[Federal Register Volume 59, Number 47 (Thursday, March 10, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-5555]
[[Page Unknown]]
[Federal Register: March 10, 1994]
_______________________________________________________________________
Part VIII
Department of Health and Human Services
_______________________________________________________________________
Agency for Toxic Substances and Disease Registry
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Status of the Superfund Substance-Specific Applied Research Program;
Notice
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Agency for Toxic Substances and Disease Registry
[ATSDR-79]
Status of the Superfund Substance-Specific Applied Research
Program
AGENCY: Agency for Toxic Substances and Disease Registry (ATSDR),
Public Health Service (PHS), Department of Health and Human Services
(HHS).
ACTION: Notice.
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SUMMARY: This notice provides the status of ATSDR's effort to implement
the Agency's Substance-Specific Applied Research Program (SSARP). This
research program, authorized by the Comprehensive Environmental
Response, Compensation, and Liability Act (CERCLA), as amended by the
Superfund Amendments and Reauthorization Act (SARA) [42 U.S.C. 9604
(i)], was initiated on October 17, 1991. At that time, a list of
priority data needs for 38 priority hazardous substances was announced
in the Federal Register (56 FR 52178). The list was subsequently
revised based on public comments, and published in final form on
November 16, 1992 (57 FR 54150).
The 38 substances, each of which is found on ATSDR's ``List of
Priority Hazardous Substances'' (56 FR 52166, October 17, 1991), are
aldrin/dieldrin, arsenic, benzene, beryllium, cadmium, carbon
tetrachloride, chloroethane, chloroform, chromium, cyanide, p,p'-
DDT,DDE,DDD, di(2-ethylhexyl)phthalate, lead, mercury, methylene
chloride, nickel, polychlorinated biphenyl compounds (PCBs), polycyclic
aromatic hydrocarbons (PAHs) (includes 15 substances), selenium,
tetrachloroethylene, toluene, trichloroethylene, vinyl chloride, and
zinc.
This notice also serves as a continuous call for voluntary research
initiatives. ATSDR encourages private sector organizations to volunteer
to conduct research to fill specific priority data needs. A Tri-Agency
Superfund Applied Research Committee (TASARC) comprised of scientists
from ATSDR, the National Toxicology Program (NTP), and the
Environmental Protection Agency (EPA) will review all proposed
voluntary research efforts.
DATES: ATSDR considers the voluntary research effort to be important to
the continuing development of the SSARP. Therefore, the Agency
encourages private sector organizations to volunteer at any time to
conduct research to fill identified data needs, until ATSDR announces
that research has been initiated for a specific data need.
ADDRESSES: Private sector organizations interested in volunteering to
conduct this type of research may write to Dr. William Cibulas, Chief,
Research Implementation Branch, Division of Toxicology, Agency for
Toxic Substances and Disease Registry, Mailstop E-29, 1600 Clifton
Road, NE., Atlanta, Georgia 30333.
FOR FURTHER INFORMATION CONTACT: Dr. William Cibulas, Chief, Research
Implementation Branch, Division of Toxicology, Agency for Toxic
Substances and Disease Registry, Mailstop E-29, 1600 Clifton Road, NE.,
Atlanta, Georgia 30333, telephone (404) 639-6306.
SUPPLEMENTARY INFORMATION:
Background
The Comprehensive Environmental Response, Compensation, and
Liability Act of 1980 (Superfund) or CERCLA, as amended by the
Superfund Amendments and Reauthorization Act (SARA) [42 U.S.C.
9604(i)], requires that ATSDR (1) jointly with the Environmental
Protection Agency (EPA), develop and prioritize a list of hazardous
substances found at National Priorities List (NPL) sites, (2) prepare
toxicological profiles for these substances, and (3) assure the
initiation of a research program to fill identified data needs
associated with the substances. Before starting such a program, ATSDR
will consider recommendations of the Interagency Testing Committee
established under section 4(e) of the Toxic Substances Control Act on
the type of research that should be done.
On October 17, 1991, ATSDR announced the identification of the
priority data needs for 38 priority hazardous substances (56 FR 52178),
requested public comments, and invited private sector organizations to
volunteer to conduct research to fill specific priority data needs. On
November 16, 1992, the Agency published a revised list of 117 priority
data needs for these priority hazardous substances (57 FR 54150).
The major goals of the ATSDR SSARP are: (1) To fill the substance-
specific information needs of the public and scientific community, and
(2) to supply information necessary to conduct comprehensive public
health assessments of populations living near hazardous waste sites.
This program also will provide data that can be generalized to other
substances or areas of science, including risk assessment of chemicals,
thus creating a scientific base for filling a broader range of data
needs.
