[Federal Register Volume 64, Number 43 (Friday, March 5, 1999)]
[Proposed Rules]
[Pages 10597-10604]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-5495]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 372
[OPPTS-400137; FRL-6054-2]
RIN 2070-AC00
Acetonitrile; Community Right-to-Know Toxic Chemical Release
Reporting
AGENCY: Environmental Protection Agency (EPA).
ACTION: Denial of petition.
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SUMMARY: EPA is denying a petition to remove acetonitrile from the list
of chemicals subject to the reporting requirements under section 313 of
the Emergency Planning and Community Right-to-Know Act of 1986 (EPCRA)
and section 6607 of the Pollution Prevention Act of 1990 (PPA). EPA has
reviewed the available data on this chemical and has determined that
acetonitrile does not meet the deletion criterion of EPCRA section
313(d)(3). Specifically, EPA is denying this petition because EPA's
review of the petition and available information resulted in the
conclusion that acetonitrile meets the listing criteria of EPCRA
section 313(d)(2)(B) and (d)(2)(C) due to its potential to cause
neurotoxicity and death in humans and its contribution to the formation
of ozone in the environment, which causes adverse human health and
environmental effects.
FOR FURTHER INFORMATION CONTACT: Daniel R. Bushman, Petitions
Coordinator, 202-260-3882 or e-mail: bushman.daniel@epa.gov, for
specific information regarding this document or for further information
on EPCRA section 313, contact the Emergency Planning and Community
Right-to-Know Information Hotline, Environmental Protection Agency,
Mail Code 5101, 401 M St., SW., Washington, DC 20460, Toll free: 1-800-
535-0202, in Virginia and Alaska: 703-412-9877, or Toll free TDD: 1-
800-553-7672.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does This Document Apply To Me?
This document does not make any changes to existing regulations.
However, you may be interested in this document if you manufacture,
process, or otherwise use acetonitrile. Potentially interested
categories and entities may include, but are not limited to the
following:
[[Page 10598]]
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Examples of Potentially
Category Interested Entities
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Chemical manufacturers Chemical manufacturers that
manufacture acetonitrile,
use acetonitrile as a
chemical intermediate, or
use acetonitrile in the
manufacturing or processing
of pharmaceuticals,
agriculture chemicals,
butadiene, isoprene and
specialty chemicals and
products (e.g., new high
density batteries)
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Chemical processors and users Facilities that use
acetonitrile as a process
or reaction solvent
------------------------------------------------------------------------
This table is not intended to be exhaustive, but rather provides a
guide for readers regarding entities likely to be interested in this
document. Other types of entities not listed in this table may also be
interested in this document. Additional businesses that may be
interested in this document are those covered under 40 CFR part 372,
subpart B. If you have any questions regarding whether a particular
entity is covered by this section of the CFR, consult the technical
person listed in the ``FOR FURTHER INFORMATION CONTACT'' section.
B. How Can I Get Additional Information or Copies of This Document or
Other Support Documents?
1. Electronically. You may obtain electronic copies of this
document from the EPA Home Page at http://www.epa.gov/. On the Home
Page select ``Laws and Regulations'' and then look up the entry for
this document under the ``Federal Register - Environmental Documents.''
You can also go directly to the ``Federal Register'' listings at http:/
/www.epa.gov/fedrgstr/.
2. In person or by phone. If you have any questions or need
additional information about this action, please contact the technical
person identified in the ``FOR FURTHER INFORMATION CONTACT'' section.
In addition, the official record for this document, including the
public version, has been established under docket control number OPPTS-
400137. This record includes not only the documents physically
contained in the docket, but all of the documents included as
references in those documents (including the references cited in Unit
VII. of this preamble). A public version of this record, which does not
include any information claimed as Confidential Business Information
(CBI), is available for inspection from 12 noon to 4:00 p.m., Monday
through Friday, excluding legal holidays. The official record is
located in the TSCA Nonconfidential Information Center, Rm. NE-B607,
401 M St., SW., Washington, DC. The TSCA Nonconfidential Information
Center telephone number is 202-260-7099.
II. Introduction
A. Statutory Authority
This action is taken under sections 313(d) and (e)(1) of EPCRA, 42
U.S.C. 11023. EPCRA is also referred to as Title III of the Superfund
Amendments and Reauthorization Act of 1986 (SARA) (Pub. L. 99-499).
B. Background
Section 313 of EPCRA requires certain facilities manufacturing,
processing, or otherwise using listed toxic chemicals in amounts above
reporting threshold levels, to report their environmental releases of
such chemicals annually. These facilities must also report pollution
prevention and recycling data for such chemicals, pursuant to section
6607 of the PPA, 42 U.S.C. 13106. EPCRA section 313 established an
initial list of toxic chemicals that comprised more than 300 chemicals
and 20 chemical categories. Acetonitrile was included on the initial
list. Section 313(d) authorizes EPA to add or delete chemicals from the
list and sets forth criteria for these actions. EPA has added and
deleted chemicals from the original statutory list. Under section
313(e)(1), any person may petition EPA to add chemicals to or delete
chemicals from the list. Pursuant to EPCRA section 313(e)(1), EPA must
respond to petitions within 180 days, either by initiating a rulemaking
or by publishing an explanation of why the petition is denied.
EPCRA section 313(d)(2) states that a chemical may be listed if any
of the listing criteria are met. Therefore, in order to add a chemical,
EPA must demonstrate that at least one criterion is met, but does not
need to examine whether all other criteria are also met. Conversely, in
order to remove a chemical from the list, EPA must demonstrate that
none of the criteria are met.
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.
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 compounds categories. EPA has also published in the
Federal Register of November 30, 1994 (59 FR 61432) (FRL-4922-2) a
statement clarifying its interpretation of the section 313(d)(2) and
(d)(3) criteria for modifying the section 313 list of toxic chemicals.
