Update on the Status of the Superfund Substance-Specific Applied Research Program

SUMMARY: This Notice is an update on the status of ATSDR's continuing

effort to implement the Substance-Specific Applied Research Program

(SSARP). Authorized by the Comprehensive Environmental Response,

Compensation, and Liability Act of 1980 (Superfund) or CERCLA, as

amended by the Superfund Amendments and Reauthorization Act of 1986

(SARA) (42 U.S.C. 9604 (i)), this research program 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, 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 (56 FR 52166, October 17, 1991).

Priority data needs for 12 additional priority hazardous substances

were recently identified and are also being announced in a Federal

Register Notice. The 12 substances, each of which is included in

ATSDR's List of Priority Hazardous Substances, are chlordane, 1,2-

dibromo- 3-chloropropane, di-n-butyl phthalate, disulfoton, endrin

(includes endrin aldehyde), endosulfan (alpha-, beta-, and endosulfan

sulfate), heptachlor (includes heptachlor epoxide),

hexachlorobutadiene, hexachlorocyclohexane (alpha-, beta-, delta- and

gamma-), manganese, methoxychlor, and toxaphene.

This Notice also serves as a continuous call for voluntary research

proposals. Private-sector organizations may volunteer to conduct

research to address specific priority data needs by indicating their

interest through submission of a research proposal to ATSDR (see

ADDRESSES section of this Notice). 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 strongly

encourages private-sector organizations to volunteer at any time to

conduct research to address identified data needs unless ATSDR

announces that research has already been initiated for that specific

data need.

ADDRESSES: Private-sector organizations interested in volunteering to

conduct research may write to Dr. William Cibulas, Chief, Research

Implementation Branch, Division of Toxicology, ATSDR, 1600 Clifton

Road, N.E., Mailstop E-29, Atlanta, Georgia 30333.

FOR FURTHER INFORMATION CONTACT: Dr. William Cibulas, Chief, Research

Implementation Branch, Division of Toxicology, ATSDR, 1600 Clifton

Road, N.E., Mailstop E-29, Atlanta, Georgia 30333, telephone 404-639-

6306.

SUPPLEMENTARY INFORMATION:

Background

CERCLA as amended by SARA (42 U.S.C. 9604(i)) requires that ATSDR

(1) jointly with the 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 address identified data needs

associated with the substances. Before starting such a program, ATSDR

will consider recommendations of the Interagency Testing Committee on

the type of research that should be done. This committee was

established under section 4(e) of the Toxic Substances Control Act of

1976 (TSCA).

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 address 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 address the

substance-specific information needs of the public and scientific

community, and (2) to supply necessary information to improve the

database to conduct comprehensive public health assessments of

populations living near hazardous waste sites. This program will also

provide data that can be generalized to other substances or areas of

science, including risk assessment of chemicals, thus creating a

scientific base for addressing a broader range of data needs.

In section 104(i)(5)(D), CERCLA 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

TSCA and by registrants under the Federal Insecticide, Fungicide, and

Rodenticide Act of 1972 (FIFRA), or by cost recovery from responsible

parties under CERCLA. To execute this statutory intent, ATSDR developed

a plan whereby parts of the SSARP are being conducted via regulatory

mechanisms (TSCA/FIFRA), private-sector voluntarism, and through the

direct use of CERCLA funds.

The TASARC, comprised of scientists from ATSDR, NTP, and the EPA

has been set up:

(1) To advise on the assignment of priorities on mechanisms for

addressing data needs;

(2) To coordinate knowledge of research activities to avoid

duplication of research in other programs and under other authorities;

(3) To advise on issues of science related to substance-specific

data needs; and

(4) To maintain a scheduled forum that provides an overall review

of the ATSDR SSARP.

The TASARC has met six times since the SSARP began. This Notice is

an update on the status of ATSDR's efforts to implement the SSARP,

focusing on ongoing activities relevant to test-rule development under

TSCA/FIFRA, private-sector voluntarism, and the 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, a total of 63

research needs associated with 38 ATSDR priority hazardous substances

(including 15 polycyclic aromatic hydrocarbons) are being addressed via

these mechanisms (Table 1).

[[Page 14421]]

ATSDR believes that these priority data needs will remain on the

agency's list until ongoing studies to address them have been

completed, peer-reviewed, and accepted by ATSDR. However, priority data

needs could be deleted from the list (Table 1) if upon re-evaluation of

the existing database, the agency determines that additional studies

are no longer needed. Three recent examples follow. ATSDR, in

consultation with the TASARC, re-evaluated the database for acute

inhalation toxicity for vinyl chloride and determined no additional

data are needed at this time (Table 1). With regard to the priority

data need for oral developmental toxicity studies for

tetrachloroethylene (PERC), ATSDR recently re-evaluated the database

during the update of the toxicological profile for this substance.