CERCLA, in section 104(i)(5)(D), states that it is the sense of
Congress that the costs for conducting this research program be borne
by the manufacturers and processors of the hazardous substances under
the Toxic Substances Control Act (TSCA) and by registrants under the
Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), or by cost
recovery from responsible parties under CERCLA. To effect this
statutory intent, ATSDR developed a plan whereby parts of the SSARP
will be conducted via regulatory mechanisms (TSCA/FIFRA), private
sector voluntarism, and the direct use of CERCLA funds.
A Tri-Agency Superfund Applied Research Committee (TASARC)
comprised of scientists from ATSDR, NTP, and the EPA has been set up
to: (1) Advise on the assignment of priorities on mechanisms for
filling data needs; (2) coordinate knowledge of research activities to
avoid duplication of research in other programs and under other
authorities; (3) advise on issues of science related to substance-
specific data needs; and (4) maintain a scheduled forum that provides
an overall review of the ATSDR SSARP. The TASARC has met four times
since the initiation of the SSARP. This notice provides the status of
ATSDR's efforts to implement the SSARP, focussing on ongoing activities
relevant to test rule development under TSCA/FIFRA, private sector
voluntarism, and direct use of CERCLA funds. Additional data needs are
being addressed through an interagency agreement with NTP, by ATSDR's
Great Lakes human health effects research program, and other Agency
programs. To date, 59 priority data needs associated with 35 ATSDR
priority hazardous substances (including 15 PAHs) are being addressed
via these mechanisms (Table 1).
A. TSCA/FIFRA
In developing and implementing the SSARP, ATSDR, NTP, and EPA have
established procedures to identify priority data needs of mutual
interest to Federal programs. These data needs will be filled through a
program of toxicological testing under TSCA. This portion of the
research will be conducted according to established TSCA procedures and
guidelines. This testing will fulfill more than one Federal program's
need. During FY 1993, a subset of the 117 priority data needs for 38
substances (about 60) was referred to the EPA under its authorities
following review and endorsement by the TASARC oversight committee.
Currently, 26 priority data needs associated with 11 ATSDR substances
have been recommended by EPA to be added to its Master Testing List,
the first step in test rule development under TSCA, section 4 (Table
2). Please note that although ATSDR has identified priority data needs
for oral exposure to tetrachloroethylene, cyanide, and beryllium, in
response to other Federal government agency needs, ATSDR will consider
proposals to conduct inhalation studies in conjunction with
pharmacokinetic studies for these substances in lieu of bioassays using
oral exposures. It is anticipated that inhalation data derived from
these studies can be used, in conjunction with pharmacokinetic
modeling, to address ATSDR's oral toxicity data needs.
Some of ATSDR's priority hazardous substances will not be added to
EPA's Master Testing list because they do not fall within the bounds of
TSCA, Section 4 authority. For example, TSCA does not require testing
chemicals that are out of production, such as PCBs. Furthermore, TSCA
is not considered the appropriate mechanism for testing PAHs, because
the PAHs are by-products of multiple industrial processes and,
therefore, it is difficult to identify specific manufacturers. In
addition, TSCA guidelines are not available for some of the ATSDR
priority data needs such as the development of analytical methods for
cadmium and beryllium, mechanistic studies on the neurotoxic effects of
lead, and the mitigation of toxicity of vinyl chloride. Moreover, some
of the ATSDR priority hazardous substances are considered more
appropriate for FIFRA than TSCA, e.g., arsenic, DDT, and aldrin/
dieldrin. The Office of Pollution, Prevention and Toxics (OPPT), EPA,
forwarded the data needs for these substances to the Office of
Pesticide Programs for evaluation.
B. Private Sector Voluntarism
As part of the SSARP, ATSDR initially announced a set of proposed
procedures for conducting voluntary research on February 7, 1992 (56 FR
4758). It was revised based on public comments and published on
November 16, 1992 (57 FR 54160). This voluntary research program fills
priority data needs along with other mechanisms such as test rule
development through EPA and CERCLA-funded research. Private sector
organizations were encouraged to volunteer to conduct research to fill
these specific priority data needs.
Currently, ATSDR is pursuing voluntary research interests with two
private sector organizations: the General Electric Company (GE) and the
Halogenated Solvents Industry Alliance (HSIA). To date, through the
voluntary research efforts of GE and HSIA, four priority data needs for
two substances are under discussion, potentially leading to the signing
of two memorandums of understanding (Table 3).
During FY 1993, ATSDR staff members met with officials from GE to
discuss the Agency's research agenda for PCBs. The Agency has
identified mutual interests in environmental fate testing and human
health endpoints assessments and has initiated discussion on these
studies with GE.
