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

Federal RegisterNov 29, 2005

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Toxic Substances and Disease Registry

[ATSDR-215]

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

AGENCY:

Agency for Toxic Substances and Disease Registry (ATSDR), U.S. Department of Health and Human Services (HHS).

ACTION:

Notice.

SUMMARY:

This Notice provides the status of ATSDR's Superfund-mandated Substance-Specific Applied Research Program (SSARP) which was last updated in a

Federal Register

notice in 2002 (67 FR 4836). Authorized by the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA, also known as the Superfund statute), 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 frequently found at waste sites 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 Priority List of Hazardous Substances (68 FR 63098, November 7, 2003), 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.

On July 30, 1997, priority data needs for 12 additional hazardous substances frequently found at waste sites were determined and announced in the

Federal Register

(62 FR 40820). The 12 substances, each of which is included in ATSDR's Priority List of 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.

More recently, priority data needs for 10 additional hazardous substances frequently found at waste sites were determined and announced in the

Federal Register

(68 FR 22704). The ten substances, each of which is included in ATSDR's Priority List of Hazardous Substances, are asbestos, benzidine, chlorinated dibenzo-p-dioxins, 1,2-dibromoethane, 1,2-dichloroethane, 1,1-dichloroethene, ethylbenzene, pentachlorophenol, 1,1,2,2-tetrachloroethane, and total xylenes.

Currently, the priority data needs for acrolein and barium are being identified and will be reported in a future

Federal Register

notice.

To date, 270 priority data needs have been identified for the 60 hazardous substances, and 86 priority data needs have been filled (Table 1). ATSDR fills these research needs through U.S. Environmental Protection Agency (EPA) regulatory mechanisms (test rules), private-sector voluntarism, and the direct use of CERCLA funds. Additional priority data needs are being addressed through collaboration with the National Toxicology Program (NTP), by ATSDR's Great Lakes Human Health Effects Research Program, and other Agency programs. Priority data needs documents describing ATSDR's rationale for prioritizing research needs for each substance are available. See

ADDRESSES

section of this Notice.

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 identified in this Notice by indicating their interest through submission of a letter of intent to ATSDR (see

ADDRESSES

section of this Notice). A Tri-Agency Superfund Applied Research Committee (TASARC) composed of scientists from ATSDR, National Institute of Environmental Health Sciences (NIEHS)/NTP, and the EPA, will review all proposed voluntary research studies.

DATES:

ATSDR provides updates on the status of its Substance-Specific Applied Research Program approximately every three years or sooner, as needed. ATSDR considers the voluntary research effort to be important to the continuing implementation of the SSARP. Therefore, the Agency strongly encourages private-sector organizations to volunteer at any time to conduct research to fill data needs until ATSDR announces that other research mechanisms are in place to address those specific data needs.

ADDRESSES:

Private-sector organizations interested in volunteering to conduct research can write to Yee-Wan Stevens, M.S., Applied Toxicology Branch, Division of Toxicology and Environmental Medicine, ATSDR, 1600 Clifton Road, NE., Mailstop F-32, Atlanta, Georgia 30333, e-mail:

YStevens@cdc.gov.

Information about pertinent ongoing or completed research that may fill priority data needs cited in this Notice should be similarly addressed.

Other Requirements:

Projects that involve the collection of information from ten or more individuals and funded by cooperative agreement will be subject to review by the Office of

Management and Budget (OMB) under the Paperwork Reduction Act.

FOR FURTHER INFORMATION CONTACT:

Yee-Wan Stevens, M.S., Applied Toxicology Branch, Division of Toxicology and Environmental Medicine, ATSDR, 1600 Clifton Road, NE., Mailstop F-32, Atlanta, Georgia 30333, telephone: (770) 488-3325, fax: (770) 488-4178.

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, in conjunction with NTP, 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 [15 U.S.C. 2604(e)](TSCA).

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 information necessary to improve the database used to conduct comprehensive public health assessments of populations living near hazardous waste sites. We anticipate that the information will help to establish linkages between levels of contaminants in the environment and levels in human tissue and organs associated with adverse health effects. Once such links have been established, strategies to mitigate potentially harmful exposures can be developed. 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 information base for addressing a broader range of data needs.

ATSDR encourages the use of

in vitro

assessment methods and other innovative tools for filling priority data needs. For example, the Agency believes that physiologically based pharmacokinetic (PBPK) modeling could serve as a valuable tool in predicting across route similarities (or differences) in toxicological responses to hazardous substances. Therefore, on a case-by-case basis, a priority data need can be filled using existing data and modeling. In addition, ATSDR is a member of NTP's InterAgency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and supports development, validation, and acceptance of alternative toxicological test methods that reduce, refine, and replace the use of animals, as appropriate.

CERCLA 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 substance in question,” as required in TSCA and the Federal Insecticide, Fungicide, and Rodenticide Act of 1972 [7 U.S.C. 136

et seq.

] (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 the regulatory mechanisms referenced (TSCA/FIFRA), private-sector voluntarism, and the direct use of CERCLA funds.

The TASARC, composed of scientists from ATSDR, NIEHS/NTP, and EPA, has been set up to:

(1) Advise ATSDR on the assignment of priorities for mechanisms to address data needs,

(2) Coordinate knowledge of research activities to avoid duplication of research in other programs and under other authorities,

(3) Advise ATSDR 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.

TASARC has met 12 times since the initiation of the SSARP. It has guided referral of priority data needs to EPA and the associated development of test rules through TSCA. In addition, it has endorsed the proposals of several private-sector organizations to conduct voluntary research. Furthermore, TASARC has become a forum for other federal agencies to bring forth their research agendas. For example, it has coordinated research efforts on hazardous pollutants with the Office of Air and Radiation, EPA. TASARC has developed testing guidelines for immunotoxicity; and has endorsed the use of decision-support methodologies such as physiologically based pharmacokinetic (PBPK) modeling and benchmark-dose modeling, where appropriate.

Additional priority data needs are being addressed through collaborative research efforts with NTP, by ATSDR's Great Lakes Human Health Effects Research Program, and other Agency programs.

Criteria for Evaluating Status of Priority Data Needs

To update the activities covered under the SSARP, criteria for evaluating the status of the priority data needs were developed. Based on these criteria and the review of the current literature, a priority data need can be filled, or unchanged.

The criteria for evaluating the status of the priority data needs are described below.

General Criteria

A priority data need is filled:

• If it has been referred to one of the implementation mechanisms and research has been initiated (Exception: priority data needs referred to EPA [i.e., included in the EPA/ATSDR test rule] and/or ATSDR Voluntary Research Program remain as priority data needs until the studies have been completed, peer reviewed and accepted by ATSDR), or

• If an updated ATSDR toxicological profile contains relevant new studies, or if other relevant, peer-reviewed, and publicly available new studies (not included in the toxicological profile) have been identified since the finalization of the priority data needs document; and based on such studies, it is generally agreed that a priority data need has been filled.

Furthermore, in the event a priority data need is considered filled, it does not necessarily mean that the study has been completed and that ATSDR has accepted the data. It does, however, indicate that the Agency no longer considers it a priority to initiate additional studies at this time.

A priority data need remains unchanged:

• If no mechanism or information has been identified to address the priority data need, or

• If the priority data need is included in the ATSDR/EPA test rule under development and/or ATSDR Voluntary Research Program, or it is associated with a pilot substance in EPA's Voluntary Children's Chemical Evaluation Program.

Specific Criteria

Examples of specific criteria for two categories of priority data needs are described below.

• Epidemiologic studies—A priority data need is filled if multiple new studies assessing key health end points are available in ATSDR's updated toxicological profile and/or ongoing studies have been identified, e.g., human health studies supported by ATSDR's Great Lakes Human Health

Effects Research Program or the Minority Health Professions Foundation Research Program. In some cases, ATSDR indicates that it will continue to evaluate new data as they become available to determine whether additional studies are needed.