III. Description of Petition and Regulatory Status of Acetonitrile
Acetonitrile is on the list of toxic chemicals subject to the
annual release reporting requirements of EPCRA section 313 and PPA
section 6607. Acetonitrile was among the list of chemicals placed on
the EPCRA section 313 list by Congress. Acetonitrile is listed under
the Clean Air Act (CAA) as a volatile organic compound (VOC) and a
hazardous air pollutant. Acetonitrile is also on the Hazardous Waste
Constituents List under the Resource Conservation and Recovery Act
(RCRA).
On February 4, 1998, EPA received a petition from BP Chemicals Inc.
(BP) and GNI Chemicals Corporation (GNICC) to delete acetonitrile from
the list of chemicals reportable under EPCRA section 313 and PPA
section 6607. Specifically, BP and GNICC believe that acetonitrile
meets all of the criteria for delisting under EPCRA section 313(d)(3)
because: (1) ``acetonitrile is not known to cause and cannot be
reasonably anticipated to cause significant adverse human health
effects at concentrations that are reasonably likely to exist beyond
facility boundaries as a result of continuous or frequently recurring
releases''; (2) ``at exposures likely to be found at facility fence
lines, acetonitrile is not known to cause and cannot be reasonably
anticipated to cause cancer or teratogenic effects of serious
irreversible reproductive dysfunction, neurological disorders,
heritable genetic mutations, or other chronic health effects''; and (3)
``acetonitrile is not known to cause or reasonably likely to cause
significant adverse effects to the environment because it is not toxic
or persistent and does not readily bioaccumulate.'' In addition, the
petitioners believe that EPA's policy requiring that a chemical not be
a VOC ``. . . is irrelevant and should not be considered for this
delisting petition.'' The petitioners argue for a revised
interpretation of the EPCRA section 313 VOC policy, contending that EPA
does not have the statutory authority to list chemicals based upon
their status as a VOC. EPA has stated in past Federal Register
documents (54 FR 4072, January 27, 1989; 54 FR 10668, March 15, 1989;
59 FR 49888, September 30, 1994; 60 FR 31643, FRL-4952-7, June 16,
1995; and 63 FR 15195, FRL-5752-6, March 30, 1998) that VOCs meet the
criteria for
[[Page 10599]]
listing under EPCRA section 313 due to the fact that VOCs contribute to
tropospheric ozone. Notwithstanding the petitioners' belief that a
chemical's VOC status is irrelevant to EPCRA section 313 listing, the
petitioners have submitted a petition to EPA's Office of Air and
Radiation (OAR) to add acetonitrile to the list of ``negligibly
photoreactive chemicals'' under 40 CFR 51.100(s)(1).
IV. EPA's Technical Review of Acetonitrile
The technical review of the petition to delete acetonitrile from
TRI reporting requirements (Ref. 1) included an analysis of the
chemistry (Ref. 2), toxicology (including metabolism and absorption,
health effects, and ecological effects) (Ref. 3), environmental fate,
and exposure (Ref. 4) data known for acetonitrile. A more detailed
discussion for each related topic can be found in EPA's technical
reports (Refs. 2, 3, 4, 5, and 6) and the studies contained and
referenced in the docket.
A. Chemistry and Use
Acetonitrile, also known as cyanomethane and methyl cyanide, is a
colorless, volatile, flammable liquid (boiling point = 81.6 deg.C;
flash point = 12.8 deg.C) with an ether-like odor. It is completely
miscible with water and many organic solvents. Its high dielectric
constant and dipole moment make it an excellent solvent for both
inorganic and organic compounds, including polymers. Acetonitrile forms
a low boiling azeotrope with other organic solvents. The impurities
present in commercial grade acetonitrile are water, unsaturated
nitriles, toluene, aldehydes, and amines. Acetonitrile is a relatively
inert material but produces hydrogen cyanide when heated to
decomposition or reacted with acids or oxidizing agents.
Acetonitrile is produced commercially as a by-product during the
manufacture of acrylonitrile by high temperature catalytic oxidation of
propylene in the presence of ammonia (the Sohio process of propylene
ammoxidation). Acetonitrile and hydrogen cyanide are principal by-
products of the process. The ratio of acetonitrile to acrylonitrile
produced is typically 1:35 (Refs. 2, 6, and 7). Reported production of
acetonitrile in the United States (US) in 1993 was 17,859,000 kilograms
(kg) (Ref. 6).
Acetonitrile is primarily used as: a reaction solvent in the
production of pharmaceuticals; an analytical instrumentation/extraction
solvent; an extraction solvent in extracting butadiene and isoprene
from reaction steams; and a solvent for the manufacture and formulation
of agricultural chemicals. Acetonitrile is also used for extracting
fatty acids (e.g., from fish liver oils and other animal and vegetable
oils) and in refining copper, dyeing textiles, recrystallizing
steroids, and other extraction applications. Acetonitrile is also used
as a chemical intermediate for many types of organic compounds (Refs.
2, 6, and 7).
B. Metabolism and Absorption
Absorption of acetonitrile occurs after oral, dermal, or inhalation
exposure. Although no quantitative absorption data were found for oral
exposure, signs of acute toxicity, observed after oral exposure,
indicate that absorption occurs. In humans, 74 percent of acetonitrile
was absorbed orally from cigarette smoke held in the mouth for 2
seconds; when inhaled into the lungs, absorption increased to 91
percent. Dogs exposed by inhalation to 16,000 parts per million (ppm)
of acetonitrile for 4 hours appeared to reach steady-state blood
concentrations within 3 to 4 hours (Ref. 3).