ATSDR met with HSIA representatives to discuss the use of
physiologically-based pharmacokinetic (PBPK) models to fill priority
data needs for six volatile organic compounds. The Agency selected
methylene chloride to start using PBPK modeling to address ATSDR's
toxicity priority data needs because of the extensive database on this
substance. The toxicity priority data needs for the remaining 5
volatile organic compounds (carbon tetrachloride, chloroethane,
chloroform, tetrachloroethylene, and trichloroethylene) may be
addressed via similar voluntary efforts in the future.
C. CERCLA-Funded Research (Minority Health Professions Foundation
Research Program)
During FY 1992, ATSDR announced a $4 million cooperative agreement
program with the Minority Health Professions Foundation (MHPF) to
support substance-specific investigations. This cooperative venture is
supported by the direct use of CERCLA funds. During FY 1993, about $4
million was allocated to continue this research program; no new
projects were initiated. Currently, 9 priority data needs for 21
priority hazardous substances (including 15 PAHs) in the SSARP are
being addressed by the MHPF institutions through this program. Also,
the MHPF research program will address 13 other substance-specific data
needs identified in the ATSDR toxicological profiles concerning
exposures and related health effects. The institutions receiving awards
and their respective research projects are listed in Table 4.
The MHPF, a not-for-profit 501(c)(3) organization, is comprised of
11 minority health professions schools. Its primary mission is to
research the persistent health problems that disproportionately plague
poor and minority citizens. The purposes of the ATSDR-MHPF cooperative
agreement are: (1) To initiate research to fill ATSDR-identified data
needs for priority hazardous substances, and (2) to enhance existing
disciplinary capacities to conduct research in environmental health at
MHPF member institutions.
The areas of research at MHPF institutions include those related to
broad areas of toxicology and environmental health science. Some of the
MHPF member institutions are conducting health studies of minority
groups exposed to ATSDR's priority hazardous substances.
D. National Toxicology Program
ATSDR maintains an interagency agreement (IAG) with NTP to conduct
toxicological testing of substances identified at NPL sites. The
studies determine levels of exposure that present a significant risk to
humans of acute, subacute, and chronic health effects. Often these
studies include an assessment of the substance's ability to cause
cancer, reproductive toxicity, and birth defects. The results of these
studies are used by regulatory agencies such as the Food and Drug
Administration and the EPA, various environmental and industrial
groups, and ATSDR to improve the ability to conduct public health
assessments at NPL sites. Under this agreement, one toxicity priority
data need identified in the SSARP (carbon tetrachloride,
immunotoxicology battery of tests via oral exposure) is currently being
addressed. This NTP study was begun in September 1993 and should be
completed in February 1994.
E. Great Lakes Human Health Effects Research Program
Some of the priority data needs identified in the SSARP have been
independently identified as research needs through the ATSDR Great
Lakes human health effects research program, a separate research
program. To date, 12 priority data needs for 19 priority hazardous
substances (including 15 PAHs) identified in the SSARP are being
addressed through this program. The institutions receiving awards and
their respective studies are listed in Table 5.
The Great Lakes Critical Programs Act of 1990 mandates EPA, in
consultation with ATSDR, to prepare a report by September 30, 1994,
that assesses the adverse effects of pollutants in the Great Lakes
system on the health of individuals in the Great Lakes states. A
variety of persistent toxic substances are prevalent in the Great
Lakes, including PCBs, DDT and its metabolites, dieldrin, toxaphene,
mirex, mercury, benzo[a]pyrene, hexachlorobenzene, furans, dioxins, and
lead. Certain populations--Native Americans, sport anglers, fetuses and
nursing infants of mothers who consume contaminated Great Lakes fish--
have a potentially higher risk of long-term adverse effects resulting
from exposure to these contaminants.
The ATSDR-supported research projects focus on these high-risk
populations to try to further define the human health consequences of
exposure to these persistently toxic substances. The research
activities include, but are not limited to: (1) Characterizing exposure
and determining the profiles and levels of Great Lakes contaminants in
biological tissues and fluids in high-risk populations; (2) identifying
sensitive and specific human reproductive/developmental end points and
correlating them to exposure to Great Lakes contaminants; (3)
determining the short- and long-term risk(s) of adverse health effects
in progeny whose parents were exposed to Great Lakes contaminants; (4)
investigating the feasibility of establishing registries and
surveillance cohorts in the Great Lakes region; and (5) establishing a
chemical mixtures database with emphasis on tissue and blood levels in
order to identify new cohorts, conduct surveillance and health effects
studies, and establish registries and surveillance cohorts.