• Exposure levels in humans (adults and/or children)—A priority data need is

filled

if (a) there are current and adequate biomonitoring data for exposed populations associated with health effects (from published or ongoing studies), or (b) there are reference range data (e.g., the Centers for Disease Control and Prevention's Third National Report on Human Exposure to Environmental Chemicals, with data from a random sample of participants from the National Health and Nutrition Examination Survey [NHANES]) or generally agreed upon background population levels. In the latter case, ATSDR acknowledges that reference concentration data can support exposure and health assessments at waste sites, but the Agency also continues to recognize the importance of collecting additional data on uniquely exposed populations at waste sites. It should be noted that for some of the chemicals listed in the National Report, the measurements are reported as below the limit of detection (LOD) for those chemicals. However, the LODs for all the chemicals monitored are available in the Report, and therefore, these data can be considered as estimates of background exposure levels.

In updating the SSARP, the status of the priority data needs may change as new information becomes available. Further, during the literature review, new studies may be identified suggesting other effects of concern, such as those related to endocrine disruptors and children's health, which were not included in the original list of priority data needs. In such cases, additional priority data needs may be added to the research agenda. For example, in addressing issues relating to children's health, ATSDR considers it a priority to obtain data on exposure levels in children; therefore, when such information is available, it is used to fill this additional priority data need (e.g., cadmium, chlordane, chlorinated dibenzo-p-dioxins, DDT, lead, and pentachlorophenol, see Table 1).

In contrast, the Agency may consider a previously identified priority data need to no longer be a priority to fill at this time and thus be deleted from the list of priority data needs. However, it remains a data need for the Agency. For example, as a result of reevaluation of the database for di-n-butyl phthalate, two of its previously identified priority data needs, i.e., immunotoxicity and neurotoxicity studies via oral exposure are no longer considered to be priority data needs. This is due to the fact that the immune system does not appear to be a target for di-n-butyl phthalate toxicity and that additional neurotoxicity studies do not seem necessary because of the lack of effects seen in long-term neurotoxicity studies. In addition, under the Agency's Voluntary Research Program, the Halogenated Solvents Industry Alliance, Inc. (HSIA) proposed to fill a trichloroethylene priority data need (dose-response data for intermediate-duration, oral exposure) by conducting PBPK modeling to obtain the data for oral exposure using existing inhalation data. However, ATSDR is concerned that, based on the existing data for this exposure duration, it is not clear if the most sensitive end point for oral exposure is the same as that for inhalation exposure. Therefore, the Agency believes it is prudent not to consider it a priority to conduct a PBPK study to obtain the oral data at this time pending evaluation of additional information. This is reflected in Table 1 from which this priority data need has been deleted.

Update of Activities in the SSARP

An update of the activities associated with the mechanisms for implementing the ATSDR Substance-Specific Applied Research Program (SSARP) is discussed below.

A. TSCA/FIFRA

In developing and implementing the SSARP, ATSDR, NIEHS/NTP, and EPA have identified a subset of priority data needs for substances of mutual interest to the federal programs. These priority data needs are being addressed through a program of toxicological testing under TSCA according to established procedures and guidelines. On several occasions when ATSDR identified priority data needs for oral exposure, other agencies needed inhalation data. In response, ATSDR considers proposals to conduct inhalation studies in conjunction with physiologically based pharmacokinetic (PBPK) studies in lieu of oral studies. ATSDR expects that inhalation data derived from these studies can be used with PBPK modeling to address its oral toxicity priority data needs. Currently, an EPA/ATSDR test rule, under development, includes eight ATSDR substances, i.e., benzene, chloroethane, cyanide (hydrogen cyanide and sodium cyanide), methylene chloride, tetrachloroethylene, toluene and trichloroethylene, and addresses 13 ATSDR priority data needs (Table 2). The test rule is presently undergoing ATSDR and EPA final review and is anticipated to be available for public comment in Spring 2006.

At least seven metals included in the ATSDR's SSARP (arsenic, beryllium, chromium, manganese, mercury, nickel, and selenium, associated with 21 priority data needs) (Table 2) have been forwarded to EPA through TASARC for toxicity testing. The EPA is currently developing a risk assessment framework for metals. Once the framework has been adopted, the EPA will solicit testing proposals for these metals and pursue appropriate testing mechanisms at a later date.

B. Private-Sector Voluntarism

As part of the Substance-Specific Applied Research Program (SSARP), ATSDR announced a set of proposed procedures for conducting voluntary research in the

Federal Register

(57 FR 4758) on February 7, 1992. Revisions based on public comments were published on November 16, 1992 (57 FR 54160). Private-sector organizations are encouraged to volunteer to conduct research to fill specific priority data needs at no expense to ATSDR. All study protocols and final reports are subjected to ATSDR's external peer review, and ATSDR accepts the study results based on the peer reviewers' recommendation and the industry groups' satisfactory response to the reviewers' comments.

To date, ATSDR has established memoranda of understanding with four industry groups. Through the voluntary research efforts of these organizations, at least 15 research needs (12 priority data needs and 3 data needs) for methylene chloride, tetrachloroethylene (perchloroethylene), trichloroethylene, polychlorinated biphenyl compounds [PCBs], and vinyl chloride have been or are being filled (Table 2).

Industry groups which conducted studies under the Voluntary Research Program include:

The American Chemistry Council (ACC) [Formerly the Chemical Manufacturers Association (CMA)]

ATSDR accepted the ACC studies “Vinyl chloride: Combined inhalation two-generation reproduction and developmental toxicity study in CD rats.”

General Electric Company (GE)

GE conducted studies on polychlorinated biphenyls including “An assessment of the chronic toxicity and oncogenicity of Aroclors 1016,

1242, 1254, and 1260 administered in diet to rats,” “PCB congener analyses,” and “Metabolite detection as a tool for determining naturally occurring aerobic PCB biodegradation.” Although these studies do not specifically address ATSDR's

priority

data needs for PCBs, they do address other Agency research needs for these substances.

Halogenated Solvents Industry Alliance, Inc. (HSIA)

To date, ATSDR has entered into five MOUs with HSIA to conduct studies to fill priority data needs for methylene chloride, tetrachloroethylene and trichloroethylene. In addition, in 2002, HSIA signed a letter of agreement with ATSDR stating that HSIA volunteers to conduct studies to fill ATSDR's remaining priority data needs for tetrachloroethylene (perchloroethylene) and trichloroethylene. These studies are being done in conjunction with the EPA/ATSDR test rule and EPA's Voluntary Children's Chemical Evaluation Program. In some cases, HSIA first conducted a study via inhalation which was followed by route extrapolation via PBPK modeling to obtain data for oral exposure. This is because, for specific chemicals, EPA requires inhalation data while ATSDR has determined that ingestion of contaminated environmental media is the primary exposure route at hazardous waste sites.

HSIA studies accepted by ATSDR include:

“Addressing priority data needs for methylene chloride with physiologically based pharmacokinetic modeling” which evaluates acute- and subchronic-duration toxicity and developmental toxicity via oral exposure.

“Methylene chloride: 28 day inhalation toxicity study in the rat to assess potential immunotoxicity.”

“Immunotoxic potential of orally administered dichloromethane from immunotoxicity studies conducted by the inhalation route.” (PBPK modeling)

“Trichloroethylene: Inhalation developmental toxicity study in CD rats.” HSIA will conduct PBPK modeling to obtain data for oral exposure based on the inhalation data.

“Trichloroethylene (TCE): Immunotoxicity potential in CD rats following a 4-week vapor inhalation exposure.” The final report of the study is undergoing ATSDR's external peer review. Pending ATSDR's acceptance of the inhalation study, HSIA will conduct PBPK modeling to obtain data for oral exposure based on the inhalation data.

“Perchloroethylene: Study of effects on embryo-fetal development in CD rats by inhalation administration.” HSIA will conduct PBPK modeling to obtain data for oral exposure based on the inhalation data.