ATSDR concluded that the database was sufficient to derive a minimal

risk level (MRL) for acute oral exposure based on a developmental

toxicity study. Although ATSDR believes that additional developmental

data would be useful to more fully characterize the effects and

increase the confidence level of the MRL, the agency now believes that

this data is more appropriately classified as a data need rather than a

priority data need. Therefore, this priority data need has also been

deleted from the list (Table 1). Similarly, the priority data need for

additional acute oral studies for trichloroethylene has been

reclassified as a data need and thus deleted from the list (Table 1)

because an MRL was derived during the updating of the toxicological

profile. Conversely, additional priority data needs could be included

in the ATSDR list based on assessment by agency programs (See Section

F, ``Other ATSDR Programs,'' which discusses exposure subregistries).

A. TSCA/FIFRA

In developing and implementing the Substance-Specific Applied

Research Program, ATSDR, NTP, and EPA have established procedures to

identify priority data needs of mutual interest to Federal programs.

These data needs are being addressed through a program of toxicologic

testing under TSCA. This research will be conducted according to

established TSCA procedures and guidelines. Generally, this testing

will address more than one Federal program's need. Following review and

endorsement by the TASARC oversight committee during fiscal year (FY)

1993, of the 117 priority data needs for 38 substances, approximately

60 priority data needs were referred to the EPA under TSCA/FIFRA

authorities.

During 1994, EPA added 11 ATSDR substances (and associated 26

priority data needs) to its master testing list, the first step in

test-rule development under TSCA, Section 4 (59 FR 11434, March 10,

1994). On September 30, 1994, EPA published a Federal Register Notice

soliciting testing proposals from industry to address the priority data

needs identified for ATSDR's priority hazardous substances (59 FR

49934). Although no manufacturers or processors of these substances

came forward with testing proposals, several industry groups responded

by submitting proposals to address some of the data needs via ATSDR's

voluntary research program described in detail in Section B, ``Private-

Sector Voluntarism.'' The priority data needs currently being addressed

by TSCA/FIFRA are listed in Table 2.

ATSDR shared its priority data needs for these substances with

other Federal agencies and programs. On several occasions when ATSDR

identified priority data needs for oral exposure, other agencies needed

inhalation data. In response, ATSDR is considering proposals to conduct

inhalation studies in conjunction with physiologically based

pharmacokinetic (PBPK) studies in lieu of oral bioassays. ATSDR expects

that inhalation data derived from these studies can be used with PBPK

modeling to address its oral toxicity data needs.

Table 2 includes the priority data needs for three metals, i.e.,

beryllium, chromium and mercury. However, the specific forms of the

metals to be tested are yet to be determined. The TASARC has

established a workgroup to address this issue. The workgroup will also

consider the needs of other Federal agencies and EPA programs. The EPA

will solicit testing proposals for these three metals at a later date.

B. Private-Sector Voluntarism

As part of the SSARP, on February 7, 1992, ATSDR initially

announced a set of proposed procedures for conducting voluntary

research (56 FR 4758). Revisions based on public comments were

published on November 16, 1992 (57 FR 54160). Private-sector

organizations were encouraged to volunteer to conduct research to

address these specific priority data needs.

ATSDR has been pursuing voluntary research interests with three

private-sector organizations: the General Electric Company (GE), the

Halogenated Solvents Industry Alliance (HSIA), and the Chemical

Manufacturers Association (CMA). Preliminary discussions are being held

with a fourth organization, the Shell Oil Company. Through the

voluntary research efforts of these organizations, data needs for two

classes of substances (PCB compounds and volatile organic compounds)

are being addressed (Table 2). To date, two memoranda of understanding

(MOU) have been signed by ATSDR and the interested parties. A third MOU

is under development.

General Electric Company (GE)

On February 8, 1995, ATSDR entered into an MOU with GE. This was

the first time a private-sector organization volunteered to conduct

research to address ATSDR's data needs identified in its SSARP. The MOU

with GE covers the following three studies on PCBs:

* Project 1, ``An assessment of the chronic toxicity and

oncogenicity of Aroclor-1016, Aroclor-1242, Aroclor-1254, and Aroclor-

1260 administered in diet to rats,'' was initiated on February 8, 1993.

