[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



_______________________________________________________________________




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.

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

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]