Electric Power Research Institute, Inc. (EPRI)

In addition to the substance-specific MOUs described above, ATSDR also signed an MOU with EPRI to conduct a study “Validation of test methods for assessing neurodevelopment in children.” In this particular case, ATSDR and three other federal agencies (the Food and Drug Administration, EPA, and NIEHS) were also funding partners.

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. A not-for-profit Internal Revenue Code 501(c)(3) organization, the MHPF comprises 11 minority health professions schools at historically black colleges and universities. The MHPF mission is to research health problems that disproportionately affect poor and minority citizens. The purpose of the cooperative agreement was to address substance-specific data needs for priority hazardous substances identified by ATSDR. In addition, the agreement strengthened the environmental health research opportunities for scientists and students at MHPF member institutions and enhanced existing disciplinary capacities to conduct research in toxicology and environmental health. The MHPF published a report, “Environmental Health and Toxicology Research Program: Meeting Environmental Health Challenges Through Research, Education, and Service,” that describes the research findings and other successes from the first 5 years of the program.

In the first five year project period that concluded during FY 1997, nine priority data needs for 21 priority hazardous substances and 22 other research needs for these and other substances were addressed. Research initiated in the second 5-year project period included studies to address 10 additional priority data needs for chlordane, di-n-butyl phthalate, lead, manganese, the polycylic aromatic hydrocarbons (PAHs), zinc, and eight other research needs. To date, 14 priority data needs have been filled through this cooperative agreement (Table 1).

During 2003, ATSDR announced a new five year cooperative agreement program with the MHPF. The purpose of the program is to apply findings from the previous ten year environmental health and Toxicology Research Program and to improve public health and environmental medicine in low-income and minority communities. The new program builds on earlier efforts and expands the Program's public environmental health impact on affected communities. Activities across the following four research and environmental public health focus areas were funded to initiate this new program: substance-specific toxicology research, environmental exposure assessment, community-based environmental health education, and environmental health education for primary-care providers. No additional priority data needs are being addressed under this new program.

To date, Program research findings and other activities have resulted in the publication of more than 50 manuscripts in peer-reviewed journals. The institutions which have received awards and their respective studies are listed in Table 2.

D. National Toxicology Program (NTP)

Section 104(i)(5) of CERCLA directs the administrator of ATSDR (in consultation with the administrator of EPA and agencies and programs of the Public Health Service) to assess whether adequate information on the health effects of priority hazardous substances found at NPL sites is available. Where adequate information is not available, ATSDR, in cooperation with the National Toxicology Program (NTP), is required to assure the initiation of a program of research designed to determine these health effects (and techniques for developing methods to determine such health effects).

ATSDR continues to collaborate with NTP to address priority data needs of mutual interest. Chemicals for which NTP has conducted studies (or is in the process of conducting studies) to fill ATSDR's priority data needs include carbon tetrachloride, 1,1-dichloroethene, di-n-butyl phthalate, disulfoton, and heptachlor (Table 2).

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.

In support of the Great Lakes Critical Programs Act of 1990, ATSDR announced in Fiscal Year 1992 the availability of $2 million for a grant

program to conduct research on the potential for short- and long-term adverse health effects from consumption of contaminated fish from the Great Lakes basin. Research undertaken through this program is intended to build on and amplify the results of past and ongoing fish consumption research in the Great Lakes basin. The ATSDR-supported research projects focus on known high-risk populations to define further the human health consequences of exposure to persistent toxic substances (PTSs) identified in the Great Lakes basin. These at-risk populations include sport anglers; African Americans, Asians and other non-English speaking populations; pregnant women; fetuses, nursing infants, and children of mothers who consume contaminated Great Lakes sport fish; the elderly, and the urban poor. To date, the research activities of the ATSDR Great Lakes Human Health Effects Research Program have resulted in 70 publications in peer-reviewed journals.

Currently, 14 priority data needs for 24 priority hazardous substances (including 15 PAHs) identified in the SSARP are being addressed through this program. The institutions which have received awards and their respective studies are listed in Table 2.

F. Other ATSDR Programs

In its role as a public health agency addressing environmental health, ATSDR may collect human data to validate substance-specific exposure and toxicity findings. The need for additional information on levels of contaminants in humans has been identified, and remains as a priority data need for 59 of the 60 priority substances (Table 1). In some cases, ATSDR anticipates obtaining 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. Regarding the priority data need for exposure subregistries, the list of the 60 priority hazardous substances in the SSARP was forwarded to ATSDR's Division of Health Studies for consideration as potential candidates for subregistries of exposed persons, based on criteria described in its 1994 document, “National Exposure Registry: Policies and Procedures Manual (Revised),” Agency for Toxic Substances and Disease Registry, Public Health Service, U.S. Department of Health and Human Services, Atlanta, Georgia, NTIS Publication No. PB95-154571. Currently, ATSDR has established exposure subregistries for benzene, dioxin, 1,1,1-trichloroethane (not included in the SSARP), trichloroethylene, and tremolite asbestos.

G. Conclusion

The results of the research conducted via the SSARP are expected to provide information necessary to improve the database used to conduct comprehensive public health assessments of populations living near hazardous waste sites. The information will enable the Agency to establish linkages between levels of contaminants in the environment and levels in human tissue and organs associated with adverse health effects, ultimately helping to determine methods for interdicting exposure and mitigating toxicity. 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 information base for addressing a broader range of data needs. The Agency plans to provide an update on the status of this research program approximately every three years or sooner, as needed.

Dated: November 17, 2005.

Kenneth Rose,

Acting Director, Office of Policy, Planning, and Evaluation, National Center for Environmental Health, Agency for Toxic Substances and Disease Registry.

Table 1.—ATSDR's Substance-Specific Priority Data Needs for 60 Priority Hazardous Substances

Substances

PDN ID

PDN description

Program

Status change

Comments

Aldrin/Dieldrin

Dose-response data in animals for intermediate-duration oral exposure

Filled

An MRL was derived in the 2000 updated ATSDR toxicological profile.

Bioavailability from soil

Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers

This priority data need, previously addressed in a study in the Great Lakes Research Program, is no longer investigated in that study.

Potential candidate for subregistry of exposed persons

ATSDR

Arsenic

Comparative toxicokinetic studies to determine if an appropriate animal species can be identified

EPA

Half-lives in surface water, groundwater

EPA

Bioavailability from soil

EPA

Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers

G. Lakes

Filled

In addition to the data from the Great Lakes Research Program, background level data are available in ATSDR's 1993 toxicological profile, and at least seven ATSDR studies that evaluated urine arsenic levels and potential adverse health effects are available. Also, additional studies are available in ATSDR's 2000 updated toxicological profile.

Asbestos

Epidemiologic studies of individuals occupationally exposed to asbestos levels lower than those experienced before the institution of current occupational standards governing the use of asbestos, but higher than current levels in the general population. These studies should be performed in conjunction with the immunotoxicity studies

Immunotoxicity studies of individuals occupationally exposed to asbestos

Development of human and rat lung retention models to aid in extrapolating between rat and human data

Improved analytical methods for screening samples and determining the chemical structure of asbestos fibers. Also, techniques are needed to normalize studies in which different analytical methods were employed

Exposure levels, fiber size distribution, and asbestos fiber type in areas with natural geologic deposits of friable asbestos and at hazardous waste sites. Also, techniques for estimating air levels of asbestos from soil concentrations and activity scenarios

Exposure levels in humans living near hazardous waste sites and in other populations, such as humans living in areas with naturally high levels of friable asbestos

Potential candidate for subregistry of exposed persons

ATSDR

Filled

ATSDR established registry to follow the health of people who were exposed to asbestos in Libby, Montana. The name of the registry is the Tremolite Asbestos Registry (TAR).

Benzene

Dose-response data in animals for acute- and intermediate-duration oral exposure. The subchronic study should include an extended reproductive organ histopathology

EPA

Reproductive toxicity study is the only component of this PDN that is included in the EPA/ATSDR test rule.