* Project 2, ``Metabolite detection as a tool for the determination

of naturally occurring aerobic PCB biodegradation,'' was initiated on

January 2, 1995.

* Project 3, ``PCB congener analyses,'' was initiated on February

8, 1993.

While the above studies do not address ATSDR's priority data needs

for PCBs, the three projects will address some of the agency's data

needs for these substances. Specifically, although ATSDR has identified

bioassays via the inhalation and dermal routes as data needs for PCBs,

agency scientists believe information gained via GE's oral bioassay

(Project 1) is pertinent to understanding the toxicity of PCBs.

Furthermore, first-pass metabolism does not appear to play a key role

for these substances. Therefore, toxicity information to be obtained

from the GE oral bioassay is expected to be relevant to the inhalation

and dermal routes.

ATSDR has identified PCB degradation in sediment as a data need.

Additional environmental fate information is needed to estimate

exposure to PCBs under various conditions of environmental release in

order to plan and conduct follow-up exposure and health studies.

Therefore, Project 2 will address ATSDR's data need for the

environmental fate of PCBs.

Although ATSDR has not identified PCB congener analyses (Project 3)

as a data need, agency scientists believe that the toxicokinetics data

(using selected tissues from Project 1) may provide important knowledge

about the correlation of health effects with relevant PCB congeners.

[[Page 14422]]

Halogenated Solvents Industry Alliance (HSIA)

On April 4, 1995, ATSDR entered into an MOU with HSIA covering

studies to address three ATSDR priority toxicity data needs for

methylene chloride. The studies consist of acute- and subchronic-

duration, and developmental toxicity via oral exposure. The data will

be obtained by using PBPK modeling. These studies were initiated on May

23, 1995.

HSIA has also proposed to conduct a 28-day immunopathology

assessment for methylene chloride via oral exposure, a priority data

need identified by ATSDR. The agency expects to receive a study

protocol from HSIA for peer review in the near future.

Currently, HSIA and ATSDR continue to discuss voluntary research

efforts for trichloroethylene (TCE) and tetrachloroethylene (PERC).

With regard to TCE, ATSDR has recently reclassified the priority

data need for acute oral data to a data need, (see Background section

of this Notice). The agency is continuing its discussion with HSIA to

assess the possibility of conducting a study or utilizing benchmark

dose modeling to address this data need. As for immunopathology data,

HSIA proposed to first review the existing data for TCE. If the data

are inadequate and the methylene chloride immunopathology study

mentioned above has provided meaningful information, HSIA would then

conduct a similar study for TCE.

Regarding the priority data needs for PERC, HSIA plans to obtain

the oral neurotoxicity data called for by the agency by PBPK modeling.

The database to be used for modeling will include the HSIA-sponsored

inhalation neurotoxicity study recently approved by EPA. EPA and ATSDR

scientists recently reviewed and accepted the HSIA-sponsored

reproductive toxicity study of PERC via inhalation. HSIA proposed to

address ATSDR's priority data need for oral reproductive data using

PBPK modeling. As for ATSDR's priority data need for immunopathology

data, HSIA would follow the same procedures as for TCE (described

above).

Finally, with regard to ATSDR's data need for oral developmental

toxicity studies for PERC (see Background section of this Notice),

ATSDR is continuing its discussion with HSIA to obtain this data via

PBPK modeling once the EPA-required inhalation developmental toxicity

study has been completed.

Chemical Manufacturers Association (CMA)

During FY 1995, the CMA submitted a study protocol addressing two

ATSDR priority data needs for vinyl chloride, specifically, inhalation

reproductive and developmental toxicity studies in rats.

ATSDR accepted the study protocol as a candidate for voluntary

research based on ATSDR peer reviews and CMA's satisfactory response to

the peer reviewers' comments. ATSDR expects to finalize an MOU with CMA

covering this study in the near future.

EPA no longer requires inhalation neurological data for vinyl

chloride as originally stated in its solicitation Notice (59 FR 49934,

September 30, 1994). Its decision is based on a recent reevaluation of

the database.

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. About $4 million was

allocated annually for FYs 1993 to 1995 to continue this research

program that ends in September 1997.

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. To date, more than 20 abstracts have been presented at

scientific meetings, 4 manuscripts have been published in peer-reviewed

journals, and 7 manuscripts are in preparation. The institutions

receiving awards and their respective research projects are listed in

Table 2.