During FY 1992, ATSDR announced a $2 million grant program to
conduct research on the impact on human health of contaminated fish
consumption in the Great Lakes region. On September 30, 1992, ATSDR
announced nine awards under this program.
In FY 1993, about $3 million was allocated to support the
continuation of the research projects conducted at the nine
institutions originally funded during FY 1992. In addition, ATSDR
awarded one new grant to the Michigan Department of Public Health to
design, establish, and operate a professionally creditable
interlaboratory quality assurance/quality control program for the ATSDR
Great Lakes human health effects research program.
F. Other ATSDR Programs
In its role as a public health agency addressing environmental
health, ATSDR may, where appropriate, collect human data to validate
substance-specific exposure and toxicity findings; information on
levels of contaminants in humans has been identified as a priority data
need for 37 of the 38 priority substances (Table 1). ATSDR will obtain
this information through exposure and health effects studies, and
through establishing and using substance-specific subregistries of
people within the Agency's National Exposure Registry who have
potentially been exposed to these substances.
The list of 38 priority hazardous substances in the SSARP was
forwarded to ATSDR's Exposure and Disease Registry Branch (EDRB),
Division of Health Studies, for consideration as potential candidates
for subregistries of exposed persons, based on criteria described in
EDRB's 1988 document, ``Policies and Procedures for Establishing a
National Registry of Persons Exposed to Hazardous Substances.'' To
date, ATSDR has selected benzene, chromium, and trichloroethylene as
primary contaminants to establish subregistries in the National
Exposure Registry. However, aldrin/dieldrin, carbon tetrachloride,
chloroethane, chloroform, cyanide, p,p'-DDT, DDE, DDD, di (2-
ethylhexyl) phthalate, mercury, methylene chloride, PAHs, selenium,
tetrachloroethylene, and vinyl chloride remain as a part of the
candidate pool. They will be considered for selection as primary
contaminants during each selection process (Table 1). Finally, arsenic,
beryllium, cadmium, lead, nickel, PCBs, toluene, and zinc are not
considered to be in the pool of candidate substances for an exposure
registry at this time. This decision will be re-evaluated as more
information on the chemicals and exposure sites become available.
With regard to epidemiologic studies, ATSDR believes that for many
of the 38 priority hazardous substances, an extensive amount of animal
data, and some human data, have already been collected; therefore,
ATSDR considers it appropriate, where feasible, to conduct
epidemiologic studies on such substances. In response to public
comments, the Agency's SSARP will address substance-specific rather
than site-specific epidemiologic studies.
The substance-specific studies are designed to determine substance-
specific cause and effect. In this case, ATSDR is not necessarily
directed toward populations exposed via the environment at hazardous
substance release sites, as in a site-specific study. Instead, any
appropriate population of suitable exposure via the environment,
consumer products, or occupation can be used to design a rigorous
analytic epidemiologic investigation. Epidemiologic studies on several
of ATSDR's 38 priority hazardous substances (such as DDT, PCBs, and
PAHs) are being conducted by the ATSDR Great Lakes human health effects
research program (Table 5).
Two epidemiologic studies on lead (identified as a data need by
ATSDR), are also being conducted by the Morehouse School of Medicine
and the King/Drew Medical Center of the Charles R. Drew University of
Medicine and Science via the ATSDR--MHPF cooperative agreement. ATSDR
expects that other substance-specific epidemiologic studies, identified
as data needs or priority data needs in the SSARP, may potentially be
conducted by other Divisions within ATSDR.
ATSDR acknowledges that the conduct of epidemiologic studies to
determine possible linkages between exposure to hazardous substances
and human health effects may be accomplished other than by Agency
programs, or under other ATSDR-sponsored auspices. Toward that end, the
Agency encourages the private sector and other government programs to
use ATSDR's priority data needs to plan research activities to identify
appropriate populations and conduct studies addressing the specific
human health issues.
Finally, the collection, evaluation, and interpretation of data
from contaminated media around hazardous waste sites have been
identified as priority data needs for all 38 priority hazardous
substances by ATSDR. However, the Agency realizes that a lot of
information has already been collected through individual state
programs and the EPA's CERCLA activities; therefore, ATSDR will
evaluate the extant information from these programs in order to help
fill data needs on substance-specific exposures.
The results of the research conducted via the SSARP will be used
for public health assessments and to reassess ATSDR's substance-
specific priority data needs. The Agency expects to re-evaluate the
priority data needs for priority hazardous substances every three
years.
Dated: March 3, 1994.
Walter R. Dowdle,
Deputy Administrator, Agency for Toxic Substances and Disease Registry.
Table 1.--Substance-Specific Priority Data Needs Currently Being Addressed Under ATSDR's Applied Research
Programs
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Substance ID Priority Data Need Addressed
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Lead........................ 1A Mechanistic studies on the neurotoxic effects of lead.