Prenatal developmental toxicity study via oral exposure

EPA

Previously planned study in the MHPF Research Program to address this priority data need was canceled.

Neurotoxicology battery of tests via oral exposure

EPA

Epidemiologic studies on the health effects of benzene (Special emphasis end points include immunotoxicity)

Filled

Based on an evaluation of the data in ATSDR's 1997 updated toxicological profile. ATSDR will continue to evaluate new data as they become available to determine if additional studies are needed.

Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers

Filled

Reference range concentrations are available (Ashley et al. 1992, 1994; Needham et al. 1995), and at least one ATSDR study that evaluated blood benzene levels and potential adverse health effects is available. ATSDR acknowledges that reference concentration data can support exposure and health assessments at waste sites, but the Agency also continues to recognize the importance of collecting additional data on uniquely exposed populations at waste sites.

Benzidine

Dose-response data for acute- and intermediate-duration exposure via the oral route (the study of intermediate-duration exposure should include evaluation of reproductive and endocrine organ histopathology, lymphoid tissues histopathology as well as examination of relevant blood components, and nervous system histopathology)

Exposure levels in humans living near hazardous waste sites

Exposure levels in children

Potential candidate for subregistry of exposed persons

ATSDR

Beryllium

Dose-response data in animals for acute- and intermediate-duration inhalation exposures. The subchronic study should include extended reproductive organ histopathology

EPA

Prenatal developmental toxicity study via inhalation exposure

EPA

Environmental fate in air; factors affecting bioavailability in air

EPA

Analytical methods to determine environmental speciation

Filled

Based on an evaluation of the data in ATSDR's 2000 updated toxicological profile.

Immunotoxicology battery of tests following oral exposure

EPA

Exposure levels in humans (adults) living near hazardous waste sites and other populations, such as exposed workers

Filled

Reference range concentrations in urine are available (Paschal et al. 1998, CDC 2005). ATSDR acknowledges that reference concentration data can support exposure and health assessments at waste sites, but the Agency also continues to recognize the importance of collecting additional data on uniquely exposed populations at waste sites.

Exposure levels in children

Filled

Reference range concentrations in urine are available (CDC 2005).

Potential candidate for subregistry of exposed persons

ATSDR

Cadmium

Analytical methods for biological tissues and fluids and environmental media

Filled

Based on an evaluation of the data in ATSDR's 1999 updated toxicological profile.

Exposure levels in humans (adults) living near hazardous waste sites and other populations, such as exposed workers

G. Lakes

Filled

In addition to the data from the Great Lakes Research Program, reference range concentrations in blood and urine are available (CDC 2005), and at least nine ATSDR studies that evaluated blood and urine cadmium levels and potential adverse health effects are available.

Exposure levels in children

Filled

Reference range concentrations in blood and urine are available (CDC 2005).

Carbon tetrachloride

Dose-response data in animals for chronic oral exposure. The study should include extended reproductive organ and nervous tissue histopathology

Immunotoxicology battery of tests via oral exposure

NTP

Filled

NTP dose-finding study and one study in ATSDR's 1994 updated toxicological profile addressed the priority data need.

Half-life in soil

Filled

One study in ATSDR's 1994 updated toxicological profile provided information on half-life in soil.

Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers

Filled

Reference range concentrations in blood are available (Ashley et al. 1992, 1994; Needham et al. 1995). ATSDR acknowledges that reference concentration data can support exposure and health assessments at waste sites, but the Agency also continues to recognize the importance of collecting additional data on uniquely exposed populations at waste sites.

Potential candidate for subregistry of exposed persons

ATSDR

Chlordane

Oral multigenerational studies to evaluate reproductive toxicity

MHPF

Filled

Availability of studies in the MHPF Research Program.

Bioavailability studies following ingestion of contaminated media

Exposure levels in humans (adults) living near hazardous waste sites and other populations potentially exposed to chlordane

Filled

Reference range concentrations in serum are available (CDC 2005). ATSDR acknowledges that reference concentration data can support exposure and health assessments at waste sites, but the Agency also continues to recognize the importance of collecting additional data on uniquely exposed populations at waste sites.

Exposure levels in children

Filled

Reference range concentrations in serum are available (CDC 2005).

Potential candidate for subregistry of exposed persons

ATSDR

Chlorinated dibenzo-p-dioxins (CDDs)

10A

Studies via oral exposure designed to assess childhood susceptibility

10B

Comparative toxicokinetic studies examining the relative absorption of CDDs across exposure routes and the relative contribution of each exposure route to total body burdens

10C

Exposure levels in humans (adults) living near hazardous waste sites

Filled

10D

Exposure levels in children

Filled

Reference range concentrations in serum are available (CDC 2005).

Chloroethane

11A

Dose-response data in animals for acute- and intermediate-duration or exposures. The subchronic study should include an evaluation of immune and nervous system tissues, and extended reproductive organ histopathology

EPA

Dose-response data in animals for chronic inhalation exposure.s The study should include an evaluation of nervous system tissues

EPA

11C

Potential candidate for subregistry of exposed persons

ATSDR

Chloroform

12A

Dose-response data in animals for intermediate-duration oral exposure

Filled

An MRL was derived in ATSDR's 1997 updated toxicological profile.

Epidemiologic studies on the health effects of chloroform (Special emphasis end points include cancer, neurotoxicity, reproductive and developmental toxicity, hepatotoxicity, and renal toxicity)

Filled

Based on an evaluation of the data in ATSDR's 1997 updated toxicological profile. ATSDR will continue to evaluate new data as they become available to determined if additional studies are needed.

12C

Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers

Filled

Reference range concentrations in blood are available (Ashley et al. 1992, 1994; and Needham et al. 1995). ATSDR acknowledges that reference concentration data can support exposure and health assessments at waste sites, but the Agency also continues to recognize the importance of collecting additional data on uniquely exposed populations at waste sites.

12D

Potential candidate for subregistry of exposed persons

ATSDR

Chromium

13A

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

EPA

13B

Multigeneration reproductive toxicity study via oral exposure to chromium (III) and (VI)

EPA

13C

Immunotoxicology battery of tests following oral exposure to chromium (III) and (VI)

EPA

13D

Prenatal developmental toxicity study via oral exposure to chromium (III) and (VI)

EPA

13E

Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers

G. Lakes

Filled

In addition to the data from the Great Lakes Research Program, reference range concentrations in urine are available (Paschal et al. 1998). Also, at least two STSDR studies that evaluated urine chromium levels and potential adverse health effects are available.

Cynaide

14A

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 end points

EPA

14B

Prenatal developmental toxicity study via oral exposure

EPA

14C

Evaluation of the environmental fate of cyanide in soil

Filled

A study addressing the priority data need was submitted by industry to EPA in response to EPA's solicitation for proposals for test rule making. Scientists from EPA and ATSDR reviewed the study and considered that this research need is no longer a priority.

14D

Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers

14E

Potential candidate for subregistry of exposed persons

ATSDR

1,2-dibromo-3-chloropropane

15A

Dose-response data in animals for acute-duration exposure via the oral route (including reproductive organ histopathology)

15B

Dose-response data in animals for chronic-duration exposure via the oral route (including reproductive organ histopathology)

15C

Prenatal developmental toxicity study via oral exposure

15D

Immunotoxicology testing battery via oral exposure

Previously planned study in the MHPF Research Program to address this priority data need was canceled.

15E

Neurotoxicology testing battery via oral exposure

Previously planned study in the MHPF Research Program to address this priority data need was canceled.