Acetonitrile and its metabolites are transported throughout the
body in the blood. After oral or inhalation exposures in experimental
animals, acetonitrile or its metabolites were found in the brain,
heart, liver, kidney, spleen, blood, stomach, and muscle. After a fatal
human inhalation exposure, metabolites were found in the brain, heart,
liver, kidney, spleen, blood, stomach, and muscle, as well as skin,
lungs, intestine, testes, and urine (Ref. 3).
Acetonitrile is metabolized to hydrogen cyanide and thiocyanate,
which are responsible for the toxic effects of the chemical. Metabolism
is mediated by the cytochrome P-450 system (Refs. 3 and 8).
Acetonitrile is excreted as acetonitrile in expired air and as
acetonitrile or its metabolite in urine. Urinary excretion of the
thiocyanate metabolite following oral exposure in rats ranged from 11.8
percent to 37 percent of the administered dose. Acetonitrile
concentrations of 2.2 to 20 micrograms/100 milliliters (ml) of urine
have been found in heavy smokers (Ref. 3).
C. Toxicity Evaluation
1. Acute effects. The only available data regarding acute effects
of acetonitrile in humans are from reports of accidental poisonings
resulting from acute exposures. It is likely that these acute exposures
were at concentrations in excess of 500 ppm (Refs. 3 and 8). At these
concentrations, acetonitrile affects the central nervous system
producing excess salivation, nausea, vomiting, anxiety, confusion,
hyperpnea, dyspnea, rapid pulse, unconsciousness, and convulsions,
followed by death from respiratory failure. These effects are
consistent with those following inorganic cyanide exposure and with
effects seen with other aliphatic nitriles, suggesting that the toxic
effects of acetonitrile may be correlated with the metabolic release of
cyanide. Acute effects of acetonitrile in humans at concentrations less
than 500 ppm consist of irritation of the mucous membranes. No other
human data were available that allow characterization of acute toxicity
at lower concentrations (Ref. 3).
In animal studies, acetonitrile induced acute toxicity at
relatively high inhalation exposures. In acute exposure inhalation
toxicity studies, the LC50 (i.e., the concentration of a
chemical that is lethal to 50 percent of the test organisms) ranges
from 2,300 to 5,700 ppm in mice and from 7,500 to 16,000 ppm in rats
(Refs. 3 and 8). Mice and guinea pigs appear to be more sensitive than
rats for acute toxicity by the oral route. The lowest LD50
(i.e., the dose of a chemical that is lethal to 50 percent of the test
organisms) values in older rats ranged from 1,300 to 6,700 milligrams
per kilogram (mg/kg); young rats appeared to be more sensitive with a
LD50 value of 157 mg/kg (Refs. 3 and 8). A LD50
range of 390 to 3,900 mg/kg was reported by the dermal route in rabbits
(Ref. 3). Non-lethal effects at 500 ppm in mice include respiratory
effects, convulsions, and eye and lung irritation (Refs. 3 and 8).
2. Chronic effects--i. Carcinogenicity. EPA has identified no human
data in the literature on the cancer effects of acetonitrile. The
carcinogenicity of acetonitrile has been studied in experimental
animals by the National Toxicological Program (NTP) in F344/N rats and
B6C3F1 mice in 2-year inhalation studies (Ref. 9). Under the conditions
of the 2-year inhalation studies, there was equivocal evidence of
carcinogenic activity of acetonitrile in male F344/N rats based on
marginally increased incidences of hepatocellular adenoma and carcinoma
in the high-dose (400 ppm) group. There was no evidence of carcinogenic
activity of acetonitrile in female F344/N rats, or male and female
B6C3F1 mice exposed to any concentration of acetonitrile (Refs. 3 and
9).
No evidence of carcinogenicity of structurally related chemicals
has been identified. Acrylonitrile is carcinogenic but it is not a good
analogue for acetonitrile because acrylonitrile contains a double bond
and is
[[Page 10600]]
genotoxic. Acetonitrile is biotransformed via a cytochrome P450
monoxygenated system to cyanohydrin, which then decomposes slowly to
hydrogen cyanide and formaldehyde and subsequently is detoxified. Based
on the results of the NTP studies, there is insufficient evidence to
conclude that acetonitrile may or has the potential to cause cancer in
humans (Refs. 3 and 9).
ii. Mutagenicity. Positive results were obtained in some in vitro
studies that would present a concern, albeit weak, for mutagenicity.
However, due to the lack of evidence for effects in the mammalian gonad
in vivo, either in mutagenicity studies or in reproductive/teratology
studies, there is no basis for concern for potential heritable gene or
chromosomal mutagenicity of acetonitrile (Ref. 3).
iii. Developmental toxicity. Information in humans reviewed by the
Agency regarding the developmental toxicity of acetonitrile is limited
to a study of laboratory workers and pregnancy outcomes, in which a
slightly elevated, although non-significant, odds ratio was reported
for congenital malformations for women exposed to acetonitrile. Seven
cases of spontaneous abortion were noted for women exposed to
acetonitrile out of a total of 206 cases reported (535 women were
involved in the study). This study was confounded by worker exposure to
other chemicals (Refs. 3, 10, and 11).
The developmental toxicity of acetonitrile has been evaluated in
rats, rabbits, and hamsters. Overall, evidence for developmental
toxicity is weak. Oral and inhalation studies in rats and rabbits have
shown no signs of developmental toxicity at doses that did not produce
excessive maternal mortality. The only data available on hamsters
utilized short durations (60 minutes on day 8 of gestation) to high
concentrations of acetonitrile vapor or by gavage on day 8 of
gestation. There were some signs of developmental toxicity in hamsters
by both routes at dose levels that did not produce overt maternal
mortality; however, these studies are difficult to interpret for human
risk assessment because: (1) Very high doses were used, and (2) no
developmental effects have been observed in other species at doses
below those which produced extreme maternal toxicity (10 percent
mortality or greater).
iv. Reproductive toxicity. Since no definitive two-generation
reproductive toxicity or fertility studies with acetonitrile have been
identified, information in animals is limited to developmental toxicity
studies in which only some reproductive parameters were assessed.
