the Draft Hazard Assessment Guidelines that objected to the Agency's
use of the terms ``sufficient,'' ``may be sufficient,'' and
``insufficient'' as titles for the toxicity screening categories. The
commenter claimed that these terms are appropriate only for the results
of a hazard assessment. The commenter stated that these terms should
not be used for screening categories because the toxicity screen only
identifies chemicals for further consideration. EPA agrees that the
screening categories only reflect a preliminary determination on each
chemical, and therefore, to avoid further confusion, will refer to the
screening categories as ``high priority,'' ``medium priority,'' and
``low priority'' to reflect the difference between a toxicity screen
and a hazard assessment. These terms will be used throughout this
document in reference to the toxicity screening categories. Chemicals
that were categorized as ``low priority'' during the screening process
were not considered further as candidates for addition to the EPCRA
section 313 list in this rulemaking.
2. Production volume screen. EPCRA section 313(f) establishes
reporting thresholds related to the amount of a chemical that is
manufactured, processed, or otherwise used. [The EPCRA section 313
manufacture (includes import) and processing thresholds are 25,000
pounds per facility per year. The otherwise use threshold is 10,000
pounds per facility per year]. EPA anticipates that the addition of
chemicals manufactured, imported, processed, or used in quantities less
than the EPCRA section 313 volume thresholds would not result in the
submission of TRI reports. Thus, EPA elected to initially focus its
attention on chemicals likely to yield reports. Accordingly, EPA also
screened potential candidates for the likelihood of meeting the EPCRA
section 313 volume thresholds. Chemicals for which there were no data
to indicate that the chemical is likely to meet or exceed the EPCRA
section 313 volume thresholds were not considered further as possible
candidates for addition to the section 313 list at this time.
Production volume data on each of the chemicals were gathered
primarily from two sources: (1) The TSCA Chemical Update System (1990);
and (2) the FIFRA Section 7 Tracking System. On June 12, 1986 (51 FR
21438), EPA promulgated a rule pursuant to section 8(a) of TSCA which
required manufacturers and importers to report every 4 years, subject
to certain threshold production quantities and other exclusions, the
quantities of chemicals they produced (40 CFR part 710). Among the
exceptions to the inventory update rule (IUR) reporting were polymers,
biological products, inorganic substances, and chemicals produced at
less than 10,000 pounds, all with certain limitations. Data from the
IUR is maintained in EPA's TSCA Chemical Update System (CUS).
Section 7 of FIFRA provides the Agency with annual production
information on registered pesticides. EPA regulations implementing
FIFRA section 7 (40 CFR part 167) require all manufacturers of
pesticidal products (which includes formulated pesticides, active
ingredients, and devices) to submit an annual report detailing the
amount of each type of pesticidal product manufactured, sold and
distributed during the past year, and estimated to be manufactured,
imported, and processed during the current year (40 CFR 167.85).
For industrial inorganic compounds not subject to FIFRA or
available on CUS, information from the public literature was used,
supplemented with information from companies.
3. Hazard evaluation. EPA conducted a hazard evaluation for each of
the addition candidates that resulted from the above analyses and
determined based on the weight-of-the evidence if there was sufficient
evidence to establish that the candidate chemical met the statutory
criteria for addition to EPCRA section 313. To make this determination,
EPA senior scientists reviewed readily available toxicity information
on each chemical for each of the following effect areas: acute human
health effects; cancer; other chronic human effects; and environmental
effects. In addition, EPA reviewed, where appropriate, information on
the environmental fate of the chemical.
The hazard assessment was conducted in accordance with relevant EPA
guidelines for each adverse human health or environmental effect (e.g.,
the appropriate guidelines for hazard evaluation of chemical
carcinogens and for the type of evidence required to substantiate a
determination of carcinogenicity are the Guidelines for Carcinogen Risk
Assessment (Ref. 2)). The guidelines that were used for each effect are
Agency guidelines that are identified in the Draft Hazard Assessment
Guidelines (Ref. 6). During this assessment the severity and
significance of the effects induced by the chemical, the dose level
causing the effect, and the quality and quantity of the available data,
including the nature of the data (e.g., human epidemiological,
laboratory animal, field or workplace studies) and confidence level in
the existing data base, were all considered. Where a careful review of
the scientific data for a particular chemical results in a high level
of confidence that the chemical causes an adverse effect at relatively
low dose levels, EPA believes that this evidence is sufficient for
listing the chemical under section 313. On the other hand, where a
review of the scientific data indicates that the chemical will cause
various adverse effects at moderate dose levels, EPA believes, based on
the total weight-of-the-evidence, that there is sufficient evidence for
listing the chemical under EPCRA section 313.
EPA also conducted an analysis of exposure for each chemical or
chemical category proposed for listing under EPCRA section 313(d)(2)(A)
(i.e., based on adverse acute human health effects), and, where
appropriate, under section 313(d)(2)(C) (i.e., based on adverse
ecological effects). For chemicals listed under EPCRA section
313(d)(2)(A), this analysis included estimated concentrations of the
chemical at or beyond the facility site boundary through the use of
estimated releases and modelling techniques. EPA requests comment on
its approach in considering exposure as a part of its evaluation of
these chemicals under sections 313(d)(2)(A) and (C).
Based on this analysis for each of the chemicals proposed for
listing, EPA determined that one or more of the statutory criteria were
met. A discussion of EPA's interpretation of the EPCRA section 313
criteria is given in Unit III. of this preamble. A discussion of the
evidence supporting EPA's proposal to add each of the chemicals to
EPCRA section 313 is presented in Unit IV. of this preamble and in the
record supporting this proposed rule.
4. Other considerations. EPA excluded certain chemicals and
chemical categories from consideration for proposed listing under EPCRA
section 313 in this rulemaking for a number of reasons. Some chemicals
were identified only as environmental degradation products rather than
chemicals that are manufactured, processed, or otherwise used by a
facility. These chemicals will only be present in the environment as a
result of the release into the environment of precursor chemicals. If
the degradation product meets the toxicity criteria of EPCRA section
313, the precursor chemical may be considered for listing on EPCRA
section 313. The degradation product would not be considered for
listing on EPCRA section 313 because a facility subject to EPCRA
section 313 is only required to file a TRI report for a chemical that
it manufactures, processes, or otherwise uses, within the facility
boundaries. Therefore, EPA does not believe that it is appropriate to
consider listing such chemicals at this time.
Some of the lists reviewed by EPA included listings that
represented waste streams from particular processes. These waste
streams, such as coke oven emissions, are not discrete chemicals or
chemical categories, but contain a wide range of chemicals, many of
which are currently listed individually on EPCRA section 313. The focus
of this rulemaking is on the addition of specific chemicals and
chemical categories and, as such, EPA believes that these waste streams
are inappropriate for listing under EPCRA section 313 at this time.
EPA also excluded chemicals whose only identified toxicity concern
was a result of their status as a volatile organic compound (VOC). VOCs
contribute to the formation of tropospheric ozone which causes a number
of health-related and environmental problems. EPA continues to believe
that VOCs meet the listing criteria of EPCRA section 313. However, EPA
intends to address the issue of how VOCs should be listed on EPCRA
section 313 separately. Therefore, chemicals whose only identified
toxicity concern is due to their status as VOCs were excluded from
consideration at this time.
EPA also identified chemicals that are routinely manufactured,
processed, or otherwise used at levels far below the reporting
thresholds of EPCRA section 313. These chemicals are not expected to
ever be manufactured, processed, or otherwise used in quantities at or
above these reporting thresholds. In this proposed rulemaking, EPA is
attempting to add chemicals to EPCRA section 313 that are manufactured,
processed, or otherwise used in quantities greater than the EPCRA
section 313 volume thresholds and thus would result in the submission
of TRI reports. Consequently, chemicals that are manufactured,
processed, or otherwise used in quantities less than the EPCRA section
313 volume thresholds were excluded from further consideration at this
time, because no reports would be filed under EPCRA section 313 for
such chemicals.
Some of the chemicals that are manufactured, processed, or
otherwise used below the EPCRA section 313 activity thresholds,
particularly those chemicals that are manufactured in trace amounts in
waste streams, are highly toxic at very low dose levels and have
physical, chemical, or biological properties that make the chemicals
persist for extended periods in the environment, and bioaccumulate
through the food chain. Persistent bioaccumulative toxic chemicals,
such as dioxins, are of particular concern in ecosystems such as the
Great Lakes Basin due to the long retention time of the individual
lakes and the cycling of the chemical from one component of the
ecosystem to another. EPA may reconsider in the future the issue of
listing such chemicals in a manner which would result in the submission
of TRI reports. EPA requests comment on the following: Is it
appropriate to list such chemicals on EPCRA section 313? If EPA were to
add this type of chemical to EPCRA section 313, what modifications to
EPCRA section 313, such as lowering the reporting thresholds and
modifying the de minimis in mixture exemptions (40 CFR part 372.38),
would be required to insure that release and transfer information would
be collected?
III. EPCRA Section 313 Statutory Criteria
EPCRA section 313(d)(2) sets out criteria for adding chemicals to
the list of chemicals subject to reporting under section 313(a). For a
chemical (or category of chemicals) to be added to the EPCRA section
313(c) list of toxic chemicals, the Administrator must determine
whether, in her judgement, there is sufficient evidence to establish
any one of the following:
(A) The chemical is known to cause or can reasonably be anticipated
to cause significant adverse acute human health effects at
concentration levels that are reasonably likely to exist beyond
facility site boundaries as a result of continuous, or frequently
recurring, releases.
(B) The chemical is known to cause or can reasonably be anticipated
to cause in humans--
(i) cancer or teratogenic effects, or
(ii) serious or irreversible--
(I) reproductive dysfunctions,
(II) neurological disorders,
(III) heritable genetic mutations, or
(IV) other chronic health effects.
(C) The chemical is known to cause or can reasonably be anticipated
to cause, because of--
(i) its toxicity,
(ii) its toxicity and persistence in the environment, or
(iii) its toxicity and tendency to bioaccumulate in the
environment, a significant adverse effect on the environment of
sufficient seriousness, in the judgement of the Administrator, to
warrant reporting under this section.
To remove a chemical from the section 313(c) list, the
Administrator must determine that there is not sufficient evidence to
establish any of the criteria described above as required by EPCRA
section 313(d)(3). Thus, the criteria for listing or delisting a
chemical are identical. However, whereas EPA can add a chemical if only
one of the criteria is met, it can only delete a chemical if none of
the criteria are met.
To ascertain whether there is sufficient or insufficient evidence
to determine that the statutory criteria are met for listing a
chemical, EPA conducts a hazard assessment on the chemical and
determines based on the weight-of-the-evidence, whether the chemical
can reasonably be anticipated to cause any of the adverse effects
specified in EPCRA section 313(d)(2). The hazard analysis is described
above in Unit II.B.3. of this preamble. EPA's interpretation of the
specific statutory criteria follows.
1. Section 313(d)(2)(A) (acute human health effects). To determine
whether the section 313(d)(2)(A) ``acute human health effects''
criterion is met, EPA must examine the adverse effects associated with
the chemical, the ``concentration levels'' which would cause acute
human health effects, and the likelihood of such levels existing
``beyond facility site boundaries as a result of continuous, or
frequently recurring, releases.'' Such a determination may include,
among other factors, consideration of production processes, workplace
procedures, pollution controls, and the volume and pattern of
production, use, and release, as well as other chemical-specific
factors. EPA believes that to make the section 313(d)(2)(A)
determination it must demonstrate that a chemical can reasonably be
anticipated to be released in quantities that result in concentration
levels, or within a reasonable margin of exposure of the concentration
levels, that would be expected to cause acute human health effects
beyond the facility site boundary. The margin of exposure applied is
dependent upon the type of hazard data (e.g., data in animals versus
human) and the confidence in this hazard data base for acute effects
(e.g., sufficiency of the hazard data). However, EPA is not required to
make a facility-specific finding, nor is it necessary for EPA to
demonstrate that these concentration levels or effects occur at or near
any particular facility (Ref. 1). Furthermore, ``EPA may, but is not
required to, conduct new studies or risk assessments or perform site-
specific analyses to establish actual ambient concentrations or to
document adverse effects at any particular location'' (Ref. 1). Nor is
EPA limited to considering concentration levels and potential acute
human health effects at the ``fenceline.'' Rather, the phrase ``beyond
facility site boundaries'' reflects Congress' recognition that the
``highest concentration to which persons outside the site boundary may
be exposed'' could occur at ``any point outside the boundaries of the
site on which the facility is located,'' including, for example, where
an air emissions plume cools and settles to the ground (Ref. 1).
Therefore, EPA believes that to make a finding under EPCRA section
313(d)(2)(A), the Agency may estimate concentrations at or beyond the
facility site boundary through the use of estimated releases and
modelling techniques. The term ``continuous or frequently recurring
releases'' is included only to distinguish routine releases that are a
normal consequence of the operation of a facility from the episodic and
accidental releases that are subject to EPCRA section 304 (Ref. 1). As
such, EPA believes that episodic and accidental releases are not
pertinent in a determination that a chemical meets the section
313(d)(2)(A) criterion.
2. Section 313(d)(2)(B) (chronic human health effects). In contrast
to the section 313(d)(2)(A) criterion, section 313(d)(2)(B) does not
require consideration of either the nature and frequency of releases or
concentration levels at facility site boundaries. Rather, section
313(d)(2)(B) is focused solely on whether the chemical is known or can
reasonably be anticipated to cause cancer, teratogenicity, or other
serious or irreversible chronic human health effects. Consequently, EPA
believes that it is sufficient to consider only the toxicity of the
subject chemical to make the section 313(d)(2)(B) determination.
3. Section 313(d)(2)(C) (environmental effects). The section
313(d)(2)(C) criterion requires EPA to consider a chemical's potential
to cause significant adverse effects on the environment. The statute
directs EPA to base its determination on a consideration of the
toxicity of the chemical, either alone or in combination with the
persistence of the chemical or the potential for the chemical to
bioaccumulate. Congress intended that EPA consider a broad range of
environmental effects when making a determination under section
313(d)(2)(C).
In determining what constitutes a significant adverse effect on
the environment...the Administrator should consider the extent to
which the toxic chemical causes or can reasonably be anticipated to
cause any of the following adverse reactions, even if restricted to
the immediate vicinity adjacent to the site: (1) Gradual or sudden
changes in the composition of animal life or plant life, including
fungal or microbial organisms in an area. (2) Abnormal number of
deaths of organisms (e.g. fish kills). (3) Reduction of the
reproductive success or the vigor of a species. (4) Reduction in
agricultural productivity, whether crops or livestock. (5)
Alterations in the behavior or distribution of a species. (6) Long
lasting or irreversible contamination of components of the physical
environment, especially in the case of groundwater, and surface
water and soil resources that have limited self-cleansing capability
(Ref. 1).
EPA believes that the environmental effects criterion inherently
contains a limited exposure component because of the statutory
requirement for EPA to find a ``significant adverse effect on the
environment of sufficient seriousness, in the judgment of the
Administrator, to warrant reporting'' under EPCRA section 313. Unlike
section 313(d)(2)(B), where EPA only has to determine whether certain
kinds of effects are ``known or reasonably anticipated'' to occur,
section 313(d)(2)(C) requires EPA to find the effect to be of
sufficient seriousness to warrant reporting, which implies the
possibility that under certain circumstances, a chemical that could
theoretically cause a significant adverse effect on the environment is
unlikely to cause one of a magnitude to warrant listing.
The extent to which exposure is factored into EPA's determination
depends upon the inherent toxicity of a chemical, and a variety of
other chemical-specific characteristics. EPA believes that when a
chemical is inherently extremely toxic, that is, it is toxic at very
low dose levels, an exposure assessment is not necessary because even
minimal releases of such a chemical may reasonably be anticipated to
result in significant adverse environmental effects. In such cases, EPA
could rely on toxicity alone under section 313(d)(2)(C)(i) as a basis
for listing.
However, for chemicals that exhibit adverse effects upon the
environment solely based on toxicity at moderately low doses, EPA
believes that consideration of potential exposure is warranted because
minimal releases may not result in significant adverse effects upon the
environment. These exposure considerations may include, among other
factors, pollution controls, the volume and pattern of production, use,
and release, environmental fate, as well as other chemical-specific
factors, and the use of estimated releases and modelling techniques.
EPCRA sections 313(d)(2)(C)(ii) and (iii) allow EPA to consider the
impacts of other characteristics of a chemical. Where a chemical
exhibits significant adverse effects in the environment based on
toxicity and persistence or toxicity and bioaccumulation at very low to
moderately low dose levels, EPA believes that exposure considerations
are not required in addition to those considerations implicit in
evaluation of the chemical's potential for persistence and
bioaccumulation. This is because even minimal releases of the chemical
may result in elevated concentrations in the environment or in an
organism that can reasonably be anticipated to result in significant
adverse effects. This reflects the increased likelihood that there will
be exposure to a chemical that persists due to its longer residence
time in the environment. Repeated minimal releases of a persistent
chemical may result in elevated concentrations in the environment. For
a chemical that bioaccumulates, even low levels of the chemical in the
environment may result in increased concentrations in an organism.
Therefore, evaluation of a chemical's persistence or bioaccumulation
potential may be considered the functional equivalent of an exposure
analysis.
In addition, for chemicals which induce well-established adverse
effects, e.g. chlorofluorocarbons, which cause stratospheric ozone
depletion, EPA believes that an exposure assessment is unnecessary. EPA
believes that these chemicals typically do not affect solely one or two
species but rather affect changes across a whole ecosystem. EPA
believes that these effects are of sufficient seriousness that
additional exposure considerations are not warranted because of the
scope of their impact and the well-documented evidence supporting the
adverse effects. EPA requests comment on its approach for considering
exposure as a part of its evaluation for listing of these chemicals
under section 313(d)(2)(C).
In Unit IV.B. of this preamble, EPA identifies each of the
chemicals proposed for addition to EPCRA section 313 and the specific
statutory criteria upon which the proposed addition is based.
IV. EPA's Technical Review
A. Introduction
Data on the chemicals and chemical categories were reviewed for
evidence indicating adverse acute and chronic toxicity,
carcinogenicity, mutagenicity, developmental and reproductive effects,
neurotoxicity, and environmental effects. Information on the
environmental fate was also reviewed.
For each chemical proposed for addition to EPCRA section 313 in
this rulemaking, EPA conducted an extensive hazard assessment, and,
where appropriate, an analysis of exposure, to determine whether the
chemical met one or more of the EPCRA section 313(d)(2) listing
criteria. This hazard assessment is discussed in detail in Unit II.B.3
of this preamble. Only after this careful review was a final
determination made as to whether one of the EPCRA section 313(d)(2)
listing criteria was met for each individual chemical or chemical
category proposed for listing below. EPA need only show that one of the
listing criteria is met in order to list a chemical or chemical
category under EPCRA section 313. The information summarized below for
each chemical or chemical category represents the key data elements
that lead EPA to believe that there is sufficient evidence to establish
that one of the section 313(d)(2) listing criteria is met. A more
extensive review of the existing data base for each chemical or
chemical category proposed for listing, which reflects the entire
weight-of-the-evidence considered by EPA, is contained in following
support documents: Support Document for the Addition of Chemicals from
Federal Insecticide, Fungicide, Rodenticide Act (FIFRA) Active
Ingredients to EPCRA Section 313 (Ref 3); Physical Properties and
Environmental Fate of Some TRI Expansion Chemicals (Ref. 5); Support
Document for the Addition of Chemicals from Section 112(b) of the Clean
Air Act Amendments and Chlorinated Paraffins to EPCRA Section 313 (Ref.
7); and Support Document for the Health and Ecological Toxicity Review
of TRI Expansion Chemicals (Ref. 8). These support documents contain a
complete list of the references (which can be found in the public
record for this proposed rulemaking) that were used in support of these
proposed additions.
A list of the 313 chemicals and chemical categories and their
Chemical Abstract Service (CAS) number, where appropriate, follows.
1. Abamectin (Avermectin B1) (CAS No. 071751-41-2)
2. Acephate (Acetylphosphoramidothioic acid O,S-dimethyl ester)
(CAS No. 030560-19-1)
3. Acifluorfen sodium salt (5-(2-Chloro-4-
(triflouromethyl)phenoxy)-2-nitro-benzoic acid, sodium salt) (CAS
No. 062476-59-9)
4. Alachlor (CAS No. 015972-60-8)
5. Aldicarb (CAS No. 000116-06-3)
6. d-trans-Allethrin [d-trans-Chrysanthemic acid of d-
allethrone] (CAS No. 028057-48-9)
7. Allylamine (CAS No. 000107-11-9)
8. Aluminum phosphide (CAS No. 020859-73-8)
9. Ametryn (N-Ethyl-N'-(1-methylethyl)-6-(methylthio)-
1,3,5,triazine- 2,4 diamine) (CAS No. 000834-12-8)
10. Amitraz (CAS No. 033089-61-1)
11. Anilazine (4,6-Dichloro-N-(2-chlorophenyl)-1,3,5-triazin-2-
amine) (CAS No. 000101-05-3)
12. Atrazine (6-Chloro-N-ethyl-N'-(1-methylethyl)-
1,3,5,triazine-2,4-diamine) (CAS No. 001912-24-9)
13. Bendiocarb (2,2-Dimethyl-1,3-benzodioxol-4-ol
methylcarbamate) (CAS No. 022781-23-3)
14. Benfluralin (N-Butyl-N-ethyl-2,6-dinitro-4-(trifluoromethyl)
benzenamine) (CAS No. 001861-40-1)
15. Benomyl (CAS No. 017804-35-2)
16. o-Benzyl-p-chlorophenol (CAS No. 000120-32-1)
17. Bifenthrin (CAS No. 082657-04-3)
18. Bis(tributyltin) oxide (CAS No. 000056-35-9)
19. Boron trichloride (CAS No. 010294-34-5)
20. Boron trifluoride (CAS No. 007637-07-2)
21. Bromacil (5-Bromo-6-methyl-3-(1-methylpropyl)-2,4-(1H,3H)-
pyrimidinedione) (CAS No. 000314-40-9)
22. Bromacil lithium salt (2,4-(1H,3H)-Pyrimidinedione, 5-bromo-
6-methyl-3-(1-methylpropyl), lithium salt) (CAS No. 053404-19-6)
23. Bromine (CAS No. 007726-95-6)
24. 1-Bromo-1-(bromomethyl)-1,3-propanedicarbonitrile (CAS No.
035691-65-7)
25. 2-Bromo-2-nitropropane-1,3-diol (Bronopol) (CAS No. 000052-
51-7)
26. Bromoxynil (3,5-Dibromo-4-hydroxybenzonitrile) (CAS No.
001689-84-5)
27. Bromoxynil octanoate (Octanoic acid, 2,6-dibromo-4-
cyanophenyl ester) (CAS No. 001689-99-2)
28. Brucine (CAS No. 000357-57-3)
29. Butylate (Bis-2-methylpropyl)carbamothioic acid S-ethyl
ester) (CAS No. 002008-41-5)
30. Butylated hydroxyanisole (CAS No. 025013-16-5)
31. C.I. Acid Red 114 (CAS No. 006459-94-5)
32. C.I. Direct Blue 218 (CAS No. 028407-37-6)
33. Calcium hypochlorite (CAS No. 007778-54-3)
34. Caprolactam (CAS No. 000105-60-2)
35. Carbofuran (CAS No. 001563-66-2)
36. Carbon monoxide (CAS No. 000630-08-0)
37. Carboxin (5,6-Dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-
carboxamide) (CAS No. 005234-68-4)
38. Chinomethionat (6-Methyl-1,3-dithiolo[4,5-b]quinoxalin-2-
one) (CAS No. 002439-01-2)
39. Chlorendic acid (CAS No. 000115-28-6)
40. Chlorimuron ethyl (Ethyl-2-[[[(4-chloro-6-methoxyprimidin-2-
yl)-carbonyl]-amino]sulfonyl]benzoate) (CAS No. 090982-32-4)
41. Chlorinated paraffins
42. 1-(3-Chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride
(CAS No. 004080-31-3)
43. p-Chloroaniline (CAS No. 000106-47-8)
44. 5-Chloro-2-(2,4-dichlorophenoxy)phenol (CAS No. 003380-34-5)
45. 3-Chloro-2-methyl-1-propene (CAS No. 000563-47-3)
46. p-Chlorophenyl isocyanate (CAS No. 000104-12-1)
47. Chloropicrin (CAS No. 000076-06-2)
48. 3-Chloropropionitrile (CAS No. 000542-76-7)
49. p-Chloro-o-toluidine (CAS No. 000095-69-2)
50. Chlorotrifluoromethane (CFC-13) (CAS No. 000075-72-9)
51. Chlorpyrifos methyl (O,O-Dimethyl-O-(3,5,6-trichloro-2-
pyridyl)phosphorothioate) (CAS No. 005598-13-0)
52. Chlorsulfuron (2-Chloro-N-[[(4-methoxy-6-methyl-1,3,5-
triazin-2-yl)amino]carbonyl]benzenesulfonamide) (CAS No. 064902-72-
3)
53. Clomazone (2-[(2-Chlorophenyl)methyl]-4,4-dimethyl-3-
isoxazolidinone) (CAS No. 081777-89-1)
54. Crotonaldehyde (CAS No. 004170-30-3)
55. Cyanazine (CAS No. 021725-46-2)
56. Cycloate (CAS No. 001134-23-2)
57. Cyclohexanol (CAS No. 000108-93-0)
58. Cyfluthrin (3-(2,2-Dichloroethenyl)-2,2-
dimethylcyclopropanecarboxylic acid, cyano(4-fluoro-3-
phenoxyphenyl)methyl ester) (CAS No. 068359-37-5)
59. Cyhalothrin (3-(2-Chloro-3,3,3-trifluoro-1-propenyl)-2,2-
dimethylcyclopropanecarboxylic acid cyano(3-phenoxyphenyl)methyl
ester) (CAS No. 068085-85-8)
60. Cyromazine (N-Cyclopropyl-1,3,5-triazine-2,4,6-triamine)
(CAS No. 066215-27-8)
61. Dazomet (Tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-
thione) (CAS No. 000533-74-4)
62. Dazomet, sodium salt (2H-1,3,5-Thiadiazine-2-thione,
tetrahydro-3,5-dimethyl-, ion(1-), sodium) (CAS No. 053404-60-7)
63. 2,4-DB (CAS No. 000094-82-6)
64. 2,4-D butoxyethyl ester (CAS No. 001929-73-3)
65. 2,4-D butyl ester (CAS No. 000094-80-4)
66. 2,4-D chlorocrotyl ester (CAS No. 002971-38-2)
67. Desmedipham (CAS No. 013684-56-5)
68. 2,4-D 2-ethylhexyl ester (CAS No. 001928-43-4)
69. 2,4-D 2-ethyl-4-methylpentyl ester (CAS No. 053404-37-8)
70. Diazinon (CAS No. 000333-41-5)
71. 2,2-Dibromo-3-nitrilopropionamide (CAS No. 010222-01-2)
72. Dicamba (3,6-Dichloro-2-methyoxybenzoic acid) (CAS No.
001918-00-9)
73. Dichloran (2,6-Dichloro-4-nitroaniline) (CAS No. 000099-30-
9)
74. 3,3'-Dichlorobenzidine dihydrochloride (CAS No. 000612-83-9)
75. 3,3'-Dichlorobenzidine sulfate (CAS No. 064969-34-2)
76. trans-1,4-Dichloro-2-butene (CAS No. 000110-57-6)
77. Dichloromethylphenylsilane (CAS No. 000149-74-6)
78. Dichlorophene (2,2'-Methylenebis(4-chlorophenol) (CAS No.
000097-23-4)
79. trans-1,3-Dichloropropene (CAS No. 010061-02-6)
80. Diclofop methyl (2-[4-(2,4-Dichlorophenoxy)
phenoxy]propanoic acid, methyl ester) (CAS No. 051338-27-3)
81. Dicyclopentadiene (CAS No. 000077-73-6)
82. Diethatyl ethyl (CAS No. 038727-55-8)
83. Diflubenzuron (CAS No. 035367-38-5)
84. Diglycidyl resorcinol ether (CAS No. 000101-90-6)
85. Dimethipin (2,3,-Dihydro-5,6-dimethyl-1,4-dithiin 1,1,4,4-
tetraoxide) (CAS No. 055290-64-7)
86. Dimethoate (CAS No. 000060-51-5)
87. 3,3'-Dimethoxybenzidine dihydrochloride (o-Dianisidine
dihydrochloride) (CAS No. 020325-40-0)
88. 3,3'-Dimethoxybenzidine hydrochloride (o-Dianisidine
hydrochloride) (CAS No. 111984-09-9)
89. Dimethylamine (CAS No. 000124-40-3)
90. Dimethylamine dicamba (CAS No. 002300-66-5)
91. 3,3'-Dimethylbenzidine dihydrochloride (o-Tolidine
dihydrochloride) (CAS No. 000612-82-8)
92. 3,3'-Dimethylbenzidine dihydrofluoride (o-Tolidine
dihydrofluoride) (CAS No. 041766-75-0)
93. Dimethyl chlorothiophosphate (CAS. No. 002524-03-0)
94. Dimethyldichlorosilane (CAS No. 000075-78-5)
95. N,N-Dimethylformamide (CAS No. 000068-12-2)
96. 2,6-Dimethylphenol (CAS No. 000576-26-1)
97. Dinocap (CAS No. 039300-45-3)
98. Dinoseb (CAS No. 000088-85-7)
99. Diphenamid (CAS No. 000957-51-7)
100. Diphenylamine (CAS No. 000122-39-4)
101. Dipotassium endothall (7-Oxabicyclo(2.2.1)heptane-2,3-
dicarboxylic acid, dipotassium salt) (CAS No. 002164-07-0)
102. Dipropyl isocinchomeronate (CAS No. 000136-45-8)
103. Disodium cyanodithioimidocarbonate (CAS No. 000138-93-2)
104. 2,4-D isopropyl ester (CAS No. 000094-11-1)
105. 2,4-Dithiobiuret (CAS No. 000541-53-7)
106. Dithiopyr (2-(Difluoromethyl)-4-(2-methylpropyl)-6-
(trifluoromethyl)-3,5-pyridinedicarbothioic acid S,S-dimethyl ester)
(CAS No. 097886-45-8)
107. Diuron (CAS No. 000330-54-1)
108. 2,4-D 2-octyl ester (CAS No. 001917-97-1)
109. Dodine (Dodecylguanidine monoacetate) (CAS No. 002439-10-3)
110. 2,4-DP (Dichlorprop) (CAS No. 000120-36-5)
111. 2,4-D propylene glycol butyl ether ester (CAS No. 001320-
18-9)
112. 2,4-D sodium salt (CAS No. 002702-72-9)
113. Ethoprop (Phosphorodithioic acid O-ethyl S,S-dipropyl
ester) (CAS No. 013194-48-4)
114. Ethyl dipropylthiocarbamate (EPTC) (CAS No. 000759-94-4)
115. Famphur (CAS No. 000052-85-7)
116. Fenarimol (.alpha.-(2-Chlorophenyl)-.alpha.-4-
chlorophenyl)-5-pyrimidinemethanol) (CAS No. 060168-88-9)
117. Fenbutatin oxide (hexakis(2-methyl-2-
phenylpropyl)distannoxane) (CAS No. 013356-08-6)
118. Fenoxaprop ethyl (2-(4-((6-Chloro-2
benzoxazolylen)oxy)phenoxy)propanoic acid, ethyl ester) (CAS No.
066441-23-4)
119. Fenoxycarb (2-(4-Phenoxyphenoxy)ethyl]carbamic acid ethyl
ester) (CAS No. 072490-01-8)
120. Fenpropathrin (2,2,3,3-Tetramethylcyclopropane carboxylic
acid cyano(3-phenoxyphenyl)methyl ester) (CAS No. 039515-41-8)
121. Fenthion (O,O-Dimethyl O-[3-methyl-4-(methylthio) phenyl]
ester, phosphorothioic acid) (CAS No. 000055-38-9)
122. Fenvalerate (4-Chloro-alpha-(1-methylethyl)benzeneacetic
acid cyano(3-phenoxyphenyl)methyl ester) (CAS No. 051630-58-1)
123. Ferbam (Tris(dimethylcarbamodithioato-S,S')iron) (CAS No.
014484-64-1)
124. Fluazifop butyl (2-[4-[[5-(Trifluoromethyl)-2-
pyridinyl]oxy]-phenoxy]propanoic acid, butyl ester) (CAS No. 069806-
50-4)
125. Flumetralin (2-Chloro-N-(2,6-dinitro-4-
(trifluoromethyl)phenyl)-N-ethyl-6-fluorobenzenemethanamine) (CAS
No. 062924-70-3)
126. Fluorine (CAS No. 007782-41-4)
127. Fluorouracil (5-Fluorouracil) (CAS No. 000051-21-8)
128. Fluvalinate (N-[2-Chloro-4-(trifluoromethyl)phenyl]-DL-
valine(+)- cyano (3-phenoxyphenyl)methyl ester) (CAS No. 069409-94-
5)
129. Folpet (CAS No. 000133-07-3)
130. Fomesafen (5-(2-Chloro-4-(trifluoromethyl)phenoxy)-N
methylsulfonyl)-2-nitrobenzamide) (CAS No. 072178-02-0)
131. alpha-Hexachlorocyclohexane (CAS NO. 000319-84-6)
132. Hexamethylene-1,6-diisocyanate (CAS No. 000822-60-0)
133. n-Hexane (CAS No. 000110-54-3)
134. Hexazinone (CAS No. 051235-04-2)
135. Hydramethylnon (Tetrahydro-5,5-dimethyl-
2(1H)pyrimidinone[3-[4-(trifluoromethyl)phenyl]-1-[2-
[4(trifluoromethyl) phenyl]ethenyl]-2 propenylidene]hydrazone) (CAS
No. 067485-29-4)
136--151. Hydrochlorofluorocarbons, specifically:
136. Dichloropentafluoropropane (CAS No. 127564-92-5)
137. 1,3-Dichloro-1,1,2,3,3-pentafluoropropane (HCFC-225ea) (CAS
No. 136013-79-1)
138. 2,2-Dichloro-1,1,1,3,3-pentafluoropropane (HCFC-225aa) (CAS
No. 128903-21-9)
139. 1,1-Dichloro-1,2,3,3,3-pentafluoropropane (HCFC-225eb) (CAS
No. 111512-56-2)
140. 1,1-Dichloro-1,2,2,3,3-pentafluoropropane (HCFC-225cc) (CAS
No. 13474-88-9)
141. 1,3-Dichloro-1,1,2,2,3-pentafluoropropane (HCFC-225cb) (CAS
No. 000507-55-1)
142. 1,2-Dichloro-1,1,3,3,3-pentafluoropropane (HCFC-225da) (CAS
No. 000431-86-7)
143. 3,3-Dichloro-1,1,1,2,2-pentafluoropropane (HCFC-225ca) (CAS
No. 000422-56-0)
144. 2,3-Dichloro-1,1,1,2,3-pentafluoropropane (HCFC-225ba) (CAS
No. 000422-48-0)
145. 1,2-Dichloro-1,1,2,3,3-pentafluoropropane (HCFC-225bb) (CAS
No. 000422-44-6)
146. Dichlorofluoromethane (HCFC-21) (CAS No. 000075-43-4)
147. 1,1,1,2-Tetrachloro-2-fluoroethane (HCFC-121a) (CAS No.
000354-11-0)
148. 1,1,2,2-Tetrachloro-1-fluoroethane (HCFC-121) (CAS No.
000354-14- 3)
149. 1,2-Dichloro-1,1-difluoroethane (HCFC-132b) (CAS No.
001649-08-7)
150. 2-Chloro-1,1,1-trifluoroethane (HCFC-133a) (CAS No. 000075-
88-7)
151. 3-Chloro-1,1,1-trifluoropropane (HCFC-253fb) (CAS No.
000460-35-5)
152. Imazalil (1-[2-(2,4-Dichlorophenyl)-2-(2-
propenyloxy)ethyl]1H-imidazole) (CAS No. 035554-44-0)
153. 3-Iodo-2-propynyl butylcarbamate (CAS No. 055406-53-6)
154. Iprodione (3-(3,5-Dichlorophenyl)-N-(1-methylethyl)-2,4-
dioxo-1-imidazolidinecarboxamide) (CAS No. 036734-19-7)
155. Iron pentacarbonyl (CAS No. 013463-40-6)
156. Isodrin (CAS No. 000465-73-6)
157. Isofenphos (2-[[Ethoxyl[(1-methylethyl)
amino]phosphinothioyl]oxy]benzoic acid 1-methylethyl ester) (CAS No.
025311-71-1)
158. Isophorone (CAS No. 000078-59-1)
159. Isophorone diisocyanate (CAS No. 004098-71-9)
160. Lactofen (5-(2-Chloro-4-(trifluoromethyl)phenoxy)-2-nitro-
2-ethoxy-1-methyl-2-oxoethyl ester) (CAS No. 077501-63-4)
161. Linuron (CAS No. 000330-55-2)
162. Lithium carbonate (CAS No. 000554-13-2)
163. Malathion (CAS No. 000121-75-5)
164. Man-made mineral fibers
165. Mecoprop (CAS No. 000093-65-2)
166. 2-Mercaptobenzothiazole (MBT) (CAS No. 000149-30-4)
167. Merphos (CAS No. 000150-50-5)
168. Metham sodium (Sodium methyldithiocarbamate) (CAS No.
000137-42-8)
169. Methazole (2-(3,4-Dichlorophenyl)-4-methyl-1,2,4-
oxadiazolidine-3,5-dione) (CAS No. 020354-26-1)
170. Methiocarb (CAS No. 002032-65-7)
171. Methoxone ((4-Chloro-2-methylphenoxy) acetic acid) (MCPA)
(CAS No. 000094-74-6)
172. Methoxone sodium salt ((4-Chloro-2-methylphenoxy) acetate
sodium salt) (CAS No. 003653-48-3)
173. 1,1-Methylene bis(4-isocyanatocyclohexane) (CAS No. 005124-
30-1)
174. Methylene bis(thiocyanate) (CAS No. 006317-18-6)
175. Methyl isothiocyanate (CAS No. 00556-61-6)
176. 2-Methyllactonitrile (CAS No. 000075-86-5)
177. N-Methylolacrylamide (CAS No. 000924-42-5)
178. Methyl parathion (CAS No. 000298-00-0)
179. N-Methyl-2-pyrrolidone (CAS No. 000872-50-4)
180. Methyltrichlorosilane (CAS No. 000075-79-6)
181. Metiram (CAS No. 009006-42-2)
182. Metribuzin (CAS No. 021087-64-5)
183. Mevinphos (CAS No. 007786-34-7)
184. Molinate (1H-Azepine-1-carbothioic acid, hexahydro-S-ethyl
ester) (CAS No. 002212-67-1)
185. Monuron (CAS No. 000150-68-5)
186. Myclobutanil (.alpha.-Butyl-.alpha.-(4-chlorophenyl)-1H-
1,2,4-triazole-1-propanenitrile) (CAS No. 088671-89-0)
187. Nabam (CAS No. 000142-59-6)
188. Naled (CAS No. 000300-76-5)
189. Nicotine and salts
190. Nitrapyrin (2-Chloro-6-(trichloromethyl) pyridine) (CAS No.
001929-82-4)
191. Nitrate ion (CAS No. 014797-55-8)
192. Nitric oxide (CAS No. 010102-43-9)
193. p-Nitroaniline (CAS No. 000100-01-6)
194. Nitrogen dioxide (CAS No. 010102-44-0)
195. Norflurazon (4-Chloro-5-(methylamino)-2-
[3(trifluoromethyl)phenyl]-3(2H)-pyridazinone) (CAS No. 027314-13-2)
196. Oryzalin (4-(Dipropylamino)-3,5-dinitrobenzenesulfonamide)
(CAS No. 019044-88-3)
197. Oxydemeton methyl (S-(2-(Ethylsulfinyl)ethyl) O,O-dimethyl
ester phosphorothioic acid) (CAS No. 000301-12-2)
198. Oxydiazon (3-[2,4-Dichloro-5-(1-methylethoxy)phenyl]-5(1,1-
dimethylethyl)-1,3,4-oxadiazol-2(3H)-one) (CAS No. 019666-30-9)
199. Oxyfluorfen (CAS No. 042874-03-3)
200. Ozone (CAS No. 010028-15-6)
201. Paraquat dichloride (CAS No. 001910-42-5)
202. Pebulate (Butylethylcarbamothioic acid S-propyl ester) (CAS
No. 001114-71-2)
203. Pendimethalin (N-(1-Ethylpropyl)-3,4-dimethyl-2,6-
dinitrobenzenamine) (CAS No. 040487-42-1)
204. Pentobarbital sodium (CAS No. 000057-33-0)
205. Perchloromethyl mercaptan (CAS No. 000594-42-3)
206. Permethrin (3-(2,2-Dichloroethenyl)-2,2-
dimethylcyclopropanecarboxylic acid, (3-phenoxyphenyl)methyl ester)
(CAS No. 052645-53-1)
207. Phenanthrene (CAS No. 000085-01-8)
208. Phenothrin (2,2-Dimethyl-3-(2-methyl-1-propenyl)
cyclopropanecarboxylic acid (3-phenoxyphenyl)methyl ester) (CAS No.
026002-80-2)
209. 1,2-Phenylenediamine (CAS No. 000095-54-5)
210. 1,3-Phenylenediamine (CAS No. 000108-45-2)
211. 1,2-Phenylenediamine dihydrochloride (CAS No. 000615-28-1)
212. 1,4-Phenylenediamine dihydrochloride (CAS No. 000624-18-0)
213. Phenytoin (CAS No. 000057-41-0)
214. Phosphine (CAS No. 007803-51-2)
215. Phosphorus oxychloride (CAS No. 010025-87-3)
216. Phosphorus pentachloride (CAS No. 010026-13-8)
217. Phosphorus pentasulfide (CAS No. 001314-80-3)
218. Phosphorus pentoxide (CAS No. 001314-56-3)
219. Picloram (CAS No. 001918-02-1)
220. Piperonyl butoxide (CAS No. 000051-03-6)
221. Pirimiphos methyl (O-(2-(Diethylamino)-6-methyl-4-
pyrimidinyl)-O,O-dimethyl phosphorothioate) (CAS No. 029232-93-7)
222-- 249. Polycyclic aromatic compounds (PACs) including:
222. Benz(a)anthracene (CAS No. 000056-55-3)
223. Benzo(a)phenanthrene (CAS No. 000218-01-9)
224. Benzo(a)pyrene (CAS No. 000050-32-8)
225. Benzo(b)fluoranthene (CAS No. 000205-99-2)
226. Benzo(j)fluoranthene (CAS No. 000205-82-3)
227. Benzo(k)fluoranthene (CAS No. 000207-08-9)
228. Benzo(rst)pentaphene (CAS No. 000189-55-9)
229. Carbazole (CAS No. 000086-74-8)
230. Cyclopenta(cd)pyrene (CAS No. 027208-37-3)
231. Dibenz(a,h)acridine (CAS No. 000226-36-8)
232. Dibenz(a,j)acridine (CAS No. 000224-42-0)
233. Dibenz(a,c)anthracene (CAS No. 000215-58-7)
234. Dibenz(a,j)anthracene (CAS No. 000224-41-9)
235. Dibenzo(a,h)anthracene (CAS No. 000053-70-3)
236. Dibenzo(a,e)fluoranthene (CAS No. 005385-75-1)
237. Dibenzo(a,e)pyrene (CAS No. 000192-65-4)
238. Dibenzo(a,h)pyrene (CAS No. 000189-64-0)
239. Dibenzo(a,l)pyrene (CAS No. 000191-30-0)
240. 7H-Dibenzo(c,g)carbazole (CAS No. 000194-59-2)
241. 7,12-Dimethylbenz(a)anthracene (CAS No. 000057-976)
242. Indeno[1,2,3-cd]pyrene (CAS No. 000193-39-5)
243. 2-Methylchrysene (CAS No. 003351-32-4)
244. 3-Methylchrysene (CAS No. 003351-31-3)
245. 4-Methylchrysene (CAS No. 003351-30-2)
246. 5-Methylchrysene (CAS No. 003697-24-3)
247. 6-Methylchrysene (CAS No. 001705-85-7)
248. 2-Methylfluoranthene (CAS No. 033543-31-6)
249. 1-Nitropyrene (CAS No. 005522-43-0)
250. Potassium bromate (CAS No. 007758-01-2)
251. Potassium dimethyldithiocarbamate (CAS No. 000128-03-0)
252. Potassium N-methyldithiocarbamate (CAS No. 000137-41-7)
253. Primisulfuron (Methyl 2-[[[[[4,6-bis(difluoromethoxy)-
2pyrimidinyl]-amino]carbonyl]amino]sulfonyl]benzoate) (CAS No.
086209-51-0)
254. Profenofos (O-(4-Bromo-2-chlorophenyl)-O-ethyl-S-propyl
phosphorothioate) (CAS No. 041198-08-7)
255. Prometryn (N,N'-Bis(1-methylethyl)-6-methylthio-1,3,5-
triazine-2,4-diamine) (CAS No. 007287-19-6)
256. Propachlor (2-Chloro-N-(1-methylethyl)-N-phenylacetamide)
(CAS No. 001918-16-7)
257. Propanil (N-(3,4-Dichlorophenyl)propanamide) (CAS No.
000709-98-8)
258. Propargite (CAS No. 002312-35-8)
259. Propargyl alcohol (CAS No. 000107-19-7)
260. Propetamphos (3-[(Ethylamino)methoxyphosphinothioyl]oxy]-2-
butenoic acid, 1-methylethyl ester) (CAS No. 031218-83-4)
261. Propiconazole (1-[2-(2,4-Dichlorophenyl)-4-propyl-1,3-
dioxolan-2-yl]-methyl-1H-1,2,4,-triazole) (CAS No. 060207-90-1)
262. Quizalofop-ethyl (2-[4-[(6-Chloro-2-quinoxalinyl)
oxy]phenoxy] propanoic acid ethyl ester) (CAS No. 076578-14-8)
263. Resmethrin ([5-(Phenylmethyl)-3-furanyl]methyl 2,2-
dimethyl-3-(2-methyl-1-propenyl) cyclopropanecarboxylate]) (CAS No.