15G

Potential candidate for subregistry of exposed persons

ATSDR

1,2-Dibromoethane

16A

Dose-response data in animals for acute- and intermediate-duration exposure by the oral route (the study of intermediate-duration exposure should include evaluation of neuropathology and observation for overt signs of neurotoxicity)

16B

Multigeneration reproductive toxicity studies via oral exposure

16C

Developmental toxicity studies via oral exposure

16D

Immunotoxicity battery studies via oral exposure

16E

Exposure levels in humans living near hazardous waste sites and in other populations, such as workers exposed to 1, 2-dibromoethane

16F

Exposure levels in children

16G

Potential candidate for subregistry of exposed persons

ATSDR

1,2-Dichloroethane

17A

Dose-response data in animals for acute-duration (14-day) exposure by the inhalation route, including a comparison of young and adult animals

17B

Dose-response data in animals for acute-duration (14-day) exposure by the oral route, including a comparison of young and adult animals

17C

Dose-response data in animals for intermediate-duration exposure by the inhalation route (the study should be performed in conjunction with the neurotoxicology battery of tests)

17D

Neurotoxicology battery of tests following inhalation exposure

17E

Neurotoxicology battery of tests following oral exposure

17F

Dose-response data in animals for chronic-duration exposure by the oral route

17G

Prenatal developmental toxicity data for inhalation exposure (assessment of developmental cardiotoxicity and neurotoxicity)

17H

Prenatal developmental toxicity data for oral exposure (assessment of developmental cardiotoxicity and neurotoxicity)

17I

Additional analyses and studies for comparative toxicokinetics across species, ages, routes, and durations >

17J

Children's susceptibility

17K

Exposure levels in humans living near hazardous waste sites

17L

Exposure levels in children

17M

Potential candidate for subregistry of exposed persons

ATSDR

1,1-Dichloroethene

18A

Dose-response data in animals for acute-duration exposure by the inhalation route

NTP

Filled

Availability of ongoing NTP study.

18B

Dose-response data in animals for chronic-duration exposure by the inhalation route

NTP

Filled

Availability of ongoing NTP study.

18C

Dose-response data in animals for acute- and intermediate-duration exposure by the oral route

18D

Carcinogenicity studies in two species following inhalation exposure

18E

Reproductive toxicity studies assessing male and female end points following inhalation exposure

18F

Prenatal developmental toxicity studies following oral exposure

18G

Immunotoxicology battery of tests following oral exposure

18H

Battery of neurobehavioral tests following inhalation exposure

18I

Children's susceptibility

18J

Exposure levels in humans living near hazardous waste sites

18K

Exposure levels in children

18L

Potential candidate for subregistry of exposed persons

ATSDR

DDT

19A

Dose-response data in animals for chronic-duration oral exposure

19B

Comparative toxicokinetic study (across routes/species)

19C

Bioavailability and bioaccumulation from soil

19D

Epidemiologic studies on the health of DDT, DDD, and DDE (Special emphasis end points include immunotoxicity, and reproductive and developmental toxicity)

G. Lakes

Filled

In addition to the data from the Great Lakes Research Program, multiple studies in ATSDR's 2000 updated toxicological profile are available.

19E

Exposure levels in humans (adults) living near hazardous waste sites and other populations, such as exposed workers

G. Lakes

Filled

In addition to the data from the Great Lakes Research Program, reference range concentrations in serum are available (CDC 2005). ATSDR acknowledges that reference concentration data can support exposure and health assessments at waste sites, but the Agency also continues to recognize the importance of collecting additional data on uniquely exposed populations at waste sites.

19F

Exposure levels in children

Filled

Reference range concentrations in serum are available (CDC 2005).

19G

Potential candidate for subregistry of exposed persons

ATSDR

Di (2-ethylhexyl) phthalate

20A

Epidemiologic studies on the health effects of DEHP (Special emphasis end points include cancer)

20B

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

This research need remains as a priority data need because the previously developed MRL for acute-duration (1993 toxicological profile) was withdrawn. However, a new MRL for intermediate-duration was derived in ATSDR's 2002 updated Toxicological Profile. Therefore, this priority data need is considered partially filled because additional adequate acute-duration data for deriving an MRL are still lacking.

20C

Multigeneration reproductive toxicity study via oral exposure

This research need is reassigned as a priority data need based on an evaluation of the data in ATSDR's 2002 updated toxicological profile. Also, the NTP Center for the Evaluation of Risks to Human Reproduction Expert Panel Report (October 2000) has identified critical data needs for reproductive toxicity.

20D

Comparative toxicokinetic studies (Studies designed to examine how primates metabolize and distribute DEHP as compared with rodents via oral exposure)

Filled

The existing database provides adequate information to fill this priority data need based on ATSDR's reevaluation of the published data.

20E

Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers

20F

Potential candidate for subregistry of exposed persons.

ATSDR

Di-n-butyl phtalate

21A

Dose-response data in animals for acute-duration exposure via the oral route

NTP

Filled

Availability of an NTP study.

21B

Dose-response data in animals for chronic-duration exposure via the oral route

21C

Carcinogenicity studies via oral exposure

21D

In vivo genotoxicity studies

MHPF

Filled

Availability of a study in the MHPF Research Program

21E

Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers

21F

Environmental fate of di-n-butyl phthalate in environmental media

21G

Bioavailability in contaminated environmental media near hazardous waste sites

21H

Potential candidate for subregistry of exposed persons.

ATSDR

Disulfoton

22A

Immunotoxicology testing battery following oral exposure

NTP

Filled

Availability of ongoing NTP study.

22B

Exposure levels of disulfoton in tissues/fluids for populations living near hazardous waste sites and other populations, such as exposed workers

22C

Disulfoton should be considered as a potential candidate for a subregistry of exposed persons

ATSDR

Endosulfan (α, β, and sulfate)

23A

Acute-duration oral exposure studies

23B

Data on sensitive neurologic end point following oral exposure

23C

Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers

23D

Data on the bioavailability of endosulfan from soil

23E

Potential candidate for subregistry of exposed persons

ATSDR

Endrin/endrin aldehyde

24A

Dose-response animal data for acute oral exposure to endrin

24B

Multigeneration reproductive toxicity studies via oral exposure to endrin

24C

Accurately describe the toxicokinetics of endrin and its degradation products and identify the animal species to be used as the most appropriate model for human exposure

24D

Exposure levels for endrin and its degradation products in humans living near hazardous waste sites

24E

Accurately describe the environmental fate of endrin, including environmental breakdown products and rates, media half-lives, and chemical and physical properties of the breakdown products that help predict mobility and volatility

24F

Potential candidate for subregistry of exposed persons

ATSDR

Ethylbenzene

25A

Dose-response data for acute-duration exposure by the inhalation route

25B

Dose-response data for chronic-duration exposure by the inhalation route

25C

Dose-response data for acute- and intermediate-duration exposure by the oral route; the study of intermediate-duration exposure should include an evaluation of clinical signs of neurotoxicity and histopathology of reproductive organs, endocrine glands, and nervous system

25D

Multigeneration toxicity study examining reproductive end points and indicators of endocrine disruption following inhalation exposure

25E

Prenatal developmental study with continued assessment of offspring during postnatal development following oral exposure

25F

Studies for comparative toxicokinetics

25G

Exposure levels in humans living near hazardous waste sites

25H

Exposure levels in children

25I

Potential candidate for subregistry of exposed persons

ATSDR

Heptachlor/heptachlor epoxide

26A

Dose-response animal data for acute- and intermediate-duration oral exposures, including immunopathology

26B

Multigeneration reproductive toxicity studies via the oral route of exposure

NTP

Filled

Availability of publication “The effects of perinatal/juvenile heptachlor exposure on adult immune and reproductive system function in rats” by Smialowicz et al. (2001), Toxicological Sciences 61:164-175.

26C

Prenatal developmental toxicity studies via the oral route of exposure

Filled

Based on ATSDR's review of the literature, i.e., Smialowicz et al. (2001), Toxicological Sciences 61:164-175 and Moser et al. (2001) Toxicological Sciences 60 (2):315-326.

26D

Exposure levels in humans (adults) living near hazardous waste sites and other populations, such as exposed workers

Filled

26E

Exposure levels in children

Filled

Reference range concentrations in serum are available (CDC 2005).