Moreover, the data appear to be equivocal. For example, there were no
changes in pregnancy rates or resorptions in rats exposed to doses as
high as 500 milligram/kilogram/day (mg/kg/day) (Ref. 14). However, in
another study, significant increases in post-implantation losses and
early resorptions in rats exposed to 275 mg/kg/day acetonitrile were
observed (Ref. 15). In other studies, acetonitrile was not shown to
produce any effects on: The testis, epididymis, and cauda epididymis
weights; sperm motility, number, or morphology; or the average estrous
cycle length, frequency of estrous stages, or terminal female body
weight (Ref. 16). In conclusion, available animal studies do not fully
characterize the reproductive toxicity of acetonitrile. Although some
reproductive parameters appeared to be unaffected in some studies, none
of the studies evaluated the reproductive performance or reproductive
system effect of offspring exposed in utero. Therefore, there is not
sufficient information to fully characterize the potential for
reproductive toxicity of acetonitrile (Ref. 3).
v. Neurotoxicity. In humans, the nervous system is a major target
for acetonitrile toxicity. In reports of accidental poisonings in
humans exposed to presumed high concentrations of acetonitrile, signs
of salivation, nausea, vomiting, anxiety, confusion, hyperpnea,
dyspnea, rapid pulse, unconsciousness, and convulsions followed by
death from respiratory failure were observed (Refs. 3 and 8). No
information was found on the adverse neurotoxic effects of long-term
human exposure to acetonitrile. Brief references appear in the
Hazardous Substances Data Bank (HSDB) (Ref. 17) suggesting that chronic
exposure to acetonitrile may cause headache, anorexia, dizziness, and
weakness, but no additional information on neurotoxicity was provided
in support of these statements (Ref. 3).
Neurotoxicity studies indicate that subchronic exposures
(subchronic is defined by EPA's Integrated Risk Information System
(IRIS) as multiple or continual exposures occurring usually over three
months (Ref. 18)) to acetonitrile can cause serious and irreversible
health effects in animals. Monkeys appeared to be more sensitive than
rats to the neurotoxic effects of acetonitrile with signs of
neurotoxicity, such as brain hemorrhages, hyper-excitability, and over-
extension reflexes, observed at or near 350 ppm. Subchronic inhalation
studies have been conducted on rats, monkeys, and dogs (Ref. 19).
Wistar rats (15 per sex per exposure level) were exposed to 0, 166,
330, and 655 ppm of acetonitrile for 7 hours a day for 5 days a week
for 90 days. One out of five rat brains examined in the 655 ppm
exposure group had focal cerebral hemorrhage. This effect was similar
to that reported in Rhesus monkeys that were exposed to acetonitrile at
330, 660, and 2,510 ppm (approximately 28, 55, and 210 mg/kg/day) for 7
hours a day for up to 99 days. The monkey exposed to 2,510 ppm died
with severe pulmonary effects after the second day of exposure, and the
two monkeys exposed to 660 ppm died after 23 and 51 days, with severe
brain hemorrhage and pulmonary abnormalities. The monkey exposed to 330
ppm acetonitrile exhibited unusual reflexes and excitability toward the
end of the study. On gross examination, brain hemorrhage was also found
in the monkey exposed to 330 ppm. Brain hemorrhages, hyper-
excitability, and over-extension reflexes were also observed in three
monkeys exposed to 350 ppm (approximately 30 mg/kg/day) of acetonitrile
(Ref. 3). There were no signs of neurotoxicity reported for dogs.
In an embryo-fetal toxicity and teratogenicity study of
acetonitrile, signs of neurotoxicity were found when acetonitrile was
tested in the bred female New Zealand white rabbits receiving 2, 15, or
30 mg/kg/day by oral gavage (Ref. 20). Observations of dams at the high
dose level showed neurological signs of ataxia, decreased motor
activity, bradypnea, dyspnea, and impaired or lost righting reflex
(Refs. 3 and 8).
Other laboratory studies also show that inhalation exposure to
acetonitrile can adversely affect the nervous system of animals. In a
report on acute exposure inhalation toxicity in rats submitted by E.I.
du Pont de Nemours and Company (Refs. 3 and 21), toxicity was evaluated
in groups of 10 male Sprague-Dawley rats exposed to acetonitrile for 4
hour periods. Dose levels and number of mortalities were not reported.
Mortality was observed up to 24 hours post-exposure and the
LC50 was determined to be 17,100 ppm. Clinical signs of
neurotoxicity during exposure included irregular respiration, hyperemia
followed by pale ears, face-pawing, and lack of coordination in all
animals and unreactivity in decedents (Ref. 3).
In summary, subchronic exposures to acetonitrile can cause serious
and irreversible health effects in animals at concentrations of
acetonitrile at or near 350 ppm (approximately 30 mg/kg/day).
Developmental studies in animals and acute inhalation studies in
animals and exposures to humans provide additional support for the
potential for acetonitrile
[[Page 10601]]
to cause severe neurological effects and even death in humans.
vi. Other chronic effects. Subchronic exposures of acetonitrile at
concentrations ranging from 100 to 2,510 ppm (in several species)
resulted in lung congestion and edema; increases in liver and kidney
weight with swelling of the proximal and convulated tubules;
cytoplasmic vacuolation of hepatocytes; brain hemorrhages; decreases in
hemoglobin and hematocrit; severe eye irritation; decreases in thymus
weight, increases in heart weight; and forestomach hyperplasia (Ref.
3). In addition, immunotoxic effects, such as a dose-dependent
significant decrease in hematocrit, hemoglobin, red blood cells (RBC),
white blood cells (WBC), and B-lymphocyte function, were observed in
mice following inhalation exposure to acetonitrile (Refs. 3 and 22).