010453-86-8)
264. Sethoxydim (2-[1-(Ethoxyimino)butyl]-5-
[2(ethylthio)propyl]-3-hydroxyl-2-cyclohexen-1-one) (CAS No.074051-
80-2)
265. Simazine (CAS No. 000122-34-9)
266. Sodium azide (CAS No. 026628-22-8)
267. Sodium chlorite (CAS No. 007758-19-2)
268. Sodium dicamba (3,6-Dichloro-2-methoxybenzoic acid, sodium
salt) (CAS No. 001982-69-0)
269. Sodium dimethyldithiocarbamate (CAS No. 000128-04-1)
270. Sodium fluoroacetate (CAS. No. 000062-74-8)
271. Sodium hypochlorite (CAS No. 007681-52-9)
272. Sodium nitrite (CAS No. 007632-00-0)
273. Sodium pentachlorophenate (CAS No. 000131-52-2)
274. Sodium o-phenylphenoxide (CAS No. 000132-27-4)
275. Sodium 2-pyridinethiol-1-oxide (CAS No. 015922-78-8)
276. Strychnine and salts
277. Sulfur dioxide (CAS No. 007446-09-5)
278. Sulfur trioxide (CAS No. 007446-11-9)
279. Sulfuryl fluoride (Vikane) (CAS No. 002699-79-8)
280. Sulprofos (O-Ethyl O-[4-
(methylthio)phenyl]phosphorodithioic acid S- propyl ester) (CAS No.
035400-43-2)
281. Tebuthiuron (N-[5-(1,1-Dimethylethyl)-1,3,4-thiadiazol-2-
yl)- N,N'-dimethylurea) (CAS No. 034014-18-1)
282. Tefluthrin (CAS No. 079538-32-2)
283. Temephos (CAS No. 003383-96-8)
284. Terbacil (5-Chloro-3-(1,1-dimethylethyl)-6-methyl- 2,4-
(1H,3H)-pyrimidinedione) (CAS No. 005902-51-2)
285. Tetracycline hydrochloride (CAS No. 000064-75-5)
286. Tetramethrin (2,2-Dimethyl-3-(2-methyl-1-propenyl)
cyclopropanecarboxylic acid (1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-
isoindol-2-yl)methyl ester) (CAS No. 007696-12-0)
287. Tetrasodium ethylenediaminetetraacetate (CAS No. 000064-02-
8)
288. Thiabendazole (2-(4-Thiazolyl)-1H-benzimidazole) (CAS No.
000148-79-8)
289. Thiabendazole, hypophosphite salt (2-(4-Thiazolyl)
benzimidazole, hypophosphite salt) (CAS No. 028558-32-9)
290. Thiobencarb (Carbamic acid, diethylthio-, S-(p-
chlorobenzyl)) (CAS No. 028249-77-6)
291. Thiodicarb (CAS No. 059669-26-0)
292. Thiophanate ethyl ([1,2-Phenylenebis (iminocarbonothioyl)]
biscarbamic acid diethyl ester) (CAS No. 023564-06-9)
293. Thiophanate-methyl (CAS No. 023564-05-8)
294. Thiosemicarbazide (CAS No. 000079-19-6)
295. Triadimefon (1-(4-Chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-
triazol-1-yl)-2-butanone) (CAS No. 043121-43-3)
296. Triallate (CAS No. 002303-17-5)
297. Tribenuron methyl (2-(((((4-Methoxy-6-methyl-1,3,5-triazin-
2-yl)-methylamino)carbonyl)amino)sulfonyl)-, methyl ester) (CAS No.
101200-48-0)
298. Tributyltin fluoride (CAS No. 001983-10-4)
299. Tributyltin methacrylate (CAS No. 002155-70-6)
300. S,S,S-Tributyltrithiophosphate (DEF) (CAS No. 000078-48-8)
301. Trichloroacetyl chloride (CAS No. 000076-02-8)
302. Trichloroethylsilane (CAS No. 000115-21-9)
303. Trichlorophenylsilane (CAS No. 000098-13-5)
304. 1,2,3-Trichloropropane (CAS No. 000096-18-4)
305. Triclopyr triethylammonium salt (CAS No. 057213-69-1)
306. Triethylamine (CAS No. 000121-44-8)
307. Triforine (N,N'-[1,4-Piperazinediylbis(2,2,2-
trichloroethylidene)] bisformamide) (CAS No. 026644-46-2)
308. Trimethylchlorosilane (CAS No. 000075-77-4)
309. 2,3,5-Trimethylphenyl methylcarbamate (CAS No. 002655-15-4)
310. Triphenyltin chloride (CAS No. 000639-58-7)
311. Triphenyltin hydroxide (CAS No. 000076-87-9)
312. Vanadium pentoxide (CAS No. 001314-62-1)
313. Vinclozolin (3-(3,5-Dichlorophenyl)-5-ethenyl-5-methyl-2,4-
oxazolidinedione) (CAS No. 050471-44-8)
A limited discussion of the health and environmental effects
associated with each of the 313 chemicals and chemical categories is
provided below in Unit IV.B. of this preamble. Each chemical is
identified by chemical name, CAS No., and the list(s) from which the
chemical originated. These lists are designated as follows:
CAA HAP: Clean Air Act section 112(b) ``Hazardous Air
Pollutants.''
CAA OD: Clean Air Act section 602(b) Class II ozone depleters.
CAL: State of California Safe Drinking Water and Toxic
Enforcement Act of 1986 (Proposition 65) ``List of Chemicals Known
to the State to Cause Reproductive Toxicity.''
CERCLA: Comprehensive Environmental Response, Compensation, and
Liability Act section 102.
CWA PPL: Clean Water Act section 307(a) ``Priority Pollutant
List.''
EPCRA EHS: EPCRA section 302 ``Extremely Hazardous Substances.''
FIFRA AI: Federal Insecticide, Fungicide, and Rodenticide Act
(FIFRA) ``Active Ingredients.''
FIFRA SR: FIFRA ``Special Review, Canceled/Denied or Suspended,
and Restricted Use Pesticides.''
IARC: Monographs of the International Agency for Research on
Cancer.
NTP: The 6th Annual Report on Carcinogens of the National
Toxicology Program.
RCRA APP8: Resource Conservation and Recovery Act (RCRA)
Chemicals listed at 40 CFR part 261 Appendix VIII.
RCRA P: RCRA Chemicals listed at 40 CFR part 261.33(e).
SDWA: Safe Drinking Water Act section 1412.
TSCA: Toxic Substances Control Act ``Existing Chemicals.''
EPA requests comment on the sufficiency of the evidence for each of
the chemicals proposed for addition. In addition, EPA requests comment
on any issues that may be specific to any of the individual chemicals
or chemical categories. For example, should chemicals be listed on
EPCRA section 313 that meet the EPCRA section 313 criteria but whose
only use is as a drug product.
B. Chemicals Proposed for Addition to EPCRA Section 313
1. Abamectin (avermectin B1) (CAS No. 071751-41-2) (FIFRA AI) (Ref.
3). This compound induces developmental toxicity in several species
with the mouse being the most sensitive species. Increased retinal
folds in weanlings, decreased viability and lactation indices, and
decreased body weight were noted in a two-generation rat reproduction
study. The lowest-observed-effect level (LOEL) was 0.4 milligram per
kilogram per day (mg/kg/day) and the no-observed-effect level (NOEL)
was 0.12 mg/kg/day. Based on the NOEL, EPA derived a reference dose
(RfD) of 0.0004 mg/kg/day. EPA believes that there is sufficient
evidence for listing abamectin on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available developmental toxicity
data.
Aquatic acute toxicity values for abamectin include a bluegill 96-
hour LC50 of 9.6 parts per billion (ppb), a rainbow trout 96-hour
LC50 of 3.6 ppb, and a daphnid 48-hour LC50 of 0.34 ppb. EPA
believes that there is sufficient evidence for listing abamectin on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the
available environmental toxicity data.
2. Acephate (acetylphosphoramidothioic acid O,S-dimethyl ester)
(CAS No. 030560-19-1) (FIFRA AI) (Ref. 3). In a 28-month feeding study
in rats, inhibition of brain, plasma, and red blood cell cholinesterase
activities was observed at 50 parts per million (ppm) (2.5 mg/kg/day).
The NOEL for this study was 5 ppm (0.25 mg/kg/day). Similar findings
were noted in a 2-year feeding study in dogs. The LOEL for this study
was 100 ppm (2.5 mg/kg/day) and the NOEL was 30 ppm (0.75 mg/kg/day).
EPA believes that there is sufficient evidence for listing acephate on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available neurotoxicity data for this chemical.
3. Acifluorfen sodium salt (5-(2-chloro-4-
(triflouromethyl)phenoxy)-2-nitro-benzoic acid, sodium salt) (CAS No.
062476-59-9) (FIFRA AI) (Ref. 3). Acifluorfen is classified as a Group
B2 compound, i.e., the chemical is a probable human carcinogen.
Acifluorfen produced an increased incidence of combined malignant and
benign liver tumors in two different strains of mice. The compound also
displayed positive mutagenic activity in several non-mammalian test
systems, and is structurally similar to four other diphenyl ether
herbicide compounds which caused increased incidences of liver tumors
in two different strains of mice. EPA believes that there is sufficient
evidence for listing acifluorfen sodium salt on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available
carcinogenicity data.
4. Alachlor (CAS No. 015972-60-8) (FIFRA SR) (Ref. 8). Alachlor is
an aniline-type herbicide. Dose-related hemolytic anemia with
reductions in red blood cell counts, hematocrit and hemoglobin, as well
as hemosiderosis in the liver, spleen and kidney occurred in male dogs
orally exposed to alachlor for 1-year. The LOEL based on these effects
was 3.0 mg/kg/day, and the NOEL was 1.0 mg/kg/day. Effects in female
dogs in the same study were not demonstrated as clearly as in males but
were considered suggestive of anemia. EPA derived an oral RfD of 0.01
mg/kg/day from this study.
In a three-generation reproduction study in rats, chronic nephritis
and increased relative and absolute kidney weights were reported in
F2 adult males and F3 pups. The LOEL was 10 mg/kg/day, and
the NOEL was 3 mg/kg/day. Rabbits (Dutch Belted strain) that received
alachlor via oral gavage during gestation days 6 to 27 had an increased
rate of preimplantation loss (49 percent) and offspring with increased
incidences of developmental malformations including major vessel
variations, presacral vertebrae, and rudimentary and full 13th ribs.
The increased incidence of rudimentary and full 13th ribs was dose-
related, and a lowest-observed-adverse-effect level (LOAEL) of 10 mg/
kg/day was determined based on this effect. The no-observed-adverse
effect level (NOAEL) was not determined.
EPA has classified alachlor as a category Group B2 compound, i.e.,
the chemical is a probable human carcinogen. In a 2-year rat feeding
study with Long-Evans rats, there were increased incidences of nasal
turbinate tumors, malignant stomach tumors and thyroid follicular
adenomas and carcinomas in both sexes at doses greater than or equal to
42 mg/kg/day. In an 18-month study in female CD-1 mice, bronchiolar
tumors occurred at an increased incidence at 200 mg/kg/day.
EPA believes that there is sufficient evidence for listing alachlor
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on
the chronic toxicity and carcinogenicity data for this chemical.
5. Aldicarb (CAS No. 000116-06-3) (CERCLA; EPCRA EHS; FIFRA SR;
RCRA APP8; RCRA P) (Ref. 8). Aquatic acute toxicity test data for
aldicarb include a measured 96-hour LC50 of 50 ppb for bluegill
and a measured 48-hour LC50 of 70 ppb for daphnid. In addition,
the measured 48-hour EC50 for daphnid is 51 ppb. Measured
terrestrial acute toxicity data for wildlife include an oral LD50
for female mallard ducks of 3.4 milligram per kilogram (mg/kg) and an
oral LD50 for California quail of 2.58 mg/kg in males and 4.67 mg/
kg in females. EPA believes that there is sufficient evidence for
listing aldicarb on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(C) based on the environmental toxicity data for this
chemical.
6. d-trans-Allethrin [d-trans-Chrysanthemic acid of dallethrone]
(CAS No. 028057-48-9) (FIFRA AI) (Ref. 3). Centrilobular hydropic
degeneration of the liver (LOEL was 1,000 ppm or 25 mg/kg/day; the NOEL
was 200 ppm or 5 mg/kg/day) was seen in dogs fed allethrin for 3
months. Increases in serum liver enzymes in female rats and increased
liver weights in male and female rats (the LOEL was 250 mg/kg/day; the
NOEL was 1,500 ppm or 75 mg/kg/day) were observed in rats fed allethrin
for 3 months. Histopathology data were not presented in this study.
Taken together, the results of these studies indicate hepatotoxic
potential for d-trans-allethrin. EPA believes that there is sufficient
evidence for listing d-trans-allethrin on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(B) based on the available hepatic toxicity
data.
7. Allylamine (CAS No. 000107-11-9) (EPCRA EHS) (Ref. 8). Repeated
inhalation exposure to 5 ppm (0.011 mg/L) allylamine for 50 exposures
of 7 hours caused liver and renal damage and myocarditis in rats.
Congestion of the liver and kidney was observed in rats, rabbits, and
dogs exposed to 5 or 20 ppm (0.011 or 0.044 milligram per liter (mg/L))
allylamine for 8 hours/day, 5 days/week, for 1-year. EPA believes that
there is sufficient evidence for listing allylamine on EPCRA section
313 pursuant to EPCRA section 313(d)(2)(B) based on the hepatotoxicity
and nephrotoxicity data for this chemical.
8. Aluminum phosphide (CAS No. 020859-73-8) (CERCLA; EPCRA EHS;
RCRA APP8; RCRA P) (Ref. 8). The median lethal dose of aluminum
phosphide in humans is 20 mg/kg. The acute inhalation toxicity of
aluminum phosphide is attributed to phosphine gas resulting from
decomposition of aluminum phosphide on contact with moisture in the
air. Symptoms of phosphine poisoning include restlessness, headache,
dizziness, fatigue, chest tightness, nausea, vomiting, lethargy,
stupor, coma, convulsions, lowered blood pressure, pulmonary edema and
respiratory failure; disorders of the kidney, liver, heart and brain
can also occur. In female CFT-Wistar rats exposed to phosphine gas
generated from aluminum phosphide pellets in distilled water, 100
percent mortality was observed after a 6-hour exposure to 40 ppm (0.1
mg/L), and exposure to 20 to 40 ppm (0.05 to 0.1 mg/L) for 6 hours
resulted in 33 percent mortality. Symptoms of toxicity reported in
these animals included dyspnea, loss of muscular coordination,
polyuria, and paralysis.
EPA's exposure analysis indicates that aluminum phosphide
concentrations are likely to exist beyond facility site boundaries, as
a result of continuous, or frequently recurring releases, at levels
that can reasonably be anticipated to cause significant adverse acute
human health effects. EPA believes that there is sufficient evidence
for listing aluminum phosphide on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(A) based on the available acute toxicity and exposure
data for this chemical.
9. Ametryn (N-Ethyl-N'-(1-methylethyl)-6-(methylthio)1,3,5,-
triazine- 2,4-diamine) (CAS No. 000834-12-8) (FIFRA AI) (Ref. 3). Fatty
degeneration of the liver was observed in rats administered 100 mg/kg/
day ametryn by gavage, 6 days per week for 13 weeks. The NOEL was 10
mg/kg/day (8.6 mg/kg/day adjusted for duration). In another study,
hepatic effects (severe vascular congestion, centrilobular liver
necrosis and fatty degeneration of individual liver cells) were
observed in rats that died following gavage administration of 500 mg/
kg/day ametryn for 6 days per week for 28 days. The NOEL was 250 mg/kg/
day. EPA believes that there is sufficient evidence for listing ametryn
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on
the available hepatotoxicity data for this chemical.
The 72-hour EC50 for green algae is 14 ppb. Ametryn is a
herbicide and may be expected to affect nontarget plants such as algae.
EPA believes that there is sufficient evidence for listing ametryn on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the
available environmental toxicity data for this chemical.
10. Amitraz (CAS No. 033089-61-1) (FIFRA SR) (Ref. 8). Amitraz is
an aniline-type insecticide. In a 2-year beagle dog feeding study,
effects noted at the LOAEL dose (1.0 mg/kg/day) at various times during
the study included significantly increased mean blood glucose
concentration, slight hypothermia, and slight central nervous system
depression (the latter effect occurred immediately after dosing on days
1 and 2). The NOAEL in this study was 0.25 mg/kg/day and the oral RfD
derived from the NOAEL was 0.0025 mg/kg/day. These findings were
supported by similar results obtained in a 90-day feeding study in
dogs. In studies with rats or mice exposed to amitraz from 90 days to 2
years, LOAELs less than or equal to 12 mg/kg/day were derived based on
effects that included decreased body weight gain and changes in organ
(brain or heart) weight (the NOELs were less than or equal to 3 mg/kg/
day).
A three-generation reproduction study in rats demonstrated
decreased litter size and increased mortality during suckling. The
fetotoxic LOAEL in this study was 5 mg/kg/day and the NOAEL was 1.6 mg/
kg/day. In a teratology study in rabbits, a fetotoxicity LOAEL of 5 mg/
kg/day and NOAEL of 1 mg/kg/day were based on the incidences of cleft
palate and meningocoele associated with small ears and displaced toes.
EPA believes that there is sufficient evidence for listing amitraz
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on
the chronic toxicity and developmental toxicity data for this chemical.
11. Anilazine (4,6-dichloro-N-(2-chlorophenyl)-1,3,5-triazin-2-
amine) (CAS No. 000101-05-3) (FIFRA AI) (Ref. 3). When anilazine was
administered to rats, maternal reproductive parameters were not
affected. The systemic maternal NOEL was 150 mg/kg and the LOEL was 500
mg/kg, based on decreased body weight gain. The developmental NOEL was
1,500 mg/kg, which was the highest dose tested. In rabbits, the
maternal toxicity NOEL was 15 mg/kg and the LOEL was 40 mg/kg, based on
increased mortalities and decreased body weight gain (also decreased
percentage of pregnant does at 75 mg/kg). The developmental NOEL was 40
mg/kg and the LOEL was 75 mg/kg, based on increased fetal mortality,
decreased fetal weight, and increased postimplantation loss and
inhibited ossification (phalanges). EPA believes that there is
sufficient evidence for listing anilazine on EPCRA section 313 pursuant
to EPCRA section 313(d)(2)(B) based on the available developmental
toxicity data.
Aquatic acute toxicity values for anilazine include a scud
(Gammarus) 96-hour LC50 of 0.27 ppb and an oyster 96-hour
EC50 (growth) of 46 ppb. EPA believes that there is sufficient
evidence for listing anilazine on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(C) based on the available environmental toxicity
data.
12. Atrazine (6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5,-triazine-
2,4-diamine) (CAS No. 001912-24-9) (FIFRA AI) (Ref. 3). Based on
sufficient evidence of carcinogenicity in animals, the International
Agency for Research on Cancer (IARC) has classified atrazine as a Group
2B compound; i.e., the chemical is possibly carcinogenic to humans.
Administration of atrazine to Sprague Dawley rats was associated with
an increased incidence of mammary gland fibroadenomas and
adenocarcinomas in female rats. A hormonal mechanism may be involved in
the induction of mammary tumors by atrazine. Therefore there is
sufficient evidence for listing atrazine on EPCRA section 313 pursuant
to EPCRA section 313(d)(2)(B) based on the available carcinogenicity
data for this chemical.
13. Bendiocarb (2,2-dimethyl-1,3-benzodioxol-4-ol methylcarbamate)
(CAS No. 022781-23-3) (FIFRA AI) (Ref. 3). Depressed blood
cholinesterase levels were reported in numerous species. In a
developmental toxicity study in rats, cholinergic signs were observed
in maternal animals at 4 mg/kg/day (LOEL). The maternal NOEL was 1 mg/
kg/day; no adverse effects were observed in fetuses. A LOEL of 2.5 mg/
kg/day for cholinesterase inhibition was reported in dogs in a 4-month
dietary study. The NOEL was 0.5 mg/kg/day. Decreases in cholinesterase
activity were observed in female rats fed 20, 30, or 40 mg/kg/day for
28 days. No NOEL was established in this study. However, no details
regarding clinical signs or histopathological changes in neural tissue
were reported. EPA believes that there is sufficient evidence for
listing bendiocarb on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available neurological toxicity data for this
chemical.
Aquatic acute toxicity values for bendiocarb include a mysid 96-
hour EC50 of 6.7 ppb and a daphnid 48-hour EC50 of 29.2 ppb.
Avian acute toxicity values include a mallard duck LD50 of 3.1 mg/
kg. EPA believes that there is sufficient evidence for listing
bendiocarb on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C)
based on the available environmental toxicity data.
14. Benfluralin (N-butyl-N-ethyl-2,6-dinitro-4(trifluoromethyl)
benzenamine) (CAS No. 001861-40-1) (FIFRA AI) (Ref. 3). Increased
relative liver weights, decreased red blood cell counts and decreased
hematocrit and hemoglobin levels were observed in dogs orally
administered benfluralin at a dose of 125 mg/kg/day for 2 years. The
NOAEL was 25 mg/kg/day. Based on the NOAEL, EPA has established an oral
RfD of 0.003 mg/kg/day. EPA believes that there is sufficient evidence
for listing benfluralin on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available hematological toxicity data for
this chemical.
15. Benomyl (CAS No. 017804-35-2) (CAL; FIFRA SR) (Ref. 8). In a
three-generation study in rats, a dietary level of 25 mg/kg/day of
benomyl resulted in decreased weanling weights. The no-effect level was
5 mg/kg/day. Microphthalmia (the LOEL was 62.5 mg/kg/day; the NOEL was
30 mg/kg/day) was reported in a rat developmental toxicity study.
Decreased fetal weight (the LOEL was 62.5 mg/kg/day; the NOEL was 30
mg/kg/day) was observed in another rat developmental toxicity study.
The developmental effects were observed at doses that were not toxic to
the maternal animal. Anomalies consisting of supra occipital scars,
subnormal vertebral centrum, supernumary ribs, and cleft palate were
reported in an oral developmental toxicity study in mice (the LOEL was
100 mg/kg/day; the NOEL was 50 mg/kg/day). An increase in the incidence
of anomalies including encephalocele, hydrocephalus, microphthalmia,
and anophthalmia was noted following administration of benomyl to rats
by intubation during the first 20 days of pregnancy at doses of 125,
250, and 500 mg/kg. The developmental effects were always associated
with death and were considered to be the cause of death. EPA believes
that there is sufficient evidence for listing benomyl on EPCRA section
313 pursuant to EPCRA section 313(d)(2)(B) based on the developmental
toxicity data for this chemical.
16. o-Benzyl-p-chlorophenol (CAS No. 000120-32-1) (FIFRA AI) (Ref.
3). In a 16-day oral rat study, dose-related increases in liver and
kidney weights (absolute and relative) and nephrosis were observed at a
dose level of greater than or equal to 62.5 mg/kg/day. A NOEL was not
established. When the compound was administered by gavage for 13 weeks,
rats developed multifocal dilation of renal tubules and increased liver
weights (16 percent) at 240 mg/kg/day. The NOEL was 120 mg/kg/day. In a
90-day oral study, mice receiving 30 mg/kg/day developed kidney
lesions. Increased liver weights were also noted. No NOEL was
established in this study. EPA believes that there is sufficient
evidence for listing o-benzyl-p-chlorophenol on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available hepatic
and renal toxicity data for this chemical.
17. Bifenthrin (CAS No. 082657-04-3) (FIFRA AI) (Ref. 3). Tremors
or head and forelimb twitching were noted in dogs, rats and rabbits
exposed to various doses. NOEL values based on the appearance of
tremors (often transient) ranged from 1 to 2.67 mg/kg/day. The oral RfD
for bifenthrin was based on a 1year beagle dog feeding study, in which
the LOEL, based on tremors observed during weeks 15 to 29, was 3.0 mg/
kg/day and the NOEL was 1.5 mg/kg/day. The RfD based on this NOEL was
0.015 mg/kg/day.
In a rat teratology study, an increased incidence of hydroureter
(without hydronephrosis) was noted in fetuses at 2 mg/kg/day (LOEL).
The NOEL was 1 mg/kg/day.
EPA believes that there is sufficient evidence for listing
bifenthrin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available neurological and developmental toxicity data.
Aquatic acute toxicity values for bifenthrin include a bluegill 96-
hour LC50 of 0.35 ppb, a rainbow trout 96-hour LC50 of 0.15
ppb, a sheepshead minnow LC50 of 17.5 ppb, and a daphnid 48-hour
EC50 of 1.6 ppb. EPA believes that there is sufficient evidence
for listing bifenthrin on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(C) based on the available environmental toxicity data.
18. Bis(tributyltin) oxide (CAS No. 000056-35-9) (FIFRA AI) (Ref.
3). Adverse effects on the immune system were reported in rats exposed
to various doses of bis(tributyltin) oxide for a duration as short as 4
weeks. SPF-derived Wistar rats were fed the compound for 17 months. In
this study, a LOEL of 0.25 mg/kg/day and a NOEL of 0.025 mg/kg/day were
based on immunotoxicity manifested as decreased resistance to
Trichinella spiralis, reduced natural killer (NK) cell activity in the
spleen and reduced macrophage function. The RfD derived from this NOEL
was 0.00003 mg/kg/day. Similar immunological effects were reported in
4- and 6-week rat feeding studies with 20 and 80 ppm (1 and 4 mg/kg/
day; the LOEL was 1 mg/kg/day).
In rats that received dietary levels (of a range of doses that
included 50 mg/kg/day) for 106 weeks, kidney function was decreased and
serum levels of alanine aminotransferase, aspartate aminotransferase
and alkaline phosphatase were increased. At the end of the 2-year
study, nephrosis and vacuolization and pigmentation of the proximal
tubular epithelium were reported in animals administered 50 mg/kg/day.
On the basis of marginal effects at 5 mg/kg/day (LOEL), a NOEL of 0.5
mg/kg/day was established.
EPA believes that there is sufficient evidence for listing
bis(tributyltin) oxide on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available immunological and renal toxicity
data.
Aquatic acute toxicity values for bis(tributyltin) oxide include a
bluegill 96-hour LC50 of 7.6 ppb, a rainbow trout 96-hour
LC50 6.9 ppb, a measured fathead minnow 96-hour LC50 of 2.7
ppb, and a daphnid 48-hour LC50 of 1.67 ppb. EPA believes that
there is sufficient evidence for listing bis(tributyltin) oxide on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the
available environmental toxicity data.
19. Boron trichloride (CAS No. 010294-34-5) (EPCRA EHS) (Ref. 8).
Boron trichloride is corrosive to the skin and mucosal tissue due to
its rapid hydrolysis to hydrochloric acid and boric acid, the former
acid being the corrosive species. Single, relatively large doses of
boron administered through any route affects the central nervous system
causing depressed circulation, diarrhea, vomiting, shock, and coma. The
kidneys are the most severely affected organ. Symptoms of acute
irritation of the upper airways were observed in humans at exposure
levels of greater than or equal to 0.004 mg/L. Inhalation of 0.48 mg/L
of boron trichloride proved fatal to certain laboratory animals.
Inhalation of 0.096 mg/L of boron trichloride for 7 hours produced
adverse effects on the respiratory tract, and weight loss.
EPA's exposure analysis indicates that boron trichloride
concentrations are likely to exist beyond facility site boundaries, as
a result of continuous, or frequently recurring releases, at levels
that can reasonably be anticipated to cause significant adverse acute
human health effects. EPA believes that there is sufficient evidence
for listing boron trichloride on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(A) based on the available acute toxicity and exposure
data for this chemical.
20. Boron trifluoride (CAS No. 007637-07-2) (EPCRA EHS) (Ref. 8).
Boron trifluoride is a colorless gas that is corrosive to tissues due
to its rapid hydrolysis to hydrofluoric acid and boric acid. The
principal acute effect in animals is irritation of the mucous membranes
of the respiratory tract and eyes; post mortem examination also
revealed pneumonia and degenerative changes in renal tubules. The
kidneys are most severely affected because boric acid concentrates in
this organ. Exposure of six animal species to 0.28 mg/L of boron
trifluoride for 4 to 7 hours a day, 5 days a week killed all animals
within 30 days. Rats, rabbits, and guinea pigs were exposed to boron
trifluoride via inhalation. Guinea pigs died of respiratory failure
after being exposed to 0.036 mg/L for 19 days; rats experienced
fluorosis of the teeth at this concentration. All three species were
minimally affected at 0.004 mg/L. In a 2-week rat inhalation study, all
animals died after 6 daily exposures to 0.18 mg/L. Rats exposed to
0.024 mg/L showed signs of respiratory irritation, increased lung
weights, and depressed liver weights. Rats exposed to 0.17 mg/L of
boron trifluoride 6 hours/day, 5 days a week for 13 weeks developed
necrosis of the proximal tubular epithelium of the kidneys. Guinea pigs
exposed to 0.035 mg/L, 7 hours/day, 5 days a week for 3 months
developed severe pneumonitis and pulmonary changes indicating chemical
irritation.
EPA believes that there is sufficient evidence for listing boron
trifluoride on EPCRA section 313 pursuant to section 313(d)(2)(B) based
on the available chronic toxicity data for this chemical.
21. Bromacil (5-bromo-6-methyl-3-(1-methylpropyl)-2,4-(1H,3H)-
pyrimidinedione) (CAS No. 000314-40-9) (FIFRA AI) (Ref. 3). Increased
thyroid activity was seen in male and female rats fed 5,000 ppm (250
mg/kg/day) bromacil for 90 days. In a 2-year dietary study, thyroid
hyperplasia was seen in female rats fed 1,250 ppm (62.5 mg/kg/day).
Thyroid follicular adenoma was observed in one female. EPA believes
that there is sufficient evidence for listing bromacil on EPCRA section
313 pursuant to EPCRA section 313(d)(2)(B) based on the available
thyroid toxicity data for this chemical.
22. Bromacil lithium salt (2,4-(1H,3H)-pyrimidinedione, 5-bromo-6-
methyl-3-(1-methylpropyl), lithium salt) (CAS No. 05340419-6) (FIFRA
AI) (Ref. 3). Bromacil lithium salt will dissociate into bromacil,
which is soluble in aqueous systems and lithium ion. Defects of the
palate, eye, and external ear were reported in the offspring of rats
administered 50 mg lithium chloride intraperitoneally on gestation days
1, 4, 7, and 9 followed by 20 mg/day until day 17. Cleft palates were
also observed in mouse fetuses when mothers were gavaged with 300 to
465 mg/kg/day lithium carbonate on gestation day 6 to 15. An increase
in Ebstein's anomaly was reported among offspring of women taking
lithium; cardiovascular defects were found in 212 offspring exposed in
utero to lithium therapy.
Increased thyroid activity was seen in male and female rats fed
5,000 ppm (250 mg/kg/day) bromacil for 90 days. In a 2-year dietary
study, thyroid hyperplasia was seen in female rats fed 1,250 ppm (62.5
mg/kg/day). Thyroid follicular adenoma was observed in one female.
EPA believes that there is sufficient evidence for listing bromacil
lithium salt on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available developmental and thyroid toxicity
data.
23. Bromine (CAS No. 007726-95-6) (EPCRA EHS) (Ref. 8). Rats fed
bromine at a dose of 0.01 mg/kg/day for 6 months experienced changes in
their reflexes and blood indexes. Rats, mice, and rabbits inhaling
0.001 mg/kg/day for 4 months developed functional abnormalities of the
respiratory, nervous, and endocrine systems. Data on the acute and
chronic effects of bromine in humans are limited. Bromine is very
corrosive to the eyes, skin, and mucous membranes in either the liquid
or vapor form. A concentration of 10 ppm of bromine in air is
intolerable in humans, and can cause severe irritation of the upper
respiratory tract. Other clinical symptoms include neurologic,
dermatologic, and gastrointestinal effects. The maximum concentration
allowable in humans for a 0.5 to 1-hour exposure to bromine is 4 ppm.
Bromine can cause lacrimation at concentrations less than 1 ppm.
Chronic exposure to bromine (estimated concentration at 0.6 ppm) can
result in eye irritation, upper respiratory irritation, coughing, and
headache. Neurological symptoms have also been reported following
chronic exposure to bromine.
EPA believes that there is sufficient evidence for listing bromine
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on
the available chronic toxicity data for this chemical.
24. 1-Bromo-1-(bromomethyl)-1,3-propanedicarbonitrile (CAS No.
035691-65-7) (FIFRA AI) (Ref. 3). In a 3-month dietary study where rats
were administered 83.5, 500, and 3,000 ppm (4, 25, and 150 mg/kg/day)
1-bromo-1-(bromomethyl)-1,3-propanedicarbonitrile, a NOEL of 83.5 ppm
(4 mg/kg/day) and a LOEL of 500 ppm (25 mg/kg/day) were established
(based on neonatal splenic hematopoiesis, decreased parental body
weight and food consumption, increased male urinary epithelial cells,
amorphous casts, and crystals). At 3,000 ppm (150 mg/kg/day) there was
decreased lactase dehydrogenase, increased total cholesterol, total
protein, and albumin, elevated female organ-to-body weight ratio for
thyroid, liver, spleen, ovaries, and pituitary. In a 13-week dietary
study in beagle dogs (administered 167, 1,000, and 4,000 ppm; 4, 25,
and 100 mg/kg/day) the LOEL was greater than 167 ppm (4 mg/kg/day)
(increased male thyroid and female ovary organ to body weight ratio).
At 1,000 ppm (25 mg/kg/day), the same signs were seen as at 167 ppm (4
mg/kg/day), plus diarrhea and increased organ to body weight ratio of
thyroid, heart, liver, and adrenals. At 4,000 ppm (100 mg/kg/day),
emesis and ataxia in males, decreased body weight gain/food
consumption, decreased hematocrit, hemoglobin, immature red blood
cells, and alkaline phosphatase, extramedullary hematopoiesis in the
liver and spleen, thyroid enlargement with follicular cell hyperplasia,
increased organ to body weight ratios for thyroid, adrenals, liver and
spleen were seen. In a 13-week dietary study where beagle dogs were
administered 167 ppm (4 mg/kg/day), thyroid stimulating hormone (TSH)-
stimulated T3 and T4 increased in both sexes. Thyroids were enlarged
(both sexes) with absolute weights and organ to body weight ratios
increased in females.
EPA believes that there is sufficient evidence for listing 1-bromo-
1-(bromomethyl)-1,3-propanedicarbonitrile on EPCRA section 313 pursuant
to EPCRA section 313(d)(2)(B) based on the available toxicity data for
this chemical.
25. 2-Bromo-2-nitropropane-1,3-diol (bronopol) (CAS No. 000052-51-
7) (FIFRA AI) (Ref. 3). Severe irritation was reported in the
gastrointestinal tracts of rats, mice or dogs administered single or
multiple oral doses of 2-bromo-2-nitropropane-1,3-diol. In an acute
oral study in mice, the LD50 of 374 mg/kg resulted in ulceration
of the stomach and duodenum, thickening of the intestinal wall, and
adhesions of the stomach to the liver. Severe gastric irritation was
reported in dogs administered a single oral dose of 250 mg/kg. The NOEL
was 100 mg/kg. Superficial ulceration with epithelial hyperplasia and
hyperkeratosis, and congested vessels in the gastrointestinal mucosa,
was observed in rats fed 80 mg/kg/day (LOEL) in their diet for 13
weeks. The NOEL was 20 mg/kg/day. Vomiting was noted in dogs fed 20 mg/
kg/day in their diet for 13 weeks. The NOEL in this study was 8 mg/kg/
day. In addition, blood was noted in the urine of these dogs.
Mortality, irritation of the gastrointestinal tract, ulceration and
stomach lesions were reported in a 2-year dietary study in rats fed 40
mg/kg/day. The NOEL was 10 mg/kg/day. EPA believes that there is
sufficient evidence for listing 2-bromo-2-nitropropane-1,3-diol on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available toxicity data.
26. Bromoxynil (3,5-dibromo-4-hydroxybenzonitrile) (CAS No. 001689-
84-5) (FIFRA AI) (Ref. 3). Developmental effects (hydrocephalus,
microphthalmia, anophthalmia and severe defects in ossification of the
skull) were observed in rabbits administered 60 mg/kg/day bromoxynil by
gavage. The NOEL was 30 mg/kg/day. Developmental toxicity (increases in
all forms of supernumerary ribs) was also observed in rats at 5 mg/kg/
day. The NOEL was 1.5 mg/kg/day. The maternal LOEL (based on body
weight loss) was 30 mg/kg/day. Several other developmental studies
indicate potential developmental toxicity of bromoxynil. EPA believes
that there is sufficient evidence for listing bromoxynil on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available developmental toxicity data for this chemical.
27. Bromoxynil octanoate (octanoic acid, 2,6-dibromo-4-cyanophenyl
ester) (CAS No. 001689-99-2) (FIFRA AI) (Ref. 3). Bromoxynil octanoate
hydrolyzes to yield bromoxynil and octanol. In a dermal developmental
toxicity study, bromoxynil octanoate was developmentally toxic to rat
fetuses (increased incidences of supernumerary ribs) at 15 mg/kg/day
(LOEL). The NOEL was 10 mg/kg/day. The maternal LOEL for decreased body
weight gain was 20 mg/kg/day. The NOEL was 15 mg/kg/day. Developmental
effects (hydrocephalus, microphthalmia, anophthalmia and severe defects
in ossification of the skull) were observed in rabbits administered 60
mg/kg/day bromoxynil by gavage. The NOEL was 30 mg/kg/day.
Developmental toxicity (increases in all forms of supernumerary ribs)
was also observed in rats at 5 mg/kg/day. The NOEL was 1.5 mg/kg/day.
The maternal LOEL (based on body weight loss) was 30 mg/kg/day. EPA
believes that there is sufficient evidence for listing bromoxynil
octanoate on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available developmental toxicity data for bromoxynil and
bromoxynil octanoate.
28. Brucine (CAS No. 000357-57-3) (CERCLA; RCRA APP8; RCRA P) (Ref.
8). Brucine is an alkaloid similar in structure to strychnine. It is
capable of causing death or permanent injury due to exposures in normal
use. In humans, brucine can cause central and peripheral paralysis,
convulsions, and respiratory failure. A potentially lethal oral dose in
small children is 5 to 10 mg. The lethal oral dose for an adult may be
as low as 30 mg. The acute oral LD50 in rabbits is 4 mg/kg.
EPA's exposure analysis indicates that brucine concentrations are
likely to exist beyond facility site boundaries, as a result of
continuous, or frequently recurring releases, at levels that can
reasonably be anticipated to cause significant adverse acute human
health effects. EPA believes that there is sufficient evidence for
listing brucine on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(A) based on the available acute toxicity and exposure data
for this chemical.
29. Butylate (Bis-2-methylpropyl)carbamothioic acid S-ethyl ester)
(CAS No. 002008-41-5) (FIFRA AI) (Ref. 3). In a 2-year feeding study in
mice, hepatic (cellular infiltrates, focal necrosis) and renal effects
(amyloidosis, chronic nephritis, lymphocytic foci) were observed at 80
mg/kg/day. The NOEL was 20 mg/kg/day. In a separate study, liver
pericholangitis was observed in rats fed 180 mg/kg/day for 56 weeks.
The NOEL was 30 mg/kg/day. An increased relative liver weight was
observed in male dogs fed 25 mg/kg/day for 1-year. The NOEL was 5 mg/
kg/day. Based on the NOEL, EPA has established a chronic oral RfD of
0.05 mg/kg/day. EPA believes that there is sufficient evidence for
listing butylate on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available hepatic and renal toxicity data for
this chemical.
30. Butylated hydroxyanisole (CAS No. 025013-16-5) (CAL; IARC; NTP)
(Ref. 8). Butylated hydroxyanisole is classified by IARC as a Group 2B
compound; i.e., the chemical is possibly carcinogenic to humans.
Butylated hydroxyanisole has been shown to induce gastrointestinal
tumors in rats and hamsters. EPA believes that there is sufficient
evidence for listing butylated hydroxyanisole on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the carcinogenicity
data for this chemical.
31. C.I. Acid Red 114 (CAS No. 006459-94-5) (TSCA) (Ref. 8). In a
2-year bioassay conducted by the National Toxicology Program (NTP) in
which F344 rats were exposed to C.I. Acid Red 114 via drinking water,
hepatocellular carcinomas of the liver, tumors of the skin, and
adenomas or carcinomas in the Zymbal's gland of both sexes were
observed. In the same study, female rats also had increased incidences
of adenoma or carcinoma in the clitoral gland, and squamous cell
papilloma or carcinoma in the oral cavity. The exposure concentrations
in this study ranged from 70 to 300 ppm (9.8 to 42 mg/kg/day) for males
and from 150 to 600 ppm (21 to 84 mg/kg/day) for females. EPA believes
that there is sufficient evidence for listing C.I. Acid Red 114 on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
carcinogenicity data for this chemical.
32. C.I. Direct Blue 218 (CAS No. 028407-37-6) (NTP) (Ref. 8). In
an NTP bioassay, there was clear evidence of carcinogenicity of C.I.
Direct Blue 218 in male and female B6C3F1 mice based on significantly
increased incidence of hepatocellular adenomas and carcinomas. In a 2-
year NTP feeding study in rats, there was some evidence of
carcinogenicity in male F344 rats based on a significant increase in
the incidence of squamous cell papillomas of the pharynx in the high
dose group (500 mg/kg/day). EPA believes that there is sufficient
evidence for listing C.I. Direct Blue 218 on EPCRA section 313 pursuant
to EPCRA section 313(d)(2)(B) based on the carcinogenicity data for
this chemical.
33. Calcium hypochlorite (CAS No. 007778-54-3) (CERCLA) (Ref. 8).
Aquatic acute toxicity data for calcium hypochlorite include a 96-hour
measured LC50 for rainbow trout of 60 ppb and a 96-hour measured
LC50 for the Atlantic silverside of 37 ppb. EPA believes that
there is sufficient evidence for listing calcium hypochlorite on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(C) based on the
available ecotoxicity data for this chemical.
34. Caprolactam (CAS No. 000105-60-2) (CAA HAP) (Ref. 7). Rats were
administered caprolactam by oral gavage at doses of 0, 100, 500, and
1,000 mg/kg/day on gestation days 6 through 20. This resulted in a
LOAEL of 1,000 mg/kg/day and a NOAEL of 500 mg/kg/day for fetal
resorption. Rabbits were administered caprolactam by oral gavage at
doses of 0, 50, 150, and 250 mg/kg/day on gestation days 6 through 28.
This resulted in a LOAEL of 150 mg/kg/day for maternal and fetal body
weight depression. In addition, a slight increase in the severity of
spontaneous nephropathy (10,000 ppm) was observed in male rats of the
first parental generation fed 10,000 ppm of caprolactam in a three-
generation reproductive study, resulting in a NOAEL of 1,000 ppm (50
mg/kg/day). Mean body weights and food consumption were reduced in both
parental generations at 5,000 and 10,000 ppm. Body weights of offspring
were also reduced at these dietary concentrations (the LOAEL was 250
mg/kg/day). EPA believes that there is sufficient evidence for listing
caprolactam on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available developmental toxicity data for this chemical.
35. Carbofuran (CAS No. 001563-66-2) (CERCLA; EPCRA EHS; FIFRA SR)
(Ref. 8). Aquatic acute toxicity test data for carbofuran include a
measured 96-hour LC50 for bluegill of 80 ppb. In addition, the
measured 48-hour EC50 for daphnids is 35 ppb. Measured terrestrial
acute toxicity data for wildlife include an oral LD50 for mallard
ducks of 0.397 mg/kg for females and 0.480 mg/kg for males and an oral
LD50 for female ring-necked pheasants of 4.15 mg/kg. EPA believes
that there is sufficient evidence for listing carbofuran on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(C) based on the
environmental toxicity data for this chemical.
36. Carbon monoxide (CAS No. 000630-08-0) (CAL) (Ref. 8).
Cardiovascular (e.g., electrocardiograph changes, atrial fibrillation,
ventricular arrhythmias) and neurological (e.g., headache, dizziness,
convulsions, and coma) effects were reported in humans exposed to
carbon monoxide. In humans, histological effects in the brain include
extensive demyelination of white matter, and necrosis. Neuropsychiatric
disorders have also been reported. Persistant electrocardiograph
changes, and degeneration of myocardial muscle fibers, hemorrhage and
necrosis were observed following inhalation exposure of dogs to 100 ppm
(0.11 mg/L) carbon monoxide, 5.5 hours/day, 6 days/week, for 11 weeks.
Some of the dogs showed disturbances in gait and in postural and
position reflexes. The toxicity of carbon monoxide results from its
combination with hemoglobin in the blood to form carboxyhemoglobin
which is a poor oxygen carrier. Thus, oxygen delivery by the blood is
severely compromised, which leads to tissue hypoxia and possibly tissue
poisoning, resulting in the toxic effects (including death) known for
this substance.
Infants born to women who survive acute exposure to high
concentrations of carbon monoxide during pregnancy often display
neurological sequelae and gross brain damage. Exposure of pregnant rats
to 150 ppm (0.17 mg/L) carbon monoxide caused reduced pup growth rate,
and altered behavior (poor performance on negative geotaxis and homing
tests) in pups.
EPA believes that there is sufficient evidence for listing carbon
monoxide on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available chronic neurological, myocardial, and
developmental toxicity data for this chemical.
Carbon monoxide is regulated under Title I of the CAA (Provisions
for Attainment and Maintenance of National Ambient Air Quality
Standards). In addition to this proposal to add carbon monoxide to
EPCRA section 313, in Units IV.B.179. and 235, EPA is proposing to add
two other chemicals, nitrogen dioxide and sulfur dioxide, that are
regulated under Title I of the CAA. Sulfur dioxide is also regulated
under Title IV of the CAA (Acid Deposition Control). Extensive data,
which are highly technical, are collected on these chemicals as
required by the CAA. EPA requests comment on the following: (1) Is the
information collected under the CAA sufficient for public right-to-know
purposes; and (2) suggestions on how the data collected on these
chemicals pursuant to CAA Titles I and IV could be used to meet the
purposes of EPCRA section 313.