26F

Bioavailability from contaminated air, water, and soil and bioaccumulation potential

26G

Potential candidate for subregistry of exposed persons

ATSDR

Hexachlorobutadiene

27A

Dose-response data in animals for acute-duration exposure via the oral route

27B

Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers

27C

Environmental fate studies that determine the extent to which hexachlorobutadiene volatilizes from soil, and studies that determine the reactions and rates which drive degradation in soil

27D

Bioavailability studies in soil and plants

27E

Potential candidate for subregistry of exposed persons

ATSDR

Hexachlorocyclohexane (α, β and γ)

28A

Dose-response data for chronic-duration oral exposure

Filled

An MRL was derived in ATSDR's 1999 updated toxicological profile.

28B

Mechanistic studies on the neurotoxicity, hepatotoxicity, reproductive toxicity, and immunotoxicity of hexachlorocyclohexane

28C

Exposure levels in humans (adults) living near hazardous waste sites and other populations, such as exposed workers

Filled

28D

Exposure levels in children

Filled

Reference range concentrations in serum are available (CDC 2005).

28E

Potential candidate for subregistry of exposed persons

ATSDR

Lead

29A

Mechanistic studies on the neurotoxic effects of lead

MHPF

Filled

Multiple studies (at least 13 publications from the MHPF Research Program + numerous studies in ATSDR's 1999 updated toxicological profile) are available.

29B

Analytical methods for tissue levels

MHPF

Filled

A publication from the MHPF Research Program and numerous studies in ATSDR's 1999 toxicological profile are available.

29C

Exposure levels in humans (adults) near hazardous waste sites and other populations, such as exposed workers

MHPF, G. Lakes

Filled

In addition to the data from Great Lakes Research Program and MHPF Research Program, reference range concentrations in blood and urine are available (CDC 2005; Paschal

et al.

1998), and at least 19 ATSDR studies that evaluated blood lead levels and potential adverse health effects are available.

29D

Exposure levels in children

Filled

Reference range concentrations in blood and urine are available (CDC 2005).

Manganese

30A

Dose-response data for acute- and intermediate-duration oral exposures (the subchronic study should include reproductive histopathology and an evaluation of immunologic parameters including manganese effects on plaque-forming cells (SRBC), surface markers (D4:D8 ratio), and delayed hypersensitivity reactions)

MHPF, EPA

Filled

Availability of studies in the MHPF Research Program.

30B

Toxicokinetic studies on animals to investigate uptake and absorption, relative uptake of differing manganese compounds, metabolism of manganese, and interaction of manganese with other substances following oral exposure

MHPF, EPA

Filled

Availability of studies in the MHPF Research Program.

30C

Epidemiological studies on the health effects of manganese (Special emphasis end points include neurologic, reproductive, developmental, immunologic, and cancer)

Filled

Based on an evaluation of the data in ATSDR's 2000 updated toxicological profile. ATSDR will continue to evaluate new data as they become available to determine if additional studies are needed.

30D

Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers

30E

Relative bioavailability of different manganese compounds and bioavailability of manganese from soil

EPA.

Mercury

31A

Multigeneration reproductive toxicity study via oral exposure

MHPF

Filled

Availability of publications from the MHPF Research Program.

31B

Dose-response data in animals from chronic-duration oral exposure

Filled

An MRL was derived in ATSDR's 1999 updated toxicological profile.

31C

Immunotoxicology battery of tests via oral exposure

EPA.

31D

Exposure levels in humans (adults) living near hazardous waste sites and other populations, such as exposed workers

G. Lakes

Filled

In addition to the data from the Great Lakes Research Program, background levels data are available in ATSDR's 1997 updated toxicological profile, and multiple ATSDR studies that evaluated blood, urine, hair mercury levels and potential adverse health effects are available. Also, reference range concentrations in blood and urine are available (CDC 2005).

31E

Exposure levels in children

Filled

Reference range concentrations in blood and urine are available (CDC 2005).

31F

Potential candidate for subregistry of exposed persons

ATSDR.

Methoxychlor

32A

Evaluate neurologic effects after long-term, low-level oral exposure

Filled

Based on an evaluation of the data in ATSDR's 2000 updated toxicological profile.

32B

Exposure levels of methoxychlor and primary metabolites in humans living near hazardous waste sites and those individuals with the potential to ingest it.

32C

Evaluate the fate, transport, and levels of the degradation products of methoxychlor in soil.

32D

Potential candidate for subregistry of exposed persons

ATSDR.

Methylene chloride

33A

Dose-response data in animals for acute- and intermediate-duration oral exposure. The subchronic study should include extended reproductive organ histopathology, neuropathology, and immunopathology

EPA, Vol Res

Filled

ATSDR accepted HSIA's toxicity study for acute- and intermediate-duration exposure duration in February 1997. Also, ATSDR accepted HSIA's immunotoxicity study via inhalation in November 2000 and the oral data obtained via PBPK modeling conducted by HSIA based on the immunotoxicity data from the inhalation study. Neurotoxicity screening battery testing remains in the ATSDR/EPA test rule under development.

33B

Prenatal developmental toxicity study via the oral route

Vol Res

Filled

ATSDR accepted HSIA's study in February 1997.

33C

Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers

Filled

33D

Potential candidate for subregistry of exposed persons

ATSDR.

Nickel

34A

Epidemilogic studies on the health effects of nickel (Special emphasis end points include reproductive toxicity)

Filled

Based on at least two relevant studies in ATSDR's 1997 updated toxicological profile. ATSDR will continue to evaluate new data as they become available to determine if additional studies are needed.

34B

Prenatal development toxicity study via the oral route

EPA

Filled

In ATSDR's 1997 updated toxicological profile, a study confirming the results of two previous studies is available.

34C

Dose-response data in animals for acute- and intermediate-duration oral exposures

EPA.

34D

Neurotoxicology battery of tests via oral exposure

EPA.

34E

Bioavailability of nickel from soil

EPA.

34F

Exposure levels in humans (adults) living near hazardous waste sites and other populations, such as exposed workers

G. Lakes

Filled

Based on availability of the data from the Great Lakes Research Program and an evaluation of ATSDR's 1997 updated toxicological profile.

34G

Potential candidate for subregistry of exposed persons

ATSDR.

Pentachlorophenol

35A

Comparative toxicokinetic studies.

35B

Exposure levels in humans (adults) living near hazardous waste sites

Filled

Reference range concentrations in urine are available (CDC 2005. ATSDR acknowledges that reference concentration data can support exposure and health assessments at waste sites, but the Agency also continues to recognize the importance of collecting additional data on uniquely exposed populations at waste sites.

35C

Exposure levels in children

Filled

Reference range concentrations in urine are available (CDC 2005).

35D

Potential candidate for subregistry of exposed persons

ATSDR.

Polychlorinated biphenyls (PCBs)

36A

Dose-response data in animals for acute- and intermediate-duration oral exposure

G. Lakes

Although an MRL for intermediate-exposure duration was derived in ATSDR's 2000 updated toxicological profile, an MRL for acute-exposure duration is still lacking.

36B

Biodegradation of PCBs in water; bioavailability of PCBs in air, water, and soil.

36C

Dose-response data in animals for acute- and intermediate-duration inhalation exposures. The subchronic study should include extended reproductive organ histopathology.

36D

Epidemiologic studies on the health effects of PCBs (Special emphasis end points include immunotoxicity, gastrointestinal toxicity, liver toxicity, kidney toxicity, thyroid toxicity, and reproductive/developmental toxicity)

G. Lakes

Filled

In addition to the data from the Great Lakes Research Program, multiple studies in ATSDR's 2000 updated toxicological profile are available.

36E

Exposure levels in humans (adults) living near hazardous waste sites and other populations, such as exposed workers

G. Lakes

Filled

In addition to the data from the Great Lakes Research Program, background levels data are available (ATSDR's 1997 updated toxicological profile, Needham et al. 1996, and CDC 2005). Also, multiple ATSDR studies that evaluated blood and breast milk PCB levels and potential adverse health effects are available.

