Status of the Superfund Substance-Specific Applied Research Program; Notice DEPARTMENT OF HEALTH AND HUMAN SERVICES

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

----------------------------------------------------------------------------------------------------------------

Substance ID Priority Data Need Addressed

----------------------------------------------------------------------------------------------------------------

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]