37. Carboxin (5,6-dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-
carboxamide) (CAS No. 005234-68-4) (FIFRA AI) (Ref. 3). Decreased body
weight gain and food consumption, increased mortality, and reduced
kidney, heart and spleen weights were observed in rats fed 600 ppm (30
mg/kg/day) carboxin for 2 years. The NOEL is 200 ppm (10 mg/kg/day). A
similar NOEL was established in a three-generation rat reproduction
study. Based on the NOEL, EPA established an oral RfD of 0.01 mg/kg/
day. In a 90-day feeding study in rats, degeneration of the kidneys was
seen at 600 ppm (30 mg/kg/day). The NOEL was 10 mg/kg/day. EPA believes
that there is sufficient evidence for listing carboxin on EPCRA section
313 pursuant to EPCRA section 313(d)(2)(B) based on the available renal
toxicity data for this chemical.
38. Chinomethionat (6-methyl-1,3-dithiolo[4,5-b]quinoxalin-2-one)
(CAS No. 002439-01-2) (FIFRA AI) (Ref. 3). Increases in liver weight,
liver protein, and both total liver and microsomal RNA levels, as well
as inhibition of mixed-function oxidase enzymes (e.g., N-demethylase,
cytochrome P-450) were noted in rats administered 75 mg/kg/day by oral
gavage for 4 days or in female rats administered 75 mg/kg/day in their
diet for 21 days. Liver enlargement was reported in rats fed 10 mg/kg/
day in their diet for 35 days. The increase in liver size was
attributed to increased cellular protein and an increase in water
content. Rats exposed orally to 2,700 mg/kg for 90 days (30 mg/kg/day)
had changes in liver weight and effects on the hepatic microsomal
oxidases as well as weight loss or decreased body weight gain. In a 1-
year dog study, the NOEL was established at 0.6 mg/kg/day for the test
material in the diet. The LOEL was 1.9 mg/kg/day as indicated by extra
medullary hematopoietic nodules in the liver.
In a developmental toxicity study in rats, increased resorption and
decreased fetal weight were reported at 37.5 mg/kg/day (the highest
dose tested). The NOEL was 12.5 mg/kg/day. In another developmental
study in rats given 30 mg/kg/day in carboxy methyl cellulose by gavage
from gestation day 6 to 20, cleft palate, anasarca and micrognathia was
observed.
EPA believes that there is sufficient evidence for listing
chinomethionat on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available hepatic and developmental toxicity
data.
39. Chlorendic acid (CAS No. 000115-28-6) (NTP) (Ref. 8). Based on
sufficient evidence of carcinogenicity in animals IARC classified
chlorendic acid as a Group 2B compound; i.e., it is possibly
carcinogenic in humans. In an NTP bioassay, there was clear evidence of
liver carcinogenicity in both rats and mice. EPA believes that there is
sufficient evidence for listing chlorendic acid on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the carcinogenicity
data for this chemical.
40. Chlorimuron ethyl (ethyl-2-[[[(4-chloro-6-methoxyprimidin-2-
yl)-carbonyl]-amino]sulfonyl]benzoate) (CAS No. 090982-32-4) (FIFRA AI)
(Ref. 3). In a 1-year dog study, dietary administration of 37.5 mg/kg/
day (LOEL) produced an increase in white blood cells in both sexes, a
decrease in red blood cells, hematocrit, and hemoglobin in females, and
an increase in alkaline phosphatase in males. The NOEL was 6.25 mg/kg/
day. Based on the NOEL, an oral RfD of 0.02 mg/kg/day was derived. This
study was given a high confidence rating. In a 2-year rat feeding
study, changes in hematology parameters were observed at the LOEL of
125 mg/kg/day. The NOEL was 12.5 mg/kg/day. In an 18-month mouse
feeding study, centrilobular hepatocellular hypertrophy was observed at
90 days at 187.5 mg/kg/day (LOEL). The NOEL was 18.75 mg/kg/day. EPA
believes that there is sufficient evidence for listing chlorimuron
ethyl on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based
on the available hematological toxicity data.
41. Chlorinated paraffins category (CAA HAP) (Ref. 7). Chlorinated
paraffins are defined as mixtures of linear saturated chlorinated
hydrocarbons obtained through the partial chlorination of paraffin,
olefin, or acetylene feedstocks which have an average chain length of
10 to 30 carbon atoms and contain average chlorine levels ranging from
40 to 70 percent by weight. Chlorinated paraffins can be described by
the general formula: CxH2x-y+2Cly where x ranges from 10
to 30 and y ranges from 3 to 26. Both 58 percent-chlorinated, short-
chain (10 to 12 carbons) and 43 percent-chlorinated, long-chain (22 to
26 carbons) chlorinated paraffins were tested in rats and mice by
gavage in a 2-year bioassay. The 58 percent-chlorinated, short-chain
(10 to 12 carbons) chlorinated paraffins were carcinogenic in rats and
mice: dosed male and female mice showed increased incidences of liver
tumors, dosed male rats had increased incidences of kidney tubular cell
hyperplasia and adenomas or adenocarcinomas (combined), and dosed
female rats and mice showed increased thyroid gland follicular cell
neoplasms, indicating an EPA Group B2 classification, i.e., a probable
human carcinogen. The 43 percent-chlorinated, long-chain (22 to 26
carbons) chlorinated paraffins were carcinogenic in male mice showing
an increased incidence of malignant lymphomas, and marginal increase in
hepatocellular neoplasms in female mice and adrenal gland
pheochromocytomas in female rats, indicating an EPA Group B2 category
classification, i.e., the chemical is a probable human carcinogen. EPA
believes that there is sufficient evidence for listing chlorinated
paraffins on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available carcinogenicity data for these chemicals.
The following ecotoxicity data (LC50s followed by experiment
duration in parenthesis) have been reported for short chain (10 to 13
carbons) and intermediate chlorination (59 percent chlorine)
chlorinated paraffins: daphnid, 46 ppb (48-hour); mysid shrimp, 14 ppb
(96-hour); marine algae, 42 ppb (96-hour); daphnid, 2 ppb and 9 ppb
(21-day chronic study); and midge, 78 ppb (49-day chronic study).
Ranges of chronic toxicity values are as follow: Freshwater
invertebrates, 2 to 162 ppb; freshwater fish, 3 to 17.2 ppb; marine
invertebrates, 2.4 to 24 ppb; and marine fish, 2.4 ppb to 620.5 ppm.
Chlorinated paraffins are persistent with a half-life of greater than
30 days in the environment. EPA believes that there is sufficient
evidence for listing the category chlorinated paraffins on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(C) based on the
available ecotoxicity data for these chemicals and their persistence in
the environment.
EPCRA section 313 requires threshold determinations for chemical
categories to be based on the total of all chemicals in the category
manufactured, processed, or otherwise used. For example, a facility
that manufactures three members of a chemical category would count the
total amount of all three chemicals manufactured towards the
manufacturing threshold for that category. When filing reports for
chemical categories the releases are determined in the same manner as
the thresholds. One report if filed for the category and all releases
are reported on this form.
42. 1-(3-Chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride (CAS
No. 004080-31-3) (FIFRA AI) (Ref. 3). Decrease in heart weight,
obliterative vasculitis, and perivasculitis of the hepatic blood
vessels were observed in dogs orally administered 1-(3-chloroallyl)-
3,5,7-triaza-1-azoniaadamantane for 90 days. The NOEL was 7.5 mg/kg/
day; the LOEL was 15 mg/kg/day. EPA believes that there is sufficient
evidence for listing 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane
chloride on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available chronic toxicity data for 1-(3-chloroallyl)-
3,5,7-triaza-1-azoniaadamantane.
43. p-Chloroaniline (CAS No. 000106-47-8) (CERCLA; RCRA APP8; RCRA
P) (Ref. 8). In a 78-week study in which rats were fed p-chloroaniline,
non-neoplastic proliferative lesions of the splenic capsule (focal
fibrosis with subcapsular mesenchymal proliferation) were observed. The
LOAEL was 12.5 mg/kg/day (the lowest dose tested) and the RfD derived
from this data is 0.004 mg/kg/day. EPA believes that there is
sufficient evidence for listing p-chloroaniline on EPCRA section 313
pursuant to section 313(d) (2)(B) based on the chronic toxicity data
for this chemical.
44. 5-Chloro-2-(2,4-dichlorophenoxy)phenol (CAS No. 003380-34-5)
(FIFRA AI) (Ref. 3). In a 3-month dog feeding study, decreased red
blood cell and hemoglobin values, increased serum alkaline phosphatase,
jaundice, and increased liver weight were observed at 25 mg/kg/day
(LOEL). No NOEL could be established. In another 3-month dog feeding
study, the LOEL of 25 mg/kg/day produced morphologic changes in the
liver (focal acidophilic granular degeneration of cytoplasm). The NOEL
was 12.5 mg/kg/day. In a 3-month rat feeding study, 125 mg/kg/day
(LOEL) produced increased liver weights in males. The NOEL was 50 mg/
kg/day. At 150 mg/kg/day (LOEL), decrease in triglycerides, increase in
creatinine, decrease in red blood cells, increase in spleen and heart
weight, and cytomegaly were observed in another 3-month rat feeding
study (NOEL was 50 mg/kg/day). In a 2-year study, dietary
administration of 15 mg/kg/day produced decreases in red blood cells,
hemoglobin concentration, and hematocrit as well as hepatic necrosis in
males. At 50 mg/kg/day, there were decreases in red blood cells in
females. EPA believes that there is sufficient evidence for listing 5-
chloro-2-(2,4-dichlorophenoxy)phenol on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(B) based on the available hematological
toxicity data for this chemical.
45. 3-Chloro-2-methyl-1-propene (CAS No. 000563-47-3) (NTP) (Ref.
8). In an NTP gavage bioassay there was clear evidence of
carcinogenicity from 3-chloro-2-methyl-1-propene in rats and mice. The
substance induced adrenal cortex, testicular and gastrointestinal
tumors in rats and adrenal cortex and gastrointestinal tumors in mice.
EPA believes that there is sufficient evidence for listing 3-chloro-2-
methyl-1-propene on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the carcinogenicity data for this chemical.
46. p-Chlorophenyl isocyanate (CAS No. 000104-12-1) (TSCA) (Ref.
8). p-Chlorophenyl isocyanate is very lethal following inhalation. The
4-hour mouse inhalation LC50 value is 0.053 mg/L. In addition,
isocyanates as a class are generally severe skin, eye, and respiratory
irritants following acute exposure.
EPA's exposure analysis indicates that p-chlorophenyl isocyanate
concentrations are likely to exist beyond facility site boundaries, as
a result of continuous, or frequently recurring releases, at levels
that can reasonably be anticipated to cause significant adverse acute
human health effects. EPA believes that there is sufficient evidence
for listing p-chlorophenyl isocyanate on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(A) based on the available acute toxicity and
exposure data for this chemical.
47. Chloropicrin (CAS No. 000076-06-2) (FIFRA AI) (Ref. 3).
Measured aquatic acute toxicity data for chloropicrin include a rainbow
trout 96-hour LC50 of 16.5 ppb, a bluegill 96-hour LC50 of
105 ppb, and a 48-hour EC50 of 80 ppb. EPA believes that there is
sufficient evidence for listing chloropicrin on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(C) based on the available
environmental toxicity data for this chemical.
48. 3-Chloropropionitrile (CAS No. 000542-76-7) (CERCLA; EPCRA EHS;
RCRA APP8; RCRA P) (Ref. 8). 3-Chloropropionitrile is metabolized by
hepatic cytochrome P450 enzymes to release cyanide. The substance is
readily absorbed both dermally and orally. The mouse oral LD50 is
51.3 mg/kg.
EPA's exposure analysis indicates that 3-chloropropionitrile
concentrations are likely to exist beyond facility site boundaries, as
a result of continuous, or frequently recurring releases, at levels
that can reasonably be anticipated to cause significant adverse acute
human health effects. EPA believes that there is sufficient evidence
for listing 3-chloropropionitrile on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(A) based on the available acute toxicity and
exposure data for this chemical.
49. p-Chloro-o-toluidine (CAS No. 000095-69-2) (IARC; NTP) (Ref.
8). p-Chloro-o-toluidine is classified as a Group B2 carcinogen by EPA;
i.e., the compound is a probable human carcinogen. It is classified as
a Group 2B carcinogen by IARC; i.e., a possible human carcinogen.
Epidemiology studies are inadequate in evaluating the carcinogenic
potential of 4-chloro-o-toluidine hydrochloride in humans. In a long-
term feeding study by NCI, p-chloro-o-toluidine hydrochloride induced
hemangiomas, hemangiosarcomas, and vascular tumors in mice. An increase
in the incidence of pituitary chromophobe adenomas was observed in
female rats following dietary administration. EPA believes that there
is sufficient evidence for listing p-chloro-o-toluidine on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available carcinogenicity data for this chemical.
50. Chlorotrifluoromethane (CFC-13) (CAS No. 000075-72-9) (CAA OD)
(Ref. 8). Chlorofluorocarbons, including chlorotrifluoromethane (CFC-
13) are known to release chlorine radicals into the stratosphere.
Chlorine radicals act as catalysts to reduce the net amount of
stratospheric ozone.
Stratospheric ozone shields the earth from ultraviolet-B (UV-B)
radiation (i.e., 290 to 320 nanometers). Decreases in total column
ozone will increase the percentage of UV-B radiation, especially at its
most harmful wavelengths, reaching the earth's surface.
Exposure to UV-B radiation has been implicated by laboratory and
epidemiologic studies as a cause of two types of nonmelanoma skin
cancers: squamous cell cancer and basal cell cancer. Studies predict
that for every 1 percent increase in UV-B radiation, nonmelanoma skin
cancer cases would increase by about 1 to 3 percent.
Recent epidemiological studies, including large case control
studies, suggest that UV-B radiation plays an important role in causing
malignant melanoma skin cancer. Recent studies predict that for each 1
percent change in UV-B intensity, the incidence of melanoma could
increase from 0.5 to 1 percent.
Studies have demonstrated that UV-B radiation can suppress the
immune response system in animals, and, possibly, in humans. Increases
in exposure to UV-B radiation are likely to increase the incidence of
cataracts and could adversely affect the retina.
Aquatic organisms, particularly phytoplankton, zooplankton, and the
larvae of many fishes, appear to be susceptible to harm from increased
exposure to UV-B radiation because they spend at least part of their
time at or near the surface of waters they inhabit.
Increased UV-B penetration has been shown to result in adverse
impacts on plants. Field studies on soybeans suggest that yield
reductions could occur in some cultivars of soybeans, while evidence
from laboratory studies suggest that two out of three cultivars are
sensitive to UV-B. Because this increased UV-B radiation can be
reasonably anticipated to lead to cancer and other chronic human health
effects and significant adverse environmental effects, there is
sufficient evidence for listing chlorotrifluoromethane (CFC-13) on
EPCRA section 313 pursuant to EPCRA sections 313(d)(2)(B) and (C).
51. Chlorpyrifos methyl (O,O-dimethyl-O-(3,5,6-trichloro-2-
pyridyl)phosphorothioate) (CAS No. 005598-13-0) (FIFRA AI) (Ref. 3).
Humans experienced a 10 percent reduction in plasma cholinesterase
activity after 10 dermal exposures to 10 mg/kg/day and a 47 percent
reduction after 4 dermal exposures to 25 mg/kg/day (exposures were for
12 hours per day). Rabbits experienced a 97 to 100 percent reduction in
plasma cholinesterase activity after 5 dermal exposures to 10 mg/kg/day
for 12 hours a day or 2 dermal exposures to 25 mg/kg/day for 12 hours a
day. In a 2-year rat feeding study, red blood cell and plasma
cholinesterase inhibition were observed at 1 mg/kg/day (LOEL). The NOEL
was 0.1 mg/kg/day. In a 2-year dog feeding study, plasma cholinesterase
inhibition was observed at 1 mg/kg/day (LOEL). The NOEL was 0.1 mg/kg/
day. The oral rat LD50 is between 1,159 mg/kg and 3,833 mg/kg.
Lethargy, ataxia, diarrhea, salivation, and tremors were observed in
these studies. EPA believes that there is sufficient evidence for
listing chlorpyrifos methyl on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available neurological toxicity data.
Aquatic acute toxicity values for chlorpyrifos methyl include a
daphnid 48-hour LC50 of 1.11 ppb and a rainbow trout 96-hour
LC50 of 12.6 ppb. EPA believes that there is sufficient evidence
for listing chlorpyrifos methyl on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(C) based on the available environmental toxicity
data.
52. Chlorsulfuron (2-chloro-N-[[(4-methoxy-6-methyl-1,3,5-triazin-
2-yl)amino]carbonyl]benzenesulfonamide) (CAS No. 064902-72-3) (FIFRA
AI) (Ref. 3). In a rabbit developmental study, an increased incidence
of fetal resorptions was observed at the LOEL of 75 mg/kg/day. The NOEL
was 25 mg/kg/day.
In a 3-generation rat reproduction study, a decrease in fertility
index was observed at 125 mg/kg/day (LOEL). The NOEL was 25 mg/kg/day.
EPA believes that there is sufficient evidence for listing
chlorsulfuron on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available developmental and reproductive
toxicity data for this chemical.
53. Clomazone (2-[(2-chlorophenyl)methyl]-4,4-dimethyl-3-
isoxazolidinone) (CAS No. 081777-89-1) (FIFRA AI) (Ref. 3). In a 90-day
dog feeding study, increased cholesterol and increased absolute and
relative liver weights were observed at 62.5 mg/kg/day (LOEL). The NOEL
was 12.5 mg/kg/day. Dietary administration of 62.5 mg/kg/day (LOEL) to
dogs for 1-year also produced increased cholesterol and increased liver
weights. The NOEL was 12.5 mg/kg/day. In a 90-day mouse feeding study,
megalocytosis of the liver cells was seen at 2.6 mg/kg/day (LOEL). No
NOEL was established. In a 2-year rat feeding study, elevated
cholesterol levels and liver-to-body weight ratios were observed at
21.5 mg/kg/day (LOEL). The NOEL was 4.3 mg/kg/day. Dietary
administration of 62.5 mg/kg/day (LOEL) to dogs for 1-year increased
cholesterol and liver weights. The NOEL was 12.5 mg/kg/day.
In a two-generation reproduction study, decreased pup viability,
reduced survival, decreased body weight, and nonfunctional limbs were
observed in the offspring of rats that were orally administered 50 mg/
kg/day (LOEL). The NOEL was 5 mg/kg/day.
EPA believes that there is sufficient evidence for listing
clomazone on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available hepatic and developmental toxicity data.
54. Crotonaldehyde (CAS No. 004170-30-3) (RCRA APP8) (Ref. 8).
Crotonaldehyde has been tested for carcinogenicity in one animal study.
When crotonaldehyde was administered to male F344 rats at 0, 42, or 421
mg/L for 113 weeks, there was a statistically significant increase in
the incidence of hepatocellular neoplasms (benign and malignant
combined) in the low dose group. The lack of tumorigenic effects at the
high-dose group is believed to be due to the hepatotoxicity observed in
this group. At high dose, crotonaldehyde is cytotoxic; cells died
before neoplasms are manifested. Crotonaldehyde and other alpha, beta-
unsaturated carbonyls are chemically reactive compounds which can
readily react with cellular macromolecules such as DNA and proteins.
Mutagenicity studies in a slightly modified preincubation Ames test
have clearly shown that crotonaldehyde is mutagenic. EPA believes that
there is sufficient evidence for listing crotonaldehyde on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available carcinogenicity and mutagenicity data for this chemical.
55. Cyanazine (CAS No. 021725-46-2) (CAL; FIFRA SR) (Ref. 8).
Cyanazine is a triazine-type herbicide. In a three-generation
reproduction study in Long-Evans rats, F3b female weanlings had
increased relative brain weights and decreased relative kidney weights.
The LOAEL was 4.05 mg/kg/day and the NOAEL was 1.35 mg/kg/day. In
rabbits that received cyanazine in gelatin capsules during gestation
days 6 to 18, there was increased postimplantation loss, decreased
litter size, and alterations in ossification. In addition, there were
increased malformations in the offspring, including anophthalmia/
microphthalmia, dilated brain ventricles, dome cranium and
thoracoschisis (the LOAEL was 2 mg/kg/day; the NOAEL was 1 mg/kg/day).
Similar developmental effects were reported in Fischer 344 rats
administered cyanazine during gestation days 6 to 15 (the LOAEL was 25
mg/kg/day; the NOAEL 5 was mg/kg/day). EPA believes that there is
sufficient evidence for listing cyanazine on EPCRA section 313 pursuant
to EPCRA section 313(d)(2)(B) based on the developmental toxicity data
for this chemical.
56. Cycloate (CAS No. 001134-23-2) (FIFRA AI) (Ref. 3). Cycloate, a
carbamate pesticide, is a cholinesterase inhibitor. Symptoms of
poisoning include salivation, lacrimation, convulsions, and death.
Depressed plasma cholinesterase was observed in a 9-week rat inhalation
study at 0.0025 mg/L. The NOEL was less than 0.0025 mg/L. Decreased
serum cholinesterase (in males and females) and Wallerian degeneration
of nerve fibers in spinal cord and sciatic nerve (females) were
observed at 0.12 mg/L in a 10-week rat inhalation study (cholinesterase
NOEL is 0.012 mg/L). In both inhalation studies, animals were exposed
for 6 hours/day, 5 days/week. Plasma, red blood cell, and brain
cholinesterase inhibition was reported in rats fed 8 mg/kg/day for 2
years. The NOEL was less than 8 mg/kg/day. Dose-related neuropathy and
muscle myopathy were observed. In a 2-year rat feeding study, distended
myelin sheath demyelination and nerve fiber loss occurred at 3 mg/kg/
day (LOEL). The NOEL was 0.5 mg/kg/day.
Decreased weight and survival were observed in the offspring of
rats orally administered 24 mg/kg/day (LOEL) and 72 mg/kg/day of
cycloate, respectively (duration and frequency of dosing not reported).
The reproductive NOEL was 8 mg/kg/day. Decreased pup weight was
observed at 20 mg/kg/day and decreased pup survival was observed at 50
mg/kg/day in a 2-generation rat reproduction study. The NOEL values for
these endpoints were 2.5 mg/kg/day and 20 mg/kg/day, respectively.
EPA believes that there is sufficient evidence for listing cycloate
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on
the available neurological and developmental toxicity data.
57. Cyclohexanol (CAS No. 000108-93-0) (TSCA) (Ref. 8). Four
rabbits exposed to 997 ppm (4 mg/L) for 11 days (6 hours/day, 5 days/
week) and a rabbit receiving dermal applications of approximately 2,500
mg/kg/day for 10 days (1 hour/day) developed tremors, central nervous
system depression, lethargy or hypothermia.
Microscopic or degenerative changes were observed in the livers and
kidneys of rabbits inhaling 145 ppm (0.59 mg/L) of cyclohexanol for 50
days (6 hours/day, 5 days/week), or repeated doses at 272 ppm (1.1 mg/
L). In addition, degenerative myocardial effects were observed at this
exposure level. Repeated inhalation exposure to higher doses (997 to
1,229 ppm; 4 to 5 mg/L) in rabbits resulted in degenerative changes in
the brain and heart as well as liver and kidneys.
Reproductive effects including testicular atrophy, loss of Type A
spermatogonia, spermatocytes and spermatozoa, ``shrinkage'' of
seminiferous tubules and Leydig cells, reductions in RNA protein,
sialic acid, and glycogen in testes, epididymis and seminal vesicles
and increased testicular cholesterol and alkaline phosphatase were
observed in male rats or gerbils exposed to 15 mg/kg of cyclohexanol
for 21 to 37 days. These changes were accompanied with decreased
fertility, and occurred at exposure levels which had no effect on the
liver or kidney.
EPA believes that there is sufficient evidence for listing
cyclohexanol on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the chronic neurological, hepatic, renal,
myocardial, and reproductive toxicity data for this chemical.
58. Cyfluthrin (3-(2,2-Dichloroethenyl)-2,2-
dimethylcyclopropanecarboxylic acid, cyano(4-fluoro-3-
phenoxyphenyl)methyl ester) (CAS No. 068359-37-5) (FIFRA AI) (Ref. 3).
In a 14-day rat study, oral administration of 60 mg/kg/day produced
tremors, uncoordinated gait, salivation, slight brain hemorrhages,
necrosis of the skeletal muscle fibers, and death. The NOEL was not
defined. In another study, salivation, straddled gait, axonal
degeneration of sciatic nerve, microtubular dilation, and mitochondria
degeneration in the sciatic and femoral nerves were observed in rats
administered 80 mg/kg/day orally for 5 days and 40 mg/kg/day for the
following 9 days. No NOEL was established.
Liver and adrenal weight increases were observed in rats orally
administered 40 to 80 mg/kg/day for 28 days. The highest dose of 80 mg/
kg/day was reduced to 40 mg/kg/day. The NOEL was 20 mg/kg/day. Liver
weight changes and urobilinogen and ketone bodies in the urine were
observed in rats fed 15 mg/kg/day for 28 days. No NOEL was established.
In a 28-day mouse feeding study, increased liver weight was observed at
50 mg/kg/day (LOEL). The NOEL was 15 mg/kg/day. Inflammatory foci in
the kidneys of females were observed at 7.5 mg/kg/day in a 2-year rat
feeding study. The NOEL was 2.5 mg/kg/day. Based on the NOEL of the
study, an oral RfD of 0.025 mg/kg/day was determined. Increased
alkaline phosphatase activity was observed in males at 7.5 mg/kg/day in
a 23-month mouse feeding study.
EPA believes that there is sufficient evidence for listing
cyfluthrin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available neurological, hepatic, and renal toxicity data.
Aquatic acute toxicity values for cyfluthrin include a rainbow
trout 96-hour LC50 of 0.68 ppb, a bluegill 96-hour LC50 of
1.5 ppb, and a daphnid 48-hour EC50 of 0.14 ppb. EPA believes that
there is sufficient evidence for listing cyfluthrin on EPCRA section
313 pursuant to EPCRA section 313(d)(2)(C) based on the available
environmental toxicity data.
59. Cyhalothrin (3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-
dimethylcyclopropanecarboxylic acid cyano(3-phenoxyphenyl)methyl ester)
(CAS No. 068085-85-8) (FIFRA AI) (Ref. 3). Cyhalothrin administered
orally (in capsules) to dogs at 10 mg/kg/day for 26 weeks produced
occasional disturbances of the nervous system (unsteadiness and/or
muscular trembling). The NOEL for these effects was not defined. In a
1-year dog study, ataxia, muscle tremors, and convulsions were observed
following oral administration at 3.5 mg/kg/day. Abnormal gait and
convulsions were observed at 0.5 mg/kg/day. The LOEL of the study was
0.5 mg/kg/day and the NOEL was 0.1 mg/kg/day. EPA believes that there
is sufficient evidence for listing cyhalothrin on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available
neurological toxicity data.
60. Cyromazine (N-cyclopropyl-1,3,5-triazine-2,4,6-triamine) (CAS
No. 066215-27-8) (FIFRA AI) (Ref. 3). In a 6-month dog feeding study,
7.5 mg/kg/day (LOEL) produced changes in hematocrit and hemoglobin
levels. The NOEL was 0.75 mg/kg/day. Based on the NOEL, an oral RfD of
0.0075 mg/kg/day was derived. In a 90-day dog feeding study, the LOEL
of 25 mg/kg/day produced an increase in relative liver weights in
males. The NOEL was 7.5 mg/kg/day. In a 90-day rat feeding study, the
LOEL of 15 mg/kg/day produced a decrease in relative liver weights in
males. The NOEL was 1.5 mg/kg/day. EPA believes that there is
sufficient evidence for listing cyromazine on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available
hematological toxicity data.
61. Dazomet (tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione)
(CAS No. 000533-74-4) (FIFRA AI) (Ref. 3). Animals fed dazomet at a
dietary dose of 40 ppm for 2 years showed focal necrosis and fatty
metamorphosis of the liver. Rats fed 30.3 mg/kg/day experienced
decreased weight gain and changes in liver weight. Renal focal tubular
necrosis was seen in rats fed 10 ppm (0.5 mg/kg/day) for 2 years. EPA
believes that there is sufficient evidence for listing dazomet on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available hepatic and renal toxicity data for this chemical.
62. Dazomet sodium salt (tetrahydro-3,5-dimethyl-2H-1,3,5-
thiadiazine-2-thione, ion(1-), sodium) (CAS No. 053404-60-7) (FIFRA AI)
(Ref. 3). The available toxicity data is on dazomet. Rats fed 80 ppm
for 2 years (4 mg/kg/day) showed focal necrosis and fatty metamorphosis
of the liver. Rats fed 30.3 mg/kg/day experienced decreased weight gain
and changes in liver weight. Renal focal tubular necrosis was seen in
rats fed 10 ppm (0.5 mg/kg/day) for 2 years. EPA believes that there is
sufficient evidence for listing dazomet sodium on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available renal
toxicity data for its free acid, dazomet.
63. 2,4-DB (CAS No. 000094-82-6) (FIFRA SR) (Ref. 8). 2,4-DB (4-
(2,4-dichlorophenoxy)butanoic acid) is a 2,4-dichlorophenoxy-type
herbicide. In a study involving beagle dogs fed a diet containing 2,4-
DB for 90 days, a LOAEL of 25 mg/kg/day was determined, based on
internal hemorrhaging and mortality observed during the first 3 to 9
weeks of treatment. The NOAEL in this study was 8 mg/kg/day. At this
dose level, slight increases in liver weights were observed, but
unaccompanied by any gross or histopathologic lesions. EPA has derived
an oral RfD of 0.008 mg/kg/day from the LOAEL. In a subchronic rat
feeding study, the LOAEL and NOAEL values determined were higher (the
LOAEL was approximately 80 to 100 mg/kg/day; the NOAEL was
approximately 25 to 30 mg/kg/day), and were based on severe liver and
kidney damage.
In the above-mentioned subchronic (90-day) dog feeding study, it
was observed that the animals exposed to doses of 2,4-DB at 25 mg/kg/
day (the LOAEL) and higher exhibited aspermatogenesis within the first
3 to 9 weeks of treatment. The offspring of rats orally exposed to 17
mg/kg of 2,4-DB during days 1 to 7 of gestation developed
abnormalities. There was also an increase in stillbirths at this dose
level. In a separate study, offspring of rats orally exposed to 416 mg/
kg on days 5 or 9 of gestation exhibited increased preimplantation loss
and/or developmental toxicity.
EPA believes that there is sufficient evidence for listing 2,4-DB
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on
the hepatic, reproductive, and developmental toxicity data for this
chemical.
64. 2,4-D butoxyethyl ester (CAS No. 001929-73-3) (CERCLA; FIFRA
AI; IARC) (Ref. 8). 2,4-D butoxyethyl ester is a 2,4-dichlorophenoxy-
type herbicide. In mammals, the butoxyethyl ester of 2,4-D is
hydrolyzed to yield the free acid, 2,4-D. Therefore, the toxicity of
2,4-D butoxyethyl ester is expected to be similar to that of 2,4-D, in
which the kidney, liver, and nervous system are the primary targets of
injury. EPA believes that there is sufficient evidence for listing 2,4-
D butoxyethyl ester on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the known chronic effects of its metabolite 2,4-
D.
65. 2,4-D butyl ester (CAS No. 000094-80-4) (CERCLA; FIFRA AI;
IARC) (Ref. 8). 2,4-D butyl ester is a 2,4-dichlorophenoxytype
herbicide. In mammals, the butyl ester of 2,4-D is hydrolyzed to yield
the free acid, 2,4-D. Therefore, the toxicity of 2,4-D butyl ester is
expected to be similar to that of 2,4-D, in which the kidney, liver,
and nervous system are the primary targets of injury. EPA believes that
there is sufficient evidence for listing 2,4-D butyl ester on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on the known
toxic effects of its metabolite 2,4-D.
66. 2,4-D chlorocrotyl ester (CAS No. 002971-38-2) (CERCLA; FIFRA
AI; IARC) (Ref. 8). 2,4-D chlorocrotyl ester is a 2,4-dichlorophenoxy-
type herbicide. In mammals, the chlorocrotyl ester of 2,4-D is
hydrolyzed to yield the free acid, 2,4-D. Therefore, the toxicity of
2,4-D chlorocrotyl ester is expected to be similar to that of 2,4-D, in
which the kidney, liver and nervous system are the primary targets of
injury. EPA believes that there is sufficient evidence for listing 2,4-
D chlorocrotyl ester on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the known toxic effects of its metabolite 2,4-D.
67. Desmedipham (CAS No. 013684-56-5) (FIFRA AI) (Ref. 3). In a 90-
day dog study, groups of four beagles/sex were fed diets containing 0
to 5.24 mg/kg/day. This caused increased methemoglobin at 5.24 mg/kg/
day (LOEL). EPA believes that there is sufficient evidence for listing
desmedipham on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available hematological toxicity data.
68. 2,4-D 2-ethylhexyl ester (CAS No. 001928-43-4) (CERCLA; FIFRA
AI; IARC) (Ref. 8). 2,4-D 2-ethylhexyl ester is a 2,4-dichlorophenoxy-
type herbicide. The 2-ethylhexyl moiety contains eight carbons and,
therefore, is an isooctyl group. Developmental toxicity following
maternal exposure to 2,4-D isooctyl esters has been demonstrated in the
rat and mouse. Fetotoxicity occurred in offspring of rats exposed to
528 mg/kg during gestation days 8 through 11. Rats orally exposed to
doses as low as 302 mg/kg during gestation days 9 through 12 had
musculoskeletal abnormalities. Exposure to a lower dose (188 mg/kg) for
a longer period during gestation (days 6 through 15) caused
developmental effects on homeostasis and effects on newborn growth
statistics. In mice, 438 mg/kg administered orally during gestation
days 8 to 12 also caused effects on newborn growth statistics.
EPA believes that there is sufficient evidence for listing 2,4-D 2-
ethylhexyl ester on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the developmental toxicity data for 2,4-D
isooctyl esters, and on the toxic effects of its metabolite 2,4-D.
The aquatic acute toxicity data for 2,4-D isooctyl esters include a
measured 48-hour LC50 of 8.8 ppm for bluegill. In addition, 2,4-D
isooctyl esters are expected to bioaccumulate based on the estimated
log Kow of 6.6. EPA believes that there is sufficient evidence for
listing 2,4-D 2-ethylhexyl ester on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(C) based on the available environmental toxicity data
and the potential for bioaccumulation.
69. 2,4-D 2-ethyl-4-methylpentyl ester (CAS No. 053404-37-8)
(CERCLA; FIFRA AI; IARC) (Ref. 8). 2,4-D 2-ethyl-4-methylpentyl ester
is a 2,4-dichlorophenoxy-type herbicide. The 2-ethyl-4-methylpentyl
ester moiety contains eight carbons and, therefore, is an isooctyl
group. Developmental toxicity following maternal exposure to 2,4-D
isooctyl esters has been demonstrated in the rat and mouse.
Fetotoxicity occurred in offspring of rats exposed to 528 mg/kg during
gestation days 8 through 11. Rats orally exposed to doses as low as 302
mg/kg during gestation days 9 through 12 had musculoskeletal
abnormalities. Exposure to a lower dose (188 mg/kg) for a longer period
during gestation (days 6 through 15) caused developmental effects on
homeostasis and effects on newborn growth statistics. In mice, 438 mg/
kg administered orally during gestation days 8 through 12 also caused
effects on newborn growth statistics.
EPA believes that there is sufficient evidence for listing 2,4-D 2-
ethyl-4-methylpentyl ester on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the developmental toxicity data for 2,4-D
isooctyl esters, the toxic effects of its metabolite 2,4-D. The aquatic
acute toxicity data for 2,4-D isooctyl esters include a measured 48-
hour LC50 of 8.8 ppm for bluegill. In addition, 2,4-D isooctyl
esters are expected to bioaccumulate based on the estimated log
Kow of 6.6. EPA believes that there is sufficient evidence for
listing 2,4-D 2-ethyl-4-methylpentyl ester on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(C) based on the available
environmental toxicity data and the potential for bioaccumulation.
70. Diazinon (CAS No. 000333-41-5) (CERCLA; FIFRA SR) (Ref. 8).
Diazinon, an organophosphate insecticide, causes plasma cholinesterase
inhibition and central nervous system depression. Significant
inhibition of plasma cholinesterase was observed in two men
administered five doses of 0.025 mg/kg/day. Diazinon administered to
men at doses of 0.05 mg/kg/day for 28 days caused a 35 to 40 percent
reduction in plasma cholinesterase. A NOEL for cholinesterase
inhibition of 0.02 mg/kg/day was identified from several controlled
studies in humans. Clinical symptoms of diazinon poisoning include
headache, nausea, sweating, vomiting, and diarrhea all of which are
indicative of neurotoxicity. Plasma cholinesterase inhibition (93
percent) and red blood cell inhibition (90 percent) occurred in monkeys
orally exposed to diazinon in doses of 5 mg/kg/day for 52 weeks. The
NOEL for inhibition of cholinesterase in this study was 0.05 mg/kg/day
and the LOEL was 0.5 mg/kg/day.
Urogenital defects in the offspring of female rats orally
administered diazinon at doses of 26.4 mg/kg on days 12 to 15 of
gestation has been reported. Diazinon also induced musculoskeletal
abnormalities in offspring when administered orally to mothers at doses
of 45 mg/kg on days 8 to 12 of gestation. Post-implantation mortality
was increased in female rats administered 63.5 mg/kg on day 10 of
gestation. Similar reproductive and developmental effects were observed
in mice. Oral administration of 3.96 mg/kg of diazinon (days 1 to 22 of
gestation) caused decreased litter size and delayed behavioral effects
in the newborn. Doses of 0.210 mg/kg and 3.78 mg/kg administered orally
on days 1 to 21 of gestation caused abnormalities in the immune and
reticuloendothelial system and biochemical and metabolic abnormalities
of the offspring, respectively.
EPA believes that there is sufficient evidence for listing diazinon
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on
the developmental and chronic neurotoxicity data for this chemical.
Measured aquatic acute toxicity data for diazinon include a 96-hour
LC50 for rainbow trout of 90 ppb and a daphnid 96-hour LC50
of 0.90 ppb. In addition, measured terrestrial wildlife acute toxicity
data for diazinon include an oral LD50 for male mallard ducks of
3.54 mg/kg and an oral LD50 for male pheasants of 4.33 mg/kg. EPA
believes that there is sufficient evidence for listing diazinon on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the
environmental toxicity data for this chemical.
71. 2,2-Dibromo-3-nitrilopropionamide (CAS No. 010222-01-2) (FIFRA
AI) (Ref. 3). Oral administration of 50 mg/kg/day (LOEL) to rats for 4
weeks produced dyspnea and weight loss. The NOEL was 25 mg/kg/day. Oral
administration of 30 mg/kg/day to rats for 13 weeks produced dyspnea.
The NOEL was 13 mg/kg/day. These data may be indicative of direct
effects of the compound on the respiratory system. EPA believes that
there is sufficient evidence for listing 2,2-dibromo-3-
nitrilopropionamide on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available chronic respiratory data.
72. Dicamba (3,6-Dichloro-2-methyoxybenzoic acid) (CAS No. 001918-
00-9) (FIFRA AI) (Ref. 3). Decreased fetal body weights and increased
post-implantation loss was observed in the offspring of rabbits
receiving 10 mg/kg/day of dicamba on days 6 through 18 of gestation.
The LOEL was 10 mg/kg/day and NOEL was 3 mg/kg/day. Based on the NOEL,
EPA derived an oral RfD value of 0.03 mg/kg/day. In a separate study,
disorders of oxidative phosphorylation and focal necrosis in the heart
were observed in newborn rats following transplacental exposure to
dicamba. In a developmental toxicity study, an increase in skeletal
malformations was seen in the offspring of rats orally administered 64
mg/kg/day on days 6 through 19 of gestation. EPA believes that there is
sufficient evidence for listing dicamba on EPCRA section 313 pursuant
to EPCRA section 313(d)(2)(B) based on the available developmental
toxicity data for this chemical.
73. Dichloran (2,6-Dichloro-4-nitroaniline) (CAS No. 000099-30-9)
(FIFRA AI) (Ref. 3). Dichloran, an aniline, is a potential inducer of
methemoglobinemia. Either single or repeated oral doses of dichloran
produced enlarged livers and induction of microsomal enzymes in the
rat. Dogs fed 21 mg/kg/day had increases in serum transaminases. In
Rhesus monkeys, where dichloran does not induce hepatic enzymes, 160
mg/kg/day for 3 months caused hepatic centrilobular fatty infiltration
and death. Inhalation exposure to 0.17 mg/L produced elevated
cholesterol levels and increased liver weight in a 3-month rabbit study
and increased liver weight in a 21-day rat study. In a 2-year mouse
study, dietary administration of 102.7 mg/kg/day (LOEL) produced
centrilobular hepatocyte enlargement, focal necrosis, acute
inflammatory cell infiltration, vacuolization of centrilobular
hepatocytes, increased weight of the liver and increased incidence of
erythropoiesis in males. The NOEL was 30 mg/kg/day. EPA believes that
there is sufficient evidence for listing dichloran on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available hepatic
toxicity data.
74. 3,3'-Dichlorobenzidine dihydrochloride (CAS No. 000612-83-9)
(TSCA) (Ref. 8). IARC has classified 3,3'dichlorobenzidine (o-
dichlorobenzidine) as a group 2B compound, i.e. this chemical is
possibly carcinogenic in humans. IARC uses the generic name 3,3'-
dichlorobenzidine interchangeably with 3,3'-dichlorobenzidine
dihydrochloride. The dihydrochloride salt of 3,3'-dichlorobenzidine is
expected to be equally as toxic as the free base (3,3'-
dichlorobenzidine). EPA believes that there is sufficient evidence for
listing 3,3'-dichlorobenzidine dihydrochloride on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on its potential to cause
cancer in humans.
75. 3,3'-Dichlorobenzidine sulfate (CAS No. 064969-34-2) (TSCA)
(Ref. 8). IARC has classified 3,3'-dichlorobenzidine (o-
dichlorobenzidine) as a group 2B compound, i.e. this chemical is
possibly carcinogenic in humans. The sulfate salt of
3,3'dichlorobenzidine is expected to be equally as toxic as the free
base (3,3'-dichlorobenzidine). EPA believes that there is sufficient
evidence for listing 3,3'-dichlorobenzidine sulfate on EPCRA section
313 pursuant to EPCRA section 313(d)(2)(B) based on its potential to
cause cancer in humans.
76. trans-1,4-Dichloro-2-butene (CAS No. 000110-57-6) (EPCRA EHS)
(Ref. 8). Mortality in two of six rats was observed following
inhalational exposure to 62 ppm (0.34 mg/L) for 4 hours. An acute
inhalation LC50 in rats was 86 ppm (0.44 mg/L). EPA's exposure
analysis indicates that trans-1,4-dichloro-2-butene concentrations are
likely to exist beyond facility site boundaries, as a result of
continuous, or frequently recurring releases, at levels that can
reasonably be anticipated to cause significant adverse acute human
health effects. EPA believes that there is sufficient evidence for
listing trans-1,4-dichloro-2-butene on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(A) based on the available acute toxicity and
exposure data for this chemical.
77. Dichloromethylphenylsilane (CAS No. 000149-74-6) (EPCRA EHS)
(Ref. 8). As a class, chlorinated silanes are very corrosive to the
skin and mucous membranes and liberate hydrochloric acid in the
presence of water. The 2-hour mouse inhalation LC50 value for
dichloromethylphenylsilane is 0.17 mg/L. EPA's exposure analysis
indicates that dichloromethylphenylsilane concentrations are likely to
exist beyond facility site boundaries, as a result of continuous, or
frequently recurring releases, at levels that can reasonably be
anticipated to cause significant adverse acute human health effects.
EPA believes that there is sufficient evidence for listing
dichloromethylphenylsilane on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(A) based on the available acute toxicity and exposure
data for this chemical.
78. Dichlorophene (2,2'-methylenebis(4-chlorophenol) (CAS No.
000097-23-4) (FIFRA AI) (Ref. 3). Increased incidence of microphthalmia
was observed in the offspring of rats administered 25 mg/kg/day
(teratogenic LOEL). The NOEL was 5.0 mg/kg/day. A dose of 75 mg/kg/day
(fetotoxic LOEL) produced delayed ossification of vertebral centra and
sternaebrae, reduced body weight and length, and increased resorptions
in rat fetuses. The fetotoxic NOEL was 5.0 mg/kg/day. No other
developmental studies were available. EPA believes that there is
sufficient evidence for listing dichlorophene on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available
developmental toxicity data.
Aquatic acute toxicity values for dichlorophene include a measured
48-hour LC50 of 50 ppb for Spicodioptomus (calanoid copipod). EPA
believes that there is sufficient evidence for listing dichlorophene on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the
available environmental toxicity data.
79. trans-1,3-Dichloropropene (CAS No. 010061-02-6) (CERCLA; CWA
PPL) (Ref. 8). Clinical reports have documented the occurrence of
histiocytic lymphoma in two firemen and acute myelomonocytic leukemia
in a farmer exposed accidently to 1,3-dichloropropene. Information on
the isomer or isomer mixture (i.e., trans/cis isomers) was not
specified. The lymphoma and leukemia were refractory to treatment, and
all three men died. There is evidence that 1,3-dichloropropene may
cause cancer in rats and mice after oral exposure. In a 2-year gavage
study, rats treated with 25 or 50 mg/kg/day 1,3-dichloropropene (53
percent cis isomer, 45 percent trans isomer, 1 percent epichlorhydrin)
developed squamous cell papillomas and carcinomas of the forestomach.
Male rats also developed neoplastic nodules of the liver. Female mice
that received 50 or 100 mg/kg/day developed squamous cell papillomas
and carcinomas of the forestomach, transitional cell carcinomas of the
urinary bladder, and an increased incidence of alveolar/bronchiolar
adenomas. A statistically significant increase in bronchioalveolar
adenomas was noted in male mice exposed to 60 ppm (272 mg/L) 1,3-
dichloropropene vapors (50 percent cis isomer, 43 percent trans
isomer). This benign lung tumor was not seen in female mice or in male
or female rats. IARC assigned 1,3-dichloropropene to Group 2B, i.e.,
possibly carcinogenic in humans. EPA believes that there is sufficient
evidence for listing trans-1,3-dichloropropene on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available
carcinogenicity data for 1,3-dichloropropene (unspecified isomer).