36F

Exposure levels in children

Filled

Reference range concentrations in serum are available (CDC 2005).

36G

Potential candidate for subregistry of exposed persons

ATSDR.

36H

Chronic toxicity and oncogenicity via oral exposure

Vol Res

Filled

ATSDR accepted the final report of the GE study in October 1997.

36I

Aerobic PCB biodegradation in sediment

Vol Res

Filled

ATSDR accepted the final report of the GE study in July 1999.

36J

PCB congener analysis

Vol Res, G. Lakes

Filled

ATSDR accepted the final report of the GE study in October 1997. Also, data from the Great Lakes Research Program are available.

Polycyclic aromatic hydrocarbons (PAHs) (Includes 15 substances)

37A

Dose-response data in animals for intermediate-duration oral exposures. The subchronic study should include extended reproductive organ histopathology and immunopathology

MHPF

Filled

MRLs for four PAHs were derived in ATSDR's 1995 updated toxicological profile. A publication from the MHPF Research Program addressing this priority data need is available.

37B

Prenatal developmental toxicity study via inhalation or oral exposure

MHPF

Filled

Data from the MHPF Research Program including a publication are available.

37C

Mechanistic studies on PAHs, on how mixtures of PAHs can influence the ultimate activation of PAHs, and on how PAHs affect rapidly proliferating tissues.

MHPF

Filled

In addition to publications from the MHPF Research Program, studies are available in ATSDR's 1995 updated toxicological profile.

37D

Dose-response data in animals for acute- and intermediate-duration inhalation exposures. The subchronic study should include extended reproductive organ histopathology and immunopathology

MHPF

Filled

Data from the MHPF Research Program including one publication are available.

37E

Epidemiologic studies on the health effects of PAHs (Special emphasis end points include cancer, dermal, hemolymphatic, and hepatic toxicity)

Filled

Multiple studies in ATSDR's 1995 updated toxicological profile are available. ATSDR will continue to evaluate new data as they become available to determine if additional studies are needed.

37F

Exposure levels in humans (adults) living near hazardous waste sites and other populations, such as exposed workers

G. Lakes

Filled

Based on data from the Great Lakes Research Program and an evaluation of the ATSDR 1995 updated toxicological profile. Also, reference range concentrations in urine are available (CDC 2005). The Agency continues to recognize the importance of collecting additional data on uniquely exposed populations at waste sites.

37G

Exposure levels in children

Filled

Reference range concentrations in urine are available (CDC 2005).

37H

Potential candidate for subregistry of exposed persons

ATSDR.

Selenium

38A

Dose-response data in animals for EPA acute-duration oral exposure

EPA.

38B

Immunotoxicology battery of tests via oral exposure

EPA.

38C

Epidemiologic studies on the health effects of selenium (Special emphasis end points include cancer, reproductive and developmental toxicity, hepatotoxicity, and adverse skin effects)

Filled

Based on an evaluation of ATSDR's 2001 updated toxicological profile. ATSDR will continue to evaluate new data as they become available to determine if additional studies are needed.

38D

Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers

G. Lakes

Filled

In addition to the data from the Great Lakes Research Program, reference range concentrations in serum are available (NHANES III). ATSDR acknowledges that reference concentration data can support exposure and health assessments at waste sites, but the Agency also continues to recognize the importance of collecting additional data on uniquely exposed populations at waste sites.

38E

Potential candidate for subregistry of exposed persons

ATSDR

1,1,2,2-Tetrachloroethane

39A

Prenatal developmental toxicity study by the oral route

39B

Immunotoxicity battery following oral exposure

39C

Mammalian in vivo genotoxicity assays

39D

Exposure levels in humans living near hazardous waste sites

39E

Exposure levels in children

39F

Potential candidate for subregistry of exposed persons

ATSDR

Tetrachloroethylene

40A

Dose-response data in animals for acute-duration oral exposure, including neuropathology and demeanor, and immunopathology

Filled

An MRL was derived in the ATSDR 1997 updated toxicological profile.

40B

Multigeneration reproductive toxicity study via oral exposure

Vol Res

HSIA's inhalation study was accepted by ATSDR and included in ATSDR's 1997 updated toxicological profile. However, ATSDR has identified ingestion of contaminated environmental media to be the primary exposure route for this chemical at waste sites. HSIA will obtain the oral data from the inhalation study by conducting PBPK modeling.

40C

Dose-response data in animals for intermediate-duration oral exposure, including neuropathology, and immunopathology

EPA, Vol Res

HSIA will obtain oral data for intermediate-duration toxicity and neurotoxicity by PBPK modeling based on existing inhalation data. Also, it will conduct an inhalation immunotoxicity study, followed by PBPK modeling to obtain oral data.

40D

Prenatal developmental toxicity study via oral exposure

Vol Res

HSIA's developmental toxicity study via inhalation was accepted by ATSDR. However, ATSDR has identified ingestion of contaminated environmental media to be the primary exposure route for this chemical at waste sites. HSIA will obtain the oral data from the inhalation study by conducting PBPK modeling.

40E

Developmental neurotoxicity study via oral exposure

EPA, Vol Res

40F

Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers

Filled

40G

Potential candidate for subregistry of exposed persons

ATSDR

Toluene

41A

Dose-response data in animals for acute- and intermediate-duration oral exposures. The subchronic study should include an extended histopathologic evaluation of the immune system

Filled

Availability of MRLs for acute- and intermediate- exposure durations in ATSDR's 2000 updated toxicological profile.

41B

Comparative toxicokinetic studies (Characterization of absorption, distribution, and excretion via oral exposure)

Filled

Based on evaluation of the data in ATSDR's 2000 updated toxicological profile.

41C

Neurotoxicology battery of tests via oral exposure

EPA, MHPF

A publication for acute exposure but not longer term exposure is available in the MHPF Research Program. Also, this priority data need is included in the EPA/ATSDR test rule.

41D

Mechanism of toluene-induced neurotoxicity

Filled

Multiple studies in ATSDR's 1994 and 2000 updated toxicological profiles are available.

41E

Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers

Filled

Reference range concentrations in blood are available (Ashley et al. 1992, 1994; Needham et al. 1995), and additional data in ATSDR's 2000 updated toxicological profile are available. ATSDR acknowledges that reference concentration data can support exposure and health assessments at waste sites, but the Agency also continues to recognize the importance of collecting additional data on uniquely exposed populations at waste sites.

41F

Potential candidate for subregistry of exposed persons

ATSDR

Toxaphene

42A

Identify the long-term health consequences of exposure to environmental toxaphene via oral exposure

42B

Conduct additional immunotoxicity studies for chronic-duration via oral route of exposure

42C

Conduct additional neurotoxicity studies for chronic-duration via oral route of exposure

42D

Exposure levels in humans living in areas near hazardous waste sites with toxaphene and in those individuals with the potential to ingest it

42E

Potential candidate for subregistry of exposed persons

ATSDR

Trichloroethylene

43A

Dose-response data in animals for acute-duration oral exposure

Filled

An MRL was derived in ATSDR's 1997 updated toxicological profile.

43B

Neurotoxicology battery of tests via the oral route

EPA, MHPF, Vol Res

A publication for acute exposure but not longer term exposure is available in the MHPF Research Program. Also, this priority data need is included in the EPA/ATSDR test rule and ATSDR's Voluntary Research Program.

43C

Immunotoxicology battery of tests via oral route

Vol Res

HSIA has completed an inhalation immunotoxicity study which is undergoing ATSDR peer review. HSIA will obtain oral data via PBPK modeling based on the inhalation data.

43D

Prenatal developmental toxicity study via oral exposure

Vol Res

ATSDR has accepted HSIA's final report for an inhalation developmental toxicity study. HSIA will use PBPK modeling to obtain data for oral exposure based on the results of its inhalation study.