A not-for-profit 501(c)(3) organization, the MHPF comprises 11

minority health professions schools. Its primary mission is to research

the health problems that disproportionately affect poor and minority

citizens. The purposes of the ATSDR-MHPF cooperative agreement are (1)

to initiate research to address 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 MHPF

members are conducting health studies of minority groups exposed to

ATSDR's priority hazardous substances.

D. National Toxicology Program (NTP)

ATSDR maintains an interagency agreement (IAG) with NTP to conduct

toxicologic testing of substances identified at NPL sites. The studies

determine levels of exposure that present a significant risk to humans

of acute, subchronic, 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 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 (immunotoxicology study of carbon tetrachloride) is being

addressed.

An area of ongoing research by the NTP is to study the

bioavailability of PCBs in soil, a priority data need for ATSDR.

Therefore, NTP research may also potentially address this ATSDR

priority data need.

During FY 1993, the existing IAG was modified to include toxicity

studies of ATSDR's priority hazardous substances via application of

structure-activity relationship (SAR) techniques and PBPK modeling. NTP

indicated future plans for SAR modeling for reproductive and

immunologic endpoints. ATSDR is continuing to work closely with NTP as

the agency has identified many reproductive and immunologic data needs

for the 38 priority hazardous substances. As discussed in Section A,

``TSCA/FIFRA,'' ATSDR will consider using PBPK modeling to address data

needs when models are well developed and validated. Therefore, ATSDR

will continue to work closely with NTP in its efforts to refine the

models.

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

[[Page 14423]]

awards and their respective studies are listed in Table 2.

The Great Lakes Critical Programs Act of 1990 mandated that EPA, in

consultation with ATSDR, prepare a report that assesses the adverse

effects of pollutants in the Great Lakes system on the health of

individuals in the Great Lakes states. This report was recently

transmitted to the Congress by the EPA Administrator.

In support of this directive, ATSDR received funds to carry out

research. The ATSDR-supported research projects focus on at-risk

populations to further define the human health consequences of exposure

to persistently toxic substances in the Great Lakes basin. The research

activities include but are not limited to the following:

(1) Characterizing exposure and determining the profiles and levels

of Great Lakes contaminants in biologic tissues and fluids in at-risk

populations;

(2) Identifying sensitive and specific human reproductive/

developmental endpoints 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 people's health from eating

contaminated fish from the Great Lakes region. On September 30, 1992,

ATSDR announced 9 awards under this program.

In FY 1993, about $3 million was allocated to support the

continuation of the research projects conducted at the 9 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. Additional funding of $3 million and

$4 million for FYs 1994 and 1995, respectively, was allocated to

continue support of the 10 research projects.

During FY 1994, ATSDR held a Great Lakes Research Symposium in

Detroit, Michigan. The proceedings of the symposium will be published

in the Journal of Toxicology and Industrial Health in the near future.

Other ATSDR Programs

In its role as a public health agency addressing environmental

health, when appropriate, ATSDR may collect human data to validate

substance-specific exposure and toxicity findings. Information on

levels of contaminants in humans has been identified and remains 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

its 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 in the candidate pool.

They will be considered for selection as primary contaminants during

each selection process (Table 1).

Since the publication of the ATSDR March 10, 1994, Federal Register

Notice (59 FR 11434), EDRB has re-evaluated the databases and included

nickel, PCBs, toluene, and zinc in the candidate pool for consideration

during each selection process (Table 1). However, arsenic, beryllium,

cadmium, and lead 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.

Finally, the need to collect, evaluate, and interpret environmental

data from contaminated media around hazardous waste sites remains a

priority data need for all 38 priority hazardous substances by ATSDR.

However, agency scientists realize that a substantial amount of this

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 to characterize

better the need for additional site-specific information.

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 26, 1996.

Claire V. Broome,

Deputy Administrator, Agency for Toxic Substances and Disease Registry

.

Table 1.--Substance-Specific Priority Data Needs (PDN) Currently Being

Addressed Under ATSDR's Applied Research Programs

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

Substance PDN ID PDN description Programs (1)

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

Lead................ 1A Mechanistic studies M

on the neurotoxic

effects of lead.

1B Analytical methods

for tissue levels.

1C Exposure levels in M, G

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 M, G

reproductive

toxicity study via

oral exposure.

3B Dose-response data E

in animals for

chronic-duration

oral exposure.

[[Page 14424]]

3C Immunotoxicology E

battery of tests

via oral exposure.

3D Exposure levels in G

humans living near

hazardous waste

sites and other

populations, such

as exposed workers.

3E Potential candidate A, G

for subregistry of

exposed persons.