80. Diclofop methyl (2-[4-(2,4-dichlorophenoxy) phenoxy]propanoic
acid, methyl ester) (CAS No. 051338-27-3) (FIFRA AI) (Ref. 3). In a rat
teratology study, increased resorptions, reduced body weights, and
dilation of the renal pelvis or distension of the ureter in offspring
were reported in rats fed 1.6 mg/kg/day (LOEL). The NOEL was 0.5 mg/kg/
day. Increased pup mortality was observed at 5 mg/kg/day (LOEL) in a 3-
generation rat reproduction study. The NOEL was 1.5 mg/kg/day.
In a 30-day rat feeding study, increased relative heart, liver, and
kidney weights were observed at the LOEL of 4 mg/kg/day. No NOEL was
established. Jaundice, increased bilirubin, increased serum glutamic-
pyruvic transaminase and serum glutamic-oxaloacetic transaminase, and
increased liver and kidney weights were observed in a 30-day dog
feeding study at 50 mg/kg/day. The NOEL was 12.5 mg/kg/day. In a 90-day
rat feeding study, elevated liver weights and centrilobular enlargement
of hepatic cells were observed at 4 mg/kg/day. The NOEL was 1.6 mg/kg/
day. Dogs fed 6.25 mg/kg/day for 90 days had increased lipid content
and focal changes in the renal cortex. The NOEL was 2 mg/kg/day. EPA
believes that there is sufficient evidence for listing diclofop methyl
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on
the available developmental, hepatic, and renal toxicity data.
81. Dicyclopentadiene (CAS No. 000077-73-6) (TSCA) (Ref. 8).
Convulsions were reported in rats or mice following inhalation of
dicyclopentadiene at dosage levels of 332 or 145 ppm (1.8 or 0.78 mg/
L), respectively, for 1 or 2 days. The reported acute oral LD50 in
rats is 353 mg/kg. Animals at this dose level had convulsions and
muscle weakness. In a 90-day inhalation study in dogs, neurotoxic
symptoms observed included diarrhea, excessive salivation and lack of
control of hind quarters. The NOAEL in this study was 8.9 ppm (0.048
mg/L); no LOEL was reported. EPA believes that there is sufficient
evidence for listing dicyclopentadiene on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(B) based on the chronic neurotoxicity data for
this chemical.
82. Diethatyl ethyl (CAS No. 038727-55-8) (FIFRA AI) (Ref. 3). In a
2-year study, groups of six beagles/sex were given doses orally from 0
to 31.25 mg/kg/day. The lowest dose (0.25 mg/kg/day) produced a
positive Coombs test. EPA believes that there is sufficient evidence
for listing diethatyl ethyl on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available hematological toxicity data
for this chemical.
83. Diflubenzuron (CAS No. 035367-38-5) (FIFRA SR) (Ref. 8). In a
2-year study in which beagle dogs received diflubenzuron daily in
gelatin capsules, the LOAEL for increases in sulfhemoglobin and
methemoglobin was 10 mg/kg/day and the NOAEL was 2 mg/kg/day. EPA has
derived an oral RfD of 0.02 mg/kg/day for this chemical from this
study. Similar effects were noted in two separate 2-year rat feeding
studies (the LOAEL was 7.8 to 8 mg/kg/day; the NOAEL was 2 mg/kg/day),
and in a lifetime oral study in mice (the LOAEL was 12 mg/kg/day; the
NOAEL was 2.4 mg/kg/day). EPA believes that there is sufficient
evidence for listing diflubenzuron on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(B) based on the available hematological
toxicity data.
Measured aquatic acute toxicity data for diflubenzuron include a
48-hour LC50 of 4.55 ppb for daphnids. EPA believes that there is
sufficient evidence for listing diflubenzuron on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(C) based on the environmental
toxicity data for this chemical.
84. Diglycidyl resorcinol ether (CAS No. 000101-90-6) (IARC; NTP)
(Ref. 8). Diglycidyl resorcinol ether is classified by IARC as a Group
2B compound, i.e., it is possibly carcinogenic in humans. In an NTP
bioassay, rats orally administered 12 mg/kg of diglycidyl resorcinol
ether 5 days a week for 103 weeks developed squamous cell papillomas
and squamous cell carcinomas of the stomach. Mice orally administered
50 mg/kg 5 days a week for 103 weeks developed squamous cell carcinomas
and squamous cell papillomas of the stomach. Mice orally administered
70.5 mg/kg/day of diglycidyl resorcinol ether for 2 years developed
blood lymphomas and Hodgkin's disease. Mice receiving dermal
applications of diglycidyl resorcinol ether for 1-year developed skin
tumors. EPA believes that there is sufficient evidence for listing
diglycidyl resorcinol ether on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the carcinogenicity data for this
chemical.
85. Dimethipin (2,3,-Dihydro-5,6-dimethyl-1,4-dithiin 1,1,4,4-
tetraoxide) (CAS No. 055290-64-7) (FIFRA AI) (Ref. 3). In a 1-year dog
feeding study, decreased erythrocyte, hemoglobin, and hematocrit levels
as well as increased platelet levels were observed at 75 mg/kg/day. The
LOEL for systemic toxicity based on decreased body weight was 7.5 mg/
kg/day. No NOEL could be established. In a 2-year rat feeding study,
increased absolute and relative liver weights were observed at 10 mg/
kg/day (LOEL). The NOEL was 2 mg/kg/day. Based on the NOEL in the
study, EPA established an oral RfD of 0.02 mg/kg/day. EPA believes that
there is sufficient evidence for listing dimethipin on EPCRA section
313 pursuant to EPCRA section 313(d)(2)(B) based on the available
hematological and hepatic toxicity data.
86. Dimethoate (CAS No. 000060-51-5) (CERCLA; EPCRA EHS; FIFRA SR;
RCRA APP8; RCRA P) (Ref. 8). Dimethoate is an organophosphate
insecticide. In humans, dimethoate causes typical symptoms of
cholinesterase inhibition (sweating, diarrhea, salivation, headache,
difficulty in breathing, etc.). In a controlled human study, subjects
were administered dimethoate for 57 days. Whole blood and erythrocyte
cholinesterase inhibition was observed from day 20 on. The NOEL was
0.202 mg/kg/day, and the LOEL was 0.434 mg/kg/day. In another study in
which humans were administered dimethoate for 57 days, the NOEL for
cholinesterase inhibition was 15 mg/day (0.2 mg/kg based on a 70 kg
person). The LOEL was not specified. Cholinergic symptoms reflective of
cholinesterase inhibition following dimethoate administration have also
been observed in laboratory animals. A 2-year feeding study in rats
determined the NOEL and LOEL for plasma and brain cholinesterase
inhibition to be 0.05 and 0.5 mg/kg/day, respectively.
Dimethoate was tested for developmental effects in Wistar rats.
Cygon 4E (47.3 percent dimethoate, 52.7 percent unspecified
constituents) was administered to pregnant females on days 6 to 15 of
gestation. The NOEL for developmental effects was 6 mg/kg/day. At a
LOEL of 12 mg/kg/day, an increase in the incidence of wavy ribs was
observed in the fetuses. An increase in offspring mortality occurred in
a five-generation chronic feeding study (actual doses were 9.5 to 10.5
mg/kg/day) in male and female CD-1 mice. At 12 mg/kg/day (120 mg/kg,
gestation days 6 to 15), musculoskeletal abnormalities were observed in
the rat offspring. EPA believes that there is sufficient evidence for
listing dimethoate on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available developmental and neurotoxicity
data for this chemical.
87. 3,3'-Dimethoxybenzidine dihydrochloride (o-Dianisidine
dihydrochloride) (CAS No. 020325-40-0) (TSCA) (Ref. 8). IARC has
classified 3,3'-dimethoxybenzidine (o-dianisidine) as a Group 2B
compound, i.e., this chemical is possibly carcinogenic. In an NTP
carcinogenicity bioassay, increases in neoplasms of the skin, oral
cavity, large intestine, liver, uterus, and cervix were noted in rats
administered this chemical in drinking water at dose levels of 6, 12,
or 21 mg/kg/day in males and 7, 14, or 23 mg/kg/day in females. The
dihydrochloride salt of o-dianisidine is expected to be equally as
toxic as the free base (o-dianisidine). EPA believes that there is
sufficient evidence for listing 3,3'-dimethoxybenzidine dihydrochloride
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on
its potential to cause cancer in humans.
88. 3,3'-Dimethoxybenzidine hydrochloride (o-Dianisidine
hydrochloride) (CAS No. 111984-09-9) (TSCA) (Ref. 8). IARC has
classified 3,3'-dimethoxybenzidine (o-dianisidine) as a Group 2B
compound, i.e., this chemical is possibly carcinogenic. In an NTP
carcinogenicity bioassay, increases in neoplasms of the skin, oral
cavity, large intestine, liver, uterus and cervix were noted in rats
administered this chemical in drinking water at dose levels of 6, 12,
or 21 mg/kg/day in males and 7, 14, or 23 mg/kg/day in females. The
hydrochloride salt of o-dianisidine is expected to be equally as toxic
as the free base (o-dianisidine). EPA believes that there is sufficient
evidence for listing 3,3'dimethoxybenzidine hydrochloride on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on its
potential to cause cancer in humans.
89. Dimethylamine (CAS No. 000124-40-3) (TSCA) (Ref. 8).
Dimethylamine is corrosive to the mucous membranes, respiratory tract
and eyes of treated animals. B6C3F1 mice and F344 rats exposed to 10 to
175 ppm (0.018 to 0.32 mg/L) dimethylamine via inhalation for 6 to 12
months developed dose-related lesions in the respiratory and olfactory
epithelium. Significant decreases in body weight occurred in high-dose
(175 ppm; 0.32 mg/L) animals of both species, and some of the high-dose
mice died following exposure.
Centrilobular fatty degeneration and necrosis of parenchymal cells
were reported in mice, rats, rabbits or guinea pigs administered 97 or
183 ppm (0.18 or 0.34 mg/L) dimethylamine via inhalation for 18 to 20
weeks. Increased liver weight without any histopathological changes
were reported following 8-month oral exposure of rats to 0.35 mg/kg/day
and guinea pigs exposed to 3.5 mg/kg/day.
Rats administered oral doses of dimethylamine as low as 0.035 mg/kg
for 8 months exhibited changes in conditional reflexes including marked
attenuation of the excitation process and speedier extinction of the
positive reflex.
EPA believes that there is sufficient evidence for listing
dimethylamine on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the chronic respiratory, hepatic, and
neurological toxicity of this chemical.
90. Dimethylamine dicamba (CAS No. 002300-66-5) (FIFRA AI) (Ref.
3). In a pilot rabbit developmental toxicity study, an increase in
early and late fetal resorptions was observed in animals receiving the
LOEL of 1.0 mg/kg/day. The NOEL was 0.5 mg/kg/day (oral doses, days 6
to 18 of gestation). In another study, increased post-implantation loss
was observed in rabbits receiving the LOEL of 10 mg/kg/day (oral doses,
days 6 to 18 of gestation). Developmental toxicity was also observed at
doses of 10 mg/kg/day in studies with dicamba. EPA believes that there
is sufficient evidence for listing dimethylamine dicamba on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available developmental toxicity data for this chemical.
91. 3,3'-Dimethylbenzidine dihydrochloride (o-Tolidine
dihydrochloride) (CAS No. 000612-82-8) (TSCA) (Ref. 8). In a bioassay
conducted by NTP, 3,3'-dimethylbenzidine dihydrochloride was found to
be carcinogenic in both mice and rats. Male and female mice exposed to
concentrations of 5 to 140 ppm (0.95 to 26.6 mg/kg/day) in drinking
water for 112 weeks developed lung alveolar cell adenoma and
adenocarcinoma. Male and female F344 rats exposed to concentrations of
30 to 150 ppm (4.2 to 21 mg/kg/day) in drinking water for 60 to 61
weeks developed tumors in the gastrointestinal tract, liver, lung and
oral cavity. Tumors in the skin, Zymbal's gland, preputial gland in
males, clitoral gland and mammary gland in females, and leukemia in
females were also noted in this study. EPA believes that there is
sufficient evidence for listing 3,3'-dimethylbenzidine dihydrochloride
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on
its potential to cause cancer in humans.
92. 3,3'-Dimethylbenzidine dihydrofluoride (o-Tolidine
dihydrofluoride) (CAS No. 041766-75-0) (TSCA) (Ref. 8). Neither IARC or
EPA has classified 3,3'-dimethylbenzidine dihydrofluoride with respect
to carcinogenicity. In a bioassay conducted by NTP, however, 3,3'-
dimethylbenzidine dihydrochloride was found to be carcinogenic in both
mice and rats. Male and female mice exposed to concentrations of 5 to
140 ppm (0.952 to 6.6 mg/kg/day) in drinking water for 112 weeks
developed lung alveolar cell adenoma and adenocarcinoma. Male and
female F344 rats exposed to concentrations of 30 to 150 ppm (4.2 to 21
mg/kg/day) in drinking water for 60 to 61 weeks developed tumors in the
gastrointestinal tract, liver, lung, and oral cavity. Tumors in the
skin, Zymbal's gland, preputial gland in males, clitoral gland and
mammary gland in females, and leukemia in females were also noted in
this study. EPA believes that there is sufficient evidence for listing
3,3'-dimethylbenzidine dihydrofluoride on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(B) based on its potential to cause cancer in
humans and on the carcinogenicity data for 3,3'-dimethylbenzidine
dihydrochloride.
93. Dimethyl chlorothiophosphate (CAS. No. 002524-03-0) (EPCRA EHS)
(Ref. 8). In a dominant lethal study, male rats were administered
dimethyl chlorothiophosphate by gavage for 5 consecutive days and mated
to untreated females. The LOEL of 7.5 mg/kg/day was determined based on
an increase in preimplantation losses and dead implants. No NOEL for
dimethyl chlorothiophosphate was determined from this study. EPA
believes that there is sufficient evidence for listing dimethyl
chlorothiophosphate on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the developmental toxicity data for this
chemical.
94. Dimethyldichlorosilane (CAS No. 000075-78-5) (CERCLA; EPCRA
EHS) (Ref. 8). As a class, however, chlorinated silanes are very
corrosive to the skin and mucous membranes and liberate hydrochloric
acid in the presence of water. Dimethyldichlorosilane causes severe
burns and the vapor is harmful to humans. The 2-hour mouse inhalation
LC50 value is 0.30 mg/L. EPA's exposure analysis indicates that
dimethyldichlorosilane concentrations are likely to exist beyond
facility site boundaries, as a result of continuous, or frequently
recurring releases, at levels that can reasonably be anticipated to
cause significant adverse acute human health effects. EPA believes that
there is sufficient evidence for listing dimethyldichlorosilane on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(A) based on the
available acute toxicity and exposure data for this chemical.
95. N,N-Dimethylformamide (CAS No. 000068-12-2) (CAA HAP) (Ref. 7).
In humans, N,N-dimethylformamide (DMF) produced an increase in
subjective symptoms suggestive of mild liver dysfunction in workers and
changes in objective measurements of liver damage (serum enzymes and
liver enlargement) via inhalation exposure, resulting in a LOAEL of 22
mg/m3 (adjusted LOAEL of 7.9 mg/m3)). Although there are several
additional studies which are generally inadequate when considered
individually, taken together, these studies demonstrate that DMF
exposure is associated with hepatic toxicity in humans. Several animal
inhalation studies further support the hepatotoxic effects of DMF. EPA
believes that there is sufficient evidence for listing N,N-
dimethylformamide on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based upon the available hepatotoxicity data for this
chemical.
96. 2,6-Dimethylphenol (000576-26-1) (TSCA) (Ref. 8). Oral
administration of 2,6-dimethylphenol to rats for 8 months produced
histologic lesions (the LOEL was 6.0 mg/kg/day; the NOEL was 0.6 mg/kg/
day) in the liver, kidneys, and spleen. Another supporting oral study
in rats that also reported histological lesions in the liver and
kidneys (the LOEL was 6.0 mg/kg/day; the NOEL was 0.06 mg/kg/day) of
rats following subchronic oral administration of 2,6-dimethylphenol.
EPA believes that there is sufficient evidence for listing 2,6-
dimethylphenol on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the hepatotoxicity and nephrotoxicity data for
this chemical.
97. Dinocap (CAS No. 039300-45-3) (CAL; FIFRA SR) (Ref. 8). Dinocap
is a dinitrophenyl-type fungicide. In mice, oral administration of 25
mg/kg/day of dinocap on days 7 to 16 of gestation has been shown to
increase post-implantation mortality and reduce newborn viability. Oral
administration of 5.0 mg/kg/day to pregnant mice produced developmental
toxicity in the offspring (administration of 10 mg/kg/day resulted in
abnormalities of the musculoskeletal and hepatobiliary system in the
offspring). In the same study, oral administration of 20 mg/kg/day on
days 7 to 16 of gestation produced craniofacial abnormalities in
offspring. In the same study, behavioral abnormalities and delayed
growth were observed in offspring of mice receiving 12 mg/kg/day on
days 7 to 16 of gestation. EPA believes that there is sufficient
evidence for listing dinocap on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the developmental toxicity data for this
chemical.
Measured aquatic acute toxicity data for dinocap indicate that the
LC50 for rainbow trout is 15 ppb and the LC50 for bluegill is
20 ppb. EPA believes that there is sufficient evidence for listing
dinocap on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C)
based on the environmental toxicity data for this chemical.
98. Dinoseb (CAS No. 000088-85-7) (CAL; EPCRA EHS; FIFRA SR; RCRA
APP8; RCRA P; SDWA) (Ref. 8). Dinoseb is a dinitrophenyl-type herbicide
and insecticide. In a three generation reproduction study dinoseb
produced decreased pup weights (the LOEL was 1 mg/kg/day; the NOEL was
not determined) in the F1b, F2a, and F3a pups. The
F1b pup weights diminished (combined sexes) by day 21 at dose
levels greater than 1 mg/kg/day. Other studies have shown biologically
and statistically significant increases in developmental malformations
and/or anomalies (the LOEL was 10 mg/kg/day; the NOEL was 3 mg/kg/day),
and an increased incidence of an absence of ossification for a number
of skeletal sites and supernumerary ribs (the LOEL was not specified;
the NOEL was 3 mg/kg/day). Dinoseb administered by gavage to rabbits
from days 6 to 18 of gestation produced neural tube defects (the LOEL
was 10 mg/kg/day; the NOEL was 3 mg/kg/day).
The fertility index in male rats was reduced in a reproductive
study in animals fed dinoseb at dose levels of 15.6 mg/kg/day or 22.2
mg/kg/day over an 11-week period. Decreased seminal vesicle weight,
decreased sperm count and increased incidence of abnormal sperm were
noted at dose levels of 9.1 mg/kg/day and higher. The NOEL was 3.8 mg/
kg/day.
EPA believes that there is sufficient evidence for listing dinoseb
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on
the developmental and reproductive toxicity data for this chemical.
Aquatic acute toxicity data for dinoseb include a measured fat-head
minnow 96-hour LC50 of 88 ppb. EPA believes that there is
sufficient evidence for listing dinoseb on EPCRA section 313 pursuant
to EPCRA section 313(d)(2)(C) based on the environmental toxicity data
for this chemical.
99. Diphenamid (CAS No. 000957-51-7) (FIFRA SR) (Ref. 8).
Diphenamid is a diphenylacetamide-type herbicide. In a 2-year study in
dogs fed diphenamid, an increase in liver weight and an increase in
portal macrophages and fibroblasts were seen at the LOEL of 10 mg/kg/
day. The NOEL was 3 mg/kg/day. Based on the NOEL, an RfD of 0.03 mg/kg/
day was derived. In a 2-year study in rats fed diphenamid, an increase
in liver weight was seen at the LOEL of 30 mg/kg/day; the NOEL was 10
mg/kg/day. Although, no histopathological changes were reported in
these studies, biochemical changes accompanied by histo-pathological
changes were observed in a 2-generation study in rat pups. EPA believes
that there is sufficient evidence for listing diphenamid on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available hepatotoxicity data for this chemical.
100. Diphenylamine (CAS No. 000122-39-4) (RCRA APP8) (Ref. 8).
Increased liver and kidney weights were noted in dogs that received 25
mg/kg/day (the LOAEL) of diphenylamine in their feed for 2 years. The
NOAEL in this study was 2.5 mg/kg/day and the oral RfD was 0.025 mg/kg/
day. Pronounced anemia and decreased body weight gain were also noted
in these animals. The hepatotoxicity induced by diphenylamine is
manifested by peripherolobular fat changes and increased lipids.
Vacuolar degeneration and hepatocyte necrosis were reported in rats or
guinea pigs that received 2 or 4 percent (i.e., 1,000 or 2,000 mg/kg/
day for rats and 800 to 1,600 mg/kg/day for guinea pigs) of
diphenylamine in the diet for 6 months. In another 2-year rat study,
changes reported in the kidney in diphenylamine-fed animals included
epithelial necrosis in the proximal tubule, cystic dilatation of
tubules, and interstitial inflammation.
EPA believes that there is sufficient evidence for listing
diphenylamine on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the chronic hepatic and renal toxicity data for
this chemical.
101. Dipotassium endothall (7-oxabicyclo(2.2.1)heptane-2,3-
dicarboxylic acid, dipotassium salt) (CAS No. 002164-07-0) (FIFRA AI)
(Ref. 3). In a 2-year dog feeding study, increased absolute and
relative weight of the stomach and small intestine was observed at 6
mg/kg/day (LOEL). The NOEL was 2 mg/kg/day. An oral RfD of 0.02 mg/kg/
day was derived based on the NOEL. EPA believes that there is
sufficient evidence for listing dipossium endothall on EPCRA section
313 pursuant to EPCRA section 313(d)(2)(B) based on the available
chronic toxicity data for this chemical.
102. Dipropyl isocinchomeronate (CAS No. 000136-45-8) (FIFRA AI)
(Ref. 3). Dipropyl isocinchomeronate has been classified by EPA as a
Group B2 compound, i.e., a probable human carcinogen. This
classification is based on the findings of multiple malignant and
benign tumors in the rat (liver adenomas and carcinomas in both sexes,
kidney carcinomas in both sexes, benign testes tumors in males and
uterine tumors in females), and multiple malignant tumors in the mouse
(liver adenomas and carcinomas in both sexes and lung/bronchiolar
adenomas and carcinomas in males). EPA believes that there is
sufficient evidence for listing dipropyl isocinchomeronate on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available carcinogenicity toxicity data.
103. Disodium cyanodithioimidocarbonate (CAS No. 000138-93-2)
(FIFRA AI) (Ref. 3). Rats administered disodium
cyanodithioimidocarbonate by gavage on gestation days 6 to 15
demonstrated increased skeletal variations in offspring. The NOEL is 6
mg/kg, and the LOEL is 18 mg/kg. In a rabbit teratology study,
increased resorptions were observed in rabbits administered the
compound by gavage on gestation days 6 to 18. The NOEL is 3 mg/kg, and
the LOEL is 10 mg/kg. EPA believes that there is sufficient evidence
for listing disodium cyanodithioimidocarbonate on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available
developmental toxicity data.
104. 2,4-D isopropyl ester (CAS No. 000094-11-1) (CERCLA; FIFRA AI:
IARC) (Ref. 8). 2,4-D isopropyl ester is a 2,4-dichlorophenoxy-type
herbicide. In mammals, the isopropyl ester of 2,4-D is hydrolyzed to
yield the free acid, 2,4-D. Therefore, the toxicity of 2,4-D isopropyl
ester is expected to be similar to that of 2,4-D, in which the kidney,
liver, and nervous system are the primary targets of injury. 2,4-D is
presently included in the EPCRA section 313 list of toxic chemicals.
EPA believes that there is sufficient evidence for listing 2,4-D
isopropyl ester on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the known toxic effects of its metabolite 2,4-D.
105. 2,4-Dithiobiuret (CAS No. 000541-53-7) (CERCLA; EPCRA EHS;
RCRA APP8; RCRA P) (Ref. 8). In experimental animals, 2,4-dithiobiuret
is a highly toxic substance that causes death through respiratory
depression and respiratory failure. Rats receiving 1 mg/kg/day for 6
days suffered from delayed onset of neuromuscular depression. Rats
given 2,4-dithiobiuret for 52 days showed signs of muscle weakness
after a latency period of 3 to 4 days. The NOEL was determined to be
0.125 mg/kg/day. The LOEL was 0.25 mg/kg/day. The cause of the muscle
weakness was depressed neuromuscular transmission. EPA believes that
there is sufficient evidence for listing 2,4-dithiobiuret on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on the chronic
neurotoxicity data for this chemical.
106. Dithiopyr (2-(difluoromethyl)-4-(2-methylpropyl)-6-
(trifluoromethyl)-3,5-pyridinedicarbothioic acid S,S-dimethyl ester)
(CAS No. 097886-45-8) (FIFRA AI) (Ref. 3). In a 2-generation rat
reproduction study, decreased body weight, diffuse hepatocellular
swelling, and ``white spots'' on the livers were observed in the
offspring of rats administered greater than or equal to 16.4 mg/kg/day.
The NOEL values were 1.7 mg/kg/day. In a 13-week rat feeding study, the
LOEL of 6.62 mg/kg/day produced diffuse hepatocellular swelling. The
NOEL was 0.662 mg/kg/day. In a 13-week dog feeding study, increased
alkaline phosphatase, discolored livers, and cholestasis was observed
at 10 mg/kg/day (LOEL). The NOEL was 1 mg/kg/day. In addition, at 30
mg/kg/day, increased serum glutamic-pyruvic transaminase and serum
glutamic oxaloacetic transaminase, increased liver and kidney weights,
and decreased cholesterol and albumin were observed. EPA believes that
there is sufficient evidence for listing dithiopyr on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available hepatic
and renal toxicity data.
107. Diuron (CAS No. 000330-54-1) (CERCLA) (Ref. 8). In a 2-year
study in dogs administered diuron, sulfhemoglobin (an abnormal blood
pigment) was detected following doses as low as 3.125 mg/kg/day
(LOAEL). The NOAEL was 0.625 mg/kg/day. Higher doses (6.25 and 31.25
mg/kg/day) caused decreased red blood cell, hemoglobin, and hematocrit
values. The highest dose tested (31.25 mg/kg/day) also caused an
increase in erythrogenic activity in the bone marrow, hemosiderosis in
the spleen, increased liver weight, and body weight loss. EPA has
derived an oral RfD of 0.002 mg/kg/day for this chemical from this
study. Similar effects (anemia, increased erythrogenic activity in the
bone marrow, and abnormal pigments in the blood) were also observed in
rats exposed orally to doses as low as 6.25 mg/kg/day for 2 years, or
to 250 mg/kg/day for 90 days. In a 7-week study, rats receiving diuron
doses of greater than or equal to 10 mg/kg/day had decreased red blood
cells and significantly increased methemoglobinemia.
Offspring of Wistar rats fed diuron during days 6 to 15 of
gestation showed developmental toxicity, that included malformed ribs,
extra ribs, and delayed ossification. The developmental LOAEL in this
study was 100 mg/kg/day. No NOAEL was determined. Maternal and fetal
body weights decreased at 400 mg/kg/day. In a three-generation
reproduction study in rats fed diuron at 6.25 mg/kg/day, decreased body
weights were reported in the F2b and F3a litters.
EPA believes that there is sufficient evidence for listing diuron
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on
the available hematological and developmental toxicity data for this
chemical.
The measured aquatic toxicity data for diuron includes a 1.5-hour
EC50 of 0.010 ppm (10 ppb) for marine green algae. EPA believes
that there is sufficient evidence for listing diuron on EPCRA section
313 pursuant to EPCRA section 313(d)(2)(C) based on the environmental
toxicity data for this chemical.
108. 2,4-D 2-octyl ester (CAS No. 001917-97-1) (CERCLA; FIFRA AI;
IARC) (Ref. 8). 2,4-D 2-octyl ester is a 2,4-dichlorophenoxy-type
herbicide. The 2-octyl moiety contains eight carbons and, therefore, is
an isooctyl group.
Developmental toxicity following maternal exposure to 2,4-D
isooctyl esters has been demonstrated in the rat and mouse.
Fetotoxicity occurred in offspring of rats exposed to 528 mg/kg during
gestation days 8 to 11. Rats orally exposed to doses as low as 302 mg/
kg during gestation days 9 through 12 had musculoskeletal
abnormalities. Exposure to a lower dose (188 mg/kg) for a longer period
during gestation (days 6 through 15) caused developmental effects on
homeostasis and effects on newborn growth statistics. In mice, 438 mg/
kg administered orally during gestation days 8 through 12 also caused
effects on newborn growth statistics.
EPA believes that there is sufficient evidence for listing 2,4-D 2-
octyl ester on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the developmental toxicity data for 2,4-D isooctyl esters, and
the toxic effects of its metabolite 2,4-D.
The aquatic acute toxicity data for 2,4-D isooctyl esters include a
measured 48-hour LC50 of 8.8 ppm for bluegill. In addition, 2,4-D
isooctyl esters are expected to bioaccumulate based on the estimated
log Kow of 6.6. EPA believes that there is sufficient evidence for
listing 2,4-D isooctyl esters on EPCRA section 313 pursuant to section
EPCRA 313(d)(2)(C) based on the available environmental toxicity data
and the potential for bioaccumulation.
109. Dodine (dodecylguanidine monoacetate) (CAS No. 002439-10-3)
(FIFRA AI) (Ref. 3). Aquatic acute toxicity values for dodine include a
daphnid 48-hour EC50 of 17.8 ppb. EPA believes that there is
sufficient evidence for listing dodine on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(C) based on the available environmental
toxicity data.
110. 2,4-DP (dichlorprop) (CAS No. 000120-36-5) (FIFRA SR; IARC)
(Ref. 8). 2,4-DP (2-(2,4-dichlorophenoxy)propionic acid) is a 2,4-
dichlorophenoxy-type herbicide. Developmental toxicity has been
reported in rats and mice administered oral doses of 2,4-DP as low as
20 mg/kg during gestation days 4 through 18. Behavioral changes and
physical effects were observed in newborn rats, while increased post-
implantation loss was observed in the mothers. Exposure of mice to much
higher doses (3,000 and 4,000 mg/kg) for shorter durations (i.e.,
gestation days 6 through 15) caused musculoskeletal abnormalities and
fetotoxicity.
EPA believes that there is sufficient evidence for listing 2,4-DP
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on
the available developmental toxicity data for this chemical.
111. 2,4-D propylene glycol butyl ether ester (CAS No. 001320-18-9)
(CERCLA; FIFRA AI; IARC) (Ref. 8). 2,4-D propylene glycol butyl ether
ester is a 2,4-dichlorophenoxy-type herbicide. In mammals, the
propylene glycol butyl ether ester is expected to hydrolyze to yield
the free acid, 2,4-D. Therefore, the toxicity of 2,4-D propylene glycol
butyl ether ester is expected to be similar to that of 2,4-D, in which
the kidney, liver, and nervous system are the primary targets of
injury. EPA believes that there is sufficient evidence for listing 2,4-
D propylene glycol butyl ether ester on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(B) based on the chronic toxicity data for this
chemical.
112. 2,4-D sodium salt (CAS No. 002702-72-9) (CERCLA; FIFRA AI;
IARC) (Ref. 8). 2,4-D sodium salt is a 2,4-dichlorophenoxy-type
herbicide. In mammals, the sodium salt is expected to hydrolyze to
yield the free acid, 2,4-D. Therefore, the toxicity of 2,4-D sodium
salt is expected to be similar to that of 2,4-D, in which the kidney,
liver, and nervous system are the primary targets of injury. 2,4-D is
presently included in the EPCRA section 313 list of toxic chemicals.
EPA believes that there is sufficient evidence for listing 2,4-D sodium
salt ester on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the systemic toxicity data for this chemical.
113. Ethoprop (phosphorodithioic acid O-ethyl S,S-dipropyl ester)
(CAS No. 013194-48-4) (FIFRA AI) (Ref. 3). Ethoprop is acutely toxic to
animals. The acute oral LD50 in rats is 5.62 mg/kg/day. Clinical
signs of toxicity observed in animals at this dose level included
depression, salivation, inactivity, convulsions and prostration.
Similar signs were reported at the 4-hour inhalation LC50 of 0.12
mg/L in rats. In a 2-year rat chronic feeding study, plasma, red blood
cell, and brain cholinesterase inhibition were observed in both sexes
at 0.5 mg/kg/day. The NOEL was 0.05 mg/kg/day. Similar results were
reported in a chronic dietary study in mice at 0.1 mg/kg/day. The NOEL
was 0.01 mg/kg/day. The two chronic studies together with the results
of acute studies indicate the potential neurotoxicity of ethoprop. EPA
believes that there is sufficient evidence for listing ethoprop on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available neurological toxicity data.
Aquatic acute toxicity values for ethoprop include a mysid 96-hour
LC50 of 7.5 ppb, a shrimp 96-hour LC50 of 13 ppb, and a
daphnid 48-hour EC50 of 93 ppb. Avian acute and dietary toxicity
data include a ring-necked pheasant 14-day LD50 of 4.2 mg/kg and a
mallard duck 14-day LD50 of 12.6 mg/kg. EPA believes that there is
sufficient evidence for listing ethoprop on EPCRA section 313 pursuant
to EPCRA section 313(d)(2)(C) based on the available environmental
toxicity data for this chemical.
114. Ethyl dipropylthiocarbamate (EPTC) (CAS No. 000759-94-4)
(FIFRA AI) (Ref. 3). EPTC is a cholinesterase inhibitor. Workers
exposed to EPTC complained of headache, malaise, nausea, and impaired
working ability. Poisoned animals exhibited salivation, lacrimation,
blepharospasm, and depression. Neuropathy was observed in rats orally
administered 25 mg/kg/day for 2 years. The LOEL was 25 mg/kg/day and
the NOEL was 5 mg/kg/day. Decreased brain cholinesterase activity was
observed in female rats orally administered 15 mg/kg/day (LOEL). The
NOEL was 3 mg/kg/day. The 4-hour inhalation rat and cat lowest-lethal-
concentration values are 0.2 mg/L and 0.4 mg/L, respectively.
Somnolence and salivation were observed in exposed animals. The dermal
rabbit LD50 is 10,000 mg/kg. Depressed righting reflexes,
prostration, and clonic convulsions were observed.
In a 2-year dietary rat study, degenerative cardiomyopathy was
observed in males receiving 9 mg/kg/day of EPTC. No NOEL was
established. This effect was observed in females at 36 mg/kg/day. The
NOEL was 18 mg/kg/day. In a 2-generation rat reproduction study,
parental toxicity included cardiomyopathy observed in rats orally
administered 10 mg/kg/day. Based on the NOEL of 2.5 mg/kg/day, EPA
derived an oral RfD of 0.025 mg/kg/day. In a 2-year dietary rat study,
chronic myocarditis was observed at the LOEL of 125 mg/kg/day. The NOEL
was 25 mg/kg/day.
An increased incidence of fetal resorptions, increased incidence of
fetal retardations, and decreased fetal body weights were observed in
rats receiving 300 mg/kg/day of EPTC on days 6 to 15 of gestation. The
LOEL was 300 mg/kg/day and the NOEL was 100 mg/kg/day. The NOEL was 10
mg/kg/day. In a 2-generation rat reproduction study, decreased pup
weight was observed in both generations at 40 mg/kg/day. The NOEL was
10 mg/kg/day.
EPA believes that there is sufficient evidence for listing EPTC on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available neurological, cardiovascular, and reproductive toxicity data
for this chemical.
115. Famphur (CAS No. 000052-85-7) (CERCLA; FIFRA AI; RCRA APP8;
RCRA P) (Ref. 8). Famphur is a thiophosphate-type cholinesterase
inhibitor. In a 90-day feeding study, rats given diets supplemented
with famphur showed decreased plasma and brain cholinesterase activity
at 1.25 mg/kg/day, and decreased whole blood cholinesterase activity at
0.15 mg/kg/day. A bull was treated with famphur for 43 days before
signs of neurotoxicity appeared. The symptoms, including paresis of all
four limbs, were attributed to focal cervical or diffuse spinal cord
lesions. Calves receiving 60.75 mg/kg showed marked inhibition of whole
blood cholinesterase. EPA believes that there is sufficient evidence
for listing famphur on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the chronic neurotoxicity known for this
chemical.
Measured terrestrial wildlife acute toxicity data for famphur
indicate that the oral LD50 values for the redwinged blackbird and
the starling are 1.78 mg/kg and 4.22 mg/kg, respectively. In addition,
the measured oral LD50 for mallard ducks is 3.45 mg/kg (based on
35 percent active ingredient). EPA believes that there is sufficient
evidence for listing famphur on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(C) based on the environmental toxicity data for this
chemical.
116. Fenarimol (.alpha.-(2-chlorophenyl)-.alpha.-4-chlorophenyl)-5-
pyrimidinemethanol) (CAS No. 060168-88-9) (FIFRA AI) (Ref. 3). In a 3-
month mouse feeding study, liver weights were increased in males at
levels greater than or equal to 620 ppm (80.6 mg/kg/day) and in females
at levels greater than 1,100 ppm (143 mg/kg/day). At higher doses (143
to 260 mg/kg/day), decreased total bilirubin, hepatomegaly, and/or
periportal fatty liver changes were observed. Mice exposed to dietary
levels of 78 mg/kg/day for 1-year had increased liver weight and slight
fatty changes. One year feeding studies in Wistar rats also resulted in
increased liver weights (the LOEL was 17.5 mg/kg/day; the NOEL was 6.5
mg/kg/day). In a 2-year feeding study with Wistar rats, fatty changes
in the liver were observed at 17.5 mg/kg/day (LOEL). The NOEL was 6.5
mg/kg/day. A 2-year feeding study in mice resulted in fatty liver
changes. The LOEL was 78 mg/kg/day and the NOEL was 22.1 mg/kg/day. EPA
believes that there is sufficient evidence for listing fenarimol on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available hepatic toxicity data.
117. Fenbutatin oxide (hexakis(2-methyl-2-
phenylpropyl)distannoxane) (CAS No. 013356-08-6) (FIFRA AI) (Ref. 3).
In a rat teratology study, the LOEL for developmental toxicity (toxic
to zygote) was 60 mg/kg/day and the NOEL was 30 mg/kg/day. In a rabbit
teratology study, oral administration of 5 mg/kg/day produced
intrauterine lethality and was also toxic to maternal animals. The NOEL
was 1 mg/kg/day. In a 3-generation rat reproduction study,
administration of 15 mg/kg/day (LOEL) produced decreased viability
index. The NOEL was 5 mg/kg/day. EPA believes that there is sufficient
evidence for listing fenbutatin oxide on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(B) based on the available developmental
toxicity data for this chemical.
Aquatic acute toxicity values for fenbutatin oxide include a
rainbow trout 96-hour LC50 of 1.7 ppb, a fathead minnow 96-hour
LC50 of 1.9 ppb, a daphnid 48-hour EC50 of 3.1 ppb, a
bluegill sunfish 96-hour of LC50 of 4.8 ppb, and a sheepshead
minnow 96-hour LC50 of 20.8 ppb. Avian acute toxicity values
include a quail oral LD50 of 0.007 mg/kg. EPA believes that there
is sufficient evidence for listing fenbutatin oxide on EPCRA section
313 pursuant to EPCRA section 313(d)(2)(C) based on the available
environmental toxicity data for this chemical.
118. Fenoxaprop ethyl (2-(4-((6-chloro-2-
benzoxazolylen)oxy)phenoxy)propanoic acid,ethyl ester) (CAS No. 066441-
23-4) (FIFRA AI) (Ref. 3). In a 30-day mouse feeding study, liver
weight increases were observed (LOEL 20 ppm or 2.6 mg/kg/day and NOEL
10 ppm or 1.3 mg/kg/day). In a 32-day rat feeding study, changes in the
liver and kidney as well as altered lipid metabolism and decreased
cholesterol were observed. The LOEL in the rat study was 80 ppm (4 mg/
kg/day). The NOEL was 20 ppm (1 mg/kg/day). Inflammatory changes in the
kidney (chronic interstitial nephritis) were reported in dogs that
received a 3-month feeding of 80 ppm (2 mg/kg/day, the LOEL). The NOEL
was 16 ppm or 0.4 mg/kg/day. Decreased serum lipids and cholesterol
were reported in rats exposed for 2 years to dietary levels greater
than or equal to 180 ppm (9 mg/kg/day, the LOEL). The NOEL in this
study was 30 ppm (1.5 mg/kg/day).
In a developmental toxicity study, fetotoxic effects (slightly
impaired growth and delayed ossification) were reported at 100 mg/kg/
day. The NOEL was 32 mg/kg/day. These effects were observed at doses
that were also toxic to maternal animals. In a 2-generation
reproductive toxicity feeding study in rats, decreased survival,
decreased body weight at study termination, and significant changes in
kidney and liver weights were reported in the F2a and F2b
litters. The fetotoxic LOEL in this study was 5 ppm (0.25 mg/kg/day,
the lowest dose tested). The LOEL and NOEL for maternal toxicity
(increased kidney and liver weights) were 80 ppm (4 mg/kg/day) and 30
ppm (1.5 mg/kg/day), respectively. Thus, the fetotoxic effects were
observed at doses lower than those that produced maternal toxicity.
EPA believes that there is sufficient evidence for listing
fenoxaprop ethyl on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available renal and developmental toxicity
data for this chemical.
Aquatic acute toxicity values for fenoxaprop ethyl include a mysid
96-hour EC50 of 98 ppb. EPA believes that there is sufficient
evidence for listing fenoxaprop ethyl on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(C) based on the available environmental
toxicity data.
119. Fenoxycarb (2-(4-phenoxyphenoxy)ethyl]carbamic acid ethyl
ester) (CAS No. 072490-01-8) (FIFRA AI) (Ref. 3). Liver changes
(including fatty changes, glycogen depletion, hepatocyte hypertrophy
and multinucleated hepatocytes) were reported in mice (the LOEL was 80
mg/kg/day; the NOEL was not determined) and rats (the LOEL was 300 mg/
kg/day; the NOEL was 100 mg/kg/day) following 3-month dietary
exposures. Dose-related changes in the liver of male rats, including
increased relative liver weight, focal necrosis, centrilobular
hypertrophy and pigmented histiocytes, were reported after the first
year of a 2-year oncogenicity study. The LOEL for these effects was 600
ppm (30 mg/kg/day) and the NOEL was 200 ppm (10 mg/kg/day). Male and
female rats exposed to a higher dose (1,800 ppm or 90 mg/kg/day) in
this study had increased alkaline phosphatase and reduced platelets and
white blood cells, and fibrosis was present in the hepatic lesions in
the males.
In a reproduction study in rats, delays in pinna unfolding and eye
opening were reported at 10 mg/kg/day.
EPA believes that there is sufficient evidence for listing
fenoxycarb on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available hepatic and developmental toxicity data for this
chemical.
120. Fenpropathrin (2,2,3,3-tetramethylcyclopropane carboxylic acid
cyano(3-phenoxyphenyl)methyl ester) (CAS No. 039515-41-8) (FIFRA AI)
(Ref. 3). In a 1-year feeding study, tremors were noted in dogs exposed
to 6.25 mg/kg/day. The NOEL was 2.5 mg/kg/day. In a developmental
toxicity study in rats, signs of neurotoxicity reported in the pregnant
dams included ataxia, tremors, convulsions, lacrimation, prostration of
death. The LOEL for maternal toxicity was 10 mg/kg/day and the NOEL was
6 mg/kg/day. In 2-year dietary studies in rats and mice, body tremors
and increased mortality were observed in male rats (the LOEL was 30 mg/
kg/day; the NOEL was 22.5 mg/kg/day), whereas only marginally increased
hyperactivity was noted in female mice (the LOEL was 65.2 mg/kg/day;
the NOEL was 16.2 mg/kg/day). EPA believes that there is sufficient
evidence for listing fenpropathrin on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(B) based on the available neurological toxicity
data for this chemical.
Aquatic acute toxicity values for fenpropathrin include a rainbow
trout 96-hour LC50 of 2.3 ppb, a bluegill 96-hour LC50 of 2.2
ppb, a sheepshead minnow 96-hour LC50 of 3.1 ppb, and a daphnid
48-hour EC50 of 0.53 ppb. EPA believes that there is sufficient
evidence for listing fenpropathrin on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(C) based on the available environmental
toxicity data for this chemical.
121. Fenthion (O,O-dimethyl O-[3-methyl-4-(methylthio) phenyl]
ester, phosphorothioic acid) (CAS No. 000055-38-9) (FIFRA AI) (Ref. 3).
In cases of human poisonings from fenthion exposure, reported
cholinergic manifestations included the following: A man who ingested
257 mg/kg had an increased pulse rate (no effect on blood pressure) and
gastrointestinal symptoms including diarrhea and nausea or vomiting; a
woman that ingested 525 mg/kg experienced muscle contraction or
spasticity, respiratory depression, and miosis; a woman that ingested
an unspecified amount of fenthion did not exhibit the initial
cholinergic crisis until 5 days postexposure, and symptoms (primarily
psychosis) recurred 24 days later. Similar signs of toxicity,
characteristic of organophosphate poisoning, were observed in rats that
were fed 300 ppm (15 mg/kg/day). Symptoms reported in these rats
included spasms, nervousness, salivation and diarrhea as well as
ophthalmological symptoms such as eyeball protrusion and corneal
turbidity. LOEL and NOEL values for cholinesterase inhibition from
animal studies of various durations include the following: In a 28-day
feeding study in rats, the LOEL was 10 ppm (0.5 mg/kg/day) and the NOEL
was 5 ppm (0.65 mg/kg/day) for brain cholinesterase inhibition; in
another 28-day rat feeding study, plasma and erythrocyte cholinesterase
recovered 2 weeks postexposure. The LOEL for cholinesterase inhibition
in a 30-day inhalation study in rats was 0.163 mg/L. In a 63-day rat
feeding study, significant cholinesterase inhibition occurred by day 3
at 25 mg/kg/day. In a 16-week feeding study in rats, the LOEL for
cholinesterase inhibition was 5 ppm in females (0.65 mg/kg/day) and the
NOEL was 3 ppm (0.15 mg/kg/day). EPA believes that there is sufficient
evidence for listing fenthion on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available neurological toxicity data
for this chemical.