1B Analytical methods for tissue levels..................
1C Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
Arsenic..................... 2A Comparative toxicokinetic studies to determine if an
appropriate animal species can be identified.
2B Half-lives in surface water, groundwater..............
2C Bioavailability from soil.............................
2D Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
Mercury..................... 3A Multigeneration reproductive toxicity study via oral
exposure.
3B Dose-response data in animals for chronic-duration
oral exposure.
3C Immunotoxicology battery of tests via oral exposure...
3D Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
3E Potential candidate for subregistry of exposed persons *
Vinyl Chloride.............. 4A Dose-response data in animals for acute-duration
inhalation exposure.
4B Multigeneration reproductive toxicity study via
inhalation.
4C Dose-response data in animals for chronic-duration
inhalation exposure.
4D Mitigation of vinyl chloride-induced toxicity.........
4E 2-species developmental toxicity study via inhalation.
4F Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
4G Potential candidate for subregistry of exposed persons *
Benzene..................... 5A Dose-response data in animals for acute- and
intermediate-duration oral exposure. The subchronic
study should include an extended reproductive organ
histopathology.
5B 2-species developmental toxicity study via oral
exposure.
5C Neurotoxicology battery of tests via oral exposure....
5D Epidemiological studies on the health effects of
benzene (Special emphasis endpoints include:
immunotoxicity).
5E Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
Cadmium..................... 6A Analytical methods for biological tissues and fluids
and environmental media.
6B Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
PCBs........................ 7A Dose-response data in animals for acute- and
intermediate-duration oral exposures.
7B Biodegradation of PCBs in water; bioavailability of
PCBs in air, water and soil.
7C Dose-response data in animals for acute- and
intermediate-duration inhalation exposures. The
subchronic study should include extended reproductive
organ histopathology.
7D Epidemiological studies on the health effects of PCBs
(Special emphasis endpoints include: immunotoxicity,
gastrointestinal toxicity, liver, kidney, thyroid
toxicity, reproductive/developmental toxicity).
7E Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
Chloroform.................. 8A Dose-response data in animals for intermediate-
duration oral exposure.
8B Epidemiological studies on the health effects of
chloroform (Special emphasis endpoints include:
cancer, neurotoxicity, reproductive and developmental
toxicity, hepatotoxicity, and renal toxicity).
8C Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
8D Potential candidate for subregistry of exposed persons *
PAHs........................ 9A Dose-response data in animals for intermediate
duration oral exposures. The subchronic study should
include extended reproductive organ histopathology
and immunopathology.
9B 2-species developmental toxicity study via inhalation
or oral exposure.
9C Mechanistic studies on PAHs, on how mixtures of PAHs
can influence the ultimate activation of PAHs, and on
how PAHs affect rapidly proliferating tissues.
9D Dose-response data in animals for acute- and
intermediate-duration inhalation exposures. The
subchronic study should include extended reproductive
organ histopathology and immunopathology.
9E Epidemiological studies on the health effects of PAHs
(Special emphasis endpoints include: cancer, dermal,
hemolymphatic, and hepatic).
9F Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
9G Potential candidate for subregistry of exposed persons *
Trichloroethylene........... 10A Dose-response data in animals for acute-duration oral
exposure.
10B Neurotoxicology battery of tests via the oral route...
10C Immunotoxicology battery of tests via the oral route..
10D Epidemiological studies on the health effects of
trichloroethylene (Special emphasis endpoints
include: cancer, hepatotoxicity, renal toxicity,
developmental toxicity, and neurotoxicity).
10E Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
DDT......................... 11A Dose-response data in animals for chronic-duration
oral exposure.
11B Comparative toxicokinetic study (across routes/
species).
11C Bioavailability and bioaccumulation from soil.........
11D Epidemiological studies on the health effects of DDT,
DDD and DDE (Special emphasis endpoints include:
immunotoxicity, reproductive and developmental
toxicity).
11E Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
11F Potential candidate for subregistry of exposed persons *
Chromium.................... 12A Dose-response data in animals for acute-duration
exposure to chromium (VI) and (III) via oral exposure
and for intermediate-duration exposure to chromium
(VI) via oral exposure.
12B Multigeneration reproductive toxicity study via oral
exposure to chromium (III) and (VI).
12C Immunotoxicology battery of tests following oral
exposure to chromium (III) and (VI).
12D 2-species developmental toxicity study via oral
exposure to chromium (III) and (VI).
12E Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
Tetrachloroethylene......... 13A Dose-response data in animals for acute-duration oral
exposure, including neuropathology and demeanor, and
immunopathology.
13B Multigeneration reproductive toxicity study via oral
exposure.