There is uncertainty regarding the biological significance of the
increases in relative liver weight, hepatic vacuolization, and some of
the immunological changes observed after subchronic exposure since
these effects were not seen following chronic dosing. It is possible
that the lack of observed effects could be, however, the result of
lower chronic exposure levels (Ref. 3). Chronic effects in rats and
mice following chronic exposure to acetonitrile included increases in
liver weights and forestomach lesions (Ref. 3). However, there is
uncertainty regarding the biological significance of the forestomach
lesions observed following inhalation exposure since oral exposure of
acetonitrile as a result of the grooming of contaminated fur may also
have been a contributing factor. Furthermore, it is difficult to assess
the significance of the increases in liver weights without any
information on the histopathological or functional changes (Ref. 3).
vii. Toxicity related to ozone formation. Acetonitrile is currently
considered a VOC and, as such, has the potential to contribute to the
formation of ozone in the troposphere (i.e., the lower atmosphere). As
EPA has previously stated, ozone can affect structure, function,
metabolism, pulmonary defense against bacterial infection, and
extrapulmonary effects (Ref. 23). 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. Accordingly, EPA has concluded that
acetonitrile, as a VOC, has the potential to cause these effects.
3. Ecotoxicity. Acetonitrile is of low concern with respect to
direct ecotoxicity based on measured data and Quantitative Structure
Activity Relationship (QSAR) analysis. Acute acetonitrile toxicity for
96-hour fish and 48-hour daphnid exposures were 1,100 to 1,640
milligrams per liter (mg/L) (measured concentrations), and 4,900 mg/L,
respectively (based on QSAR). Chronic acetonitrile toxicity for 21-day
daphnid (reproduction) was greater than 200 mg/L (measured), and 470
mg/L for fish (based on QSAR) (Refs. 3 and 24).
Based on the limited number of laboratory studies conducted to
date, the terrestrial toxicity of acetonitrile is low. No published
experimental data are available for evaluating its bioaccummulation.
Log bioconcentration factors for acetonitrile estimated using Lyman
regression equations were -1.81 to 0.6 indicating no potential
bioaccumulation (Refs. 3 and 25).
As a VOC, acetonitrile contributes to the formation of ozone in the
environment. As EPA has previously stated (Ref. 23), ozone's effects 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 known
interrelationships of different components of ecosystems, such effects,
if of sufficient magnitude, may potentially lead to irreversible
changes of sweeping nature to ecosystems.
D. Acute Exposure Assessment
Based on the results of animal studies, there are concerns for
acute health effects associated with exposure to acetonitrile. Thus,
pursuant to EPCRA section 313(d)(2)(A), EPA performed exposure
assessments to determine whether acute health effects from acetonitrile
would occur at concentrations reasonably likely to exist beyond the
facility site boundaries as a result of continuous, or frequently
recurring, releases. EPA's Toxic Release Inventory (TRI) release data
were used to estimate acetonitrile exposures to the general population
near the release sites. The fugitive emissions to air were the largest
contributors to these exposures. Potential exposures due to water
releases were also estimated.
1. Ambient air exposure assessment. Acetonitrile releases reported
to TRI for 1995 and 1996 were used for the exposure assessment.
Significant changes occurred between 1995 and 1996 with a greater than
50 percent increase in releases of acetonitrile occurring at the
highest air releasing site. Short-term (acute exposure) air
concentrations were estimated using the SCREEN3 and ISCST3 models.
Among the ten top sites chosen for modeling, a plant in Memphis,
Tennessee had the highest air releases for both 1995 and 1996,
dominated by fugitive air releases. Using the SCREEN3 model, the
estimated air concentrations of acetonitrile beyond facility site
boundaries at sites with fugitive air emissions greater than 10,000
kilograms per year (kg/year) for 1995 and 1996 ranged from 4 to 36
milligrams per cubic meter (mg/m3) (2.4 to 22 ppm) for 1
hour, and 1 to 14 mg/m3 (0.9 to 8 ppm) for 24 hours,
respectively.
Based on the 1995 data and the ISCST3 model, the 1 and 24 hours
short-term (acute exposure) acetonitrile concentrations in air, at 100
meters distance from the source center of highest release, in the
direction of highest concentration, are 16 and 2.3 mg/m3 (or
9.52 and 1.37 ppm), respectively. Under the same model scenario, the
1996 data gave an estimated 23 and 3.3 mg/m3 (or 13.5 and
2.0 ppm) of acetonitrile concentrations in air for the 1 and 24 hour
short-term exposure, respectively. Other air concentrations of
acetonitrile for ten top facilities were also modeled and the estimated
data are summarized in the General Sciences Corporation (GSC) modeling
support for exposure assessment of acetonitrile (Ref. 26). The highest
estimates were at those facilities with boundaries of approximately \1/
4\ mile (400 meters) from the site center or less (Refs. 4 and 26).
The short-term air modeling was intended to represent acute
exposure scenarios for populations spending time in the surroundings of
facilities, outside site boundaries, but not necessarily resident.
However, the results should be considered ``what-if'' rather than
established as high end, because of factors such as variability in
meteorology, and uncertainties in release quantities and durations. It
is important to recognize that the ambient air concentration estimates
use the assumption that releases continue over 365 days per year, 24
hours per day at a constant rate. If annual releases occurred over
shorter time periods, the corresponding short-term concentrations would
be higher than those presented in the exposure assessment report. For
example, if a facility releases approximately 10,000 kilograms of
fugitive air releases per year over 30 days per year rather than 365
days per year, then the upper limit of the screening range would exceed
40 mg/m3, exceeding the value (36 mg/m3) shown
for the highest release of more than 200,000 pounds per year. The
[[Page 10602]]
concentrations estimated show a screening range (using SCREEN3 model at
a distance of 100 meters from the source center) and provide key
results for selected sites. The data also shows maximum results beyond
facility boundaries, using distances from site centers indicated by
site layouts in the industry report (Refs. 4 and 27). These estimated
values of acetonitrile in air are well below those concentration levels
that produced acute effects in animal studies.