Aquatic acute toxicity values for fenthion include a daphnid 48-
hour LC50 of 0.62 ppb for immobilization. Acute toxicity values
for other non-standard aquatic invertebrates range from a 48-hour
EC50 of 0.024 ppb for brown shrimp to a 96-hour EC50 of 110
ppb for scud. Avian acute toxicity values include a male mallard duck
oral LD50 of 5.94 mg/kg, a male bobwhite quail LD50 of 4 mg/
kg, and a mourning dove oral LD50 of 4.63 mg/kg. EPA believes that
there is sufficient evidence for listing fenthion on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(C) based on the available
environmental toxicity data for this chemical.
122. Fenvalerate (4-chloro-alpha-(1-methylethyl)benzeneacetic acid
cyano(3-phenoxyphenyl)methyl ester) (CAS No. 051630-58-1) (FIFRA AI)
(Ref. 3). Excitement and ataxia were observed in rats administered
fenvalerate at the oral LD50 dose of 70.2 mg/kg. The oral mouse
LD50 for fenvalerate is 185 mg/kg. Tremor, convulsions, and ataxia
were observed in this study. Neurological dysfunctions consisting of
jerky leg movements, exaggerated flexion of the hind limb, and unsteady
gait were observed in rats fed 7.5 mg/kg/day (LOEL) of fenvalerate for
13 weeks. The NOEL was 2.5 mg/kg/day. Based on the NOEL of the study,
EPA derived an oral RfD of 0.0025 mg/kg/day. Peripheral nerve and
spinal cord lesions were observed in rats orally administered 360 mg/
kg.
In a 6-month dog feeding study, normocytic anemia, increased serum
cholesterol levels, and hepatic microgranulomatosis were observed in
animals administered fenvalerate at 6.25 mg/kg/day (LOEL). No NOEL was
defined. In a 2-year mouse feeding study, multifocal granulomata in the
liver was observed in males and females fed fenvalerate at 7.5 and 37.5
mg/kg/day, respectively. The male NOEL was 1.5 mg/kg/day and the female
NOEL was 7.5 mg/kg/day. In a 20-month mouse feeding study, decreased
erythrocyte count, increased mean cell volume of the blood, and
granulomatous changes in the liver were observed at 15 mg/kg/day
(LOEL). The NOEL was 4.5 mg/kg/day.
EPA believes that there is sufficient evidence for listing
fenvalerate on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available neurological, hepatic, and hematological
toxicity data for this chemical.
Measured aquatic acute toxicity data for fenvalerate include a
bluegill 96-hour LC50 of 0.26 ppb, a fathead minnow 96-hour
LC50 of 0.33 ppb, a rainbow trout 96-hour LC50 of 1.2 ppb, an
Atlantic salmon 96-hour LC50 of 1.2 ppb, and a sheepshead minnow
96-hour LC50 of 4.4 ppb. In addition, the 48-hour LC50 for
daphnids is 0.05 ppb. EPA believes that there is sufficient evidence
for listing fenvalerate on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(C) based on the environmental toxicity data for this
chemical.
123. Ferbam (tris(dimethylcarbamodithioato-S,S')iron) (CAS No.
014484-64-1) (FIFRA AI) (Ref. 3). In an 80-week feeding study in rats,
females fed 96 mg/kg/day had ataxia that progressed to hind limb
paralysis. The NOEL was not determined. Symptoms of neurotoxicity
reported in mice following acute oral exposure included somnolence,
excitement and ataxia, although the doses at which these signs occurred
were much higher (the LD50 in this study was 3,400 mg/kg). EPA
believes that there is sufficient evidence for listing ferbam on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available neurological toxicity data.
Aquatic acute toxicity values for ferbam include a daphnid 48-hour
LC50 of 90 ppb, a 96-hour LC50 of 52 ppb for the eastern
oyster, and a guppy 96-hour LC50 of 90 ppb. EPA believes that
there is sufficient evidence for listing ferbam on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(C) based on the available
environmental toxicity data for this chemical.
124. Fluazifop butyl (2-[4-[[5-(trifluoromethyl)-2-pyridinyl]oxy]-
phenoxy]propanoic acid, butyl ester) (CAS No. 069806-50-4) (FIFRA AI)
(Ref. 3). A 3-month rat feeding study demonstrated hepatocyte
hypertrophy in males (the LOEL was 5 mg/kg/day; the NOEL was 0.5 mg/kg/
day). In a 1-year feeding study, dogs had changes in serum alkaline
phosphatase and alanine aminotransferase and/or alanine
sulfatransferase (the LOEL was 25 mg/kg/day; the NOEL was 5 mg/kg/day).
Similar changes were also reported in dogs following 3 months exposure
in their diet (the LOEL was 125 mg/kg/day). In a carcinogenicity study,
male mice fed 20 ppm (2.6 mg/kg/day, the LOEL) had an increased
incidence of hepatocyte hypertrophy. The NOEL was 5 ppm or 0.65 mg/kg/
day. Male and female mice exposed to a higher dose of 80 ppm (10.4 mg/
kg/day) had increased liver weight (relative and absolute) and
hypertrophy of periacinal hepatocytes. Males in this dose group also
had increased pigmentation in hepatocytes and Kupffer cells.
In a teratogenicity study in Sprague-Dawley rats exposed via oral
gavage, delayed ossification and an increased incidence of hydroureter
were observed in fetuses (the fetotoxic LOEL was 5 mg/kg/day; the NOEL
1 mg/kg/day) and a teratogenic LOEL of 200 mg/kg/day (the NOEL was 10
mg/kg/day) was determined based on the incidence of diaphragmatic
hernia. Maternal toxicity was observed in this study at doses higher
than those causing fetotoxicity and included reduced body weight gain
and decreased gravid uterus (the maternal LOEL was 200 mg/kg/day; the
NOEL was 10 mg/kg/day). In a 2-generation reproductive toxicity dietary
study in Wistar rats, the reproductive LOEL of 250 ppm (12.5 mg/kg/day;
the NOEL was 80 ppm or 4 mg/kg/day) was based on reduced litter sizes,
reduced viability, reduced testis and epididymis weights and tubular
atrophy in offspring. Fetotoxicity (delayed ossification and eye
opacities) was also demonstrated in New Zealand White rabbits (the LOEL
was 30 mg/kg/day; the NOEL was 10 mg/kg/day). EPA believes that there
is sufficient evidence for listing fluazifop butyl on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available hepatic
and developmental toxicity data for this chemical.
125. Flumetralin (2-chloro-N-(2,6-dinitro-4-(trifluoromethyl)-
phenyl)-N-ethyl-6-fluorobenzenemethanamine) (CAS No. 062924-70-3)
(FIFRA AI) (Ref. 3). Aquatic acute toxicity values for flumetralin
include a daphnid 48-hour EC50 of greater than 2.8 ppb, a bluegill
sunfish 96-hour LC50 of greater than 3.2 ppb, and a rainbow trout
96-hour LC50 of greater than 3.2 ppb. EPA believes that there is
sufficient evidence for listing flumetralin on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(C) based on the available
environmental toxicity data for this chemical.
126. Fluorine (CAS No. 007782-41-4) (CERCLA; EPCRA EHS; RCRA APP8;
RCRA P) (Ref. 8). Inhalation of fluorine causes initial coughing,
choking and chills, which is followed 1 or 2 days later with pulmonary
edema. Fluorine has a strong caustic action on mucous membranes, eyes
and skin. In human volunteers exposed to 100 ppm (0.16 mg/L) for 30
seconds, much irritation to the nose and eyes was reported. In acute
inhalation studies in animals, lethality occurs at a fairly uniform
level and is the result of pulmonary edema. Following 1 hour exposures
in mice, rats or guinea pigs, the inhalation LC50 values ranged
from 150 to 185 ppm (0.23 to 0.29 mg/L). The LC50 for rabbits
following a 30-minute exposure was 270 ppm (0.42 mg/L). EPA's exposure
analysis indicates that fluorine concentrations are likely to exist
beyond facility site boundaries, as a result of continuous, or
frequently recurring releases, at levels that can reasonably be
anticipated to cause significant adverse acute human health effects.
EPA believes that there is sufficient evidence for listing fluorine on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(A) based on the
available acute toxicity and exposure data for this chemical.
127. Fluorouracil (5-Fluorouracil) (CAS No. 000051-21-8) (CAL;
EPCRA EHS) (Ref. 8). A major use of fluorouracil is in the palliative
treatment of carcinoma of the colon, rectum, breast, stomach, and
pancreas that is not amenable to surgery or irradiation. The major
toxic effects of fluorouracil are on the normal, rapidly proliferating
tissues particularly of the bone marrow and lining of the
gastrointestinal tract. Leukopenia, predominantly of the
granulocytopenic type, thrombocytopenia, and anemia occur commonly with
intravenous fluorouracil therapy at doses ranging from 6 to 12 mg/kg.
Pancytopenia and agranulocytosis also have occurred.
Developmental abnormalities or other effects on newborns were
reported in offspring of women receiving 150 or 240 mg/kg fluorouracil
intravenously during weeks 11 to 14 or 20 to 31 of pregnancy. In
addition, maternal toxicity to the reproductive organs, toxicity to the
fetus, and developmental abnormalities have been reported in mice,
rats, and hamsters receiving oral, intraperitoneal, or intramuscular
doses of fluorouracil ranging from 10 to 700 mg/kg.
Chronic neurotoxic effects were noted in dogs fed fluorouracil at a
dietary dose of 2 mg/kg/day for 6 months. In this study, animals were
examined at the end of 3 months and 6 months. At the end of the
experiment, or at death, the brain was removed and examined (only one
dog survived the entire 6-month period). Histological sections of the
brain showed the presence large multiple monolocular vacuoles in the
wall of the fornix of the third ventricle.
EPA believes that there is sufficient evidence for listing
fluorouracil on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the toxicity of this substance to bone marrow,
and on the developmental and chronic neurotoxicity data for this
chemical.
128. Fluvalinate (N-[2-chloro-4-(trifluoromethyl)phenyl]DL-
valine(+)- cyano (3-phenoxyphenyl)methyl ester) (CAS No. 069409-94-5)
(FIFRA AI) (Ref. 3). Delayed ossification and decreased weight and
length of fetuses were observed in offspring of rats orally
administered 50 mg/kg/day (LOEL) on days 6 to 15 of gestation. The NOEL
was 10 mg/kg/day. These effects were observed at doses that produced
maternal toxicity. Curved tibia and fibula were observed in the
offspring of rabbits orally administered 125 mg/kg/day (LOEL). The NOEL
was 25 mg/kg/day. In a 2-generation reproduction study, a decrease in
pup weight and growth were observed in offspring of rats orally
administered 5 mg/kg/day (LOEL). The NOEL was 1 mg/kg/day.
Significantly decreased weight and survival were observed in offspring
of rats orally administered 25 mg/kg/day.
In a range finding study, dietary administration of 50 mg/kg/day
for 30 days produced skin lesions in rats. The NOEL was not determined.
A 2-year rat feeding study was terminated at 64 weeks due to dermal
lesions produced in animals at 15 mg/kg/day. The NOEL was 2 mg/kg/day.
Dietary administration of 10 mg/kg/day (LOEL for effect) to mice for 2
years produced scabbing and dermal abrasion. No NOEL for these effects
was established. An increase in plantar ulcers was observed in rats fed
2.5 mg/kg/day (LOEL) for 2 years. The NOEL was 1 mg/kg/day. Decreases
in body weight gain were also observed in this study. Based on the NOEL
of the study, an oral RfD of 0.01 mg/kg/day was derived. In a 2-
generation rat reproduction study, dietary administration of 5 mg/kg/
day produced decreased body weight gain and skin lesions in parents and
offspring.
Dietary administration of 2.5 mg/kg/day to rats for 13 weeks
produced anemia in blood parameters (decreased hematocrit, hemaglobin,
and red blood cells). The NOEL was 1.0 mg/kg/day. Dietary
administration of 30 mg/kg/day (LOEL) to rats for 3 months produced
decreased hemoglobin, hematocrit, and red blood cell count in rats. The
NOEL was 3 mg/kg/day.
EPA believes that there is sufficient evidence for listing
fluvinate on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available developmental, dermal, and hematological
toxicity data for this chemical.
Aquatic acute toxicity values for fluvalinate include a daphnid 48-
hour EC50 of 0.40 ppb, a bluegill sunfish 96-hour LC50 of 0.9
ppb, a rainbow trout 96-hour LC50 of 2.9 ppb, and a sheepshead
minnow 96-hour LC50 of 10.8 ppb. EPA believes that there is
sufficient evidence for listing fluvinate on EPCRA section 313 pursuant
to EPCRA section 313(d)(2)(C) based on the available environmental
toxicity data for this chemical.
129. Folpet (CAS No. 000133-07-3) (CAL) (Ref. 8). Folpet is
classified as a Group B2 compound by EPA; i.e., the substance is a
probable human carcinogen. Folpet has been shown to induce carcinoma
and adenoma of the duodenum in both sexes of CD-1 and B6C3F1 mice. EPA
believes that there is sufficient evidence for listing folpet on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available carcinogenicity data for this chemical.
Aquatic acute toxicity test data for folpet include a measured 96-
hour LC50 of 39 ppb for rainbow trout, and a measured 96-hour
LC50 of 72 ppb (0.072 ppm) for bluegill. EPA believes that there
is sufficient evidence for listing folpet on EPCRA section 313 pursuant
to EPCRA section 313(d)(2)(C) based on the environmental toxicity data
for this chemical.
130. Fomesafen (5-(2-chloro-4-(trifluoromethyl)phenoxy)-N
methylsulfonyl)-2-nitrobenzamide) (CAS No. 072178-02-0) (FIFRA AI)
(Ref. 3). Decreased plasma cholesterol and triglycerides and increased
liver weights (reversible at 7 days post-treatment) were observed at 50
mg/kg/day (only dose tested) when administered in the diet of rats for
4 weeks. In a 90-day rat study, dietary administration of 5 mg/kg/day
(LOEL) produced alterations in lipid metabolism and increases in liver
weight. The NOEL was 0.25 mg/kg/day. In a 26-week dog study, dietary
administration of 25 mg/kg/day (LOEL) produced alterations in lipid
metabolism and liver changes (changes not defined). The NOEL was 1 mg/
kg/day. Liver toxicity (increased liver masses, discolored hepatocytes,
and pigmented Kupffer cells) was observed in a 2-year rat feeding study
at 50 mg/kg/day (LOEL). The NOEL was 5 mg/kg/day. Metabolism studies
have shown that fomesafen accumulates in the liver. EPA believes that
there is sufficient evidence for listing fomesafen on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available hepatic
toxicity data for this chemical.
131. alpha-Hexachlorocyclohexane (CAS No. 000319-84-6) (CERCLA; CWA
PPL; FIFRA SR) (Ref. 8). alpha-Hexachlorocyclohexane is classified by
EPA as a Group B2 compound; i.e., the substance is a probable human
carcinogen. Although human data are limited, there is a case report of
acute leukemia in a Japanese sanitation employee following occupational
exposure to alpha-hexachlorocyclohexane and DDT. alpha-
Hexachlorocyclohexane has been shown in dietary studies to cause an
increase in the incidence of liver tumors in five mouse strains and in
Wistar rats. EPA believes that there is sufficient evidence for listing
alpha-hexachlorocyclohexane on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the carcinogenicity data for this
chemical.
Measured aquatic acute toxicity test data for alpha-
hexachlorocyclohexane include a 48-hour EC50 of 800 ppb for
daphnids. This chemical is expected to bioaccumulate in aquatic systems
because the measured bioconcentration factor (BCF) for rainbow trout is
1950. EPA believes that there is sufficient evidence for listing alpha-
hexachlorocyclohexane on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(C) based on the environmental toxicity data for this chemical
and its potential for bioaccumulation.
132. Hexamethylene-1,6-diisocyanate or Diisocyanates category (CAS
No. 000822-60-0) (CAA HAP) (Ref. 7). Hexamethylene-1,6-diisocyanate
(HDI) is extremely toxic via the inhalation route. The rat LC50
for HDI ranges from 56 (385 mg/m3) to 45 ppm (310 mg/m3). The
mouse LC50 for HDI is 4 ppm (30 mg/m3). HDI also induces
irritation of the upper respiratory tract in mice after acute exposure.
The mouse LOAEL was 0.062 ppm (0.43 mg/m3) for a 3-hour exposure.
A NOAEL was not established. Acute exposures to HDI vapors may induce
pulmonary irritation in the rat at 60 mg/m3, but data were
insufficient to generate a LOAEL or NOAEL for this effect.
Although the data are insufficient to evaluate the potential for
HDI to produce pulmonary hypersensitivity, indirect evidence suggests
that inhalation of monomeric HDI may cause pulmonary sensitivity. In
addition, data are insufficient to evaluate the potential for HDI to
elicit an allergic reaction in previously sensitized animals or people;
however, indirect evidence suggests that inhalation of monomeric HDI
may elicit allergic responses (i.e., asthma, alveolitis) in isocyanate-
sensitized individuals.
EPA's exposure analysis indicates that HDI concentrations are
likely to exist beyond facility site boundaries, as a result of
continuous, or frequently recurring releases, at levels that can
reasonably be anticipated to cause significant adverse acute human
health effects. EPA believes that there is sufficient evidence for
listing hexamethylene-1,6-diisocyanate on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(A) based on the available acute toxicity and
exposure data for this chemical.
EPA is proposing to list HDI as an individual chemical on EPCRA
section 313. In addition, in Units IV.B.144. and 158. of this preamble,
EPA is proposing to individually list isophorone diisocyanate and 1,1-
methylene bis(4-isocyanatocyclohexane) on EPCRA section 313. As an
alternative proposal to the individual listing of HDI, isophorone
diisocyanate, and 1,1-methylene bis(4-isocyanatocyclohexane), EPA is
proposing to create a diisocyanates category that includes HDI,
isophorone diisocyanate, 1,1-methylene bis(4-isocyanatocyclohexane),
and 16 other diisocyanates.
EPCRA section 313 requires threshold determinations for chemical
categories to be based on the total of all chemicals in the category
manufactured, processed, or otherwise used. For example, a facility
that manufactures three members of a chemical category would count the
total amount of all three chemicals manufactured towards the
manufacturing threshold for that category. When filing reports for
chemical categories, the releases are determined in the same manner as
the thresholds. One report is filed for the category and all releases
are reported on this form.
The chemicals selected for this proposed category are members of
the diisocyanates category under review by EPA's Office of Pollution
Prevention and Toxics. This category has been defined as monomeric
diisocyanates of molecular weight less than or equal to 300, plus
polymeric diphenylmethane diisocyanate (which is only 40 to 60 percent
polymerized). Chemicals were included in this category based on similar
chronic and acute adverse respiratory effects. The following chemicals
are the proposed members of the EPCRA section 313 diisocyanates
category:
1,3-Bis(methylisocyanate)cyclohexane (CAS No. 038661-72-2)
1,4-Bis(methylisocyanate)cyclohexane (CAS No. 010347-54-3)
1,4-Cyclohexane diisocyanate (CAS No. 002556-36-7)
Diethyldiisocyanatobenzene (CAS No. 134190-37-7)
4,4'-Diisocyanatodiphenyl ether (CAS No. 004128-73-8)
2,4'-Diisocyanatodiphenyl sulfide (CAS No. 075790-87-3)
3,3'-Dimethoxybenzidine-4,4'-diisocyanate (CAS No. 000091-93-0)
3,3'-Dimethyl-4,4'-diphenylene diisocyanate (CAS No. 000091-97-4)
3,3'-Dimethyldiphenylmethane-4,4'-diisocyanate (CAS No. 000139-25-
3)
Hexamethylene-1,6-diisocyanate (CAS No. 000822-06-0)
Isophorone diisocyanate (CAS No. 004098-71-0)
4-Methyldiphenylmethane-3,4-diisocyanate (CAS No. 075790-84-0)
1,1-Methylene bis(4-isocyanatocyclohexane) (CAS No. 005124-30-1)
1,5-Naphthalene diisocyanate (CAS No. 003173-72-6)
1,3-Phenylene diisocyanate (CAS No. 000123-61-5)
1,4-Phenylene diisocyanate (CAS No. 000104-49-4)
Polymeric diphenylmethane diisocyanate (CAS No. 009016-87-9)
2,2,4-Trimethylhexamethylene diisocyanate (CAS No. 016938-22-0)
2,4,4-Trimethylhexamethylene diisocyanate (CAS No. 015646-96-5)
These diisocyanates represent a category of chemicals that may
effect many organ systems. However, the primary toxicity target for
diisocyanates is the upper and lower respiratory tract resulting in
chronic pulmonary irritation. Diisocyanates are also known respiratory
and dermal sensitizing agents. Both acute and chronic effects may
result from acute or chronic exposures. These effects may be immune- or
non-immune mediated. EPA believes that diisocyanates should be listed
as a category because it is the isocyanate functionality that is
responsible for the observed chronic pulmonary irritation associated
with exposures to members of this category. The other part of the
molecule does not mitigate to any large degree the observed toxic
effects. EPA believes that there is sufficient evidence for listing
diisocyanates as a category on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available toxicity data for members
of the category.
Currently there are four other diisocyanates listed on EPCRA
section 313, these are:
Toluene-2,4-diisocyanate (CAS No. 000584-84-9)
Toluene-2,6-diisocyanate (CAS No. 000091-08-7)
Toluenediisocyanate (mixed isomers) (CAS No. 026471-62-5)
Methylenebis(phenylisocyanate) (CAS No. 000101-68-8)
EPA intends to maintain the individual listings for the three
toluene diisocyanate compounds. In addition to the effects discussed
above, these compounds have been classified as probable carcinogens.
EPA intends to continue to individually list diisocyanates that are
possible of probable carcinogens. Methylenebis(phenylisocyanate) has
not been shown to be a carcinogen and EPA is proposing to remove it as
an individually listed chemical, and add it to the diisocyanates
category if the alternative proposal for creation of the category is
finalized.
EPA requests comment on the alternative proposal to create a
diisocyanates category and what other diisocyanates should be included
in such a category.
133. n-Hexane (CAS No. 000110-54-3) (CAA HAP) (Ref. 7). In an
epidemiology study, no neurological abnormalities were noted in
workers. However, neurophysiological tests showed that the mean motor
nerve conduction velocities of the exposed group was significantly
decreased over the values for the control group. Also, the residual
latency of motor nerve conduction of the posterior tibial nerve in the
exposed group was significantly slowed when compared with the
nonexposed group. A LOAEL of 204 mg/m3 (58 ppm, LOAEL(ADJ) of 73
mg/m3) was established for these electrophysiological alterations
in humans. The alterations observed are consistent with n-hexane-
induced peripheral neuropathy observed in other studies in humans and
in animals. EPA believes that there is sufficient evidence for listing
n-hexane on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based upon the available neurotoxicity data for this chemical.
134. Hexazinone (CAS No. 051235-04-2) (FIFRA AI) (Ref. 3). In a 2-
year mouse feeding study, liver hypertrophy, hyperplastic nodules and
focal necrosis were observed at 375 mg/kg/day (LOEL). The NOEL was 30
mg/kg/day. In a 90-day feeding study in dogs, decreased body weight,
increased alkaline phosphatase activity, decreased albumin/globulin
ratio and increased absolute and relative liver weights were noted in
both sexes at 5,000 ppm (125 mg/kg/day; LOEL). The NOEL was 1,000 ppm
(25 mg/kg/day). EPA believes that there is sufficient evidence for
listing hexazinone on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available toxicity data for this chemical.
Measured aquatic acute toxicity test data for hexazinone include an
EC50 of 7 ppb for S. capricornutum. EPA believes that there is
sufficient evidence for listing hexazinone on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(C) based on the available
environmental toxicity data for this chemical.
135. Hydramethylnon (tetrahydro-5,5-dimethyl-2(1H)-pyrimidinone[3-
[4- (trifluoromethyl)phenyl]-1-[2-[4(trifluoromethyl) phenyl]ethenyl]-
2-propenylidene]hydrazone) (CAS No. 067485-29-4) (FIFRA AI) (Ref. 3).
In a 90-day dog feeding study, testicular atrophy was observed at 6 mg/
kg/day (LOEL). The NOEL was 3 mg/kg/day. In a 90-day rat study, dietary
administration of 5 mg/kg/day (LOEL) produced testicular atrophy. The
NOEL was 2.5 mg/kg/day. Dietary administration of 6.5 mg/kg/day for 18
months produced testicular lesions in mice. The NOEL was 2.75 mg/kg/
day. In a 2-year rat study, dietary administration of 5 mg/kg/day
produced decreased testicular weight and testicular atrophy. The NOEL
was 2.5 mg/kg/day. In a 3-generation rat reproduction study, oral
administration of 5 mg/kg/day produced male infertility. The NOEL was
2.5 mg/kg/day.
Decreased fetal weight was observed in the offspring of rats
administered 30 mg/kg/day (LOEL). The NOEL was 10 mg/kg/day. Increased
post implantation loss and decreased fetal viability were observed in
the offspring of rabbits administered 15 mg/kg/day (LOEL). The NOEL was
5 mg/kg/day. Vertebral anomalies were seen in the offspring of rabbits
administered 10 mg/kg/day (LOEL). The NOEL was 5 mg/kg/day.
Dietary administration of 1 mg/kg/day (LOEL) for 6 months to dogs
produced increased absolute and relative liver weights. The NOEL was
0.33 mg/kg/day. Based on the NOEL of the study, an oral RfD of 0.0003
mg/kg/day was derived.
EPA believes that there is sufficient evidence for listing
hydramethylnon on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available reproductive, developmental, and
hepatic toxicity data for this chemical.
The 96-hour LC50 in the Chanel Catfish was 90 ppb.
Bioaccumulation factors in bluegill sunfish are 1300 for the whole
fish, 780 for the fillet, and 1900 for viscera. EPA believes that there
is sufficient evidence for listing hydramethylon on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(C) based on the available
environmental toxicity data and the potential for bioaccumulation.
136. Hydrochlorofluorocarbons (CAA OD) (Ref. 8).
Hydrochlorofluorocarbons are known to release chlorine radicals into
the stratosphere. Chlorine radicals act as catalysts to reduce the net
amount of stratospheric ozone.
Stratospheric ozone shields the earth from ultraviolet-B (UV-B)
radiation (i.e., 290 to 320 nanometers). Decreases in total column
ozone will increase the percentage of UV-B radiation, especially at its
most harmful wavelengths, reaching the earth's surface.
Exposure to UV-B radiation has been implicated by laboratory and
epidemiologic studies as a cause of two types of nonmelanoma skin
cancers: squamous cell cancer and basal cell cancer. Studies predict
that for every 1 percent increase in UV-B radiation, nonmelanoma skin
cancer cases would increase by about 1 to 3 percent.
Recent epidemiological studies, including large case control
studies, suggest that UV-B radiation plays an important role in causing
malignant melanoma skin cancer. Recent studies predict that for each 1
percent change in UV-B intensity, the incidence of melanoma could
increase from 0.5 to 1 percent.
Studies have demonstrated that UV-B radiation can suppress the
immune response system in animals, and, possibly, in humans. Increases
in exposure to UV-B radiation are likely to increase the incidence of
cataracts and could adversely affect the retina.
Aquatic organisms, particularly phytoplankton, zooplankton, and the
larvae of many fishes, appear to be susceptible to harm from increased
exposure to UV-B radiation because they spend at least part of their
time at or near the surface of waters they inhabit.
Increased UV-B penetration has been shown to result in adverse
impacts on plants. Field studies on soybeans suggest that yield
reductions could occur in some cultivars of soybeans, while evidence
from laboratory studies suggest that two out of three cultivars are
sensitive to UV-B.
Because this increased UV-B radiation can be reasonably anticipated
to lead to cancer and other chronic human health effects and
significant adverse environmental effects, EPA believes there is
sufficient evidence for listing the following HCFCs that are
commercially viable on EPCRA section 313 pursuant to EPCRA sections
313(d)(2)(B) and (C). EPA is proposing that the following HCFCs be
added individually to EPCRA section 313:
Dichloropentafluoropropane (CAS No. 127564-92-5)
1,3-Dichloro-1,1,2,3,3-pentafluoropropane (HCFC-225ea) (CAS No.
136013-79-1)
2,2-Dichloro-1,1,1,3,3-pentafluoropropane (HCFC-225aa) (CAS No.
128903-21-9)
1,1-Dichloro-1,2,3,3,3-pentafluoropropane (HCFC-225eb) (CAS No.
111512-56-2)
1,1-Dichloro-1,2,2,3,3-pentafluoropropane (HCFC-225cc) (CAS No.
13474-88-9)
1,3-Dichloro-1,1,2,2,3-pentafluoropropane (HCFC-225cb) (CAS No.
000507-55-1)
1,2-Dichloro-1,1,3,3,3-pentafluoropropane (HCFC-225da) (CAS No.
000431-86-7)
3,3-Dichloro-1,1,1,2,2-pentafluoropropane (HCFC-225ca) (CAS No.
000422-56-0)
2,3-Dichloro-1,1,1,2,3-pentafluoropropane (HCFC-225ba) (CAS No.
000422-48-0)
1,2-Dichloro-1,1,2,3,3-pentafluoropropane (HCFC-225bb) (CAS No.
000422-44-6)
Dichlorofluoromethane (HCFC-21) (CAS No. 000075-43-4)
1,1,1,2-Tetrachloro-2-fluoroethane (HCFC-121a) (CAS No. 000354-11-
0)
1,1,2,2-Tetrachloro-1-fluoroethane (HCFC-121) (CAS No. 000354-14-3)
1,2-Dichloro-1,1-difluoroethane (HCFC-132b) (CAS No. 001649-08-7)
2-Chloro-1,1,1-trifluoroethane (HCFC-133a) (CAS No. 000075-88-7)
3-Chloro-1,1,1-trifluoropropane (HCFC-253fb) (CAS No. 000460-35-5).
137. Imazalil (1-[2-(2,4-dichlorophenyl)-2-(2-propenyloxy)ethyl]-
1H-imidazole) (CAS No. 035554-44-0) (FIFRA AI) (Ref. 3). In a rat
teratology study, increased maternal mortality, decreased litter size,
and increased number of dead fetuses were observed in animals
administered 40 mg/kg/day (LOEL). The NOEL was 10 mg/kg/day.
Stillbirths and altered live birth index were observed in rats orally
administered 80 mg/kg/day days 16 through 22 of gestation and 21 days
post gestation. Altered lactation index was observed in rats orally
administered 20 mg/kg/day on days 16 through 22 of gestation and 21
days post gestation. Post-implantation loss was observed in rabbits
orally administered 0.63 mg/kg/day on days 6 through 18 of gestation.
Altered viability index was observed in rabbits orally administered 2.5
mg/kg/day on days 6 through 18 of gestation. EPA believes that there is
sufficient evidence for listing imazalil on EPCRA section 313 pursuant
to EPCRA section 313(d)(2)(B) based on the available developmental
toxicity data for this chemical.
138. 3-Iodo-2-propynyl butylcarbamate (CAS No. 055406-53-6) (FIFRA
AI) (Ref. 3). In a 90-day rat study, oral administration of 50 mg/kg/
day (LOEL) produced increased liver-to-body-weight ratios. The NOEL was
20 mg/kg/day. In a 2-year rat study, dietary administration of 40 and
80 mg/kg/day produced significant non-neoplastic pathological changes
in the stomach. No NOEL was established; the LOEL was 20 mg/kg/day.
Based on this study, EPA derived an oral RfD of 0.07 mg/kg/day. EPA
believes that there is sufficient evidence for listing 3-iodo-2-
propynyl butylcarbamate on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available chronic toxicity data for this
chemical.
139. Iprodione (3-(3,5-dichlorophenyl)-N-(1-methylethyl)-2,4-dioxo-
1-imidazolidinecarboxamide) (CAS No. 036734-19-7) (FIFRA AI) (Ref. 3).
Increased red blood cell Heinz bodies and decreased prostate weight
(the LOEL was 15 mg/kg/day; the NOEL was 4.2 mg/kg/day) were observed
in dogs fed iprodione for 1-year. Increased Heinz bodies were also seen
in females at 15 mg/kg/day. At 90 mg/kg/day, increased liver weight was
noted in male and female dogs. Based on the NOEL, an oral RfD of 0.04
mg/kg/day was derived. In another 1-year feeding study in dogs,
decreased red blood cell counts and hemoglobin and hematocrit levels
(the LOEL was 600 ppm or 15 mg/kg/day; the NOEL was 100 ppm or 2.5 mg/
kg/day) were observed. At 3,600 ppm (90 mg/kg/day), increased absolute
and relative liver weights and increase liver alkaline phosphatase,
serum glutamic-pyruvic transaminase, serum glutamic-oxaloacetic
transaminase, and lactate dehydrogenase activities were noted.
Decreased red blood cell count and decreased hemoglobin and hematocrit
levels (the LOEL was 24.6 mg/kg/day in males, 26.4 mg/kg/day in
females; the NOEL was 17.5 mg/kg/day in males, 18.4 mg/kg/day in
females). EPA believes that there is sufficient evidence for listing
iprodione on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available hematological and hepatic toxicity data for this
chemical.
Acute aquatic toxicity data include a green algae 120-hour
EC50 of 21 ppb. EPA believes that there is sufficient evidence for
listing iprodione on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(C) based on the available environmental toxicity data for
this chemical.
140. Iron pentacarbonyl (CAS No. 013463-40-6) (EPCRA EHS) (Ref. 8).
Humans exposed to high concentrations of iron pentacarbonyl immediately
experience headache and dizziness. These effects are followed 12 to 36
hours after exposure by symptoms such as fever, cyanosis, cough, and
shortness of breath. In humans, iron pentacarbonyl has also been known
to cause adverse effects on the respiratory and central nervous system,
liver, and kidney. The rat oral LD50 is 25 mg/kg and the rat
inhalation LC50 value is 0.044 mg/L. The 4-hour inhalation
LC100 in mice is 0.007 mg/L. The rabbit oral LD50 is 12 mg/
kg. EPA's exposure analysis indicates that iron pentacarbonyl
concentrations are likely to exist beyond facility site boundaries, as
a result of continuous, or frequently recurring releases, at levels
that can reasonably be anticipated to cause significant adverse acute
human health effects. EPA believes that there is sufficient evidence
for listing iron pentacarbonyl on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(A) based on the available acute toxicity and exposure
data for this chemical.
141. Isodrin (CAS No. 000465-73-6) (CERCLA; EPCRA EHS; RCRA APP8;
RCRA P) (Ref. 8). Measured aquatic acute toxicity data for isodrin
include a 24-hour LC50 of 12 ppb for bluegills and a 24-hour
LC50 of 6 ppb for minnows. EPA believes that there is sufficient
evidence for listing isodrin on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(C) based on the environmental toxicity data for this
chemical.
142. Isofenphos (2-[[ethoxyl[(1-methylethyl) amino]
phosphinothioyl] oxy] benzoic acid 1-methylethyl ester) (CAS No.
025311-71-1) (FIFRA AI) (Ref. 3). In a 108-week feeding study in mice,
inhibition of brain cholinesterase (the LOEL was 100 ppm or 13 mg/kg/
day; the NOEL was 10 ppm or 1.3 mg/kg/day) and plasma cholinesterase
(the LOEL was 10 ppm or 1.3 mg/kg/day; the NOEL was 0.13 mg/kg/day) was
observed. Inhibition of red blood cell cholinesterase (the LOEL was 10
ppm or 0.5 mg/kg/day; the NOEL was 1 ppm or 0.05 mg/kg/day) was seen in
a 2-year feeding study in rats. Other studies (14- and 90-day feeding
studies in dogs, 30- and 90-day studies in rats, and a 3-week
inhalation study in rats) also demonstrate cholinesterase (plasma, red
blood cell or brain) inhibition in rats and dogs. EPA believes that
there is sufficient evidence for listing isophenphos on EPCRA section
313 pursuant to EPCRA section 313(d)(2)(B) based on the available
neurological toxicity data for this chemical.
Aquatic acute toxicity values for isofenphos include a daphnid 48-
hour EC50 of 1.6 ppb and a mysid 96-hour EC50 of 1.7 ppb. EPA
believes that there is sufficient evidence for listing isofenphos on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the
available environmental toxicity data.
143. Isophorone (CAS No. 000078-59-1) (CAA HAP) (Ref. 7).
Isophorone has been shown to cause neurotoxic effects in humans exposed
to atmospheric concentrations of 5 to 8 ppm. After being exposed for 1
month, workers complained of fatigue and malaise. Neurotoxicity was
also observed in humans following acute exposure. At 40 to 85 ppm,
effects included nausea, headache, dizziness, faintness, inebriation,
and a feeling of suffocation. Increasing exposure concentrations
resulted in increasing severity of symptoms. Irritation and central
nervous system (CNS) depression were observed at concentrations of 200
to 400 ppm. EPA believes that there is sufficient evidence for listing
isophorone on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available neurotoxicity data for this chemical.
144. Isophorone diisocyanate (CAS No. 004098-71-9) (TSCA) (Ref. 8).
The 4-hour inhalation LC50 value of isophorone diisocyanate in
rats is 0.123 mg/L. The rat and mouse 3-hour inhalation RD50 (50
percent reduction in respiratory rate) values are 0.0046 mg/L and
0.0019 mg/L, respectively. A 50-year old man developed severe asthma
after exposure to an unspecified amount of paint containing isophorone
diisocyanate. A 1-hour exposure to an unspecified amount of the
compound caused eczema in three out of four workers. In addition,
isocyanates as a class are generally severe skin, eye and respiratory
irritants. EPA's exposure analysis indicates that isophorone
diisocyanate concentrations are likely to exist beyond facility site
boundaries, as a result of continuous, or frequently recurring
releases, at levels that can reasonably be anticipated to cause
significant adverse acute human health effects. EPA believes that there
is sufficient evidence for listing isophorone diisocyanate on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(A) based on the
available acute toxicity and exposure data for this chemical.
As detailed in Unit IV.B.132. of this preamble, as an alternative
proposal to the individual listing of HDI, isophorone diisocyanate, and
1,1-methylene bis(4-isocyanatocyclohexane), EPA is proposing to create
a diisocyanates category that includes HDI, isophorone diisocyanate,
1,1-methylene bis(4-isocyanatocyclohexane), and 16 other diisocyanates.
145. Lactofen (5-(2-chloro-4-(trifluoromethyl)phenoxy)-2-nitro-2-
ethoxy-1-methyl-2-oxoethyl ester) (CAS No. 077501-63-4) (FIFRA AI)
(Ref. 3). Lactofen meets the criteria of an EPA Group B2 compound,
i.e., a probable human carcinogen. This conclusion was based on an
increased incidence of hepatocellular carcinomas in males and combined
incidence of hepatocellular adenomas and carcinomas in both sexes of
CD-1 mice following dietary administration of lactofen. In CD rats,
there was increased incidence of liver neoplastic nodules in both
sexes. Four structurally similar chemicals, acifluorfen, nitrofen,
oxyfluorfen, and fomesafen, all produced hepatocellular tumors in
rodents.
Results of several subchronic and chronic studies indicated the
liver and kidney as target organs for lactofen. Increased absolute and
relative liver weight and hepatocytomegaly (the LOEL was 1.5 mg/kg/day;
the NOEL was not determined) were observed in male mice fed lactofen
for 78 weeks. At 37.5 mg/kg/day, there was also an increased incidence
of cataracts and renal pigmentation. Based on the LOEL, an oral RfD of
0.002 mg/kg/day was derived. Renal dysfunction and decreased hemoglobin
and hematocrit levels and red blood cell counts (the LOEL was 25/75 mg/
kg/day; the NOEL was 5 mg/kg/day) were observed in a 1-year feeding
study in dogs. Increased renal and hepatic pigmentation (the LOEL was
50 mg/kg/day; the NOEL was 25 mg/kg/day) were noted in a 2-year feeding
study in rats. In a 90-day mouse study, increased alkaline phosphatase,
serum glutamate oxaloacetate transaminase (SGOT), and serum gleutanic
pyruvic transaminase (SGPT) activities, increased liver weight, hepatic
necrosis, biliary hyperplasia, decreased hematocrit and hemoglobin
levels and red blood cell counts, extramedullary hematopoiesis, and
kidney nephrosis and fibrosis (the LOEL was 26 mg/kg/day; the NOEL was
not determined) were seen. Decreased hemoglobin and hematocrit levels,
decreased red blood cell counts, and brown pigment in the kidney and
liver (the LOEL was 50 mg/kg/day) were noted in a 90-day feeding study
in rats.
EPA believes that there is sufficient evidence for listing lactofen
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on
the available carcinogenicity data and hepatic, renal, and
hematological toxicity data for this chemical.
146. Linuron (CAS No. 000330-55-2) (FIFRA SR) (Ref. 8). The
appearance of sulfhemoglobin in the blood of dogs, rats, or mice
exposed to linuron has been reported. In fact, available animal data
from feeding studies of various durations (30 days to 2 years) with
linuron as well as from studies with structurally similar urea-based
herbicides indicate that the presence of sulfhemoglobin (abnormal blood
pigment) and morphological changes in red blood cells provide the most
sensitive indicator of exposure to linuron. In a 2-year feeding study
with beagle dogs, the LOAEL, based on the presence of the
sulfhemoglobin, was 0.625 mg/kg/day. This was the lowest dose tested.
Red blood cell counts were decreased in dogs exposed to higher doses of
linuron. EPA has derived an oral RfD of 0.002 mg/kg/day for linuron
from this study. Similar findings were reported in two separate 2-year
rat feeding studies. In one of these studies, the LOAEL was 31.25 mg/
kg/day and the NOAEL was 6.25 mg/kg/day. These values were based on
spleen and bone marrow changes indicative of hemolysis, and an increase
in mortality and growth retardation. In the other 2-year rat study, a
LOAEL of 2.5 mg/kg/day (the lowest dose tested) was based on decreased
red blood cell counts and reticulocytosis. Elevated sulfhemoglobin
levels were reported in rats exposed for as little as 30 days to 150
mg/kg/day. This exposure level also caused severe growth retardation
and increased mortality. The LOAEL for decreased body weight gain was
15 mg/kg/day and the NOAEL was 3 mg/kg/day. Chronic administration of
linuron at 4 mg/kg/day to rats caused hypochromic anemia, decreased
cholinesterase and peroxidase activities in the blood.
A LOAEL of 31.25 mg/kg/day was established in a 3-generation
reproductive toxicity study in which linuron (in the diet) caused
reduced weanling weights, reduced liver and kidney weights, liver
atrophy, and reduced pup survival. In a separate developmental toxicity
study in rats administered linuron orally, a LOAEL of 31.25 mg/kg/day
was based on an increased incidence of fetal resorptions. The LOAEL for
maternal toxicity in this study was 6.25 mg/kg/day (NOAEL 2.50 mg/kg/
day), and was based on decreased food consumption and decreased body
weight gain. An oral teratology study in rabbits indicated a LOAEL of 5
mg/kg/day (lowest dose tested) based on decreased fetal body weight,
decreased litter size and an increase in skull malformations.
EPA believes that there is sufficient evidence for listing linuron
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on
the hematological and developmental toxicity data for this chemical.
147. Lithium carbonate (CAS No. 000554-13-2) (CAL) (Ref. 8). A
major use of lithium carbonate is in the treatment of manic episodes of
manic-depressive illness. Decreases in the number of implantations,
number of live fetuses and fetal body weight, and increases in
resorptions and various limb/skeletal anomalies were reported in the
offspring of Wistar rats that received 100 mg/kg (the fetotoxic LOEL;
the fetotoxic NOEL was 50 mg/kg) during gestation days 6 through 15.
Offspring of mice that received 465 mg/kg/day during gestation days 6
through 15 had increased craniofacial abnormalities. Fetal death and
reductions in litter size were also noted. EPA believes that there is
sufficient evidence for listing lithium carbonate on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available
developmental toxicity data for this chemical.
148. Malathion (CAS No. 000121-75-5) (CERCLA) (Ref. 8). Malathion
is a phosphorothioate insecticide. Its insecticidal properties are due
to cholinesterase inhibition. A 42-year old woman ingested a minimum of
120 ml of a 50 percent solution (approximately 850 mg/kg). She quickly
became comatose, cyanotic, flaccid, devoid of tendon reflexes, and
miotic. Her serum cholinesterase activity was 22 percent of normal for
9 days and her red blood cell cholinesterase activity was 10 to 25
percent of normal for 45 days. Thirty-five cases of poisoning by
ingestion were reported in India. The symptoms observed were cyanosis,
excess salivation, pinpoint pupils, pulmonary edema, and
electrocardiographic abnormalities; all of which are indicative of
cholinesterase inhibition. Autopsy of the fatalities indicated damage
to the myocardium. In a 56-day study in which men were orally
administered malathion, the NOEL for neurotoxic effects was 0.23 mg/kg/
day and the LOEL was 0.34 mg/kg/day. Plasma and red blood cell
cholinesterase inhibition was observed at 0.34 mg/kg/day; however, no
clinical signs of overt toxicity were noted at this dose. Based on the
NOEL, EPA has derived an oral RfD of 0.02 mg/kg/day for this chemical.
Cholinesterase inhibition symptoms have also been observed in
experimental animals exposed to malathion. EPA believes that there is
sufficient evidence for listing malathion on EPCRA section 313 pursuant
to EPCRA section 313(d)(2)(B) based on the chronic neurotoxicity data
for this chemical.
Measured aquatic acute toxicity data for malathion include a 96-
hour LC50 of 68 ppb for rainbow trout, a 96-hour LC50 of 51
ppb for sheepshead minnow, and a 96-hour LC50 of 76 ppb for lake
trout. In addition, the measured 48-hour EC50 for daphnids is 0.9
ppb. EPA believes that there is sufficient evidence for listing
malathion on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C)
based on the environmental toxicity data for this chemical.