13C Dose-response data in animals for chronic-duration
oral exposure, including neuropathology and demeanor,
and immunopathology.
13D 2-species developmental toxicity study via oral
exposure.
13E Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
13F Potential candidate for subregistry of exposed persons *
Aldrin/Dieldrin............. 14A Dose-response data in animals for intermediate-
duration oral exposure.
14B Bioavailability from soil.............................
14C Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
14D Potential candidate for subregistry of exposed persons *
Cyanide..................... 15A Dose-response data in animals for acute- and
intermediate-duration exposures via inhalation. The
subchronic study should include extended reproductive
organ histopathology and evaluation of
neurobehavioral and neuropathological endpoints.
15B 2-species developmental toxicity study via oral
exposure.
15C Evaluation of the environmental fate of cyanide in
soil.
15D Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
15E Potential candidate for subregistry of exposed persons *
Carbon Tetrachloride........ 16A Dose-response data in animals for chronic oral
exposure. The study should include extended
reproductive organ and nervous tissue (and demeanor)
histopathology.
16B Immunotoxicology battery of tests via oral exposure...
16C Half-life in soil.....................................
16D Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
16E Potential candidate for subregistry of exposed persons *
Beryllium................... 17A Dose-response data in animals for acute- and
intermediate-duration inhalation exposures. The
subchronic study should include extended reproductive
organ histopathology.
17B 2-species developmental toxicity study via inhalation
exposure.
17C Environmental fate in air; factors affecting
bioavailability in air.
17D Analytical methods to determine environmental
speciation.
17E Immunotoxicology battery of tests following oral
exposure.
17F Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
Toluene..................... 18A Dose-response data in animals for acute- and
intermediate-duration oral exposures. The subchronic
study should include an extended histopathological
evaluation of the immune system.
18B Comparative toxicokinetic studies (Characterization of
absorption, distribution, and excretion via oral
exposure).
18C Neurotoxicology battery of tests via oral exposure....
18D Mechanism of toluene-induced neurotoxicity............
18E Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
Nickel...................... 19A Epidemiological studies on the health effects of
nickel (Special emphasis endpoints include:
reproductive toxicity).
19B 2-species developmental toxicity study via the oral
route.
19C Dose-response data in animals for acute- and
intermediate-duration oral exposures.
19D Neurotoxicology battery of tests via oral exposure....
19E Bioavailability of nickel from soil...................
19F Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
Methylene Chloride.......... 20A Dose-response data in animals for acute- and
intermediate-duration oral exposure. The subchronic
study should include extended reproductive organ
histopathology, neuropathology and demeanor, and
immunopathology.
20B 2-species developmental toxicity study via the oral
route.
20C Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
20D Potential candidate for subregistry of exposed persons *
Zinc........................ 21A Dose-response data in animals for acute- and
intermediate-duration oral exposures. The subchronic
study should include an extended histopathological
evaluation of the immunologic and neurological
systems.
21B Multigeneration reproductive toxicity study via oral
exposure.
21C Carcinogenicity testing (2-year bioassay) via oral
exposure.
21D Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
DEHP........................ 22A Epidemiological studies on the health effects of DEHP
(Special emphasis endpoints include: cancer).
22B Dose-response data in animals for acute- and
intermediate-duration oral exposures. The subchronic
study should include an extended histopathological
evaluation of the immunologic and neurologic systems.
22C Multigeneration reproductive toxicity study via oral
exposure.
22D Comparative toxicokinetic studies (Studies designed to
examine how primates metabolize and distribute DEHP
as compared to rodents via oral exposure).
22E Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
22F Potential candidate for subregistry of exposed persons *
Selenium.................... 23A Dose-response data in animals for acute-duration oral
exposure.
23B Immunotoxicology battery of tests via oral exposure...
23C Epidemiological studies on the health effects of
selenium (Special emphasis endpoints include: cancer,
reproductive and developmental toxicity,
hepatotoxicity and adverse skin effects).
23D Exposure levels in humans living near hazardous waste
sites and other populations, such as exposed workers.
23E Potential candidate for subregistry of exposed persons *
Chloroethane................ 24A Dose-response data in animals for acute- and
intermediate-duration oral exposures. The subchronic
study should include an evaluation of immune and
nervous system (and behavior, demeanor) tissues, and
extended reproductive organ histopathology.
24B Dose-response data in animals for chronic inhalation
exposures. The study should include an evaluation of
nervous system (and behavior) tissues.
24C Potential candidate for subregistry of exposed persons *
----------------------------------------------------------------------------------------------------------------
*These substances are included in the pool of candidate substances for subregistry development. These substances
will be considered for selection as primary contaminants by the Division of Health Studies, ATSDR, during each
selection process.