2. Drinking water exposure assessment. Both direct and indirect
releases to water were modeled using river reach harmonic mean flows
for long-term and low flow data for short term. The REACHSCAN model was
used to estimate the contamination of acetonitrile at drinking water
utility intakes downstream from facilities releasing to water or making
offsite transfers to waste-water treatment facilities. While some
locations have low to mid parts per billion (ppb) levels, few intake
locations of drinking water utilities have levels above 1 ppb (1
microgram per liter). Based on 1995 TRI water release data, the highest
exposure potential with drinking water intakes downstream were found
for an indirect discharger in Pennsylvania, with annual concentration
of 100 ppb and the short-term concentration of 350 ppb. However, that
facility changed reporting from ``transfers to publicly owned treatment
works (POTWs)'' to ``other offsite transfers'' for 1996; several other
facilities also reduced or ended water releases or transfers to POTWs
for 1996. The highest drinking water utility intake level found using
1996 TRI data was approximately 2 ppb for low flow conditions, and 0.7
ppb for typical conditions (downstream from a facility in Rock Hill,
South Carolina). Several fresh-water locations without verified
drinking water intakes have mid ppb (e.g., 200 ppb) estimated levels
(Ref. 4).
Some potential drinking water situations have not been quantified
due to lack of data. For example, offsite transfers to POTWs include
several sites in Puerto Rico, for which surface water data have not
been retrieved. Underground injection wells also may form sources of
contamination to drinking water wells in ground water, in the event of
containment failure (Ref. 4). Atmospheric deposition of acetonitrile
can also contribute to surface water contamination near facilities
releasing to air (Ref. 4).
3. Exposure evaluation. EPA's exposure assessment attempted to
determine whether, as a result of releases from EPCRA section 313
covered facilities, acetonitrile 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. The modeling used released data reported under
EPCRA section 313 and included both conservative and non-conservative
assumptions concerning releases and facility site information. Non-
conservative assumptions included the assumption that EPCRA section 313
reported releases are spread over 365 days per year and 24 hours per
day. Given a shorter release period, estimated exposures could be
significantly higher. Under the conditions modeled here EPA believes it
is unlikely that concentrations of acetonitrile sufficient to cause
acute toxicity will exist beyond a facility's boundaries as a result of
continuous, or frequently reoccurring, releases. This is because the
exposure concentrations that resulted from the modeling (9.52 and 1.37
ppm) are below the concentrations that have caused acute toxicity in
laboratory animals (500 ppm).
V. Summary of Technical Review
There is sufficient evidence to support a high level of concern for
potential neurotoxicity and death following repeated exposure to
acetonitrile. This comes from several lines of evidence. In repeated
dose (subchronic) inhalation experiments in monkeys, neurological signs
of toxicity (brain hemorrhages, hyper-excitability, and over-extension
reflexes) and death were observed at concentrations of acetonitrile at
or near 350 ppm (approximately 30 mg/kg/day). For effects seen in both
the monkey and rabbit studies, the neurotoxicity risk assessment
guidelines recommend that these endpoints be included as examples of
possible indicators of an adverse neurotoxic effect (Ref. 28).
Structural or neuropathological endpoints could include hemorrhage in
nerve tissue. Neurological endpoints could include increases or
decreases in motor activity and changes in motor coordination. When
pregnant rabbits were exposed to the same amount of acetonitrile during
gestation, signs of neurotoxicity (including ataxia (muscle
incoordination), decreased motor activity, bradypnea (abnormally slow
breathing), dyspnea (labored or difficult breathing), and impaired or
lost righting reflex) and an increased incidence of maternal mortality
were also observed. These effects are consistent with acute inhalation
exposures to high concentrations of acetonitrile in humans in which the
central nervous system is widely affected (exhibiting signs of
salivation, nausea, vomiting, anxiety, confusion, hyperpnea, dyspnea,
rapid pulse, unconsciousness, and convulsions followed by death from
respiratory failure). The neurological effects seen in the
developmental and acute studies provide supplemental support for the
determination that acetonitrile can reasonably be anticipated to cause
chronic neurotoxicity. These results are also consistent with those
effects seen with inorganic cyanide and other aliphatic nitriles
exposures, suggesting that the toxic effects of acetonitrile may be
correlated with the metabolic release of cyanide.
Acetonitrile is currently considered a VOC and, as such, it
contributes to the formation of tropospheric ozone which, as EPA has
previously determined, can cause significant adverse effects to human
health and the environment (Ref. 23).
The main effects of acetonitrile reported in humans (from
accidental poisoning) are likely due to acute inhalation exposures to
high concentrations. Based on the results of animal studies, there are
concerns for acute health effects associated with exposure to
acetonitrile. However, based on EPA's exposure assessment, it is
unlikely that concentrations of acetonitrile, sufficient to cause acute
toxicity, will exist beyond a facility's boundaries as a result of
continuous, or frequently recurring, releases. There is not sufficient
information to support a concern for carcinogenicity, mutagenicity, or
reproductive toxicity. The case for developmental toxicity is weak.
Some studies in rats produced no signs of developmental toxicity even
in the presence of maternal toxicity. Other studies exhibited signs of
developmental toxicity, however, in the presence of extreme maternal
mortality. There is uncertainty regarding the biological significance
of the increases in relative liver weight, hepatic vacuolization, and
some of the immunological changes observed after subchronic exposure
since these effects were not seen following chronic dosing. It is
possible that the lack of observed effects could be, however, the
result of lower chronic exposure levels. Acetonitrile is of low concern
with respect to direct ecotoxicity based on measured data and QSAR
analysis.