43E

Developmental neurotoxicity study via oral exposure

EPA, Vol Res

43F

Epidemiologic studies on the health effects of trichloroethylene (Special emphasis end points include cancer, hepatotoxicity, renal toxicity, developmental toxicity, and neurotoxicity)

Filled

Based on evaluation of the data in ATSDR's 1997 updated toxicological profile. ATSDR will continue to evaluate new data as they become available to determine if additional studies are needed.

43G

Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers

Filled

Vinyl chloride

44A

Dose-response data in animals for acute-duration inhalation exposure

Filled

An MRL was derived in ATSDR's 1997 updated toxicological profile.

44B

Multigeneration reproductive toxicity study via inhalation

Vol Res

Filled

ATSDR accepted the final report of ACC's study in November 2000.

44C

Dose-response data in animals for chronic-duration inhalation exposure.

44D

Mitigation of vinyl chloride-induced toxicity

44E

Prenatal developmental toxicity study via inhalation

Vol Res

Filled

ATSDR accepted the final report of ACC's study in November 2000.

44F

Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers.

44G

Potential candidate for subregistry of exposed persons

ATSDR.

Xylenes

45A

Dose-response data for chronic-duration exposure by the oral route. This study should be done in conjunction with the neurotoxicology battery of tests

45B

Neurotoxicology battery of tests following oral exposure.

45C

Two-generation reproductive study following oral exposure.

45D

Developmental toxicity study that includes neurodevelopmental end points following oral exposure.

45E

Exposure levels in humans living near hazardous waste sites.

45F

Exposure levels in children.

45G

Potential candidate for subregistry of exposed persons

ATSDR.

Zinc

46A

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

MHPF

Filled

Availability of ongoing studies in the MHPF Research Program.

46B

Multigeneration reproductive toxicity study via oral exposure

MHPF

Filled

Availability of ongoing studies in the MHPF Research Program.

46C

Carcinogenicity testing (2-year bioassay) via oral exposure.

46D

Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers

This priority data need, previously anticipated to be addressed under the voluntary research program, is not being investigated under any of the ATSDR research programs.

46E

Potential candidate for subregistry of exposed persons

ATSDR.

Priority data need identification number.

Programs addressing priority data needs. ATSDR = ATSDR's Division of Health Studies; EPA = U.S. Environmental Protection Agency; G. Lakes = Great Lakes Human Health Effects Research Program; MHPF = Minority Health Professions Foundation; NTP = National Toxicology Program; Vol Res = Voluntary research.

PDN can be

filled

or remain unchanged based on reevaluation of the database using criteria developed by ATSDR.

ACC = American Chemistry Council; Ashley

et al.

1992 = Ashley DL, Bonin MA, Cardinali FL,

et al.

Anal Chem (1992) 64:1021-29; Ashley

et al.

1994 = Ashley DL, Bonin MA, Cardinali FL

et al.

, Clin Chem (1994) 40/7:1401-4; ATSDR studies = Studies conducted by ATSDR's Division of Health Studies; GE = General Electric Company ; HSIA = Halogenated Solvents Industry Alliance, Inc.; MHPF = Minority Health Professions Foundation; MRL = Minimal Risk Level; CDC 2005 = The third National Report on Human Exposure to Environmental Chemicals, prepared by the National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA; Needham

et al.

1995 = Needham LL, Hill RH Jr, Ashley DL, Pirkle JL, and Sampson EJ. Environ Health Perspect 103(Suppl 3):89-94; Needham

et al.

1996 = Needham LL, Patterson DG Jr, Burse VW, Paschal DC, Turner WE, and Hill VW Jr. Toxicol Ind Health 12:507-513; NHANES III = The Third National Health and Nutrition Examination Survey, conducted by the National Center for Health Statistics, Centers for Disease Control and Prevention, Atlanta, GA; NTP = National Toxicology Program; Paschal

et al.

1998 = Paschal DC, Ting BC, Morrow JC,

et al.

Environ Res, Section A 76: 53-59; PBPK modeling = physiologically based pharmacokinetic modeling; Toxicological profile = ATSDR's toxicological profiles for the Agency's priority hazardous substances.

Not a priority data need.

Table 2.—Groups Which Are Addressing/Have Addressed ATSDR's Substance-Specific Priority Data Needs (PDNs)

Program

Firm, institution, agency, or consortium

Substance

PDN ID

Voluntarism

American Chemistry Council

Vinyl Chloride

44B, 44E

General Electric Company

PCBs

36H

, 36I

, 36J

Halogenated Solvents Industry Alliance, Inc.

Methylene chloride

33A, 33B

Tetrachloroethylene

40B, 40C, 40D, 40E

Trichloroethylene

43B, 43C, 43D, 43E

Minority Health Professions Foundation

Florida A & M University

Lead

29A

The King/Drew Medical Center of the Charles R. Drew University of Medicine and Science

Lead

29B, 29C

Meharry Medical College

PAHs

37A, 37B, 37C, 37D

Morehouse School of Medicine

Lead

29C

Texas Southern University

Di-n-butyl phthalate

21D

Lead

29A

Toluene

41C

Trichloroethylene

43B

Tuskegee University

Chlordane

Mercury

31A

Zinc

46A, 46B

Xavier University

Manganese

30A, 30B

Zinc

46A

Great Lakes Human Health Effects Research Program

Michigan State University

DDT/DDE

19D, 19E

Lead

29C

Mercury

31D

PCBs

36D, 36E, 36J

Selenium

38D

New York State Health Department

DDT/DDE

19E

Lead

29C

Mercury

31D

PCBs

36D, 36E, 36J

State University of New York at Albany

PCBs

36E

State University of New York at Buffalo

DDT/DDE

19D, 19E

Lead

29C

Mercury

31D

PCBs

36D, 36E, 36J

State University of New York at Oswego

DDT/DDE

19D, 19E

Lead

29C

Mercury

31D

PCBs

36D, 36E, 36J

University of Illinois at Chicago

DDT/DDE

19D, 19E

Lead

29C

Mercury

31D

PCBs

36D, 36E, 36J

University of Illinois at Urbana-Champaign

DDT/DDE

19D, 19E

Lead

29C

Mercury

31D

PCBs

36D, 36E, 36J

University of Wisconsin-Milwaukee

DDT/DDE

19D, 19E

Lead

29C

Mercury

31D

PCBs

36A, 36D, 36E, 36J

Selenium

38D

Wisconsin Department of Health and Social Services—5 State Consortium

Arsenic

Cadmium

Chromium

13E

DDT/DDE

19D, 19E

Lead

29C

Mercury

31D

Nickel

34F

PAHs

37F

PCBs

36D, 36E, 36J

Environmental Protection Agency TSCA/FIFRA

EPA/ATSDR Test Rule

Benzene

4A, 4B, 4C

Chloroethane

11A, 11B

Cyanide (hydrogen cyanide and sodium cyanide)

14A, 14B

Methylene chloride

33A

Tetrachloroethylene

40C, 40E

Toluene

41C

Trichloroethylene

43B, 43E

Metals Testing Task Force (TASARC)

Arsenic

2A, 2B, 2C

Beryllium

6A, 6B, 6C, 6E

Chromium

13A, 13B, 13C, 13D

Manganese

30A, 30B, 30E

Mercury

31C

Nickel

34B, 34C, 34D, 34E

Selenium

38A, 38B

National Toxicology Program

National Institute of Carbon Environmental Health Sciences

Carbon tetrachloride

1,1-dichloroethene

18A, 18B

Di-n-butyl phthalate

21A

Disulfoton

22A

Heptachlor

26B

Not priority data needs.

[FR Doc. 05-23361 Filed 11-28-05; 8:45 am]

BILLING CODE 4163-70-P

This is a copy of a public record, reproduced as it was published. It is not legal advice, and it may not be the version a court would rely on. Check the official source before you cite it.