Table 2.--Priority Data Needs Being Addressed by EPA Rule Making
----------------------------------------------------------------------------------------------------------------
Substance ID Priority Data Need TSCA/FIFRA
----------------------------------------------------------------------------------------------------------------
Mercury......................... 3B Dose-response data in animals for chronic- TSCA.
duration oral exposure.
3C Immunotoxicology battery of tests via oral TSCA.
exposure.
Vinyl Chloride.................. 4B Multigeneration reproductive toxicity study via TSCA.
inhalation.
4E 2-species developmental toxicity study via TSCA.
inhalation.
Benzene......................... 5A Dose-response data in animals for intermediate- TSCA.
duration oral exposure. The subchronic study
should include an extended reproductive organ
histopathology.
5C Neurotoxicology battery of tests via oral TSCA.
exposure.
Trichloroethylene............... 10A Dose-response data in animals for acute-duration TSCA.
oral exposure.
10C Immunotoxicology battery of tests via the oral TSCA.
route.
Chromium........................ 12A Dose-response data in animals for acute-duration TSCA.
exposure to chromium(VI) and (III) via oral
exposure.
12B Multigeneration reproductive toxicity study via TSCA.
oral exposure to chromium (III) and (VI).
12C Immunotoxicology battery of tests following oral TSCA.
exposure to chromium (III) and (VI).
Tetrachloroethylene............. 13A Dose-response data in animals for acute-duration TSCA
oral exposure, including neuropathology and (inhalation
demeanor, and immunopathology. study).
13B Multigeneration reproductive toxicity study via TSCA
oral exposure. (inhalation
study).
13D 2-Species developmental toxicity study via oral TSCA
exposure. (inhalation
study).
Cyanide......................... 15A Dose-response data in animals for acute- and TSCA.
intermediate-duration exposures via inhalation.
The subacute study should include extended
reproductive organ histopathology and evaluation
of neurobehavioral and neuropathological
endpoints.
15B 2-Species developmental toxicity study via oral TSCA
exposure. (inhalation
study).
15C Evaluation of the environmental fate of cyanide TSCA.
in soil.
Beryllium....................... 17A Dose-response data in animals for acute- and TSCA.
intermediate-duration inhalation exposures. The
subchronic study should include extended
reproductive organ histopathology.
17B 2-species developmental toxicity study via TSCA.
inhalation exposure.
17C Environmental fate in air; factors affecting TSCA.
bioavailability in air.
17E Immunotoxicology battery of tests following oral TSCA
exposure. (inhalation
study).
Toluene......................... 18A Dose-response data in animals for TSCA.
intermediateduration oral exposures. The study
should include an extended histopathological
evaluation of the immune system.
18B Comparative toxicokinetic studies TSCA.
(Characterization of absorption, distribution,
and excretion via oral exposure).
Methylene Chloride.............. 20A Dose-response data in animals for intermediate- TSCA.
duration oral exposure. The study should include
extended immunopathology and neuropathology.
20B 2-species developmental toxicity study via the TSCA.
oral route.
Chloroethane.................... 24A Dose-response data in animals for acute- and TSCA. (EPA will
intermediate-duration oral exposures. The only address
subchronic study should include an evaluation of the immune
immune and nervous system (and behavior, system
demeanor) tissues, and extended reproductive requirement of
organ histopathology. this Priority
Data Need)
----------------------------------------------------------------------------------------------------------------
Table 3.--Priority Data Needs Potentially Being Addressed by Voluntary Research
----------------------------------------------------------------------------------------------------------------
Substance ID Priority data need Firm
----------------------------------------------------------------------------------------------------------------
PCBs............................ 7B Biodegradation of PCBs General Electric Company.
in water.
7E Epidemiological studies General Electric Company.
on the health effects
of PCBs (Special
emphasis endpoints
include:
immunotoxicity,
gastrointestinal,
toxicity, liver,
kidney, thyroid,
toxicity, reproductive/
developmental,
toxicity).
Methylene chloride.............. 20A Dose-response data in Halogenated Solvents Industry Alliance.
animals for acute- and
intermediate-duration
oral exposure. The
subchronic study should
include extended
reproductive organ
histopathology,
neuropathology and
demeanor, and
immunopathology.
20B 2-species developmental Halogenated Solvents Industry Alliance.
toxicity study via the
oral route.
----------------------------------------------------------------------------------------------------------------
Table 4.--Priority Data Needs Being Addressed by MHPF Institutions
--------------------------------------------------------------------------------------------------------------------------------------------------------
Substance ID Priority data need Institution
--------------------------------------------------------------------------------------------------------------------------------------------------------
Lead........................ 1A Mechanistic studies on the neurotoxic effects of Florida A & M University.
lead. Texas Southern University.