149. Man-made mineral fibers category (CAA HAP) (Ref. 7). Man-made
mineral fibers are synthetic, amorphous (noncrystalline) fibers which
consist of three major groups: Glass fibers; mineral wool fibers (which
includes mainly rock wool and slag wool); and refractory ceramic
fibers. Health concerns for these fibers are based on the morphological
and toxicologic similarities with asbestos, a known human carcinogen,
causing lung cancer and mesotheliomas in humans and non-malignant
respiratory diseases (e.g. lung fibrosis). Injection studies, in which
glass wool and glass microfibers were directly placed into the
respiratory airways, the pleural or abdominal cavities of laboratory
animals, have shown consistent evidence of carcinogenesis. Experimental
studies have shown evidence of carcinogenesis by injection of rock wool
and slag wool. IARC has classified glass wool, rock wool, and slag wool
fibers as Group 2B compounds, i.e., possible human carcinogens. EPA has
classified refractory ceramic fibers as Group B2 compounds, i.e.,
probable human carcinogen. EPA believes that there is sufficient
evidence for listing man-made mineral fibers as a category on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available carcinogenicity data for these fibers.
EPCRA section 313 requires threshold determinations for chemical
categories to be based on the total of all chemicals in the category
manufactured, processed, or otherwise used. For example, a facility
that manufactures three members of a chemical category would count the
total amount of all three chemicals manufactured towards the
manufacturing threshold for that category. When filing reports for
chemical categories, the releases are determined in the same manner as
the thresholds. One report is filed for the category and all releases
are reported on this form.
EPA considered a number of options for listing man-made mineral
fibers on EPCRA section 313. In 1977, the National Institute for
Occupational Safety and Health (NIOSH) recommended that exposures to
fibers be limited to 3 fibers per cubic centimeters (f/cc) for fibers
that are less than 3.5 micrometers in diameter and longer than 10
micrometers in length. NIOSH has since commented that in order to
protect workers from lung cancer it will be necessary to lower the
exposure to 0.2 f/cc for fibrous glass. In 1992, the Occupational
Safety and Health Administration (OSHA) proposed a 1 f/cc 8-hour time-
weighted average (TWA) limit for respirable fibers of fibrous glass,
including refractory ceramic fibers. Respirable fibers are generally
defined as fibers with a diameter of less than 3.5 micrometers whose
length is at least 3 times the diameter (i.e., an aspect ratio (fiber
length divided by fiber diameter) of 3 or greater). In order to ease
the burden of reporting, EPA considered listing fibers based on an
aspect ratio that simply discriminates between particles and fibers.
This, however, seemed to be overly inclusive in that it would cover
nonrespirable as well as respirable fibers. EPA also considered using a
diameter criteria without an aspect ratio but this option also appears
to be too inclusive since it may include particles as well as fibers.
EPA is proposing to list man-made mineral fibers as a category that
includes glass microfibers, glass wool fibers, rock wool fibers, slag
wool fibers, and refractory ceramic fibers that have a diameter less
than 3.5 micrometers and an aspect ratio greater than 3. This
definition is consistent with both the NIOSH and OSHA recommendations
and is limited to fibers that are respirable. EPA requests comment on
this definition of man-made mineral fibers and any other options for
defining a fibers category.
150. Mecoprop (CAS No. 000093-65-2) (IARC) (Ref. 8). Mecoprop is a
mono-chloro, mono-methylphenoxy isopropanoic acid type herbicide. IARC
has assigned mecoprop to Group 2B, i.e., it is possibly carcinogenic to
humans.
In several animal studies, changes in liver or kidney weights were
the most sensitive indicators of mecoprop toxicity. In a 90-day rat
feeding study, the LOAEL was 9 mg/kg/day and the NOAEL was 3 mg/kg/day.
At 26 mg/kg/day, the changes in organ weights were accompanied by
decreased glucose levels in males and increased creatinine levels in
females. EPA has derived an oral RfD of 0.001 mg/kg/day from this
study.
EPA believes that there is sufficient evidence for listing mecoprop
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on
the hepatic and renal toxicity data for this chemical.
151. 2-Mercaptobenzothiazole (MBT) (CAS No. 000149-30-4) (TSCA)
(Ref. 8). The 21-day maximum acceptable toxicant concentration (MATC)
for daphnids range from 240 to 470 ppb. The 60-day MATC for rainbow
trout range from 41 to 78 ppb. EPA's exposure analysis indicates that
releases of 2-mercaptobenzothiazole will result in concentration levels
that can reasonably be anticipated to cause significant adverse
environmental effects. EPA believes that there is sufficient evidence
for listing 2-mercaptobenzothiazole on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(C) based on the available environmental
toxicity data and exposure data for this chemical.
152. Merphos (CAS No. 000150-50-5) (FIFRA SR) (Ref. 8). Merphos is
a thiophosphate-type cholinesterase inhibitor. Delayed neurotoxic
effects have been reported in a 28-year old man following accidental
exposure to the chemical over a period of 3 days. Fourteen days later,
he developed complete facial diplegia and decreased conduction velocity
in his nerve fibers. He recovered completely. Both immediate and
delayed neurotoxic effects following exposure to merphos have been
reported in experimental animals. In a 3-month hen feeding study the
NOEL for neurotoxic effects was 0.1 mg/kg/day and the LOEL was 0.5 mg/
kg/day. At 0.5 mg/kg, hens showed delayed neurotoxicity, ataxia, and
equivocal changes in the spinal cord and peripheral nerves. Based on
the NOEL, EPA derived an oral RfD of 0.00003 mg/kg/day for this
chemical. In a 112-day rat feeding study, females showed red blood cell
cholinesterase inhibition at the LOEL of 0.25 mg/kg/day. The NOEL was
0.1 mg/kg/day. In a 90-day rat feeding study, animals showed reduced
brain cholinesterase activity at the LOEL of 3.8 mg/kg/day. The NOEL
was 1.8 mg/kg/day. In a 90-day dog feeding study, plasma cholinesterase
inhibition was observed at the LOEL of 2.5 mg/kg/day. The NOEL was 0.75
mg/kg/day. Fourteen cattle and 20 sheep administered single doses of
merphos (25 to 200 mg/kg) or 10 daily doses of merphos (2.5 mg/kg/day)
showed emaciation, diarrhea, and depression of blood cholinesterase.
Ingested merphos is rapidly metabolized to n-butyl mercaptan within the
gastrointestinal tract. n-Butyl mercaptan has been shown to be
responsible for the acute neurotoxic effects of merphos. Thus, oral
exposure to merphos is expected to cause acute neurotoxic symptoms
while dermal exposure to merphos is expected to cause delayed
neurotoxic symptoms. EPA believes that there is sufficient evidence for
listing merphos on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the chronic neurotoxicity data for this chemical.
153. Metham sodium (sodium methyldithiocarbamate) (CAS No. 000137-
42-8) (FIFRA AI) (Ref. 3). Postimplanatation loss was observed in
rabbits administered metham sodium at 30 mg/kg/day (LOEL) on days 6 to
18 of gestation. The NOEL was 10 mg/kg/day (4.2 mg/kg/day based on
active ingredient). In rats fed metham sodium, increased variations,
retardations, and anomalies were reported at doses of 10 mg/kg/day
(LOEL) administered on days 6 to 15. The NOEL was less than or equal to
10 mg/kg/day (less than or equal to 4.2 mg/kg/day based on active
ingredient). Although neither study was considered to be fully adequate
due to study design and reporting deficiencies, the weight of evidence
indicates that metham sodium induces developmental toxicity. In
addition, metham sodium is metabolized to carbon disulfide, a potent
developmental toxicant. EPA believes that there is sufficient evidence
for listing metham sodium on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available developmental toxicity data
for this chemical and its metabolite, carbon disulfide.
154. Methazole (2-(3,4-dichlorophenyl)-4-methyl-1,2,4-
oxadiazolidine-3,5-dione) (CAS No. 020354-26-1) (FIFRA AI) (Ref. 3).
Rabbits receiving 30 or 60 mg/kg/day by gavage on days 6 to 18 of
gestation exhibited increased embryolethality. The NOEL was 10 mg/kg/
day. EPA believes that there is sufficient evidence for listing
methazole on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available developmental toxicity data for this chemical.
155. Methiocarb (CAS No. 002032-65-7) (CERCLA; EPCRA EHS) (Ref. 8).
Measured terrestrial acute toxicity data for wildlife include an oral
LD50 of 4.6 mg/kg for red-winged blackbirds. EPA believes that
there is sufficient evidence for listing methiocarb on EPCRA section
313 pursuant to EPCRA section 313(d)(2)(C) based on the environmental
toxicity data for this chemical.
156. Methoxone ((4-Chloro-2-methylphenoxy) acetic acid) (MCPA) (CAS
No. 000094-74-6) (FIFRA SR; IARC) (Ref. 8). Methoxone is a
chlorophenoxy-type herbicide. Animal studies indicate that the kidney
and liver are the primary target organs of methoxone toxicity. Beagle
dogs fed diets containing methoxone for 1-year developed liver
toxicity, which was demonstrated by increased liver weights associated
with alterations in serum glutamate-pyruvate transaminase, serum
glutamate-oxaloacetate transaminase, bilirubin, triglyceride and
cholesterol levels. These effects occurred at doses of 0.75 mg/kg/day
(LOAEL) and higher. The NOAEL was 0.15 mg/kg/day. Kidney changes in the
treated animals included deposition of kidney pigment in the proximal
tubular epithelium (the LOAEL was 0.75 mg/kg/day; the NOAEL was 0.15
mg/kg/day), and was accompanied by alterations in creatinine, urea, and
potassium levels. EPA derived an oral RfD of 0.0005 mg/kg/day from this
study. Similar changes suggesting liver and kidney toxicity were
reported in another 90-day dog feeding study (the LOAEL was 3 mg/kg/
day; the NOAEL was 1 mg/kg/day) and in rats in a 90-day feeding study
(the LOAEL was 7.5 mg/kg/day; the NOAEL was 2.5 mg/kg/day).
EPA believes that there is sufficient evidence for listing
methoxone on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available hepatic and renal toxicity data for this
chemical.
157. Methoxone sodium salt ((4-chloro-2-methylphenoxy) acetate
sodium salt) (CAS No. 003653-48-3) (FIFRA SR; IARC) (Ref. 8). Methoxone
sodium salt is a chlorophenoxy-type herbicide. Animal studies indicate
that the kidney and liver are the primary target organs of methoxone
toxicity. Beagle dogs fed diets containing methoxone for 1-year
developed liver toxicity, which was demonstrated by increased liver
weights associated with alterations in serum glutamate-pyruvate
transaminase, serum glutamate-oxaloacetate transaminase, bilirubin,
triglyceride and cholesterol levels. These effects occurred at doses of
0.75 mg/kg/day (LOAEL) and higher. The NOAEL was 0.15 mg/kg/day. Kidney
changes in the treated animals included deposition of kidney pigment in
the proximal tubular epithelium (the LOAEL was 0.75 mg/kg/day; the
NOAEL was 0.15 mg/kg/day), and was accompanied by alterations in
creatinine, urea, and potassium levels. EPA derived an oral RfD of
0.0005 mg/kg/day from this study. Similar changes suggesting liver and
kidney toxicity were reported in another 90-day dog feeding study (the
LOAEL was 3 mg/kg/day; the NOAEL was 1 mg/kg/day) and in rats in a 90-
day feeding study (the LOAEL was 7.5 mg/kg/day; the NOAEL was 2.5 mg/
kg/day).
EPA believes that there is sufficient evidence for listing
methoxone sodium salt on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on its potential to cause cancer and on the
available hepatic and renal toxicity data for this chemical.
158. 1,1-Methylene bis(4-isocyanatocyclohexane) (CAS No. 005124-30-
1) (TSCA) (Ref. 8). The 5-hour rat inhalation LC50 value for 1,1-
methylenebis(4-isocyanatocyclohexane) is 0.21 mg/L. The 3-hour mouse
inhalation RD50 (50 percent reduction in respiratory rate) value
is 0.027 mg/L. In addition, isocyanates as a class are generally severe
skin, eye, and respiratory irritants. EPA's exposure analysis indicates
that 1,1-methylenebis(4-isocyanatocyclohexane) concentrations are
likely to exist beyond facility site boundaries, as a result of
continuous, or frequently recurring releases, at levels that can
reasonably be anticipated to cause significant adverse acute human
health effects. EPA believes that there is sufficient evidence for
listing 1,1-methylenebis(4-isocyanatocyclohexane) on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(A) based on the available acute
toxicity and exposure data for this chemical.
As detailed in Unit IV.B.132. of this preamble, as an alternative
proposal to the individual listing of HDI, isophorone diisocyanate, and
1,1-methylene bis(4-isocyanatocyclohexane), EPA is proposing to create
a diisocyanates category that includes HDI, isophorone diisocyanate,
1,1-methylene bis(4-isocyanatocyclohexane), and 16 other diisocyanates.
159. Methylene bis(thiocyanate) (CAS No. 006317-18-6) (FIFRA AI)
(Ref. 3). The minimal human lethal dose for methylene bis(thiocyanate)
is 15 to 30 g (214 to 429 mg/kg), although fatalities have been
reported at 300 mg (4.3 mg/kg). Clinical effects may include decreased
blood pressure, apnea, cerebral excitation, convulsions, coma,
vomiting, diarrhea, abdominal cramping, albuminuria, skin rashes,
exfoliative dermatitis, muscle weakness, goiter, and toxic psychosis.
The intravenous mouse LD50 is 3.6 mg/kg. The subcutaneous rabbit
DLo is 20 mg/kg; convulsions and lowered blood pressure were observed
in this study. EPA believes that there is sufficient evidence for
listing methylene bis(thiocyanate) on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(B) based on the available neurological toxicity
data for this chemical.
160. Methyl isothiocyanate (CAS No. 00556-61-6) (FIFRA AI) (Ref.
3). Aquatic acute toxicity values for methyl isothiocyanate include a
fish 96-hour LC50 of 94 ppb, a 96-hour LC50 of 130 ppb for
bluegills, and a daphnid 48-hour LC50 of 55 ppb. EPA believes that
there is sufficient evidence for listing methyl isothiocyanate on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(C) based on the
available environmental toxicity data.
161. 2-Methyllactonitrile (CAS No. 000075-86-5) (CERCLA; EPCRA EHS;
RCRA APP8; RCRA P) (Ref. 8). 2-Methyllactonitrile belongs to a class of
substances known as the cyanohydrins. Cyanohydrins are generally quite
toxic because they can release hydrogen cyanide. An oral dose of 5 mg/
rat (approximately 14 mg/kg) of 2-methyllactonitrile administered twice
weekly for 3 to 8 months produced liver and kidney lesions. Inhalation
of 10.2 mg/L twice weekly for 3 to 8 months (duration of each
individual exposure not reported) produced kidney lesions, desquamation
of the bronchial epithelium, and bronchial ulcerations. EPA believes
that there is sufficient evidence for listing 2-methyllactonitrile on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
chronic toxic effects to the liver, kidney, and bronchi caused by this
chemical.
162. N-Methylolacrylamide (CAS No. 000924-42-5) (CAL) (Ref. 8).
There was clear evidence of carcinogenicity from N-methylolacrylamide
in a 2-year study using B6C3F1 mice administered the substance by oral
gavage. In both sexes, there were increased incidences of Harderian
gland adenomas or carcinomas, hepatocellular adenomas or carcinomas,
and alveolar or bronchiolar adenomas and carcinomas. There was also an
increase in ovarian granulosa cell tumors. EPA believes that there is
sufficient evidence for listing N-methylolacrylamide on EPCRA section
313 pursuant to EPCRA section 313(d)(2)(B) based on the carcinogenicity
data for this chemical.
163. Methyl parathion (CAS No. 000298-00-0) (CERCLA; FIFRA SR; RCRA
APP8; RCRA P) (Ref. 8). Methyl parathion is a thiophosphate-type
cholinesterase inhibitor. Methyl parathion is highly toxic when
administered to experimental animals at low doses. The rat and mouse
oral LD50 values are reported to be 6.01 mg/kg and 18 mg/kg,
respectively. The rat and mouse 4-hour inhalation LC50 values are
reported to be 0.034 mg/L and 0.12 mg/L, respectively, at which
symptoms of cholinesterase inhibition were observed.
Human volunteers showed a 37 percent decrease in red blood cell
cholinesterase activity following oral administration of 0.43 mg/kg/day
of methyl parathion for 10 days. The LOEL was 0.43 mg/kg/day and the
NOEL was 0.31 mg/kg/day. In a 90-day dog feeding study, brain, red
blood cell, and plasma cholinesterase inhibition was observed at the
LOEL of 1.0 mg/kg/day. The NOEL was 0.3 mg/kg/day. In a chronic rat
feeding study, plasma and erythrocyte cholinesterase were inhibited
throughout the study and brain cholinesterase was depressed at the
termination of the study at 2.5 mg/kg/day. The NOEL for systemic
toxicity was 0.025 mg/kg/day. An adequate NOEL for neurologic changes
was not defined. Overt signs of cholinergic toxicity (tremors, abnormal
gait, alopecia) were observed in the animals at a dose of 2.5 mg/kg/
day. Histologic examination revealed evidence of peripheral neuropathy
in animals administered this dose. EPA has derived an oral RfD of
0.00025 mg/kg/day based on the systemic NOEL for this chemical.
Hepatocellular swelling, degeneration, and fatty change have been
observed in humans acutely intoxicated with methyl parathion.
Hepatocellular changes were observed in patients that survived for 28
hours to 9 days after intoxication. Methyl parathion was orally
administered to rats in increasing doses for 36 days (starting with
0.37 mg/kg/day and increasing by a factor of 1.5 on every 4th day).
Weight loss, hyperglycemia, and macrocytic anemia, all secondary to
hepatotoxicity, were observed.
EPA believes that there is sufficient evidence for listing methyl
parathion on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the chronic neurotoxicity and hepatic toxicity data for this
chemical.
Measured aquatic acute toxicity data for methyl parathion include a
48-hour EC50 of 0.14 ppb for daphnids and a 96-hour LC50 of
15 ppb for crayfish. EPA believes that there is sufficient evidence for
listing methyl parathion on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(C) based on the available environmental toxicity data for
this chemical.
164. N-Methyl-2-pyrrolidone (CAS No. 000872-50-4) (TSCA) (Ref. 8).
In a 2-generation reproductive study, there was evidence of
reproductive toxicity in the F1 generation after exposure to 50
mg/kg/day (LOAEL; no NOAEL was established). Exposure to 50 mg/kg/day
or more resulted in significant reductions in the male fertility index
and in the female fecundity index. In addition, exposure to 500 mg/kg/
day resulted in an increased incidence of dams with decreased corpora
lutea. There was also evidence of developmental toxicity in both
generations after exposure to 500 mg/kg/day as demonstrated by reduced
litter size, reduced postnatal survival, and reduced pup weight.
Maternal toxicity (significant reduction in mean body weight gain)
was observed in rabbits receiving 175 mg/kg by gavage on days 6 through
18 of gestation (The NOAEL was 55 mg/kg/day). Exposure to 540 mg/kg/day
(LOAEL) resulted in developmental toxicity as demonstrated by a
significant increase in resorptions, and malformations (misshapen skull
bone and cardiovascular malformations). The NOAEL for developmental
toxicity was 175 mg/kg/day.
EPA believes that there is sufficient evidence for listing N-
methylpyrrolidone on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available developmental and reproductive
toxicity data for this chemical.
165. Methyltrichlorosilane (CAS No. 000075-79-6) (EPCRA EHS) (Ref.
8). As a class, chlorinated silanes are very corrosive to the skin and
mucous membranes and liberate hydrochloric acid in the presence of
water. Methyltrichlorosilane causes severe burns and the vapor is
harmful to humans. The 2-hour mouse inhalation LC50 value is 0.180
mg/L. EPA's exposure analysis indicates that methyltrichlorosilane
concentrations are likely to exist beyond facility site boundaries, as
a result of continuous, or frequently recurring releases, at levels
that can reasonably be anticipated to cause significant adverse acute
human health effects. EPA believes that there is sufficient evidence
for listing methyltrichlorosilane on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(A) based on the available acute toxicity and
exposure data for this chemical.
166. Metiram (CAS No. 009006-42-2) (FIFRA SR) (Ref. 8). Metiram is
an ethylene bisdithiocarbamate (EBDC) fungicide. Evidence suggests that
ethylene bisthiocarbamate fungicides and ethylenethiourea (a common
contaminant, metabolite, and degradation product of these fungicides)
cause cancer and adverse developmental effects in experimental animals.
In a 2-year diet study, ethylenethiourea caused liver adenomas and
carcinomas in mice, and thyroid follicular cell adenomas and carcinomas
in mice and rats. A NOAEL of less than or equal to 5 mg/kg has been
reported for ethylenethiourea, based on a rat developmental toxicity
study. Ethylenethiourea caused delayed ossification or hardening of the
parietal bone in pups. EPA believes that there is sufficient evidence
for listing metiram on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the carcinogenicity and developmental toxicity
data for ethylenethiourea, a metabolite and degradation product of
metiram.
In Unit IV.B.172. of this preamble, EPA is proposing to add another
ethylene bisdithiocarbamate (EBDC), nabam. An additional two EBDCs,
zineb and maneb, are currently individually listed on the EPCRA section
313 list of toxic chemicals. The category of EBDCs has recently been
added to EPCRA section 313 (December 1, 1993, 58 FR 63500). EPA
requests comment on the following: (1) Should the individual EBDCs,
metiram and nabam, be added individually to EPCRA section 313 even
though they are members of the EBDC category, which is listed on EPCRA
section 313; and (2) should the individual listings for two EBDCs,
zineb and maneb, be deleted and added as members of the newly created
EBDC category.
167. Metribuzin (CAS No. 021087-64-5) (FIFRA AI) (Ref. 3). In a
rabbit teratology study, the NOEL for maternal and fetotoxicity was 15
mg/kg/day, and the LOEL was 45 mg/kg/day. Developmental effects
including irregular spinus process and decreased pup body weight were
observed in rats treated with metribuzin (Sencor) during gestation day
7 to 19 at 85 mg/kg/day (LOEL). The NOEL for developmental toxicity was
30 mg/kg/day. The LOEL and NOEL for maternal toxicity were 30 and 10
mg/kg/day, respectively.
In a 2-year dog feeding study, adverse effects observed at 1,500
ppm (37.5 mg/kg/day; LOEL) included weight reduction, increased
mortality, hematologic changes, and liver/kidney damage. The systemic
NOEL was 100 ppm (2.5 mg/kg/day). In a 2-year rat feeding study,
decreased weight gain, mortality, and pathological changes in the liver
and kidney were observed at 300 ppm (15 mg/kg/day). The NOEL was 100
ppm (5 mg/kg/day).
EPA believes that there is sufficient evidence for listing
metribuzin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available hepatic, renal, and developmental toxicity data
for this chemical.
168. Mevinphos (CAS No. 007786-34-7) (CERCLA; EPCRA EHS) (Ref. 8).
Measured aquatic acute toxicity values for mevinphos include a 96-hour
LC50 of 70 ppb for bluegills, and a 96-hour LC50 of 0.16 ppb
for daphnids. Measured acute avian toxicity data include a pheasant
oral LD50 of 1.37 mg/kg, a mallard duck oral LD50 of 4.63 mg/
kg, and a sharp-tailed grouse oral LD50 of 1.34 mg/kg. EPA
believes that there is sufficient evidence for listing mevinphos on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the
environmental toxicity data for this chemical.
169. Molinate (1H-azepine-1-carbothioic acid, hexahydro-S-ethyl
ester) (CAS No. 002212-67-1) (FIFRA AI) (Ref 3). In a rat developmental
toxicity study, adverse effects observed following administration of
molinate at 35 mg/kg/day (LOEL) included increased post-implantation
loss, lower fetal body weight, increased incidence of runts, and
external/soft tissue/skeletal variants; the NOEL was 2.2 mg/kg. In a
rabbit developmental study, adverse effects such as an increase in the
number of abortions, and a decrease in the number of females with live
fetuses were noted at 200 mg/kg/day. The NOEL was 20 mg/kg/day. The
developmental effects were observed at levels which were toxic to
maternal animals.
In a rat fertility test, reductions in fertility, dose-related
altered sperm morphology, and a reduction in the number of viable
fetuses were observed following administration of molinate. The NOEL
was 0.2 mg/kg/day and the LOEL was 4 mg/kg/day. Based on the NOEL of
the study, an oral RfD of 0.002 mg/kg/day was derived. In a 90-day
study in male rats, the lowest toxic oral dose of 324 mg/kg produced
adverse effects on spermatogenesis, male fertility, and viability
index. The 20-day inhalation male rat lowest-toxic contentration (TCLo)
is 0.0006 mg/L. At this exposure level adverse effects on
spermatogenesis and male fertility index were reported. In a 2-
generation rat reproduction study, the reproductive NOEL was 0.3 mg/kg/
day, and the LOEL was 2.5 mg/kg/day based on reduced fecundity and
increased incidence of ovarian vacuolation/hypertrophy. In a 3-month
rat inhalation study, testicular degeneration and abnormal spermatozoa
were observed at 0.002 mg/L (LOEL). No NOEL was determined.
In a 2-year study in rats fed molinate, adverse effects seen at
0.35 mg/kg/day included degeneration and demyelination of the sciatic
nerve and skeletal muscle atrophy/reserve cell hyperplasia; no NOEL was
determined. In a 1-year study in dogs administered molinate orally,
adverse effects observed at 50 mg/kg/day included anemia, loss of
ability to bark, ataxia, splayed hind limbs, vacuolation of the
medulla, demyelination of the pons and spinal cord, tremors, and
eosinophilic bodies in the nervous system.
EPA believes that there is sufficient evidence for listing molinate
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on
the available developmental, reproductive, and neurological toxicity
data for this chemical.
170. Monuron (CAS No. 000150-68-5) (FIFRA SR) (Ref. 8). The
measured aquatic toxicity data for monuron include a 1.5-hour EC50
of 90 ppb and a 10-day EC50 of 100 ppb for marine algae. EPA
believes that there is sufficient evidence for listing monuron on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(C) based on the
environmental toxicity data for this chemical.
171. Myclobutanil (alpha-butyl-alpha-(4-chlorophenyl)-1H-1,2,4-
triazole-1-propanenitrile) (CAS No. 088671-89-0) (FIFRA AI) (Ref. 3).
Hepatocellular hypertrophy (the LOEL was 5.9 mg/kg/day; the NOEL was
0.3 mg/kg/day) was seen in a 90-day feeding study in dogs. In another
90-day feeding study, hepatocellular necrosis and hypertrophy (the LOEL
was 147.2 mg/kg/day; the NOEL was 49.1 mg/kg/day) were observed in
rats. Hepatocellular hypertrophy (the LOEL was 14.3 mg/kg/day in males
and 15.7 mg/kg/day in females; the NOEL was 3.1 mg/kg/day in males and
3.83 mg/kg/day in females) was noted in a 1-year feeding study in dogs.
Hepatic effects (centrilobular hepatocytic hypertrophy, kupffer cell
pigmentation, periportal vacuolation and altered foci) were observed in
mice fed 75 mg/kg/day myclobutanil for 2 years. At 15 mg/kg/day,
increased liver mixed function oxidase (the NOEL was 3 mg/kg/day) was
also seen.
Testicular atrophy (the LOEL was 9.84 mg/kg/day; the NOEL was 2.49
mg/kg/day) was observed in a 2-year chronic feeding study in rats. The
seminiferous tubules were frequently devoid of spermatid formation and
germinal epithelial cells. Based on the NOEL, an oral RfD of 0.025 mg/
kg/day was derived. Testicular atrophy (the LOEL was 46.4 mg/kg/day;
the NOEL was 9.28 mg/kg/day) was also noted in a 2-generation
reproduction study.
In a developmental toxicity study in rats, increased resorption and
decreased viability were observed at 93.8 mg/kg/day (LOEL). The NOEL
was 31.3 mg/kg/day. In a developmental toxicity study in rabbits, an
increased number of resorptions per litter, reduced viability index,
and reduced litter size were observed at 200 mg/kg/day (LOEL). The NOEL
was 60 mg/kg/day.
EPA believes that there is sufficient evidence for listing
myclobutanil on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available hepatic, reproductive, and
developmental toxicity data for this chemical.
172. Nabam (CAS No. 000142-59-6) (FIFRA SR) (Ref. 8). Nabam is an
ethylene bisthiocarbamate fungicide. Evidence suggests that ethylene
bisthiocarbamate fungicides and ethylenethiourea (a common contaminant,
metabolite, and degradation product of these fungicides) cause cancer
and adverse developmental effects in experimental animals. In a 2-year
diet study ethylenethiourea caused liver adenomas and carcinomas in
mice, and thyroid follicular cell adenomas and carcinomas in mice and
rats. A NOAEL of less than or equal to 5 mg/kg has been reported for
ethylenethiourea, based on a rat developmental toxicity study.
Ethylenethiourea caused delayed ossification or hardening of the
parietal bone in pups. EPA believes that there is sufficient evidence
for listing nabam on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the carcinogenicity and developmental toxicity
data for ethylenethiourea, a metabolite and degradation product of
nabam.
173. Naled (CAS No. 000300-76-5) (CERCLA; FIFRA SR) (Ref. 8). Naled
is an organophosphate-type cholinesterase inhibitor. In a human acute
poisoning case, toxic symptoms included abdominal cramps,
hypersecretion, emesis, perspiration, anxiety, vertigo and horizontal
nystagmus, and persisted for 4 months. In a 2-year rat feeding study
the NOEL for neurotoxic effects was 0.2 mg/kg/day and the LOEL was 2.0
mg/kg/day. It was observed in this study that, at 2.0 mg/kg/day, brain
cholinesterase activity was inhibited by approximately 24 percent. At
10.0 mg/kg/day, brain cholinesterase activity was inhibited by
approximately 60 percent, and both plasma and red blood cell
cholinesterase were also inhibited. Based on the NOEL, EPA has an oral
RfD of 0.002 mg/kg/day for this chemical. In a 1-year feeding study
using dogs as the test species, plasma and red blood cell
cholinesterase activity were inhibited at 2.0 mg/kg/day. The NOEL was
0.2 mg/kg/day and the LOEL was 2.0 mg/kg/day.
In a 2-generation reproduction study of naled in rats, the NOEL was
6 mg/kg/day. At 18 mg/kg/day, decreased litter size, survival, and pup
body weight were observed.
EPA believes that there is sufficient evidence for listing naled on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
chronic neurotoxicity and reproductive toxicity data for this chemical.
Measured aquatic acute toxicity values for naled include a 48-hour
EC50 of 0.35 ppb for daphnids and a 96-hour LC50 of 87 ppb
for lake trout. EPA believes that there is sufficient evidence for
listing naled on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(C) based on the environmental toxicity data for this
chemical.
174. Nicotine and salts (CAL; CERCLA; EPCRA EHS; FIFRA AI; RCRA
APP8; RCRA P) (Ref. 8). Nicotine salts will dissociate in aqueous
solutions to yield soluble nicotine. Nicotine is highly toxic in
humans. The estimated lethal oral dose in adults is approximately 40 to
60 mg. The onset of toxicity is rapid. Symptoms include nausea,
salivation, abdominal pain, vomiting, diarrhea, headache, weakness,
sweating, and confusion. Nicotine markedly stimulates the central
nervous system, causing tremors and convulsions. The stimulation is
followed by depression, and death resulting from paralysis of
respiratory muscles. Nicotine can also activate parasympathetic ganglia
and cholinergic nerve endings resulting in gastrointestinal
hyperactivity.
Skeletal defects and occasional cleft palates were observed in mice
injected with 25 mg/kg nicotine on gestation days 9 to 11. Reduced size
in the newborn of rats and limb deformities in the offspring of swine
were reported in swine and rats following oral exposure to 1,058 ppm
nicotine (approximately 53 mg/kg/day). Deformities were found in some
rabbit fetuses when dams were administered nicotine at a dose of 20 mg/
kg 5 times during pregnancy. Pregnant swine fed aqueous leaf extracts
of tobacco at the rate of 16 and 32 mg/kg nicotine produced
arthrogrypotic newborn pigs.
EPA believes that there is sufficient evidence for listing nicotine
and its salts as a category on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the developmental toxicity data for these
substances.
EPCRA section 313 requires threshold determinations for chemical
categories to be based on the total of all chemicals in the category
manufactured, processed, or otherwise used. For example, a facility
that manufactures three members of a chemical category would count the
total amount of all three chemicals manufactured towards the
manufacturing threshold for that category. When filing reports for
chemical categories, the releases are determined in the same manner as
the thresholds. One report if filed for the category and all releases
are reported on this form.
175. Nitrapyrin (2-chloro-6-(trichloromethyl) pyridine) (CAS No.
001929-82-4) (FIFRA AI) (Ref. 3). In a 1-year study in dogs fed
nitrapyrin adverse effects noted included increased cholesterol and
alkaline phosphatase, increased absolute and relative liver weight and
panlobular/centrilobular hepatocellular hypertrophy. The NOEL was 3 mg/
kg/day and the LOEL was 15 mg/kg/day. In a 10-week reproductive rat
study, adverse effects observed included increased incidence of fetal
liver hypertrophy and vacuolization at 75 mg/kg/day (LOEL). The NOEL
was 20 mg/kg/day. In a 90-day rat feeding study, hepatocellular fatty
change and necrosis, renal tubule epithelial cell swelling and
increasingly severe interstitial nephritis were observed at 50 mg/kg/
day. The NOEL was 15 mg/kg/day. In a 2-year rat feeding study, an
increase in glomerulonephropathy was observed in males dosed with 60
mg/kg/day and an increase in hepatic hypertrophy and vacuolization was
observed in males and females dosed with 60 mg/kg/day. The NOEL was 20
mg/kg/day.
Increased incidence of crooked hyoid bone and craniofacial
abnormalities were observed in the offspring of rabbits orally
administered nitrapyrin at 30 mg/kg/day (LOEL) on days 6 through 18 of
gestation. The NOEL was 10 mg/kg/day. Decreased weight and hypertrophy
and vacuolization of the liver were observed in offspring of rats dosed
with 75 mg/kg/day (LOEL) for 10 weeks prior to mating. The NOEL was 20
mg/kg/day. EPA believes that there is sufficient evidence for listing
nitrapyrin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available renal, hepatic, and developmental toxicity data
for this chemical.
176. Nitrate ion (CAS No. 014797-55-8) (SDWA) (Ref. 8). Nitrate
refers to the nitrate ion (NO3-). Infantile methemoglobinemia
occurs in human infants exposed to aqueous solutions of nitrate ion and
can progress to cyanosis and death. Based on numerous epidemiological
and clinical studies, EPA has determined a LOAEL of 1.8 to 3.2 mg/kg/
day and a NOAEL and RfD of 1.6 mg/kg/day, corresponding to 10 mg/L
nitrate-nitrogen or 44 mg/L nitrate ion in drinking water. Infants
weighing an average of 4 kg (0 to 3 months of age) are the most
sensitive population to nitrate-induced methemoglobinemia. This is
primarily due to their higher stomach pH which favors the growth of
nitrate-reducing bacteria, the immaturity of their metabolic enzyme
systems, and reduced capacity of their erythrocytes to reduce
methemoglobin to hemoglobin. EPA believes that there is sufficient
evidence for listing nitrate ion on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available hematological toxicity data
for this chemical.
In nitrogen-limited waters, nitrates have the potential to cause
increased algal growth leading to eutrophication in the aquatic
environment. (Nitrate-nitrogen is the form of nitrogen most available
to plants.) Studies of estuarine water at several locations along the
eastern coast of the United States have indicated that low
concentrations of dissolved nitrogen (e.g., nitrate) limit primary
production of plants.
Additions of nitrate to such estuarine systems stimulate primary
production of plants and can produce changes in the dominant species of
plants, leading to cultural eutrophication and ultimately to
deterioration of water quality, including algal blooms.
It has been determined that lakes with a spring maximum
concentration of more than 300 ug/L of inorganic nitrogen (e.g.,
nitrates) could be expected to have algal nuisances in the summer.
Toxic effects result from oxygen depletion as the algae die and
decay. Toxic effects have also been related to the release of decay
products or direct excretion of toxic substances from sources such as
blue-green algae.
EPA believes that there is sufficient evidence for listing nitrate
ion on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based
on the available environmental toxicity data.
177. Nitric oxide (CAS No. 010102-43-9) (CERCLA; EPCRA EHS; RCRA
APP8; RCRA P) (Ref. 8). The acute toxicity of nitric oxide has been
rated high. Nitric oxide causes death or permanent injury after very
short exposure to small quantities. Exposure to nitric oxide can result
in acute and chronic changes of the pulmonary system including
pulmonary edema, pneumonitis, bronchitis, bronchiolitis, emphysema, and
methemoglobinemia. Neurologic effects (fatigue, restlessness, anxiety,
mental confusion, lethargy, loss of consciousness) have also been
reported. The effects of nitric oxide may be related to the formation
of methemoglobin. EPA believes that there is sufficient evidence for
listing nitric oxide on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available neurological and hematological
toxicity data for this chemical.
178. p-Nitroaniline (CAS No. 000100-01-6) (CERCLA; RCRA APP8; RCRA
P) (Ref. 8). In a 14-day study in mice fed p-nitroaniline in doses as
low as 10 mg/kg, 5 days per week, methemoglobin concentrations were
found to be significantly higher than those in control animals. In the
same study, hematocrit values in mice that received 300 mg/kg, and
total erythrocyte counts in mice that received 100 or 300 mg/kg, were
significantly lower than those of control animals. Similar effects were
observed in 13-week and 2-year mouse studies. In the 2-year study,
lesions related to the administration of p-nitroaniline occurred in the
spleen, liver, and bone marrow (primarily in mice receiving 30 or 100
mg/kg) and were observed at 9 and 15 months. In addition, increases in
the incidence or severity of splenic congestion, hematopoiesis, pigment
(hemosiderin) accumulation, Kupffer cell pigmentation in the liver, and
bone marrow hypercellularity (hyperplasia). EPA believes that there is
sufficient evidence for listing p-nitroaniline on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the chronic toxicity
data for this chemical.
179. Nitrogen dioxide (CAS No. 010102-44-0) (CERCLA; EPCRA EHS;
RCRA APP8; RCRA P) (Ref. 8). Acid precipitation occurs in large regions
of the Eastern United States and Canada, Europe, and Japan. This
widespread occurrence of acid precipitation and dry deposition results
in large part from man-made emissions of oxides of sulfur and nitrogen
(e.g., nitrogen dioxide). These substances are transformed in the
atmosphere into sulfuric acid and nitric acid, transported over great
distances and deposited on vegetation, soils, surface waters, and
materials. These substances are transferred from the atmosphere into
ecosystems by the absorption of gases, the impaction and gravitational
settling of fine aerosols and coarse particles, and precipitation.
Acids contained in polluted snow are released as contaminated
meltwater. The resulting release of pollutants can cause major or rapid
changes in the acidity of streams and lake waters. Interference with
normal reproduction in fish populations is induced by acidity of lake
and stream waters. Reproduction of frogs and salamanders is also
inhibited by atmospheric acidification of surface waters.
Atmospheric deposition of sulfuric acid and nitric acid can cause
serious damage to crops and forests. Biological effects include
induction of necrotic lesions, loss of nutrients due to leaching from
foliar organs, accelerated erosion of waxes and leaf surfaces, and
interference with normal reproductive processes. Acidification also
decreases the rate of many soil processes such as nitrogen fixation and
the breakdown of organic matter.
EPA believes that there is sufficient evidence for listing nitrogen
dioxide on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C)
based on the available environmental toxicity data for this chemical.
Nitrogen dioxide is regulated under Title I of the CAA (Provisions
for Attainment and Maintenance of National Ambient Air Quality
Standards). In addition to this proposal to add nitrogen dioxide to
EPCRA section 313, in Units IV.B.36. and 235, EPA is proposing to add
two other chemicals, carbon monoxide and sulfur dioxide, that are
regulated by Title I of the CAA. Sulfur dioxide is also regulated by
Title IV of the CAA (Acid Deposition Control). Extensive data, which
are highly technical, are collected on these chemicals as required by
the CAA. EPA requests comment on the following: (1) Is the information
collected under the CAA sufficient for public right-to-know purposes;
and (2) suggestions on how the data collected on these chemicals
pursuant to CAA Titles I and IV could be used to meet the purposes of
EPCRA section 313.
180. Norflurazon (4-Chloro-5-(methylamino)-2-
[3(trifluoromethyl)phenyl]-3(2H)-pyridazinone) (CAS No. 027314-13-2)
(FIFRA AI) (Ref. 3). Congestion of the liver, hepatocyte swelling and
increased liver weights, and increase in colloid vacuole in the thyroid
were observed in dogs fed 450 ppm (10.25 mg/kg/day) norflurazon for 6
months. The NOEL was 150 ppm (3.75 mg/kg/day). An oral RfD of 0.04 mg/
kg/day has been determined. Increased relative liver weight and
hypertrophy of the thyroid with depletion of colloid were seen in rats
fed 2,500 ppm (125 mg/kg/day) norflurazon for 90 days. The NOEL was 500
ppm (25 mg/kg/day). Hepatic hyperplasia and hypertrophy and increased
relative liver weight were noted in a 28-day feeding study in rats. The
LOEL was 1,000 ppm (50 mg/kg/day) and the NOEL was 500 ppm (25 mg/kg/
day). Increased relative liver weight and diffuse and smooth granular
livers were seen in a 28-day feeding study in mice. The LOEL was 2,520
ppm (328 mg/kg/day) and the NOEL was 420 ppm (55 mg/kg/day). EPA
believes that there is sufficient evidence for listing norflurazon on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available hepatic and thyroid toxicity data.
181. Oryzalin (4-(Dipropylamino)-3,5-dinitrobenzene sulfonamide)
(CAS No. 019044-88-3) (FIFRA AI) (Ref. 3). Reduced hemoglobin and
hematocrit levels, decreased red blood cell count, increased blood urea
nitrogen (BUN) and alkaline phosphatase and SGPT, anemia, hepatic
changes, splenic hematopoiesis and hyperplastic bone marrow were
observed in dogs fed 56.25 mg/kg/day (the NOEL was 18.75 mg/kg/day) for
3 months. Increases in serum cholesterol levels, alkaline phosphatase
activity, and relative liver and kidney weights and decreases in
alanine transaminase (the LOEL was 50 mg/kg/day; the NOEL was 5 mg/kg/
day) were observed in dogs fed oryzalin for 1-year. Decreased red blood
cell count and hematocrit and hemoglobin levels (LOEL was 45 mg/kg/day;
NOEL was 15 mg/kg/day) were noted in a 1-year feeding study in rats. In
a 2-year feeding study in rats, decreased red blood cell count and
hematocrit and hemoglobin levels, and increased BUN and liver and
kidney weights (the LOEL was 45 mg/kg/day; the NOEL was 15 mg/kg/day)
were observed. EPA believes that there is sufficient evidence for
listing oryzalin on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available hepatic and hematological toxicity
data for this chemical.
182. Oxydemeton methyl (S-(2-(Ethylsulfinyl)ethyl) O,O-dimethyl
ester phosphorothioic acid) (CAS No. 000301-12-2) (FIFRA AI) (Ref. 3).
Two multigeneration reproduction studies indicate a variety of
reproductive effects at 2.1 to 2.5 mg/kg/day. These effects include
decreased litter size and viability, decreased weight of the testes and
ovaries, and increased epididymal vacuolation. The NOELs were 0.38 and
0.5 mg/kg/day. A NOEL of 0.9 mg/kg/day was determined in a 5-day study
in the rat. The LOEL for decreased fertility and epididymal sperm
motility was 5 mg/kg/day.
Oxydemeton methyl can cause inhibition of brain, plasma, and red
blood cell cholinesterase. In a 2-generation reproduction study,
statistically significant inhibition of red blood cell and brain
cholinesterase activity (the NOEL was less than 0.043 mg/kg/day) was
observed in adult males and females of the F0 and F1
generations. In a 5-day feeding (dominant lethal plus) study,
inhibition of plasma cholinesterase activity (the LOEL was 1.5 mg/kg/
day; the NOEL was 0.45 mg/kg/day) was observed. EPA believes that there
is sufficient evidence for listing oxydemeton methyl on EPCRA section
313 pursuant to EPCRA section 313(d)(2)(B) based on the available
reproductive and neurological toxicity data for this chemical.
183. Oxydiazon (3-[2,4-Dichloro-5-(1-methylethoxy)phenyl]5- (1,1-
dimethylethyl)-1,3,4-oxadiazol-2(3H)-one) (CAS No. 019666-30-9) (FIFRA
AI) (Ref. 3). Rats given 40 mg/kg/day by gavage on days 6 to 15 of
gestation exhibited increased fetal resorptions. The NOEL was 12 mg/kg/
day.
Increased liver and kidney weight (associated with no pathology)
and increased alkaline phosphatase activity were observed in rats fed
100 mg/kg/day (the NOEL was 25 mg/kg/day) for 90 days. Increased levels
of SGPT and alkaline phosphatase activities and increased liver weight
(the LOEL was 5 mg/kg/day; the NOEL was 0.5 mg/kg/day) were observed in
a 2-year feeding study in rats. Effects noted at 150 mg/kg/day included
liver pathology, hemolytic anemia, increased kidney weight, and pigment
nephrosis. Based on the NOEL, an oral RfD of 0.005 mg/kg/day was
derived. EPA believes that there is sufficient evidence for listing
oxydiazon on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available developmental, hepatic, and renal toxicity data
for this chemical.
184. Oxyfluorfen (CAS No. 042874-03-3) (FIFRA SR) (Ref. 8).
Oxyfluorfen is a phenoxyphenyl-type herbicide. Several chronic oral
toxicity studies suggest that oxyfluorfen may be hepatotoxic. Hepatic
effects (e.g. increased absolute liver weight, necrosis, regeneration,
and hyperplastic nodules) were observed in mice fed diets containing
greater than 3 mg/kg/day oxyfluorfen for 20 months (the NOEL was 0.3
mg/kg/day). Based on these findings, an oral RfD value of 0.003 mg/kg/
day was derived. This study was supported by other chronic feeding
studies that demonstrated increases in liver weight, alkaline
phosphatase activity, and bile pigmented hepatocytes (the LOEL was 15
mg/kg/day; the NOEL was 2.5 mg/kg/day) in dogs, and minimal hypertrophy
of centrilobular hepatocytes (the LOEL was 40 mg/kg/day; the NOEL was 2
mg/kg/day) in rats. EPA believes that there is sufficient evidence for
listing oxyfluorfen on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the hepatotoxic effects of this chemical.