Vinyl Chloride...... 4A Dose-response data O (2)

in animals for

acute-duration

inhalation exposure.

4B Multigeneration V (7)

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 V (7)

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 A

for subregistry of

exposed persons.

Benzene............. 5A Dose-response data E

in animals for

acute- and

intermediate-

duration oral

exposure. The

subchronic study

should include an

extended

reproductive organ

histopathology.

5B 2-species M

developmental

toxicity study via

oral exposure.

5C Neurotoxicology E

battery of tests

via oral exposure.

5D Epidemiologic

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 G

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 Epidemiologic G

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 G

humans living near

hazardous waste

sites and other

populations, such

as exposed workers.

7F Potential candidate A (3)

for subregistry of

exposed persons.

7G (8) Chronic toxicity and V

oncogenicity via

oral exposure.

7H (8) Aerobic PCB V

biodegradation in

sediment.

7I (8) PCB congener V

analysis.

Chloroform.......... 8A Dose-response data

in animals for

intermediate-

duration oral

exposure.

8B Epidemiologic

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 A

for subregistry of

exposed persons.

PAHs.............. 9A Dose-response data M

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 M

in animals for

acute- and

intermediate-

duration inhalation

exposures. The

subchronic study

should include

extended

reproductive organ

histopathology and

immunopathology.

9E Epidemiologic G

studies on the

health effects of

PAHs (Special

emphasis endpoints

include cancer,

dermal,

hemolymphatic, and

hepatic).

9F Exposure levels in G

humans living near

hazardous waste

sites and other

populations, such

as exposed workers.

9G Potential candidate A

for subregistry of

exposed persons.

Trichloro-ethylene.. 10A Dose-response data O (2)

in animals for

acute- duration

oral exposure..

10B Neurotoxicology M

battery of tests

via the oral route.

10C Immunotoxicology V (4)

battery of tests

via the oral route.

10D Epidemiologic

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 Epidemiologic G

studies on the

health effects of

DDT, DDD and DDE

(Special emphasis

endpoints include

immunotoxicity,

reproductive and

developmental

toxicity).

11E Exposure levels in G

humans living near

hazardous waste

sites and other

populations, such

as exposed workers.

[[Page 14425]]

11F Potential candidate A, G

for subregistry of

exposed persons.

Chromium............ 12A Dose-response data E

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 E

reproductive

toxicity study via

oral exposure to

chromium (III) and

(VI).

12C Immunotoxicology E

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.

Tetrachloro- 13A Dose-response data V(4, 5)

ethylene. in animals for

acute-duration oral

exposure, including

neuropathology and

demeanor, and

immunopathology.

13B Multigeneration V(4, 5)

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 O (2)

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 A

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 A

for subregistry of

exposed persons.

Cyanide............. 15A Dose-response data E

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 E

developmental

toxicity study via

oral exposure.

15C Evaluation of the E

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 A

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 NTP

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 A

for subregistry of

exposed persons.

Beryllium........... 17A Dose-response data E

in animals for

acute- and

intermediate-

duration inhalation

exposures. The

subchronic study

should include

extended

reproductive organ

histopathology.

17B 2-Species E

developmental

toxicity study via

inhalation exposure.

17C Environmental fate E

in air; factors

affecting

bioavialability in

air.

17D Analytical methods

to determine

environmental

speciation.

17E Immunotoxicology E

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 E

in animals for

acute- and

intermediate-

duration oral

exposures. The

subchronic study

should include an

extended

histopathologic

evaluation of the

immune system.

18B Comparative E

toxicokinetic

studies

(Characterization

of absorption,

distribution, and

excretion via oral

exposure).

18C Neurotoxicology M

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.

18F Potential candidate A (3)

for subregistry of

exposed persons.

Nickel.............. 19A Epidemiologic

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.

19G Potential candidate A (3)

for subregistry of

exposed persons.

Methylene Chloride.. 20A Dose-response data V (5,6)

in animals for

acute- and

intermediate-

duration oral

exposure. The sub-

chronic study

should include

extended

reproductive organ

histopathology,

neuropathology and

demeanor, and

immunopathology.

20B 2-Species V (5)

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 A

for subregistry of

exposed persons.

[[Page 14426]]

Zinc................ 21A Dose-response data M

in animals for

acute- and

intermediate-

duration oral

exposures. The sub-

chronic study

should include an

extended

histopathologic

evaluation of the

immunologic and

neurologic 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.

21E Potential candidate A (3)

for subregistry of

exposed persons.