1C Exposure levels in humans living near hazardous The King/Drew Medical Center of the Charles R. Drew
waste sites and other populations, such as University of Medicine and Science.
exposed workers. Morehouse School of Medicine.
Mercury..................... 3A Multigeneration reproductive toxicity study via Tuskegee University.
oral exposure.
Benzene..................... 5B 2-species developmental toxicity study via oral Xavier University.
exposure.
PAHs........................ 9A Dose-response data in animals for intermediate Meharry Medical College.
duration oral exposures. The subchronic study
should include extended reproductive organ
histopathology and immunopathology.
9D Dose-response data in animals for acute- and Meharry Medical College.
intermediate-duration inhalation exposures. The
subchronic study should include extended
reproductive organ histopathology and
immunopathology.
Trichloroethylene........... 10B Neurotoxicology battery of tests via oral Texas Southern University.
exposure.
Toluene..................... 18C Neurotoxicology battery of tests via oral Texas Southern University.
exposure.
Zinc........................ 21A Dose-response data in animals for acute- and Xavier University.
intermediate-duration oral exposures. The Tuskegee University.
subchronic study should include an extended
histopathological evaluation of the immunologic
and neurological systems.
--------------------------------------------------------------------------------------------------------------------------------------------------------
Table 5.--Priority Data Needs Being Addressed by the ATSDR Great Lakes Human Health Effects Research Program
----------------------------------------------------------------------------------------------------------------
Substance ID Priority data need Institution
----------------------------------------------------------------------------------------------------------------
Lead........................ 1C Exposure levels in humans State University of New York at Buffalo.
living near hazardous State University of New York at Oswego.
waste sites and other Michigan State University.
populations, such as University of Wisconsin--Superior.
exposed workers.
New York State Health Department.
University of Illinois at Chicago.
University of Illinois at Urbana-
Champaign.
Wisconsin Department of Health and Social
Services.
Mercury..................... 3A Multigeneration State University of New York at Oswego.
reproductive toxicity University of Illinois at Chicago.
study via oral exposure.
3D Exposure levels in humans State University of New York at Buffalo.
living near hazardous State University of New York at Oswego.
waste sites and other Michigan State University.
populations, such as University of Wisconsin--Superior.
exposed workers.
New York State Health Department.
University of Illinois at Chicago.
University of Illinois at Urbana-
Champaign.
Wisconsin Department of Health and Social
Services.
3E Potential candidate for Wisconsin Department of Health and Social
subregistry of exposed Services.
persons.
PCBs........................ 7A Dose-response data in University of Wisconsin--Superior.
animals for acute- and
intermediate-duration
oral exposures.
7E Epidemiological studies on State University of New York at Buffalo.
the health effects of State University of New York at Oswego.
PCBs (special emphasis University of Wisconsin--Superior.
endpoints include: University of Illinois at Chicago.
immunotoxicity, University of Illinois at Urbana-
gastrointestinal Champaign.
toxicity, liver, kidney,
thyroid toxicity,
reproductive/developmenta
l toxicity).
7F Exposure levels in humans State University of New York at Buffalo.
living near hazardous State University of New York at Oswego.
waste sites and other Michigan State University.
populations, such as University of Wisconsin--Superior.
exposed workers.
New York State Health Department.
University of Illinois at Chicago.
University of Illinois at Urbana-
Champaign.
Wisconsin Department of Health and Social
Services.
PAHs........................ 9E Epidemiological studies on Wisconsin Department of Health and Social
the health effects of Services.
PAHs (special emphasis
endpoints include:
cancer, dermal,
hemolymphatic, and
hepatic).
9F Exposure levels in humans Wisconsin Department of Health and Social
living near hazardous Services.
waste sites and other
populations, such as
exposed workers.
DDT......................... 11D Epidemiological studies on State University of New York at Buffalo.
the health effects of State University of New York at Oswego.
DDT, DDD and DDE (special Michigan State University.
emphasis endpoints University of Illinois at Chicago.
include: immunotoxicity, Wisconsin Department of Health and Social
reproductive and Services.
developmental toxicity).
11E Exposure levels in humans State University of New York at Buffalo.
living near hazardous State University of New York at Oswego.
waste sites and other Michigan State University.
populations, such as University of Illinois at Chicago.
exposed workers. Wisconsin Department of Health and Social
Services.
11F Potential candidate for Wisconsin Department of Health and Social
subregistry of exposed Services.
persons.
----------------------------------------------------------------------------------------------------------------
[FR Doc. 94-5555 Filed 3-9-94; 8:45 am]