The estimated chronic MATC values for fish and daphnids are 9 ppb
and 20 ppb oxyfluorfen, respectively. The estimated log Kow is
6.1. EPA believes that there is sufficient evidence for listing
oxyfluorfen on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C)
based on the environmental toxicity data and potential for
bioaccumulation for this chemical.
185. Ozone (CAS No. 010028-15-6) (EPCRA EHS) (Ref. 8). Information
from a large number of studies of both humans and animals indicate that
ozone can affect structure, function, metabolism, pulmonary defense
against bacterial infection, and extrapulmonary effects. Among these
extrapulmonary effects are: (1) Cardiovascular effects; (2)
reproductive and teratological effects; (3) central nervous system
effects; (4) alterations in red blood cell morphology; (5) enzymatic
activity; and (6) cytogenetic effects on circulating lymphocytes. EPA
believes that there is sufficient evidence for listing ozone on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available toxicity data for this chemical.
Effects of ozone on green plants include injury to foliage,
reductions in growth, losses in yield, alterations in reproductive
capacity, and alterations in susceptibility to pests and pathogens.
Based on the known interrelationships of different components of
ecosystems, such effects, if of sufficient magnitude, may potentially
lead to irreversible changes of sweeping nature to ecosystems.
Measured aquatic acute toxicity values for ozone include a 96-hour
LC50 of 80 ppb for striped bass, a 96-hour LC50 of 30 ppb for
channel catfish, and a 96-hour LC50 of 9.3 ppb for rainbow trout.
EPA believes that there is sufficient evidence for listing ozone on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the
available ecotoxicity data for this chemical.
186. Paraquat dichloride (CAS No. 001910-42-5) (EPCRA EHS; FIFRA
SR) (Ref. 8). Paraquat can cause death in humans as a consequence of
severe injury to the lungs, or as a result of kidney, liver, or heart
failure. Following exposure, death may occur in 24 hours or less. The
acute oral LD50 values for paraquat are reported as 57, 120, 25,
50 and 35 mg/kg in the rat, mouse, dog, monkey, and cat, respectively.
Chronic pneumonitis (the LOEL was 0.93 mg/kg/day; the NOEL was 0.45 mg/
kg/day) was reported in dogs fed diets containing paraquat dichloride
for 52 weeks. These results are supported by the results of a 2-year
feeding study in rats (the LOEL was 3.75 mg/kg/day based on
nonneoplastic lung lesions; the NOEL was 1.25 mg/kg/day) and a 90-day
feeding study in dogs (the LOEL was 1.5 mg/kg/day based on increased
lung weight, alveolitis, and alveolar collapse; the NOEL was 0.5 mg/kg/
day).
EPA believes that there is sufficient evidence for listing paraquat
dichloride on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the chronic toxicity data for this chemical.
187. Pebulate (Butylethylcarbamothioic acid S-propyl ester) (CAS
No. 001114-71-2) (FIFRA AI) (Ref. 3). In a 1-year dog feeding study, a
NOEL of greater than 5 mg/kg/day was established due to abnormal
behavior, ataxia, convulsions, and neurological effects in the brain
and spinal cord at 100 mg/kg/day. EPA believes that there is sufficient
evidence for listing pebulate on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available neurological toxicity data.
188. Pendimethalin (N-(1-Ethylpropyl)-3,4-dimethyl-2,6-
dinitrobenzenamine) (CAS No. 040487-42-1) (FIFRA AI) (Ref. 3).
Increased liver weights and alkaline phosphatase activity and hepatic
lesions (the LOEL was 50 mg/kg/day; the NOEL was 12.5 mg/kg/day) were
observed in dogs fed pendimethalin for 2 years. EPA derived an oral RfD
of 0.04 mg/kg/day. Hypertrophy of the liver and increased liver weights
were observed in rats fed 5,000 ppm (250 mg/kg/day) for 3 months. The
NOEL was 25 mg/kg/day. EPA believes that there is sufficient evidence
for listing pendimethalin on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available hepatic toxicity data.
189. Pentobarbital sodium (CAS No. 000057-33-0) (CAL) (Ref. 8).
Pentobarbital sodium is commonly used as a sedative hypnotic. The
average adult sedative dose is 20 to 40 mg orally. The average adult
hypnotic dose is 100 to 200 mg orally. Pentobarbital is also used
parenterally or rectally to provide basal hypnosis for general, spinal,
or regional anesthesia. Like other barbiturates, a common adverse
effect to using pentobabital sodium is central nervous system
depression. Chronic exposure to pentobarbital sodium may lead to
psychological and physical dependence.
Intraperitoneal injection of 20 mg/kg on day 1 of pregnancy
produced adverse effects on fertility in rats. Intraperitoneal
injections of 80 mg/kg to rats on day 1 of pregnancy caused
preimplantation loss. Intraperitoneal injection of 94.5 mg/kg on day 2
of pregnancy decreased fertility and caused fetal death in rats.
Intraperitoneal injection of 22 mg/kg on day 10 of pregnancy caused
adverse effects in rat fetuses (details of study not reported).
Subcutaneous injection of 520 mg/kg of pentobarbital sodium on days 9
to 21, or administration of 30 mg/kg on day 19 of pregnancy produced
abnormal behavioral effects in rat offspring. Exposure to pentobarbital
sodium during pregnancy can cause fetal addiction to the substance.
EPA believes that there is sufficient evidence for listing
pentobarbital sodium on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the developmental, reproductive, and chronic
neurological toxicity data for this chemical.
190. Perchloromethyl mercaptan (CAS No. 000594-42-3) (CERCLA; EPCRA
EHS) (Ref. 8). The rat oral LD50 and 4-hour rat inhalation
LC50 values for perchloromethyl mercaptan are 8.26 mg/kg and 0.26
mg/L, respectively. The 2-hour mouse inhalation LC50 value is
reported to be 0.296 mg/L. In an eye irritation test, 50 micrograms
(g) (0.13 mg/kg/day) placed in a rabbit's eye for 24 hours
produced a severe reaction. EPA's exposure analysis indicates that
perchloromethyl mercaptan concentrations are likely to exist beyond
facility site boundaries, as a result of continuous, or frequently
recurring releases, at levels that can reasonably be anticipated to
cause significant adverse acute human health effects. EPA believes that
there is sufficient evidence for listing perchloromethyl mercaptan on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(A) based on the
available acute toxicity and exposure data for this chemical.
191. Permethrin (3-(2,2-Dichloroethenyl)-2,2-
dimethylcyclopropanecarboxylic acid, (3-phenoxyphenyl)methyl ester)
(CAS No. 052645-53-1) (FIFRA AI) (Ref. 3). Increased liver weights (the
LOEL was 500 ppm or 25 mg/kg/day; the NOEL was 100 ppm or 5 mg/kg/day)
were observed in rats fed permethrin for 2 years. Based on the NOEL,
EPA derived an oral RfD of 0.05 mg/kg/day. Decreased alkaline
phosphatase activity, hepatocellular swelling, and increased liver
weight (the LOEL was 100 mg/kg/day; the NOEL was 5 mg/kg/day) were
observed in dogs orally administered (in capsules) permethrin for 1-
year. Tremors, excessive salivation, convulsions, and incoordination
were noted at 1,000 mg/kg/day. EPA believes that there is sufficient
evidence for listing permethrin on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available hepatic toxicity data.
Aquatic acute toxicity values for permethrin include a fathead
minnow 96-hour LC50 of 3.5 ppb, a rainbow trout 96-hour measured
LC50 of 0.62 ppb, a bluegill 96-hour LC50 of 2.52 ppb, an
Atlantic silverside 96-hour measured LC50 2.2 ppb, and a daphnid
48-hour LC50 of 0.32 ppb. EPA believes that there is sufficient
evidence for listing permethrin on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(C) based on the available environmental toxicity
data.
192. Phenanthrene (CAS No. 000085-01-8) (CERCLA; CWA PP) (Ref. 8).
Measured aquatic acute toxicity data for phenanthrene include a 48-hour
LC50 of 700 ppb for daphnids. The measured 28-day LC50 for
rainbow trout is 40 ppb, and teratogenetic effects were noted. The
measured bioconcentration factor (BCF) values include a fathead minnow
28-day BCF of 5,100 and a daphnid 24-hour BCF of 1,165. EPA believes
that there is sufficient evidence for listing phenanthrene on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(C) based on the
available environmental toxicity data for this chemical and its
potential to bioaccumulate.
193. Phenothrin (2,2-dimethyl-3-(2-methyl-1-propenyl)
cyclopropanecarboxylic acid (3-phenoxyphenyl)methyl ester) (CAS No.
026002-80-2) (FIFRA AI) (Ref. 3). Hepatocellular enlargement and
increased absolute and relative liver weights were observed in a
chronic feeding study in dogs. The LOEL was 27.7 mg/kg/day in males and
26.8 mg/kg/day in females. The NOEL was 8.2 mg/kg/day in males and 7.1
mg/kg/day in females. Hepatocellular hypertrophy and increased relative
liver weight (the LOEL was 150 mg/kg/day; the NOEL was 50 mg/kg/day)
were observed in a chronic oncogenicity study in rats. Increased liver
weight (the LOEL was 150 mg/kg/day, the NOEL was 45 mg/kg/day) was
noted in another chronic oncogenicity feeding study in mice. EPA
believes that there is sufficient evidence for listing phenothrin on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available hepatic toxicity data for this chemical.
Aquatic acute toxicity values for phenothrin include a rainbow
trout 96-hour LC50 of 16.7 ppb and a goldfish 48-hour LC50 of
100 ppb. EPA believes that there is sufficient evidence for listing
phenothrin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C)
based on the available environmental toxicity data for this chemical.
194. 1,2-Phenylenediamine (CAS No. 000095-54-5) (RCRA APP8) (Ref.
8). EPA has classified 1,2-phenylenediamine as a Group B2 compound,
i.e., a probable human carcinogen. 1,2-Phenylenediamine dihydrochloride
appeared to be carcinogenic in both rats and mice, as evidenced by an
increased incidence of hepatocellular carcinomas in both species. A
significantly increased incidence of hepatocellular carcinomas was
observed in high dose group male rats and mice, and female mice of both
treated groups. EPA believes that there is sufficient evidence for
listing 1,2-phenylenediamine on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the carcinogenicity data for 1,2-
phenylenediamine dihydrochloride.
195. 1,3-Phenylenediamine (CAS No. 000108-45-2) (RCRA APP8) (Ref.
8). Increased absolute and relative liver weights and degenerative
liver lesions (the LOEL was 18 mg/kg/day; the NOEL was 6.0 mg/kg/day)
were noted in a 90-day oral study in rats exposed to 1,3-
phenylenediamine. EPA believes that there is sufficient evidence for
listing 1,3-phenylenediamine on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the hepatotoxicity data for this
chemical.
196. 1,2-Phenylenediamine dihydrochloride (CAS No. 000615-28-1)
(RCRA APP8) (Ref. 8). EPA has classified 1,2-phenylenediamine as a
Group B2 compound, i.e., a probable human carcinogen. 1,2-
Phenylenediamine dihydrochloride appeared to be carcinogenic in both
rats and mice, as evidenced by an increased incidence of hepatocellular
carcinomas in both species. A significantly increased incidence of
hepatocellular carcinomas was observed in high dose group male rats and
mice, and female mice of both treated groups. EPA believes that there
is sufficient evidence for listing 1,2-phenylenediamine dihydrochloride
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on
the carcinogenicity data for this chemical.
197. 1,4-Phenylenediamine dihydrochloride (CAS No. 000624-18-0)
(RCRA APP8) (Ref. 8). Measured aquatic acute toxicity for 1,4-
phenylenediamine include a fish 96-hour LC50 of 60 ppb. EPA
believes that there is sufficient evidence for listing 1,4-
phenylenediamine dihydrochloride on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(C) based on the available environmental toxicity data
for 1,4-phenylenediamine.
198. Phenytoin (CAS No. 000057-41-0) (CAL; IARC; NTP) (Ref. 8).
Phenytoin is a hydantoin-type anticonvulsant, and is used mainly in the
prophylactic management of tonic-clonic (grand mal) seizures and
partial seizures with complex symptomatology. In doses used to treat
seizure disorders (i.e., 300 mg/day in adults, 5 mg/kg/day in children)
phenytoin can cause adverse effects such as constipation, dysphagia,
nausea, vomiting, anorexia and weight loss. Ingestion of 4.5 g (64 mg/
kg/day) by adults and 0.6 g (60 mg/kg/day) by children has produced
transient coma with motor restlessness. Ingestion of 11 mg/kg/day
produced changes in motor activity in a child (duration of study not
reported). Oral administration of 7.8 mg/kg/day for 4 days produced
encephalitis, hallucinations, and irritability in a man. Ingestion of
7.6 mg/kg/day for 2 weeks caused encephalitis, hallucinations, and
ataxia in a woman.
Phenytoin is classified as a Group 2B compound by IARC; i.e.,
possible human carcinogen. Ingestion of 16.5 mg/kg/day for 1-year
produced lymphoma including Hodgkin's disease and skin tumors in a
child. Oral exposure to phenytoin produced lymphoma in mice (doses and
duration of study not reported).
Oral administration of 5.9 mg/kg/day to a woman for the first 39
weeks of pregnancy induced kidney tumors in the offspring. In another
study, oral administration of 5.9 mg/kg/day to a woman for the first 39
weeks of pregnancy induced brain tumors in the offspring. Oral
administration of 2 mg/kg/day to a woman for 1-year produced lymphoma
including Hodgkin's disease. Congenital malformation was reported in
6.12 percent of births to 98 epileptic mothers receiving phenytoin
regularly during the first 4 months of pregnancy. Hypothrombinemia and
hemorrhage has occurred in newborns of mothers who received phenytoin
during pregnancy. Oral doses of 4.0 to 5.9 mg/kg/day administered to
women for the first 39 weeks of pregnancy produced craniofacial
abnormalities, nervous system disorders, and delayed physical effects
in their children. Doses of 2.0 mg/kg/day given to a woman for the
first 39 weeks of pregnancy produced abnormalities of skin, appendages,
and musculoskeletal system in her child as well as other developmental
abnormalities. Oral doses of 5.0 mg/kg/day produced biochemical and
metabolic abnormalities in the offspring. Higher doses of phenytoin
(130 mg/kg/day) orally administered to rats produced behavioral,
growth, musculoskeletal, and nervous system abnormalities in the
offspring.
EPA believes that there is sufficient evidence for listing
phenytoin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the chronic neurological and developmental toxicity data and
on the carcinogenicity data for this chemical.
199. Phosphine (CAS No. 007803-51-2) (CAA HAP) (Ref. 7). Available
data on phosphine indicate that its inhalation LC50 for rats is
between 4 and 40 ppm (the exposure time was 4 hours). Phosphine is a
highly-toxic gas with a probable oral lethal dose of 5 mg/kg. An air
concentration of 3 ppm is safe for long-term exposure, 500 ppm is
lethal in 30 minutes, and a concentration of 1,000 ppm is lethal after
a few breaths.
EPA's exposure analysis indicates that phosphine concentrations are
likely to exist beyond facility site boundaries, as a result of
continuous, or frequently recurring releases, at levels that can
reasonably be anticipated to cause significant adverse acute human
health effects. EPA believes that there is sufficient evidence for
listing phosphine on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(A) based on the available acute toxicity and exposure data
for this chemical.
200. Phosphorus oxychloride (CAS No. 010025-87-3) (CERCLA; EPCRA
EHS) (Refs. 5 and 8). Phosphorus oxychloride reacts with water to yield
phosphoric acid and hydrochloric acid.
Phosphoric acid, as well as other phosphates, have the potential to
cause increased algal growth leading to eutrophication in the aquatic
environment.
Eutrophication may result when nutrients, especially phosphates,
enter into an aquatic ecosystem in the presence of sunlight and
nitrogen. The phosphate ion is a plant nutrient, which can be a major
limiting factor for plant growth in freshwater environments. In excess,
phosphates can cause algal blooms. Toxic effects result from oxygen
depletion as the algae die and decay. Toxic effects have also been
related to the release of decay products or direct excretion of toxic
substances from sources such as blue-green algae.
Laboratory studies indicate that eutrophication may occur at
phosphate concentrations as low as 50 ppb in lakes. The resulting
oxygen depletion and toxic decay products (e.g., hydrogen sulfide) kill
many invertebrates and fish.
Although green algae are more sensitive to growth stimulation by
phosphates in fresh water, blue-green algal blooms may cause greater
damage. At least three species of blue-green algae are known to excrete
toxins. Secretion by cyanobacteria of dyalyzable metabolites have
inhibited the growth of other species of algae and may result in algal
monoculture. When algal blooms of these toxic species occur in a
reservoir, lake, slough, or pond, the cells and toxins can become
sufficiently concentrated to cause illness or death in invertebrates
and vertebrates. Major losses have been reported for cattle, sheep,
hogs, birds (domestic or wild) and fishes, minor losses for dogs,
horses, small wild animals, amphibians, and invertebrates.
Eutrophication may occur in slow moving rivers, but is less likely
in swift rivers where rapid mixing occurs. Light is the most important
limiting factor because rivers are murkier than lakes thus, the chances
of eutrophication in swift rivers are slight. However, lakes and
reservoirs collect phosphates from influent streams and store a
fraction of them within consolidated sediments, thus serving as a
phosphate sink.
The available information derived from animal and controlled human
studies clearly indicates that exposure to acid aerosols can produce
health effects of concern, particularly in sensitive subgroups of the
population and after chronic exposure. The bulk of these studies,
however, have examined sulfuric acid exposures. Data for other acid
species and mixtures are extremely limited. However, as the effects
appear to be due to the acidity of the species, this data should
pertain to acid aerosols consisting of other mineral acids, such as
hydrochloric acid. The effects seen range from mild and transient
changes, such as small, reversible functional effects in exercising
asthmatics, to more substantial effects that may have acute or chronic
health consequences, such as persistently altered clearance and
structural changes that may be suggestive of chronic lung disease. In
addition, there are some notable consistencies in the health effects
information across various studies and disciplines.
EPA believes that there is sufficient evidence for listing
phosphorous oxychloride on EPCRA section 313 pursuant to EPCRA sections
313(d)(2)(B) and (C) based on the available chronic human and
environmental toxicity data for its degradation products phoshoric acid
and hydrochloric acid.
201. Phosphorus pentachloride (CAS No. 010026-13-8) (EPCRA EHS)
(Refs. 5 and 8). Phosphorus pentachloride reacts with water to yield
phosphoric acid and hydrochloric acid. As described in Unit IV.B.200.
of this preamble, phosphates, including phosphoric acid, have the
potential to cause increased algal growth leading to eutrophication and
fish kills in the aquatic environment.
The available information derived from animal and controlled human
studies clearly indicates that exposure to acid aerosols can produce
health effects of concern, particularly in sensitive subgroups of the
population and after chronic exposure. The bulk of these studies,
however, have examined sulfuric acid exposures. Data for other acid
species and mixtures are extremely limited. However, as the effects
appear to be due to the acidity of the species, this data should
pertain to acid aerosols consisting of other mineral acids, such as
hydrochloric acid. The effects seen range from mild and transient
changes, such as small, reversible functional effects in exercising
asthmatics, to more substantial effects that may have acute or chronic
health consequences, such as persistently altered clearance and
structural changes that may be suggestive of chronic lung disease. In
addition, there are some notable consistencies in the health effects
information across various studies and disciplines.
EPA believes that there is sufficient evidence for listing
phosphorus pentachloride on EPCRA section 313 pursuant to EPCRA
sections 313(d)(2)(B) and (C) based on the available chronic human and
environmental toxicity data for its degradation products phoshoric acid
and hydrochloric acid.
202. Phosphorus pentasulfide (CAS No. 001314-80-3) (CERCLA) (Refs.
5 and 8). Phosphorus pentasulfide reacts in water to yield phosphoric
acid and hydrogen sulfide.
As described in Unit IV.B.200. of this preamble, phosphates,
including phosphoric acid, have the potential to cause increased algal
growth leading to eutrophication and fish kills in the aquatic
environment.
Acute exposures to large amounts of hydrogen sulfide (approximately
250 ppm or more) have produced pulmonary edema, unconsciousness,
respiratory paralysis, asphyxiation, and/or death in some individuals.
Similar effects are also noted in animals. In a subchronic study,
inflammation of the nasal mucosa occurred in mice following 90-day
inhalation of hydrogen sulfide, resulting in a NOAEL of 42.5 mg/m3
(30.5 ppm; Human Equivalent Concentration (HEC) is 0.93 mg/m3) and
a LOAEL of 110 mg/m3 (80 ppm; HEC is 2.4 mg/m3). Other
respiratory effects, such as alveolar edema, infiltrates in the
bronchioles, cellular necrosis, hyperplasia, and exfoliation in various
respiratory tissues, have been reported in rats.
Aquatic toxicity test data for hydrogen sulfide show that measured
fish 96-hour LC50 values range from 7 to 776 ppb.
EPA believes that there is sufficient evidence for listing
phosphorus pentasulfide on EPCRA section 313 pursuant to EPCRA sections
313(d)(2)(B) and (C) based on the available chronic human and
environmental toxicity data for its degradation products, phosphoric
acid and hydrogen sulfide.
203. Phosphorus pentoxide (CAS No. 001314-56-3) (EPCRA EHS) (Refs.
5 and 8). Phosphorus pentoxide rapidly hydrolyzes in the presence of
water to yield phosphoric acid.
As described in Unit IV.B.200. of this preamble, phosphates,
including phosphoric acid, have the potential to cause increased algal
growth leading to eutrophication and fish kills in the aquatic
environment. EPA believes that there is sufficient evidence for listing
phosphorous pentoxide on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(C) based on the available environmental toxicity data for its
degradation product phosphoric acid.
204. Picloram (CAS No. 001918-02-1) (FIFRA AI; SDWA) (Ref. 8).
Animal studies in dogs, rats, or mice for various durations (2 weeks to
2 years) have indicated the liver as the primary target of picloram
toxicity. In a 6-month feeding study in beagle dogs, a LOAEL of 35 mg/
kg/day and a NOAEL of 7 mg/kg/day were determined for increased liver
weights (relative and absolute). At a higher dose (175 mg/kg/day),
there were increases in serum alkaline phosphatase concomitant with the
increases in liver weight. Other toxic effects in the higher dosed
animals included reduced food consumption and body weight. EPA has
derived an oral RfD of 0.07 mg/kg/day for this chemical based on the
findings of this study. Hepatotoxicity has also been reported in a 2-
year rat feeding study. The LOAEL was 60 mg/kg/day based on changes in
liver histopathology. The NOAEL was 20 mg/kg/day. Hepatotoxicity was
also observed in a 90-day rat feeding study. The LOAEL was 150 mg/kg/
day based on changes in liver histopathology, necrosis, and bile duct
proliferation. The NOAEL was 50 mg/kg/day. Increased liver weights were
also reported in mice following dietary exposure to picloram for 13
weeks. The LOAEL was 1,000 mg/kg/day. Liver swelling was reported in
rats administered picloram in feed for 13 weeks. The LOAEL was 150 mg/
kg/day. EPA believes that there is sufficient evidence for listing
picloram on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available hepatotoxicity data for this chemical.
205. Piperonyl butoxide (CAS No. 000051-03-6) (FIFRA SR) (Ref. 8).
Measured aquatic acute toxicity data for piperonyl butoxide include a
96-hour LC50 of 3.4 ppb for rainbow trout and a 96-hour LC50
of 4.2 ppb for bluegill. EPA believes that there is sufficient evidence
for listing piperonyl butoxide on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(C) based on the environmental toxicity data for this
chemical.
206. Pirimiphos methyl (O-(2-(diethylamino)-6-methyl-4-
pyrimidinyl)-O,O-dimethyl phosphorothioate) (CAS No. 029232-93-7)
(FIFRA AI) (Ref. 3). Pirimiphos methyl is a cholinesterase inhibitor in
humans and other mammalian species. A mild and transient decrease in
plasma cholinesterase activity was observed in 2 of 4 female humans
given pirimiphos methyl daily in a capsule at dose levels of 0.25 mg/
kg/day for 56 days. This effect was not seen in 3 of 3 males. The dose
level of 0.25 mg/kg/day was considered a NOEL for plasma cholinesterase
inhibition. Based on the NOEL, an oral RfD of 0.01 mg/kg/day was
derived. The findings of the 56-day study were corroborated by the 28-
day feeding study (capsule) with 5 male human volunteers where 1
individual showed borderline cholinesterase depression. Inhibition of
brain cholinesterase (LOEL was 0.5 mg/kg/day, the NOEL for
cholinesterase inhibition was not determined) was observed in a 2-year
feeding study in dogs. Inhibition of plasma cholinesterase activity
(the LOEL was 2.5 mg/kg/day; the NOEL was 0.5 mg/kg/day) was seen in a
2-year feeding study in rats. No clinical signs were reported for the
above studies. EPA believes that there is sufficient evidence for
listing pirimiphos methyl on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available neurological toxicity data
for this chemical.
207. Polycyclic aromatic compounds (PACs) (CAS No. NA) (CAA HAP)
(Ref. 7). Polycyclic aromatic compounds are a class of chemicals that
include polycyclic aromatic hydrocarbons, azapolycyclic aromatic
hydrocarbons, thio-polycyclic aromatic hydrocarbons, nitroarenes, and
others. PACs can be formed in any combustion process that involves the
burning of fuels or, more generally, materials containing carbon and
hydrogen. Some industrial sources include coke ovens, catalytic
cracking of crude oil, carbon black production, and iron and steel
processes.
Materials containing mixtures of PACs have been shown to be
carcinogenic. Several epidemiology studies have shown increased
mortality due to lung cancer in humans exposed to coke-oven emissions,
roofing-tar emissions, and cigarette smoke. Each of these mixtures
contains benzo(a)pyrene, benzo(a)anthracene, benzo(b)fluoranthene,
benzo(a)phenanthrene, and dibenzo(a,h)anthracene as well as other
potentially carcinogenic PACs and other carcinogenic and potentially
carcinogenic chemicals, tumor promotors, initiators, and co-carcinogens
such as nitrosoamines, coal tar pitch, and creosote. Although it is
impossible to evaluate the contribution of any individual PAC to the
total carcinogenicity of these mixtures to humans, reports of this
nature provide qualitative evidence of the potential for mixtures
containing PACs to cause cancer in humans. In addition, several PACs
caused cancer in animals when orally (e.g., benz(a)anthracene,
benzo(a)pyrene, dibenz(a,h)anthracene), dermally (e.g.,
benz(a)anthracene, benzo(a)phenanthrene, benzo(b)fluoranthene,
benzo(a)pyrene, dibenz(a,h)anthracene, and indeno (1,2,3-cd)pyrene) or
inhalationally (e.g., benzo(a)pyrene) exposed. EPA believes that there
is sufficient evidence for listing these PACs on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available
carcinogenicity data for these chemicals. EPA is proposing to create a
delimited category for PACs that includes the chemicals discussed
below.
a. Benzo(b)fluoranthene (CAS No. 000205-99-2). Benzo(b)fluoranthene
is classified as a Group B2 compound by EPA, i.e., the compound is a
probable human carcinogen. It is classified as a Group 2B compound by
IARC, i.e., the compound is a possible human carcinogen.
Benzo(b)fluoranthene produced tumors in mice after lung implantation,
intraperitoneal or subcutaneous injection and skin painting. EPA
believes that there is sufficient evidence for listing
benzo(b)fluoranthene on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available carcinogenicity data for this
chemical.
b. Benzo(j)fluoranthene (CAS No. 000205-82-3). Benzo(j)fluoranthene
is classified as a Group 2B compound by IARC, i.e., the compound is a
possible human carcinogen. In multiple skin painting assays and in a
mouse-skin initiation-promotion assay, benzo(j)fluoranthene produced
tumors in female mice. EPA believes that there is sufficient evidence
for listing benzo(j)fluoranthene on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available carcinogenicity data for
this chemical.
c. Benzo(k)fluoranthene (CAS No. 000207-08-9). Benzo(k)fluoranthene
is classified as a Group B2 compound by EPA, i.e., the compound is a
probable human carcinogen. It is also classified as a Group 2B compound
by IARC, i.e., the compound is a possible human carcinogen.
Benzo(k)fluoranthene produced tumors after lung implantation in mice
and when administered with a promoting agent in skin painting studies.
Equivocal results have been found in a lung adenoma assay in mice.
Benzo(k)fluoranthene is mutagenic in bacteria. EPA believes that there
is sufficient evidence for listing benzo(k)fluoranthene on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available carcinogenicity data for this chemical.
d. Carbazole (CAS No. 000086-74-8). Mice fed a basal diet
containing carbazole showed a dose-related increase in liver nodules
and hepatocellular carcinomas after oral administration. EPA believes
that there is sufficient evidence for listing carbazole on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available carcinogenicity data for this chemical.
e. Cyclopenta(cd)pyrene (CAS No. 027208-37-3). In a skin painting
assay and in several mouse-skin initiation-promotion assays,
cyclopenta(cd)pyrene produced tumors in female mice.
Cyclopenta(cd)pyrene is also mutagenic to Salmonella and mammalian
cells in vitro and induces morphologic transformation in C3H10T1/2
cells in vitro. EPA believes that there is sufficient evidence for
listing cyclopenta(cd)pyrene on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available carcinogenicity data for
this chemical.
f. Dibenz(a,c)anthracene (CAS No. 000215-58-7). In a skin painting
assay and in several mouse-skin initiation-promotion assays,
dibenz(a,c)anthracene produced tumors in female mice. EPA believes that
there is sufficient evidence for listing dibenz(a,c)-anthracene on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available carcinogenicity data for this chemical.
g. Dibenz(a,h)acridine (CAS No. 000226-36-8). Dibenz(a,h)acridine
is classified as a Group 2A compound by IARC, i.e., the compound is a
probable human carcinogen. Dibenz(a,h)acridine has been shown to be
carcinogenic in animals. EPA believes that there is sufficient evidence
for listing dibenz(a,h)acridine on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available carcinogenicity data for
this chemical.
h. Dibenz(a,j)acridine (CAS No. 000224-42-0). Dibenz(a,j)acridine
is classified as a Group 2B compound by IARC, i.e., the compound is a
possible human carcinogen. Dibenz(a,j)acridine has been shown to be
carcinogenic in animals. EPA believes that there is sufficient evidence
for listing dibenz(a,j)acridine on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available carcinogenicity data for
this chemical.
i. Dibenz(a,j)anthracene (CAS No. 000224-41-9).
Dibenz(a,j)anthracene produced tumors after subcutaneous injection and
after skin painting in female mice. EPA believes that there is
sufficient evidence for listing dibenz(a,j)anthracene on EPCRA section
313 pursuant to EPCRA section 313(d)(2)(B) based on the available
carcinogenicity data for this chemical.
j. Dibenzo(a,e)fluoranthene (CAS No. 005385-75-1).
Dibenzo(a,e)fluoranthene produced tumors in female mice after mouse-
skin initiation-promotion assay and skin painting.
Dibenzo(a,e)fluoranthene also produced tumors in both male and female
mice after subcutaneous injection. EPA believes that there is
sufficient evidence for listing dibenzo(a,e)fluoranthene on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available carcinogenicity data for this chemical.
k. Dibenzo(a,e)pyrene (CAS No. 000192-65-4). Dibenzo(a,e)pyrene is
classified as a Group 2B compound by IARC, i.e., the compound is a
possible human carcinogen. Dibenzo(a,e)pyrene has been shown to be
carcinogenic in animals. EPA believes that there is sufficient evidence
for listing dibenzo(a,e)pyrene on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available carcinogenicity data for
this chemical.
l. Dibenzo(a,h)pyrene (CAS No. 000189-64-0). Dibenzo(a,h)pyrene is
classified as a Group 2B compound by IARC, i.e., the compound is a
possible human carcinogen. Dibenzo(a,h)pyrene has been shown to be
carcinogenic in animals. EPA believes that there is sufficient evidence
for listing dibenzo(a,h)pyrene on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available carcinogenicity data for
this chemical.
m. Dibenzo(a,l)pyrene (CAS No. 000191-30-0). Dibenzo(a,l)pyrene is
classified as a Group 2B compound by IARC, i.e., the compound is a
possible human carcinogen. Dibenzo(a,l)pyrene produced tumors in both
male and female mice after subcutaneous (s.c.) injection and tumors in
female mice after skin painting. EPA believes that there is sufficient
evidence for listing dibenzo-(a,l)pyrene on EPCRA section 313 pursuant
to EPCRA section 313(d)(2)(B) based on the available carcinogenicity
data for this chemical.
n. 7H-Dibenzo(c,g)carbazole (CAS No. 000194-59-2). 7H-
Dibenzo(c,g)carbazole is classified as a Group 2B compound by IARC,
i.e., the compound is a possible human carcinogen. 7H-
Dibenzo(c,g)carbazole has been shown to be carcinogenic in animals. EPA
believes that there is sufficient evidence for listing 7H-
dibenzo(c,g)carbazole on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available carcinogenicity data for this
chemical.
o. 2-Methylchrysene (CAS No. 003351-32-4). In a skin painting assay
and in a mouse-skin initiation-promotion assay, 2-methylchrysene
produced tumors in female mice. EPA believes that there is sufficient
evidence for listing 2-methylchrysene on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(B) based on the available carcinogenicity data
for this chemical.
p. 3-Methylchrysene (CAS No. 003351-31-3). In a skin painting assay
and in a mouse-skin initiation-promotion assay, 3-methylchrysene
produced tumors in female mice. EPA believes that there is sufficient
evidence for listing 3-methylchrysene on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(B) based on the available carcinogenicity data
for this chemical.
q. 4-Methylchrysene (CAS No. 003351-30-2). In a skin painting assay
and in a mouse-skin initiation-promotion assay, 4-methylchrysene
produced tumors in female mice. EPA believes that there is sufficient
evidence for listing 4-methylchrysene on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(B) based on the available carcinogenicity data
for this chemical.
r. 5-Methylchrysene (CAS No. 003697-24-3). 5-Methylchrysene is
classified as a Group 2B compound by IARC, i.e., the compound is a
possible human carcinogen. In a skin-painting assay and in a mouse-skin
initiation-promotion assay, 5-methylchrysene produced tumors in female
mice. EPA believes that there is sufficient evidence for listing 5-
methylchrysene on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available carcinogenicity data for this
chemical.
s. 6-Methylchrysene (CAS No. 001705-85-7). In a skin painting assay
and in a mouse-skin initiation-promotion assay, 6-methylchrysene
produced tumors in female mice. EPA believes that there is sufficient
evidence for listing 6-methylchrysene on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(B) based on the available carcinogenicity data
for this chemical.
t. 2-Methylfluoranthene (CAS No. 033543-31-6). In a skin painting
assay, 2-methylfluoranthene produced benign and malignant skin tumors
in female mice. In a female mouse-skin initiation-promotion assay, 2-
methylfluoranthene produced skin papillomas. EPA believes that there is
sufficient evidence for listing 2-methylfluoranthene on EPCRA section
313 pursuant to EPCRA section 313(d)(2)(B) based on the available
carcinogenicity data for this chemical.
u. 1-Nitropyrene (CAS No. 005522-43-0). 1-Nitropyrene is classified
as a Group 2B compound by IARC, i.e., the compound is a possible human
carcinogen. 1-Nitropyrene produced mammary adenocarcinomas and
squamous-cell carcinomas in a dose-dependent manner by oral
administration in rats, papillomas (not statistically significant) by
skin application in mice, and lung adenomas by intratracheal
instillation in hamsters. In a s.c. injection study, 1-nitropyrene
produced tumors (i.e., one extraskeletal osteosarcoma and seven
malignant fibrous histiocytomas) at the injection site in male Fisher
rats. In another s.c. injection study, 1-nitropyrene produced tumors at
the injection site in both male and female CD rats and mammary tumors
in females. EPA believes that there is sufficient evidence for listing
1-nitropyrene on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available carcinogenicity data for this
chemical.
In addition to the above compounds, EPA proposes that the PAC
category also include the following seven PACs:
Benz(a)anthracene (CAS No. 000056-55-3)
Benzo(a)phenanthrene (CAS No. 000218-01-9)
Benzo(a)pyrene (CAS No. 000050-32-8)
Benzo(rst)pentaphene (CAS No. 000189-55-9)
Dibenzo(a,h)anthracene (CAS No. 000053-70-3)
7,12-Dimethylbenz(a)anthracene (CAS No. 000057-97-6)
Indeno[1,2,3-cd]pyrene (CAS No. 000193-39-5)
These PACs were proposed for listing individually in EPA's response
to a petition to add certain chemicals that appear on the RCRA list of
toxic wastes under 40 CFR 261.33(f) to EPCRA section 313 (57 FR 41020,
September 8, 1992). These chemicals were proposed for addition based on
the available carcinogenicity data. Due to the similarities of these
seven PACs to the chemicals listed in Unit IV.B.207.a. through
IV.B.207.u. of this preamble, EPA believes that these chemicals should
be added to EPCRA section 313 as part of the delineated PAC category
rather than listed individually.
EPCRA section 313 requires threshold determinations for chemical
categories to be based on the total of all chemicals in the category
manufactured, processed, or otherwise used. For example, a facility
that manufactures three members of a chemical category would count the
total amount of all three chemicals manufactured towards the
manufacturing threshold for that category. When filing reports for
chemical categories the releases are determined in the same manner as
the thresholds. One report is filed for the category and all releases
are reported on this form. In the case of the delimited PAC category,
only the 28 chemicals listed above would be included for purposes of
making the threshold determinations and in filing reports on releases.
The Clean Air Act Amendments section 112(b) Hazardous Air
Pollutants list includes a listing for polycyclic organic matter (POM)
that includes PACs. The definition given for the POM category is broad
and chemically non-specific and may be delineated by test method. For
the purpose of listing under EPCRA section 313, EPA considered the
following more chemically-specific definition for a PAC category:
``includes all chemical species from the polycyclic aromatic
hydrocarbon, aza-polycyclic, thio-polycyclic, or nitroarene families
where polycyclic means three or more fused rings. More specifically, it
means any combination of three or more fused six or five membered
hydrocarbon rings with at least two or more rings being aromatic. The
structure may contain fused non-aromatic five-membered rings, a ring
nitrogen, a ring sulfur, one or more attached nitro groups, or one or
more attached alkyl groups.'' As an alternative to the delimited
category, EPA is proposing to add a PAC category based on this broad
definition. Although this definition may include chemicals of low or no
concern, it may be less of a burden for facilities to report their
total PACs rather than trying to determine which and how much of the
specific PACs covered by the delimited category they are producing and
releasing. EPA requests comment on the addition of the delimited PACs
category versus the alternative PAC category based on the broader
definition.
208. Potassium bromate (CAS No. 007758-01-2) (IARC) (Ref. 8). IARC
has assigned potassium bromate to Group 2B, i.e., it is possibly
carcinogenic to humans. Male and female rats orally exposed to 250 or
500 ppm (35 to 70 mg/kg/day) potassium bromate in drinking water for
110 weeks had an increased incidence of renal cell adenomas and
adenocarcinomas and, in males, there was also an increased incidence of
mesothelioma in the peritoneal cavity. EPA believes that there is
sufficient evidence for listing potassium bromate on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available
carcinogenicity data for this chemical.
209. Potassium dimethyldithiocarbamate (CAS No. 000128-03-0) (FIFRA
AI) (Ref. 3). New Zealand White rabbits given 38 mg/kg/day by gavage on
days 6 to 18 of gestation exhibited malalignment of sternebrae, total
postimplantation loss, and fetal weight decrement. Also at this dose
level, various malformations including adactyly, gastroschisis, short
tail, anal atresia, spina bifida, atelectasis, costal cartilage
anomaly, vertebral anomaly with/without rib, caudal vertebrea anomaly,
and severe sternebrae malalignment were observed in 6 of 52 fetuses
from 5 of 11 litters. At the 77 mg/kg/day dose level, there was severe
fetal/embryo lethality. The NOEL was 12.8 mg/kg/day. EPA believes that
there is sufficient evidence for listing potassium
dimethyldithiocarbamate on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available developmental toxicity data for
this chemical.
210. Potassium N-methyldithiocarbamate (CAS No. 000137-41-7) (FIFRA
AI) (Ref. 3). By analogy to the analogue, potassium
dimethyldithiocarbamate, potassium N-methyldithiocarbamate can
reasonably be anticipated to cause fetotoxicity, postimplantation loss
and malformations. Data on potassium dimethyldithiocarbamate follows.
New Zealand White rabbits given 38 mg/kg/day by gavage on days 6 to 18
of gestation exhibited malalignment of sternebrae, total
postimplantation loss, and fetal weight decrement. Also at this dose
level various possible malformations including adactyly, gastroschisis,
short tail, anal atresia, spina bifida, atelectasis, costal cartilage
anomaly, vertebral anomaly with/without rib, caudal vertebrea anomaly,
and severe sternebrae malalignment in 6 of 52 fetuses from 5 of 11
litters. At the 77 mg/kg/day dose level, there was severe fetal/embryo
lethality. The NOEL was 12.8 mg/kg/day. EPA believes that there is
sufficient evidence for listing potassium N-methyldithiocarbamate on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available developmental toxicity data for potassium
dimethyldithiocarbamate.
211. Primisulfuron (methyl 2-[[[[[4,6-bis(difluoromethoxy)2-
pyrimidinyl]-amino] carbonyl] amino]sulfonyl] benzoate) (CAS No.
086209-51-0) (FIFRA AI) (Ref. 3). In a 90-day dog feeding study,
reduced thyroid weights accompanied by colloid depletion and
parafollicular hyperplasia and anemia were observed at the LOEL of 25
mg/kg/day. The NOEL was 0.625 mg/kg/day. In a 1-year dog study, dietary
administration of 250/125 mg/kg/day (LOEL: the dose was changed after
week 10 in the study) produced thyroid hyperplasia, anemia, increased
platelet levels, vacuolar changes, and increased absolute and relative
liver weights. The NOEL was 25 mg/kg/day. In an 18-month study in mice,
dietary administration of 1.7 mg/kg/day produced increased absolute and
relative liver weights in females. No NOEL was established. Based on
this study, an oral RfD of 0.006 mg/kg/day was derived. In a 2-year
mouse study, increases in absolute and relative liver weights were
observed at 408 mg/kg/day in males and 1.7 mg/kg/day in females. The
systemic LOEL and NOEL in males was 408 mg/kg/day and 40.2 mg/kg/day,
respectively. The systemic LOEL in females was 1.7 mg/kg/day and a NOEL
could not be established. EPA believes that there is sufficient
evidence for listing primisulfuron on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(B) based on the available thyroid and liver
toxicity data for this chemical.
Plant toxicity values include a duckweed 14-day EC50 of 0.27
ppb and an algae 7-day EC50 of 24 ppb. EPA believes that there is
sufficient evidence for listing primisulfuron on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(C) based on the available
environmental toxicity data for this chemical.
212. Profenofos (O-(4-bromo-2-chlorophenyl)-O-ethyl-Spropyl
phosphorothioate) (CAS No. 041198-08-7) (FIFRA AI) (Ref. 3). In a 6-
month feeding study in dogs, inhibition of plasma and red blood cell
cholinesterase activities were observed at 2 ppm (0.05 mg/kg/day). The
NOEL was 0.2 ppm (0.005 mg/kg/day). Based on the NOEL, EPA derived an
oral RfD of 0.00005 mg/kg/day. Other studies (21, 28, and 90-day
studies in rat, rabbit and dog) also demonstrate cholinesterase
(plasma, red blood cell or brain) inhibition in rats and mice. EPA
believes that there is sufficient evidence for listing profenofos on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available neurological toxicity data.
213. Prometryn (N,N'-bis(1-methylethyl)-6-methylthio-1,3,5-
triazine-2,4-diamine) (CAS No. 007287-19-6) (FIFRA AI) (Ref. 3).
Degenerative changes in the liver and kidney, and bone marrow atrophy
(the LOEL was 37.5 mg/kg/day; the NOEL was 3.75 mg/kg/day) were
observed in dogs fed prometryn for 2 years. Based on the NOEL, EPA
derived an oral RfD of 0.004 mg/kg/day. Fatty liver degeneration (the
LOEL was 500 mg/kg; the NOEL was 250 mg/kg) was observed in rats fed
prometryn for 28 days.
In a teratology study in rabbits, test material was administered by
gavage from gestation day 7 to 19. Increased abortions and late
resorptions occurred at 72 mg/kg/day. The NOEL was 12 mg/kg/day.
EPA believes that there is sufficient evidence for listing
prometryn on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available hepatic, renal, bone marrow, and developmental
toxicity data.
214. Propachlor (2-chloro-N-(1-methylethyl)-N-phenylacetamide) (CAS
No. 001918-16-7) (FIFRA AI) (Ref. 3). No evidence of maternal toxicity
was seen in rabbits administered propachlor by gavage at 0, 5, 15, or
50 mg/kg/day on days 7 to 19 of gestation. Statistically significant
increases in mean resorptions/postimplantation loss with corresponding
decreases in the mean number of viable fetuses were reported at 15 and
50 mg/kg/day when compared to controls. EPA believes that there is
sufficient evidence for listing propachlor on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available
developmental toxicity data.
215. Propanil (N-(3,4-dichlorophenyl)propanamide) (CAS No. 000709-
98-8) (FIFRA AI) (Ref. 3). Results of several subchronic and chronic
toxicity studies indicated the liver and spleen as the target organs
for propanil. Increased relative spleen weight (the LOEL was 20 mg/kg/
day; the NOEL was 5 mg/kg/day) was noted in female rats fed propanil
for 2 years. Based on the NOEL, EPA derived an oral RfD of 0.005 mg/kg/
day. Histopathological changes (the LOEL was 30 mg/kg/day; the NOEL was
25 mg/kg/day) in the liver and spleen were observed in mice orally
administered propanil for 90 days. At higher dose levels (i.e., 240 and
1,920 mg/kg/day) cyanosis, methemoglobinemia, and increased liver and
spleen weight were noted. In a 90-day rat study, increased spleen
weight (the LOEL was 50 mg/kg/day; the NOEL was 16.5 mg/kg/day) was
seen in females. Decreased hemoglobin levels was seen in males.