DEHP................ 22A Epidemiologic

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

histopathologic

evaluation of the

immunologic and

neurologic systems.

22C Multigeneration

reproductive

toxicity study via

oral exposure.

22D Comparative E

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 A

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 Epidemiologic

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 A

for subregistry of

exposed persons.

Chloroethane........ 24A Dose-response data E

in animals for

acute- and

intermediate-

duration oral

exposures. The

subchronic study

should include an

evaluation of

immune and nervous

system 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

tissues.

24C Potential candidate A

for subregistry of

exposed persons.

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

\1\ ATSDR programs for addressing data needs. A=ATSDR Division of Health

Studies; E=Environmental Protection Agency-TSCA/FIFRA testing; G=Great

Lakes Human Health Research Program; M=Minority Health Professions

Foundation Schools; NTP=National Toxicology Program; V=Voluntary

research; O=Other.

\2\ No longer considered a priority data need based on recent evaluation

of the database by ATSDR.

\3\ These substances have been included in the pool of candidate

substances for subregistry development since the publication of the

Federal Register notice on March 10, 1994 (59 FR 11434).

\4\ Potentially to be addressed by ATSDR's Voluntary Research Program.

\5\ Data to be obtained by PBPK modeling.

\6\ Initiation of immunopathology study pending submission and peer

review of study protocol.

\7\ Data to be obtained from a combined 2-generation reproduction and

developmental toxicity study in rats.

\8\ Not a priority data need.

Table 2.--Groups Addressing ATSDR Priority Data Needs (PDN)

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

Firm, institution, agency,

ATSDR Program or Consortium Substance PDN ID

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

Voluntarism....................... Chemical Manufacturers Vinyl Chloride...... 4B, 4E

Association.

General Electric Company.. PCBs................ 7G, 7H, 7I

Halogenated Solvents Trichloroethylene... 10C

Industry Alliance.

Tetrachloroethylene. 13A, 13B

Methylene chloride.. 20A, 20B

Minority Health Professions Florida A & M University.. Lead................ 1A

Foundation Schools.

The King/Drew Medical Lead................ 1C

Center of the Charles R.

Drew University of

Medicine and Science.

Meharry Medical College... PAHs................ 9A, 9D

Morehouse School of Lead................ 1C

Medicine.

Texas Southern University. Lead................ 1A

Trichloroethylene... 10B

Toluene............. 18C

Tuskegee University....... Mercury............. 3A

Zinc................ 21A

Xavier University......... Benzene............. 5B

Zinc................ 21A

Great Lakes Human Health Research Michigan State University. Lead................ 1C

Program.

Mercury............. 3D

PCBs................ 7F

[[Page 14427]]

DDT................. 11D, 11E

New York State Health Lead................ 1C

Department.

Mercury............. 3D

PCBs................ 7F

State University of New Lead................ 1C

York at Buffalo.

Mercury............. 3D

PCBs................ 7E, 7F

DDT................. 11D, 11E

State University of New Lead................ 1C

York at Oswego.

Mercury............. 3A, 3D

PCBs................ 7E, 7F

DDT................. 11D, 11E

University of Illinois at Lead................ 1C

Chicago.

Mercury............. 3A, 3D

PCBs................ 7E, 7F

DDT................. 11D, 11E

University of Illinois at Lead................ 1C

Urbana-Champaign.

Mercury............. 3D

PCBs................ 7E, 7F

University of Wisconsin-- Lead................ 1C

Superior.

Mercury............. 3D

PCBs................ 7A, 7E, 7F

Wisconsin Department of Lead................ 1C

Health and Social

Services.

Mercury............. 3D, 3E

PCBs................ 7F

PAHs................ 9E, 9F

.......................... DDT................. 11D, 11E, 11F

TSCA/FIFRA........................ Environmental Protection Mercury............. 3B

Agency.

Mercury............. 3C

Benzene............. 5A

Benzene............. 5C

Chromium............ 12A

Chromium............ 12B

Chromium............ 12C

Cyanide............. 15A

Cyanide............. 15B

Cyanide............. 15C

Beryllium........... 17A

Beryllium........... 17B

Beryllium........... 17C

Beryllium........... 17E

Toluene............. 18A

Toluene............. 18B

DEHP................ 22D

Chloroethane........ 24A

National Toxicology Program....... National Institute of Carbon Tetrachloride 16B

Environmental Health

Sciences.

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

[FR Doc. 96-7852 Filed 3-29-96; 8:45 am]

BILLING CODE 4163-70-P