VI. Rationale for Denial
EPA is denying the petition submitted by BP and GNICC to delete
acetonitrile from the EPCRA section 313 list of toxic
[[Page 10603]]
chemicals. This denial is based on EPA's conclusion that acetonitrile
can reasonably be anticipated to cause serious or irreversible chronic
health effects in humans, including neurotoxicity and death. Chronic
health effects may result after acute, subchronic, or chronic
exposures. EPA determines whether an effect is best considered to be
chronic by looking at a number of factors, among which is the length of
time it takes for the effect to manifest and the extent to which it
persists after exposure to the toxicant ends. Acute or subchronic
exposure to acetonitrile can produce serious and irreversible health
effects, including brain hemorrhages and death. In addition, acute or
subchronic exposure to acetonitrile produce the following serious
health effects: Hyper-excitability, over-extension reflexes, ataxia
(muscle incoordination), decreased motor activity, bradypnea
(abnormally slow breathing), dyspnea (labored or difficult breathing),
and impaired or lost righting reflex. Many of these effects (e.g.,
over-extension reflexes and hyper excitability) manifest toward the end
of the exposure period and are thus considered chronic effects. Data
from animal studies indicate that neurotoxicity and death can occur at
the relatively low dose of approximately 30 mg/kg/day. Based on these
data, EPA considers acetonitrile to have moderately high to high
chronic toxicity. Therefore, EPA has concluded that acetonitrile meets
the listing criteria of EPCRA section 313 (d)(2)(B).
EPA has concluded that acetonitrile meets the listing criteria of
EPCRA section 313(d)(2)(B) and (d)(2)(C) due to it contributing to the
formation of ozone. EPA has concluded that VOCs, such as acetonitrile,
contribute to the formation of tropospheric ozone which is known to
cause significant adverse effects to human health and the environment.
EPA has previously stated that ozone meets the listing criteria of
EPCRA section 313(d)(2)(B) and (d)(2)(C) (59 FR 61432, November 30,
1994). EPA has stated in prior Federal Register notices (54 FR 4072,
January 27, 1989; 54 FR 10668, March 15, 1989; 59 FR 49888, September
30, 1994; 60 FR 31643, June 16, 1995; and 63 FR 15195, March 30, 1998)
that, because VOCs contribute to the formation of tropospheric ozone,
they meet the criteria for listing under EPCRA section 313. EPA has
also stated (54 FR 4072, January 27, 1989 and 54 FR 10668, March 15,
1989) that while it is not EPA's intention to include all VOC chemicals
on the EPCRA section 313 list, those VOCs whose volume of use or
emissions are large enough to raise substantial VOC concerns would be
retained on the EPCRA section 313 list. Acetonitrile is a VOC with a
high production volume, and therefore, EPA has determined that
acetonitrile should remain on the EPCRA section 313 list of toxic
chemicals. In EPA's most recent petition denial based on VOC concerns
(63 FR 15195, March 30, 1998), the Agency provided further explanation
concerning its rationale for determining that indirect effects, such as
those caused by VOCs, meet the EPCRA section 313 listing criteria.
Because EPA believes that acetonitrile has moderately high to high
chronic toxicity, EPA does not believe that an exposure assessment is
appropriate for determining whether acetonitrile meets the criteria of
EPCRA section 313(d)(2)(B). This determination is consistent with EPA's
published statement clarifying its interpretation of the section
313(d)(2) and (d)(3) criteria for modifying the section 313 list of
toxic chemicals (59 FR 61432, November 30, 1994).
As mentioned under Unit III. of this preamble, the petitioner's
have submitted a petition to EPA's OAR to add acetonitrile to the list
of negligibly photoreactive chemicals under 40 CFR 51.100(s)(1).
Chemicals that appear on this list are excluded from EPA's definition
of a VOC, since they have been determined to have a negligible
contribution to tropospheric ozone formation. OAR's initial review of
the petition indicates that acetonitrile may be a negligibly
photoreactive chemical (Ref. 29). If OAR's initial assessment is
confirmed and a rule is issued that adds acetonitrile to the list of
negligibly photoreactive chemicals under 40 CFR 51.100(s)(1), then any
concerns based solely on acetonitrile being listed as a VOC would no
longer be a basis for listing acetonitrile under EPCRA section 313.
However, since EPA has also concluded that acetonitrile meets the EPCRA
section 313 criteria for listing based on concerns for chronic
neurotoxicity, EPA's decision to deny the petition to delete
acetonitrile from the EPCRA section 313 list of toxic chemicals would
not be affected by a change in acetonitrile's status as a VOC.
VII. References
1. British Petroleum, Inc. (BP) and GNI Chemicals Corporation
(GNICC), 1998. Petition to Delist Acetonitrile from the List of Toxic
Chemicals under the Authority of Section 313 of the Emergency Planning
and Community Right-to-Know Act (EPCRA) of 1986. BP Chemicals Inc. and
GNI Chemicals Corp. (February 1998).
2. United States Environmental Protection Agency (U.S. EPA), Office
of Pollution Prevention and Toxics (OPPT), Tou, Jenny, 1998. Chemistry
Report for Acetonitrile in Response to EPCRA Section 313 Delisting
Petition. (June 1998).
3. USEPA, OPPT, Anitole, Katherine, 1998. Hazard Assessment for
Acetonitrile in Response to Section 313 Delisting Petition of BP
Chemicals Inc. and GNI Chemicals Corporation. (June 1998).
4. USEPA, OPPT, Nold, Annett, 1998. Exposure Assessment for
Acetonitrile in Response to Delisting Petition. (July 1998).
5. USEPA, OPPT, Miller, Jim, 1998. Economic Analysis of the
Proposed Deletion of Acetonitrile from the EPCRA Section 313 List of
Toxic Chemicals. (March 1998).