Increased SGOT and SAP activities (the LOEL was 100 mg/kg/day; the NOEL
was 15 mg/kg/day) were observed in dogs orally administered propanil
for 2 years. EPA believes that there is sufficient evidence for listing
propanil on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available hepatic toxicity data.
216. Propargite (CAS No. 002312-35-8) (CERCLA) (Ref. 8). In a
developmental toxicity study in which rabbits were exposed via oral
gavage to doses greater than or equal to 6 mg/kg/day (fetotoxic LOAEL)
of propargite during gestation days 6 to 18, delayed ossification,
increased fetal resorption, decreased fetal viability and reductions in
fetal body weight were noted. The maternal LOAEL in this study was also
6 mg/kg/day and was based on body weight reductions. The NOEL for
maternal and fetal toxicity was 2 mg/kg/day. Developmental effects
(increased incidence of missing sternebrae) were also reported in
offspring of rats exposed orally during gestation days 6 to 15. The
fetotoxicity LOAEL was 25 mg/kg/day and the NOAEL was 6 mg/kg/day. EPA
believes that there is sufficient evidence for listing propargite on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
developmental toxicity data for this chemical.
Measured aquatic acute toxicity data for propargite include a
bluegill sunfish LC50 of 31 ppb. EPA believes that there is
sufficient evidence for listing propargite on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(C) based on the environmental
toxicity data for this chemical.
217. Propargyl alcohol (CAS No. 000107-19-7) (CERCLA; RCRA APP8;
RCRA P) (Ref. 8). Histopathological changes in the liver and kidney
were reported in a subchronic rat feeding study following exposure to
propargyl alcohol in the diet for as little as 4 weeks. The liver
changes included increased organ weight, hepatocytic megalocytosis with
proliferation of bile ducts and cytoplasmic vacuolization of
hepatocytes, as well as hematological and serum enzyme changes
indicative of liver damage. The kidney weights were increased in
females only, and both sexes had karyomegaly of the renal tubular
epithelial cells. The LOAEL for these changes was 15 mg/kg/day and the
NOAEL was 5 mg/kg/day. EPA derived an oral RfD of 0.002 mg/kg/day from
this study. EPA believes that there is sufficient evidence for listing
propargyl alcohol on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the hepatotoxicity and nephrotoxicity data for
this chemical.
218. Propetamphos (3-[[(Ethylamino)methoxyphosphinothioyl] oxy]-2-
butenoic acid, 1-methylethyl ester) (CAS No. 031218-83-4) (FIFRA AI)
(Ref. 3). Purebred beagle dogs were given propetamphos for 52 weeks in
feed. A dose of 2.5 mg/kg/day caused increased relative liver weight
and increased liver enzymes. Dogs given 12.5 mg/kg/day developed
hepatocellular necrosis. The NOEL was 0.5 mg/kg/day.
Red blood cell and plasma cholinesterase inhibition were seen in a
2-week rat inhalation study at 1 mg/kg/day (LOEL). No NOEL could be
established. Cholinesterase inhibition was observed at 0.4 mg/kg/day in
a 13-week rat dietary study. The NOEL was 0.2 mg/kg/day. Cholinesterase
inhibition was also observed at 0.1 mg/kg/day (LOEL) in a 6-month dog
dietary study. The NOEL was 0.05 mg/kg/day. In a 92-week mouse feeding
study, red blood cell, brain, and plasma cholinesterase were inhibited
at 1.0 mg/kg/day (LOEL). The NOEL was 0.5 mg/kg/day. Based on this
study, an oral RfD of 0.005 mg/kg/day was derived. In a 2-year dietary
rat study, plasma cholinesterase depression was observed at 0.6 mg/kg/
day (LOEL). The cholinesterase NOEL was 0.3 mg/kg/day. Alopecia and
hyperflexia were observed at 6 mg/kg/day (systemic LOEL). The systemic
NOEL was 0.6 mg/kg/day. In a lifetime mouse study, dietary
administration of 1 mg/kg/day produced plasma, red blood cell, liver,
and brain cholinesterase depression. The NOEL was 0.05 mg/kg/day.
EPA believes that there is sufficient evidence for listing
propetamphos on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available hepatic and neurological toxicity
data for this chemical.
219. Propiconazole (1-[2-(2,4-dichlorophenyl)-4-propyl-1,3-
dioxolan-2-yl]- methyl-1H-1,2,4,-triazole) (CAS No. 060207-90-1) (FIFRA
AI) (Ref. 3). In a 2-generation rat reproduction study, dietary
administration of 25 mg/kg/day produced an increased incidence of
hepatic clear cell change in parental animals and administration of 125
mg/kg/day produced an increased incidence of hepatic lesions in
offspring. The parental NOEL was 5 mg/kg/day and the developmental NOEL
was 25 mg/kg/day. In a 2-year mouse study, dietary administration of 65
mg/kg/day (LOEL) produced increased liver lesions and liver weight in
males, whereas, administration of 325 mg/kg/day produced increased
liver tumors, increased SGPT and SGOT levels, increased liver weight,
hepatocyte enlargement, and vacuolation and fat deposition in the liver
of both sexes. The NOEL was 13 mg/kg/day.
In a 3-month dog dietary study, lymphoid follicles were observed in
the mucous membranes of the pyloric part of the stomach at 6.25 mg/kg/
day. The NOEL was 1.25 mg/kg/day. In a 1-year dog study, dietary
administration of 6.25 mg/kg/day produced mild gastric mucosal
irritation. The NOEL was 1.25 mg/kg/day. Based on the NOEL of the
study, an oral RfD of 0.013 mg/kg/day was derived.
EPA believes that there is sufficient evidence for listing
propiconazole on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available hepatic and gastrointestinal
toxicity data for this chemical.
220. Quizalofop-ethyl (2-[4-[(6-chloro-2-quinoxalinyl) oxy]phenoxy]
propanoic acid ethyl ester) (CAS No. 076578-14-8) (FIFRA AI) (Ref. 3).
In a 3-month rat study, dietary administration of 6.4 mg/kg/day
produced changes in liver weight and liver lesions. The NOEL was 2 mg/
kg/day. In a 6-month dietary dog study, 10 mg/kg/day produced
testicular atrophy in males. The NOEL was 2.5 mg/kg/day. Liver cell
enlargement was observed at 3.7 mg/kg/day in males and 4.6 mg/kg/day in
females (LOELs) in a 2-year rat dietary study. The NOELs for males and
females were 0.9 mg/kg/day and 1.1 mg/kg/day, respectively. Based on
the study, an oral RfD of 0.009 mg/kg/day was derived. Increased liver
weights were observed in pregnant rats in a teratology study. The
maternal LOEL was 100 mg/kg/day and the NOEL was 30 mg/kg/day. No
teratogenic NOEL could be established. In a 2-generation rat
reproduction study, increased liver weights and increased incidence of
eosinophilic changes in the liver were observed in the offspring at 5
mg/kg/day (LOEL). The NOEL was 1.25 mg/kg/day.
EPA believes that there is sufficient evidence for listing
quizalofop-ethyl on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available reproductive and hepatic toxicity
data for this chemical.
221. Resmethrin ([5-(phenylmethyl)-3-furanyl]methyl 2,2-dimethyl-3-
(2-methyl-1-propenyl) cyclopropanecarboxylate]) (CAS No. 010453-86-8)
(FIFRA AI) (Ref. 3). Oral administration of 30 mg/kg/day (LOEL) in
capsules for 6 months produced increases in liver weights in female
dogs. The NOEL was 10 mg/kg/day. In a 2-year rat study, dietary
administration of 125 mg/kg/day produced increases in liver weight and
pathological lesions. The NOEL was 25 mg/kg/day.
In a one-generation reproduction rat study, administration of 25
mg/kg/day (LOEL) in the diet produced an increase in dead pups and
lower pup weight among survivors. No NOEL could be established. In a 3-
generation reproduction rat study, dietary administration of 25 mg/kg/
day (LOEL) produced an increase in pups cast dead and lower pup weight
among survivors. No NOEL could be established. Based on the NOEL of the
study, an oral RfD of 0.03 mg/kg/day was derived.
Signs of neurotoxicity, including piloerection, ataxia, sensory
changes in peripheral nerves, changes in locomotor activity,
salivation, tremors, and convulsions were observed in rats, dogs, mice,
and rabbits given acute oral, intravenous or intraperitoneal injections
greater than or equal to 160 mg/kg. In a 3-month rat inhalation study,
0.1 mg/L (LOEL) produced behavioral effects and 1 mg/L produced
decreased locomotor activity, tremors, and other behavioral changes. No
NOEL could be established.
EPA believes that there is sufficient evidence for listing
resmethrin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available hepatic, reproductive, and neurological toxicity
data for this chemical.
Aquatic acute toxicity values for resmethrin include a rainbow
trout 96-hour LC50 of 0.275 ppb (89 percent a.i.), a bluegill
sunfish 96-hour LC50 of 0.750 ppb (89 percent a.i.), a lake trout
96-hour LC50 of 1.7 ppb (84.5 percent a.i.), and a fathead minnow
96-hour LC50 of 3.0 ppb. EPA believes that there is sufficient
evidence for listing resmethrin on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(C) based on the available environmental toxicity data
for this chemical.
222. Sethoxydim (2-[1-(ethoxyimino)butyl]-5-[2(ethylthio)propyl]-3-
hydroxy-2-cyclohexen-1-one) (CAS No. 074051-80-2) (FIFRA AI) (Ref. 3).
Mild anemia (the LOEL was 17.5 mg/kg/day; the NOEL was 8.9 mg/kg/day)
was observed in male dogs fed sethoxydim for 1-year. Based on the NOEL,
EPA derived an oral RfD of 0.09 mg/kg/day. Swollen liver cells (the
LOEL was 117 mg/kg/day; the NOEL was 45 mg/kg/day) were seen in mice
fed sethoxydim for 14 weeks. Pathological effects in the liver (the
LOEL was 45 mg/kg/day; the NOEL was 15 mg/kg/day) were noted in rats
fed sethoxydim for 14 weeks. Nonneoplastic liver lesions (the LOEL was
54 mg/kg/day; the NOEL was 18 mg/kg/day) were observed in mice fed
sethoxydim for 2 years. Decreased phenosulfophthalein (PSP) clearance
(the NOEL was greater than 3 mg/kg/day; the LOEL not determined) was
noted in dogs given sethoxydim in the diet for 26 weeks. Decreased PSP
clearance (the LOEL was 20 mg/kg/day; the NOEL was 2 mg/kg/day) was
also noted in a 6-month feeding study in dogs. EPA believes that there
is sufficient evidence for listing sethoxydim on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available
hematological, hepatic, and renal toxicity data.
223. Simazine (CAS No. 000122-34-9) (FIFRA SR; SDWA) (Ref. 8).
Simazine is a triazine-type herbicide. Chronic exposure of sheep to low
doses (approximately 1.4 to 6 mg/kg/day) of simazine caused fatty and
granular degeneration in the liver, and increased SGOT and alkaline
phosphatase. Neuronophagia, diffuse kidney degeneration, diffuse glial
proliferation and degeneration of ganglion cells in the cerebrum and
medulla were also reported in these animals. Dogs that received 1,500
ppm (37.5 mg/kg/day) simazine in a 2-year feeding study also had slight
increases in serum alkaline phosphatase and SGOT, indicative of liver
damage.
Sheep that received 1.4 mg/kg/day simazine for 37 to 111 days had
necrotic changes in the germinal epithelium of the testis and
disturbances in spermatogenesis.
EPA believes that there is sufficient evidence for listing simazine
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on
the hepatic, renal, neurological, and reproductive toxicity of this
chemical.
224. Sodium azide (CAS No. 026628-22-8) (CERCLA; EPCRA EHS; RCRA P)
(Ref. 8). Although not used clinically, sodium azide is a direct acting
vasodilator. A reduction in blood pressure was noted in hypertensive
patients orally exposed to sodium azide during an investigation of the
substance in treating cancer. Reductions in blood pressure were also
reported in animals following acute exposure. The minimal hypotensive
dose in humans has been estimated to be approximately 0.2 to 0.4
g/kg (0.0002 to 0.0004 mg/kg). EPA believes that there is
sufficient evidence for listing sodium azide on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the ability of this
substance to lower blood pressure.
225. Sodium chlorite (CAS No. 007758-19-2) (FIFRA AI) (Ref. 3). A
decrease in erythrocyte half-life (the LOEL was 100 ppm or 7.3 mg/kg/
day; the NOEL was 50 ppm or 3.65 mg/kg/day) was observed in cats
administered sodium chlorite in the drinking water for 90 days.
Increase in glucose-6-phosphatase dehydrogenase activity, mean
corpuscular volume (MCV), osmotic fragility, and acanthocytes were
observed in mice administered 100 ppm (19 mg/kg/day) in the drinking
water for 30 days. In another 30-day drinking water study, increased
glucose-6-phosphatase dehydrogenase activity, MCV, and osmotic
fragility were noted in mice administered 100 ppm (19 mg/kg/day). The
NOEL was 1.9 mg/kg/day. The results of in vitro studies show that
sodium chlorite can result in oxidative damage to erythrocytes. EPA
believes that there is sufficient evidence for listing sodium chlorite
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on
the available hematological toxicity data.
226. Sodium dicamba (3,6-Dichloro-2-methoxybenzoic acid, sodium
salt) (CAS No. 001982-69-0) (FIFRA AI) (Ref. 3). No toxicity data are
available for sodium dicamba. However, data are available on dicamba as
discussed below. In solution, sodium dicamba will dissociate into
sodium ion and the dicamba anion. Decreased fetal body weights and
increased postimplantation loss were observed in the offspring of
rabbits receiving 10 mg/kg/day on days 6 through 18 of gestation. The
LOEL was 10 mg/kg/day and NOEL was 3 mg/kg/day. Based on the NOEL, EPA
derived an oral RfD value of 0.03 mg/kg/day. In a separate study,
disorders of oxidative phosphorylation and focal necrosis in the heart
were observed in newborn rats following transplacental exposure to
dicamba. In a developmental toxicity study, an increase in skeletal
malformations was seen in the offspring of rats orally administered 64
mg/kg/day on days 6 through 19 of gestation. EPA believes that there is
sufficient evidence for listing sodium dicamba on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available
developmental toxicity data for dicamba.
227. Sodium dimethyldithiocarbamate (CAS No. 000128-04-1) (FIFRA
AI) (Ref. 3). By analogy to potassium dimethyldithiocarbamate, sodium
dimethyldithiocarbamate can reasonably be anticipated to cause
fetotoxicity, postimplantation loss and malformations. Data on
potassium dimethyldithiocarbamate follows. New Zealand white rabbits
given 38 mg/kg/day by gavage on days 6 to 18 of gestation exhibited
malalignment of sternebrae, total postimplantation loss, and fetal
weight decrement. Also at this dose level, various possible
malformations including adactyly, gastroschisis, short tail, anal
atresia, spina bifida, atelectasis, costal cartilage anomaly, vertebral
anomaly with/without rib, caudal vertebrea anomaly, and severe
sternebrae malalignment in 6 of 52 fetuses from 5 of 11 litters. At the
77 mg/kg/day dose level, there was severe fetal/embryo lethality. The
NOEL was 12.8 mg/kg/day. EPA believes that there is sufficient evidence
for listing sodium dimethyldithiocarbamate on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available
developmental toxicity data for the analogue potassium
dimethyldithiocarbamate.
228. Sodium fluoroacetate (CAS. No. 000062-74-8) (CERCLA; EPCRA
EHS; FIFRA SR; RCRA APP8; RCRA P) (Ref. 8). In a 13-week oral study in
rats, gavage administration of sodium fluoroacetate (0.02 mg/kg/day)
resulted in decreased testis weight and altered spermatogenesis in
males (the NOAEL was 0.05 mg/kg/day). In addition, increased heart
weight was noted in females and males administered 0.20 mg/kg/day of
sodium fluoroacetate. The increase in heart weight, however, was only
accompanied by subacute, minimal inflammation (not dose-related). Also,
fluorocitrate levels were significantly increased after 4 weeks in
males administered 0.50 mg/kg/day and after 13 weeks in both male and
female rats administered 0.20 or 0.50 mg/kg/day. The testicular and
cardiac effects were reported to be consistent with those noted in the
literature.
A case study reported a deliberate ingestion of an unspecified dose
of sodium fluroacetate by a healthy female. The woman experienced
nausea, vomiting, and abdominal pain 30 minutes after ingestion, with
subsequent seizures occurring 60 minutes after the initial onset of
symptoms. Neurological examination after 2 weeks revealed severe
cerebellar dysfunction. By 18 months, memory disturbances and
depressive behavior persisted. Inhalation exposure to unspecified
levels of sodium fluoroacetate caused salivation, loss of speech,
violent convulsions, and coma in a male worker. The patient ultimately
recovered. Neurological effects have also been reported in rats in a
13-week oral study. Four of 20 female rats treated with 0.50 mg/kg/day
(the highest dose tested) exhibited convulsions at day 79, with no
recurrences for the remainder of the study. An estimated lethal dose of
sodium fluoroacetate in humans ranges from 5 to 10 mg/kg.
EPA believes that there is sufficient evidence for listing sodium
fluoroacetate on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the neurologic, reproductive, and myocardial
toxicity data for this chemical.
Measured oral LD50 values of fluoroacetate in the house
sparrow, redwinged blackbird, starling and golden eagle are 3.0, 4.22,
2.37, and 1.25 to 5 mg/kg, respectively. In addition, measured acute
toxicity data for mammalian wildlife include an oral LD50 of 0.22
to 0.44 mg/kg for mule deer, an oral LD50 of 1.41 mg/kg for male
ferrets, and an oral LD50 of 0.5 to 1.0 mg/kg for bears. EPA
believes that there is sufficient evidence for listing sodium
fluoroacetate on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(C) based on the environmental toxicity data for this
chemical.
229. Sodium hypochlorite (CAS No. 007681-52-9) (CERCLA) (Ref. 8).
Aquatic acute toxicity data for sodium hypochlorite include a 96-hour
measured LC50 of 100 ppb for bluegill and a 96-hour measured
LC50 of 80 ppb for fathead minnow. In addition, the 96-hour
measured LC50 values for non-standard test species range from 32
ppb for coho salmon to 82 ppb for Pacific sand lance. EPA believes that
there is sufficient evidence for listing sodium hypochlorite on EPCRA
section 313(d)(2)(C) based on the available ecotoxicity data for this
chemical.
230. Sodium nitrite (CAS No. 007632-00-0) (CERCLA) (Ref. 8). Sodium
nitrite causes conversion (oxidation) of hemoglobin to methemoglobin.
Methemoglobin cannot combine reversibly with oxygen and its formation
can cause anemic hypoxia which may lead to intense cyanosis. Infants
are particularly susceptible to this effect because of their higher
stomach pH, immature enzyme systems, the reduced capacity of newborn
erythrocytes to reduce methemoglobin to hemoglobin, and the increased
rate of nitrite-induced oxidation of fetal hemoglobin to methemoglobin
(approximately twice the rate of adult hemoglobin oxidation). Coma and
methemoglobinemia/ carboxyhemoglobinemia were reported in a human that
received sodium nitrite (71 mg/kg) orally. In animal studies,
methemoglobinemia was reported in dogs that received an intravenous
dose of 30 mg/kg sodium nitrite and in rats administered a 10 mg/kg
dose of sodium nitrite subcutaneously.
Fetotoxicity (fetal death) was reported following oral exposure of
pregnant rats to sodium nitrite (30 mg/kg/day) during gestation days 1
through 22. In mice exposed orally to 80 mg/kg/day during gestation
days 6 to 15 there was increased preimplantation loss and fetal death,
and in mice exposed to a lower dose (20 mg/kg/day) during gestation
days 1 to 14, abnormalities of the blood or lymphatic system were
reported in offspring. In offspring of rats orally exposed to 26 to 256
mg/kg/day during pregnancy (gestation days 1 through 22) and/or during
lactation (20 to 21 days after birth), effects on growth including
biochemical and/or metabolic changes were noted.
EPA believes that there is sufficient evidence for listing sodium
nitrite on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available chronic hematological and developmental toxicity
data for this chemical.
231. Sodium pentachlorophenate (CAS No. 000131-52-2) (FIFRA AI)
(Ref. 3). Pentachlorophenol has been classified by EPA as a Group B2
compound, i.e., a probable human carcinogen. This was based on
occurrence of increased combined incidence of hemangiosarcomas, liver
tumors, and pheochromocytomas in female mice. EPA believes that there
is sufficient evidence for listing sodium pentachlorophenate on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available carcinogenicity data for its parent compound,
pentachlorophenol.
Aquatic acute toxicity values for sodium pentachlorophenate include
a rainbow trout 96-hour LC50 of 55 ppb, a bluegill 96-hour
LC50 of 44 ppb, a fathead minnow 96-hour LC50 of 20 ppb, and
a shrimp 96-hour LC50 of 84 ppb. EPA believes that there is
sufficient evidence for listing sodium pentachlorophenate on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(C) based on the
available environmental toxicity data for this chemical.
232. Sodium o-phenylphenoxide (CAS No. 000132-27-4) (CERCLA; IARC)
(Ref. 8). Sodium o-phenylphenoxide has been classified by IARC as a
Group 2B compound; i.e., the substance is possibly carcinogenic in
humans. EPA believes that there is sufficient evidence for listing
sodium o-phenylphenoxide on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the carcinogenicity data for this chemical.
233. Sodium 2-pyridinethiol-1-oxide (CAS No. 015922-78-8) (FIFRA
AI) (Ref. 3). New Zealand white rabbits were tested with test material
dermally on days 6 to 18 of gestation. At 0.5 mg/kg/day, pups exhibited
missing or defective vertebrae, ribs and sternebrae. No NOEL was
established. EPA believes that there is sufficient evidence for listing
sodium 2-pyridinethiol-1-oxide on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available developmental toxicity data
for this chemical.
234. Strychnine and salts (CERCLA; EPCRA EHS; FIFRA SR; RCRA APP8;
RCRA P) (Ref. 8). Strychnine salts will dissociate in aqueous solutions
to yield soluble strychnine. Strychnine, an alkaloid, can cause violent
convulsions in humans. Other effects include agitation, hypertonicity
of muscles, and painful muscle spasms. Renal failure and respiratory
paralysis generally ensues, from severe or prolonged convulsions. A
potentially lethal oral dose in a small child is 5 to 10 mg. The lethal
oral dose for an adult may be as low as 30 mg. Similar effects have
also been reported in animals exposed at lethal doses ranging from 0.25
to 2.35 mg/kg via oral and parenteral routes of exposure. EPA's
exposure analysis indicates that strychnine and strychnine salts
concentrations are likely to exist beyond facility site boundaries, as
a result of continuous, or frequently recurring releases, at levels
that can reasonably be anticipated to cause significant adverse acute
human health effects. EPA believes that there is sufficient evidence
for listing strychnine and salts as a category on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(A) based on the available acute
toxicity and exposure data for this chemical.
EPCRA section 313 requires threshold determinations for chemical
categories to be based on the total of all chemicals in the category
manufactured, processed, or otherwise used. For example, a facility
that manufactures three members of a chemical category would count the
total amount of all three chemicals manufactured towards the
manufacturing threshold for that category. When filing reports for
chemical categories, the releases are determined in the same manner as
the thresholds. One report if filed for the category and all releases
are reported on this form.
235. Sulfur dioxide (CAS No. 007446-09-5) (CERCLA; EPCRA EHS) (Ref.
8). Acid precipitation occurs in large regions of the Eastern United
States and Canada, Europe, and Japan. This widespread occurrence of
acid precipitation and dry deposition results in large part from man-
made emissions of oxides of sulfur (e.g., sulfur dioxide) and oxides of
nitrogen. These substances are transformed in the atmosphere into
sulfuric acid and nitric acid, transported over great distances and
deposited on vegetation, soils, surface waters, and materials. These
substances are transferred from the atmosphere into ecosystems by the
absorption of gases, the impaction and gravitational settling of fine
aerosols and coarse particles and, precipitation.
Acids contained in polluted snow are released as contaminated
meltwater. The resulting release of pollutants can cause major or rapid
changes in the acidity of streams and lake waters. Interference with
normal reproduction in fish populations is induced by acidity of lake
and stream waters. Reproduction of frogs and salamanders is also
inhibited by atmospheric acidification of surface waters.
Atmospheric deposition of sulfuric acid and nitric acid can cause
serious damage to crops and forests. Biological effects include
induction of necrotic lesions, loss of nutrients due to leaching from
foliar organs, accelerated erosion of waxes and leaf surfaces, and
interference with normal reproductive processes. Acidification
decreases the rate of many soil processes such as nitrogen fixation and
the breakdown of organic matter.
EPA believes that there is sufficient evidence for listing sulfur
dioxide on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C)
based on the available environmental toxicity data for this chemical.
Limited data on long-term human exposure to sulfuric acid with
respect to occupational settings are available. Recent studies suggest
that sulfuric acid aerosols at levels as low as 0.02 to 0.04 mg/m3
may cause significant effects on lung function in humans. Effects noted
include increased risk of chronic bronchitis in smokers and reduced
tracheobronchial clearance rate. Other studies suggest that sulfuric
acid at concentrations as low as 0.04 mg/m3 may act
synergistically with copollutants such as ozone, NO2, and metal
particulates in causing decreased pulmonary diffusing capacity and
bronchial hypersensitivity. These effects are presumably attributable
to the acidic and oxidative properties of sulfuric acid, and are
therefore pH and concentration dependent. EPA believes that there is
sufficient evidence for listing sulfur dioxide on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available chronic
toxicity data for sulfuric acid, the hydrolysis product of sulfur
dioxide.
Sulfur dioxide is regulated under Title I of the CAA (Provisions
for Attainment and Maintenance of National Ambient Air Quality
Standards) and Title IV of the CAA (Acid Deposition Control). In
addition to this proposal to add sulfur dioxide to EPCRA section 313,
in Units IV.B.36. and 179, EPA is proposing to add two other chemicals,
carbon monoxide and nitrogen dioxide, that are regulated under Title I
of the CAA. Extensive data, which are highly technical, are collected
on these chemicals as required by the CAA. EPA requests comment on the
following: (1) Is the information collected under the CAA sufficient
for public right-to-know purposes; and (2) suggestions on how the data
collected on these chemicals pursuant to CAA Titles I and IV could be
used to meet the purposes of EPCRA section 313.
236. Sulfur trioxide (CAS No. 007446-11-9) (EPCRA EHS) (Ref. 8).
IARC has classified sulfur trioxide in Group 1, i.e., the chemical is
carcinogenic to humans based on sufficient evidence of carcinogenicity
in humans. EPA believes that there is sufficient evidence for listing
sulfur trioxide on EPCRA section 313 pursuant to section 313(d)(2)(B)
based on the carcinogenicity data for this chemical.
Acid precipitation occurs in large regions of the Eastern United
States and Canada, Europe, and Japan. This widespread occurrence of
acid precipitation and dry deposition results in large part from man-
made emissions of oxides of sulfur (e.g., sulfur trioxide) and oxides
of nitrogen. These substances are transformed in the atmosphere into
sulfuric acid and nitric acid, transported over great distances and
deposited on vegetation, soils, surface water, and materials. These
substances are transferred from the atmosphere into ecosystems by the
absorption of gases, the impaction and gravitational settling of fine
aerosols and coarse particles and, precipitation.
Acids contained in polluted snow are released as contaminated
meltwater. The resulting release of pollutants can cause major or rapid
changes in the acidity of streams and lake waters. Interference with
normal reproduction in fish populations is induced by acidity of lake
and stream waters. Reproduction of frogs and salamanders is also
inhibited by atmospheric acidification of surface waters.
Atmospheric deposition of sulfuric acid and nitric acid can cause
serious damage to crops and forests. Biological effects include
induction of necrotic lesions, loss of nutrients due to leaching from
foliar organs, accelerated erosion of waxes and leaf surfaces, and
interference with normal reproductive processes. Acidification
decreases the rate of many soil processes such as nitrogen fixation and
the breakdown of organic matter.
EPA believes that there is sufficient evidence for listing sulfur
trioxide on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C)
based on the available environmental toxicity data for this chemical.
Limited data on long-term human exposure to sulfuric acid with
respect to occupational settings are available. Recent studies suggest
that sulfuric acid aerosols at levels as low as 0.02 to 0.04 mg/m3
may cause significant effects on lung function in humans. Effects noted
include increased risk of chronic bronchitis in smokers and reduced
tracheobronchial clearance rate. Other studies suggest that sulfuric
acid at concentrations as low as 0.04 mg/m3 may act
synergistically with copollutants such as ozone, NO2, and metal
particulates in causing decreased pulmonary diffusing capacity and
bronchial hypersensitivity. These effects are presumably attributable
to the acidic and oxidative properties of sulfuric acid, and are
therefore pH and concentration dependent. EPA believes that there is
sufficient evidence for listing sulfur trioxide on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available chronic
toxicity data for sulfuric acid, the hydrolysis product of sulfur
trioxide.
237. Sulfuryl fluoride (Vikane) (CAS No. 002699-79-8) (FIFRA AI)
(Ref. 3). The primary effects of sulfuryl fluoride in humans are
respiratory irritation and central nervous system depression, followed
by excitation and possibly convulsions. Rabbits exposed via inhalation
(6 hours/day, 5 days/week, for 2 weeks) to sulfuryl fluoride showed
hyperactivity, convulsions and vacuolation of the cerebrum at 600 ppm
(2.5 mg/L). Renal lesions were present in all rats exposed by
inhalation (6 hours/day, 5 days/week, for 2 weeks) to 600 ppm (2.5 mg/
L) sulfuryl fluoride. Minimal renal changes were noted in rats exposed
to 300 ppm (1252 mg/L), whereas no effects occurred at 100 ppm (4.2 mg/
L). Convulsions at near lethal concentrations were reported in rabbits,
mice, and rats. In a 30-day inhalation study, loss of control, tremors
of the hind quarters, and histopathological changes in the lung, liver,
and kidney were reported in rabbits exposed to 400 ppm (1.6 mg/L) for 7
hours/day, 5 days/week for 5 weeks. The NOEL was 200 ppm (0.83 mg/L).
Cerebral vacuolation and/or malacia and inflammation of nasal tissues
were observed in rabbits exposed by inhalation to 100 or 300 ppm (0.4
or 1.25 mg/L) for 13 weeks. The NOEL was 30 ppm (0.125 mg/L). Rats
exposed by inhalation to 100 to 600 ppm (0.4 to 0.25 mg/L) sulfuryl
fluoride for 13 weeks developed mottled teeth (indicative of fluoride
toxicity), renal and respiratory effects, and cerebral vacuolation. EPA
believes that there is sufficient evidence for listing sulfuryl
fluoride on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available neurological, renal, and respiratory toxicity
data for this chemical.
238. Sulprofos (O-Ethyl O-[4-(methylthio)phenyl] phosphorodithioic
acid S-propyl ester) (CAS No. 035400-43-2) (FIFRA AI) (Ref. 3). The
acute dermal rabbit LD50 is between 745 mg/kg and 994 mg/kg.
Ataxia, tremors, and diarrhea were observed. In a 28-day dietary study,
administration of 1 mg/kg/day produced decreased red blood cell and
brain cholinesterase activity. The NOEL was 0.1 mg/kg. Dietary
administration of 15 mg/kg/day for 3 months produced hyperactivity in
female rats. The NOEL was 5 mg/kg/day. In the same study, 5 mg/kg/day
produced red blood cell and brain cholinesterase inhibition in both
sexes. The cholinesterase NOEL was 1.5 mg/kg/day. Red blood cell and
brain cholinesterase inhibition, diarrhea, vomiting, and some hind limb
paralysis were seen in dogs orally administered 5 mg/kg/day (LOEL) for
3 months. The NOEL was 0.5 mg/kg/day. In a 22-month dietary mouse
study, plasma and red blood cell cholinesterase were inhibited at 3.25
mg/kg/day. The NOEL was 0.325 mg/kg/day. Plasma, red blood cell, and
brain cholinesterase inhibition were seen at a dietary administration
of 2.5 mg/kg/day (LOEL) in a 2-year dog study. The NOEL was 0.25 mg/kg/
day. Based on this study, an oral RfD of 0.003 mg/kg/day was derived.
Dietary administration of 3 mg/kg/day (LOEL) produced plasma and red
blood cell cholinesterase depression in a 2-year rat study. The NOEL
was 0.3 mg/kg/day.
Increased unossified sternebrae were observed in the offspring of
rats given 10 mg/kg/day (LOEL) by gavage during days 6 to 15 of
gestation. No NOEL was established.
EPA believes that there is sufficient evidence for listing
sulprofos on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available neurological and developmental toxicity data for
this chemical.
The aquatic acute values for sulprofos include bluegill 96-hour
LC50 value of 1.03 ppm and 11 ppm (technical product). The channel
catfish bioconcentration factor for whole fish is 704 to 1006. EPA
believes that there is sufficient evidence for listing sulprofos on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the
available environmental toxicity data and the potential for
bioconcentration.
239. Tebuthiuron (N-[5-(1,1-Dimethylethyl)-1,3,4-thiadiazol-2-yl)-
N,N'-dimethylurea) (CAS No. 034014-18-1) (FIFRA AI) (Ref. 3).
Administration of 25 mg/kg/day (LOEL) on days 6 through 18 of gestation
produced reduced body weights in offspring of rabbits. The NOEL was 10
mg/kg/day. In a 3-month rat study, dietary administration of 125 mg/kg/
day (LOEL) produced growth suppression and pancreatic lesions. The NOEL
was 50 mg/kg/day. In a 2-generation rat reproduction study, depressed
body weight gain was observed in the female parental generation at 14
mg/kg/day. The NOEL was 7 mg/kg/day. Based on the NOEL of the study, an
oral RfD of 0.07 mg/kg/day was derived. In a 3-generation rat
reproduction study, decreased body weight was observed in the offspring
of animals administered 20 mg/kg/day (LOEL). No NOEL was established.
Dietary administration of 40 mg/kg/day to rats for 2 years produced
growth suppression. The NOEL was 20 mg/kg/day. EPA believes that there
is sufficient evidence for listing tebuthiuron on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available
developmental toxicity data for this chemical.
240. Tefluthrin (CAS No. 079538-32-2) (FIFRA AI) (Ref. 3). Delayed
ossification was seen in the offspring of rats administered 5 mg/kg/day
(LOEL) orally on days 7 through 16 of gestation. The NOEL was 3 mg/kg/
day.
In a 3-month rat study, dietary administration of 10 mg/kg/day
produced plasma, red blood cell, and brain cholinesterase inhibition.
The NOEL was 5 mg/kg/day. In a 6-month dog study, dietary
administration of 10 mg/kg/day (LOEL) produced plasma cholinesterase
inhibition. The NOEL was 1 mg/kg/day.
In a 21-day rat dietary study, administration of 20 mg/kg/day (LOEL
for females) produced decreased platelet counts, increased white blood
cell, lymphocyte, and neutrophil counts in males and females. The NOEL
for females was 5 mg/kg/day. Increased absolute and relative liver
weights were observed at 5 mg/kg/day in males, thus no NOEL could be
established for males. Dietary administration of 10 mg/kg/day (LOEL)
for 3 months to rats produced increased absolute liver weights,
decreased bilirubin levels, and hepatocellular hypertrophy. The NOEL
was 5 mg/kg/day. In a 6-month dog study, dietary administration of 10
mg/kg/day (LOEL) produced hepatotoxicity (effects not reported). The
NOEL was 1 mg/kg/day. In a 2-year mouse study, dietary administration
of 13.5 mg/kg/day produced liver necrosis. The NOEL was 3.4 mg/kg/day.
EPA believes that there is sufficient evidence for listing
tefluthrin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available developmental, neurological, hepatic, and
hematological toxicity data for this chemical.
Aquatic acute toxicity values for tefluthrin include a rainbow
trout 96-hour LC50 of 0.06 ppb, a bluegill 96-hour LC50 of
0.13 ppb, a sheepshead minnow 96-hour LC50 of 0.13 ppb, a daphnid
48-hour EC50 of 0.07 ppb, and a mysid 96-hour EC50 of 0.053
ppb. EPA believes that there is sufficient evidence for listing
teflurin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C)
based on the available environmental toxicity data for this chemical.
241. Temephos (CAS No. 003383-96-8) (FIFRA AI) (Ref. 3). Temephos
is a cholinesterase inhibitor in many mammalian species. The LOELs at
which the cholinesterase inhibition was observed ranged from 0.3 to 10
mg/kg/day. However, human subjects that ingested 256 mg/day for 5 days
or 64 mg/day for 4 weeks showed no clinical signs or effects on plasma
or red blood cell cholinesterase activities. Dietary exposure of rats
to 350 mg/kg/day for 90 days resulted in cholinesterase inhibition
only; no clinical signs were reported. Rabbits and guinea pigs
tolerated 10 mg/kg/day for extended periods without clinical effects,
and dogs tolerated 3 to 4 mg/kg/day, the highest dose tested. EPA
believes that there is sufficient evidence for listing temephos on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available neurological toxicity data.
242. Terbacil (5-chloro-3-(1,1-dimethylethyl)-6-methyl- 2,4-
(1H,3H)-pyrimidinedione) (CAS No. 005902-51-2) (FIFRA AI) (Ref. 3).
Decreases in the number of implantations and live fetuses, were
observed in rats administered 62.5 mg/kg/day (LOEL) orally for days 6
to 15. The NOEL was 12.5 mg/kg/day. Significantly reduced body weights
were observed in the offspring of rabbits orally administered 600 mg/
kg/day (LOEL) orally on days 6 to 18 of gestation. The NOEL was 200 mg/
kg/day.
In a 2-week rat dietary study, administration of 1,000 mg/kg/day
produced increased absolute and relative liver weights. In a 3-month
rat dietary study, administration of 25 mg/kg/day (LOEL) produced
increased liver weights and vacuolization and hypertophy of
hepatocytes. The NOEL was 5 mg/kg/day. In a 1-year dog study, dietary
administration of 48 mg/kg/day to males and 12 (LOEL) and 48 mg/kg/day
to females produced increased alkaline phosphatase and alanine
transaminase levels. The NOEL was 3 mg/kg/day. In a 2-year dog study,
dietary administration of 6.25 mg/kg/day (LOEL) produced slight
increases in liver weights, elevated alkaline phosphatase levels, and
increased thyroid-to-body-weight ratios. The NOEL was 1.25 mg/kg/day.
Based on the NOEL, an oral RfD of 0.013 mg/kg/day was established.
Hypertrophy of centrilobular hepatocytes was observed in male mice
administered 162.5 mg/kg/day (LOEL) in the diet. The NOEL was 6.5 mg/
kg/day.
EPA believes that there is sufficient evidence for listing terbacil
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on
the available hepatic and developmental toxicity data for this
chemical.
243. Tetracycline hydrochloride (CAS No. 000064-75-5) (CAL) (Ref.
8). Tetracycline hydrochloride is widely used as an antibiotic for the
treatment of many common infections. The average oral adult dose for
most infections is 1 to 2 grams per day in equally divided doses. The
most frequent adverse reactions to orally administered tetracycline
hydrochloride are gastrointestinal effects including nausea, vomiting,
diarrhea, bulky loose stools, and abdominal discomfort.
Photosensitivity, manifested as an exaggerated sunburn reaction on sun-
exposed areas of the body has occurred following oral therapy with
tetracycline hydrochloride. Photosensitivity reactions of this type
generally develop within a few minutes to several hours after sun
exposure and usually persist 1 to 2 days after discontinuance of
tetracycline hydrochloride.
Manufacturers of tetracycline hydrochloride state that this
substance should not be used in women during the last half of pregnancy
or in children younger than 8 years of age unless other appropriate
drugs are ineffective or contraindicated. The American Academy of
Pediatrics recommends that tetracycline hydrochloride be used only in
children who are 9 years of age or older, except under unusual
circumstances. Use of tetracycline hydrochloride in pregnant women or
infants has resulted in retardation of skeletal development and bone
growth in the fetus or child. Because tetracycline hydrochloride
localizes in the dentin and enamel of developing teeth, use of this
substance during tooth development may cause enamel hypoplasia and
permanent yellow-gray to brown discoloration of the teeth. Use of
tetracycline hydrochloride may result in discoloration of the deciduous
teeth of children if the substance is used during pregnancy or in
children up to 4 to 6 months of age. These effects are most common
following long-term use of tetracycline hydrochloride but have occured
following repeated short-term use. Premature infants treated with
tetracycline have demonstrated a 40 percent depression of bone growth.
This effect is readily reversible if exposure to the substance is
short.
Intraperitoneal injection of 85 mg/kg/day on days 14 to 18 of
gestation has resulted in abortion and extra embryonic structures in
rat offspring. Subcutaneous injection of 48 mg/kg/day on days 16
through 20 of gestation and intramuscular injection of 40 mg/kg/day to
rats on days 10 through 15 of gestation resulted in embryo/
fetotoxicity. Exposure to 50 mg/kg/day on days 7 to 15 of pregnancy
resulted in postimplantation loss and fetotoxicity in rats. Exposure to
85 mg/kg/day on days 7 to 15 of pregnancy resulted in abortion in rats.
Fetotoxicity was observed in mice receiving 86 mg/kg/day of
tetracycline hydrochloride on days 8 to 13 of gestation.
EPA believes that there is sufficient evidence for listing
tetracycline hydrochloride on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available developmental toxicity data
and other chronic toxicity data for this chemical.
244. Tetramethrin (2,2-Dimethyl-3-(2-methyl-1-propenyl)
cyclopropanecarboxylic acid (1,3,4,5,6,7-hexahydro-1,3-dioxo-2-H-
isoindol-2-yl)methyl ester (CAS No. 007696-12-0) (FIFRA AI) (Ref. 3).
Depression, salivation, ataxia, lethargy, and convulsions were observed
in acute rat studies in which the oral LD50 values were greater
than or equal to 4,400 mg/kg. Tremors, excitement, and increased urine
volume were observed in an acute dermal rat study in which the
LD50 was greater than 2,500 mg/kg. Tremors, ataxia, dyspnea,
gastointestinal hypermotility, and diarrhea were observed in rats and
mice administered tetramethrin subcutaneously or intraperitonealy. The
LD50 was greater than 500 mg/kg. In a 6-month dog dietary study,
administration of 62.5 mg/kg/day produced nervouseness and tremors. The
NOEL was 31.25 mg/kg/day.
EPA believes that there is sufficient evidence for listing
tetramethrin on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available neurological toxicity data for this
chemical.
Aquatic acute toxicity values for tetramethrin include a bluegill
96-hour LC50 of 21 ppb (mixed isomers, technical product) and 69
ppb. EPA believes that there is sufficient evidence for listing
tetramethrin on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(C) based on the available environmental toxicity data for
this chemical.
245. Tetrasodium ethylenediaminetetraacetate (CAS No. 000064-02-8)
(FIFRA AI) (Ref. 3). Increased occurrence of 13th rudimentary ribs was
observed in the offspring of rats orally administered 5 mg/kg/day
(LOEL). No NOEL was established and the dosing duration was not
reported. EPA believes that there is sufficient evidence for listing
tetrasodium ethylenediaminetetraacetate on EPCRA section 313 pursuant
to EPCRA section 313(d)(2)(B) based on the available developmental
toxicity data for this chemical.
246. Thiabendazole (2-(4-Thiazolyl)-1H-benzimidazole) (CAS No.
000148-79-8) (FIFRA AI) (Ref. 3). Oral administration of 600 mg/kg/day
(LOEL) to rats on days 6 through 15 of gestation produced cleft palate
and open eyes. Musculoskeletal abnormalities were observed in the
offspring of mice orally administered 240 mg/kg on day 9 of gestation.
Musculoskeletal abnormalities were also observed in the offspring of
rats orally administered 296 mg/kg/day on days 8 through 15 of
gestation. Decreased litter size, and skin abnormalities were observed
in the offspring of rats orally administered 667 mg/kg/day on days 8
through 15 of gestation. Oral administration of 1,300 mg/kg/day
produced musculoskeletal abnormalities and fetal death in the offspring
of mice. Oral administration of 2,400 mg/kg/day on day 11 of gestation
produced craniofacial abnormalities in the offspring of mice. EPA
believes there is sufficient evidence for listing thiabendazole on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available developmental toxicity data for this chemical.
Aquatic acute toxicity values for thiabendazole include a rainbow
trout 96-hour LC50 of 560 ppb, a daphnid 48-hour EC50 of 0.31
ppb, and a mysid 96-hour LC50 of 340 ppb. EPA believes that there
is sufficient evidence for listing thiabendazole on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(C) based on the available
environmental toxicity data.
247. Thiabendazole, hypophosphite salt (2-(4-thiazolyl)
benzimidazole, hypophosphite salt) (CAS No. 028558-32-9) (FIFRA AI)
(Ref. 3). Few toxicity data are available on thiabendazole,
hypophosphite salt. However, data are available on the parent compound,
thiabendazole, as discussed below.
Oral administration of 600 mg/kg/day (LOEL) to rats on days 6
through 15 of gestation produced cleft palate and open eyes.
Musculoskeletal abnormalities were observed in the offspring of mice
orally administered 240 mg/kg on day 9 of gestation. Musculoskeletal
abnormalities were also observed in the offspring of rats orally
administered 296 mg/kg/day on days 8 through 15 of gestation. Decreased
litter size and skin abnormalities were observed in the offspring of
rats orally administered 667 mg/kg/day on days 8 through 15 of
gestation. Oral administration of 1,300 mg/kg/day produced
musculoskeletal abnormalities and fetal death in the offspring of mice.
Oral administration of 2,400 mg/kg/day on day 11 of gestation produced
craniofacial abnormalities in the offspring of mice. EPA believes that
there is sufficient evidence for listing thiabendazole hypophosphite
salt on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based
on the available developmental toxicity data for this chemical.
No laboratory data are available for thiabendazole hypophosphite
salt. Ecotoxicity data are available for the parent compound
thiabendazole. Aquatic acute toxicity values for thiabendazole include
a rainbow trout 96-hour LC