6. USEPA, OPPT, Blouin, John, 1998. Engineering Analysis of the
Proposed Deletion of Acetonitrile from the EPCRA Section 313 List of
Toxic Chemicals. (April 1998).
7. The Merck Index. An Encyclopedia of Chemicals, Drugs, and
Biologicals, 11th Edition, p.63, 1989, Merck Co., Inc.
8. World Health Organization (WHO), 1993. International Program on
Chemical Safety (IPCS), Environmental Health Criteria 154 -
Acetonitrile, World Health Organization.
9. National Cancer Institute (NCI)/National Toxicological Program
(NTP), 1996. NTP Technical Report of the Toxicology and Carcinogenesis
of Acetonitrile (CAS No. 75-05-8) in F344/N Rats and B6C3F1 Mice
(inhalation studies). Carcinogenesis Technical Report Series; National
Cancer Institute/National Toxicology Program; U.S. Department of Health
and Human Services (U.S. HHS).
10. Taskinen, H., Kyyronen, P., Hemminki, K., Hoikkala, M.,
Lajunen, K., and Lindbohm, M., 1994. Laboratory Work and Pregnancy
Outcome. JOM 36:311-319.
11. USEPA, OPPT, 1998. Hazard Assessment Emphasizing
Epidemiological Data for the Acetonitrile Delisting Petition.
Memorandum dated March 13, 1998, from Andrea Pfahles-Hutchens, Existing
Chemicals Assessment Branch, to Katherine Anitole, Existing Chemicals
Assessment Branch, RAD. Washington, DC: USEPA.
12. USEPA, OPPT, 1998, Health Effects Test Guidelines OPPTS
870.3700: Prenatal Development Toxicity Study, (EPA 712-C-98-207,
August 1998).
13. Willhite, C. 1983. Developmental Toxicity of Acetonitrile in
the Syrian
[[Page 10604]]
Golden Hamster. Teratology 27, 313-325.
14. Smith, M.K., George, E.L., Zenick, H., Manson, J.M., and
Stober, J.A. 1987. Developmental Toxicity of Halogenated Acetonitriles:
Drinking Water By-Products of Chlorine Disinfection. Toxicol. 46, 83-
93.
15. Johannsen, F.R., G.L., Levinskas, P.E., Berteau and D.E.
Rodwell. 1986. Evaluation of the Teratogenic Potential of Three
Aliphatic Nitriles in the Rat. Fund. Appl. Toxicol. 7, 33-40.
16. Morrissey, R.E., Schwetz, B.A., Lamb, J.C., Ross, M.Dd.,
Teague, J.L. and Morris, R.W. 1988. Evaluation of Rodent Sperm, Vaginal
Cytology, and Reproductive Organ Weight Data from National Toxicology
Program 13-Week Studies. Fund. Appl. Toxicol. 11, 343-358.
17. Hazardous Substances Data Bank (HSDB), 1994. MEDLARS Online
Information Retrieval System, National Library of Medicine. (Retrieved
August, 1994).
18. IRIS. U.S. Environmental Protection Agency's Integrated Risk
Information System (IRIS).
19. Pozzani, U.C., Carpenter, C.P., Palm. P.E., Weil, C.S. and
Nair, J.H. 1959. An Investigation of the Mammalian Toxicity of
Acetonitrile. J. Occup. Med. 12, 634-642.
20. Argus Research Laboratories, Inc., 1984. Embryo-fetal Toxicity
and Teratogenicity Study of Acetonitrile in New Zealand White Rabbits
(Segment II Evaluation). Argus Research Laboratories, Inc. Project No.
419-001, Final Report. EPA Document No. 40-8446070, Fiche No.
OTS0507279.
21. E.I. du Pont de Nemours Company, 1968. Acute Inhalation
Toxicity in Rats with Cover Letter, Haskell Laboratory for Toxicology
and Industrial Medicine. EPA Document No. 878220234, Fiche No.
OTS0215023.
22. Immunquest (1984). EPA Docket Office: FYI-OTS-0284-0292.
23. USEPA. ``Addition of Certain Chemicals.'' Proposed rule, (59 FR
1788, January 12, 1994).
24. USEPA, OPPT, 1994. Estimating Toxicity of Industrial Chemicals
to Aquatic Organisms using Structure-Activity Relationships. (May 1994)
25. Screening Information Data Set (SIDS)/Organization for Economic
Cooperation and Development (OECD), 1997. SIDS Initial Assessment
Profile (Draft) on Acetonitrile. (March 1997).
26. General Sciences Corporation (GSC), 1998. ``Modeling Support
for Exposure Assessment of Acetonitrile,'' prepared for Exposure
Assessment Branch, OPPT. EPA Contract No. 68-W7-0030, Work Assignment
No. II-1. (Final Report for Acetonitrile, July 1998).
27. Trinity Consultants (Dallas, Texas), 1998. ``Refined Modeling
for Ten Acetonitrile Emitting Facilities,'' prepared for BP Chemicals
and GNI Group, Inc., (January 20, 1998), Project 97440.0200.
28. USEPA. ``Proposed Guidelines for Neurotoxicity Risk
Assessment.'' Notice, (60 FR 192, October 4, 1995).
29. USEPA. ``Photochemical Reactivity of Acetonitrile.'' Memorandum
from G. T. Helms to Maria Doa, (October 1, 1998).
List of Subjects in 40 CFR Part 372
Environmental protection, Chemicals, Community right-to-know,
Hazardous substances, Intergovernmental relations, Reporting and
recordkeeping requirements, Superfund, Toxic chemicals.
Dated: February 24, 1999.
Susan H. Wayland,
Acting Assistant Administrator for Prevention, Pesticides and Toxic
Substances.
[FR Doc. 99-5495 Filed 3-4-99; 8:45 am]
BILLING CODE 6560-50-F
