[Federal Register Volume 70, Number 238 (Tuesday, December 13, 2005)] [Notices] [Pages 73749-73773] From the Federal Register Online via the Government Publishing Office [www.gpo.gov] [FR Doc No: R5-23361] ----------------------------------------------------------------------- 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 Editorial Note: FR Doc. 05-23361 was originally published at page 71506 in the issue of Tuesday, November 29, 2005. The corrected document is republished below in its entirety, due to printing errors. 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: [email protected]. 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 [[Page 73750]] 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 [[Page 73751]] 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 neurotoxicty 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 neurotoxicty studies do not seem necessary because of the lack of effects seen in long-term neurotoxicty 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 [[Page 73752]] 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 immunotoxicty 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 [[Page 73753]] 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 ---------------------------------------------------------------------------------------------------------------- Status change Substances PDN ID \1\ PDN description Program \2\ \3\ Comments \4\ ---------------------------------------------------------------------------------------------------------------- Aldrin/Dieldrin............... 1A.......... Dose-response .............. Filled........ An MRL was data in animals derived in the for 2000 updated intermediate- ATSDR duration oral toxicological exposure. profile. 1B.......... Bioavailability from soil. 1C.......... Exposure levels .............. .............. This priority in humans data need, living near previously hazardous waste addressed in a sites and other study in the populations, Great Lakes such as exposed Research workers. Program, is no longer investigated in that study. 1D.......... Potential ATSDR......... candidate for subregistry of exposed persons. Arsenic....................... 2A.......... Comparative EPA........... toxicokinetic studies to determine if an appropriate animal species can be identified. 2B.......... Half-lives in EPA........... surface water, groundwater. 2C.......... Bioavailability EPA........... from soil. 2D.......... Exposure levels G. Lakes...... Filled........ In addition to in humans the data from living near the Great Lakes hazardous waste Research sites and other Program, populations, background such as exposed level data are workers. 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. [[Page 73754]] Asbestos...................... 3A.......... 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. 3B.......... Immunotoxicity studies of individuals occupationally exposed to asbestos. 3C.......... Development of human and rat lung retention models to aid in extrapolating between rat and human data. 3D.......... 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. 3E.......... 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. 3F.......... 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. 3G.......... Potential ATSDR......... Filled........ ATSDR candidate for established subregistry of registry to exposed persons. 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....................... 4A.......... Dose-response EPA........... .............. Reproductive data in animals toxicity study for acute- and is the only intermediate- component of duration oral this PDN that exposure. The is included in subchronic the EPA/ATSDR study should test rule. include an extended reproductive organ histopathology. 4B.......... Prenatal EPA........... .............. Previously developmental planned study toxicity study in the MHPF via oral Research exposure. Program to address this priority data need was canceled. 4C.......... Neurotoxicology EPA........... battery of tests via oral exposure. 4D.......... Epidemiologic .............. Filled........ Based on an studies on the evaluation of health effects the data in of benzene ATSDR's 1997 (Special updated emphasis end toxicological points include profile. ATSDR immunotoxicity). will continue to evaluate new data as they become available to determine if additional studies are needed. [[Page 73755]] 4E.......... Exposure levels .............. Filled........ Reference range in humans concentrations living near are available hazardous waste (Ashley et al. sites and other 1992, 1994; populations, Needham et al. such as exposed 1995), and at workers. 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..................... 5A.......... 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). 5B.......... Exposure levels in humans living near hazardous waste sites. 5C.......... Exposure levels in children. 5D.......... Potential ATSDR......... candidate for subregistry of exposed persons. Beryllium..................... 6A.......... Dose-response EPA........... data in animals for acute- and intermediate- duration inhalation exposures. The subchronic study should include extended reproductive organ histopathology. 6B.......... Prenatal EPA........... developmental toxicity study via inhalation exposure. 6C.......... Environmental EPA........... fate in air; factors affecting bioavailability in air. 6D.......... Analytical .............. Filled........ Based on an methods to evaluation of determine the data in environmental ATSDR's 2000 speciation. updated toxicological profile. 6E.......... Immunotoxicology EPA........... battery of tests following oral exposure. 6F.......... Exposure levels .............. Filled........ Reference range in humans concentrations (adults) living in urine are near hazardous available waste sites and (Paschal et al. other 1998, CDC populations, 2005). ATSDR such as exposed acknowledges workers. 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. 6G.......... Exposure levels .............. Filled........ Reference range in children. concentrations in urine are available (CDC 2005). 6H.......... Potential ATSDR......... candidate for subregistry of exposed persons. Cadmium....................... 7A.......... Analytical .............. Filled........ Based on an methods for evaluation of biological the data in tissues and ATSDR's 1999 fluids and updated environmental toxicological media. profile. [[Page 73756]] 7B.......... Exposure levels G. Lakes...... Filled........ In addition to in humans the data from (adults) living the Great Lakes near hazardous Research waste sites and Program, other reference range populations, concentrations such as exposed in blood and workers. 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. 7C.......... Exposure levels .............. Filled........ Reference range in children. concentrations in blood and urine are available (CDC 2005). Carbon tetrachloride.......... 8A.......... Dose-response data in animals for chronic oral exposure. The study should include extended reproductive organ and nervous tissue histopathology. 8B.......... Immunotoxicology NTP........... Filled........ NTP dose-finding battery of study and one tests via oral study in exposure. ATSDR's 1994 updated toxicological profile addressed the priority data need. 8C.......... Half-life in .............. Filled........ One study in soil. ATSDR's 1994 updated toxicological profile provided information on half-life in soil. 8D.......... Exposure levels .............. Filled........ Reference range in humans concentrations living near in blood are hazardous waste available sites and other (Ashley et al. populations, 1992, 1994; such as exposed Needham et al. workers. 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. 8E.......... Potential ATSDR......... candidate for subregistry of exposed persons. Chlordane..................... 9A.......... Oral MHPF.......... Filled........ Availability of multigeneration studies in the al studies to MHPF Research evaluate Program. reproductive toxicity. 9B.......... Bioavailability studies following ingestion of contaminated media. 9C.......... Exposure levels .............. Filled........ Reference range in humans concentrations (adults) living in serum are near hazardous available (CDC waste sites and 2005). ATSDR other acknowledges populations that reference potentially concentration exposed to data can chlordane. 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. 9D.......... Exposure levels .............. Filled........ Reference range in children. concentrations in serum are available (CDC 2005). 9E.......... Potential ATSDR......... candidate for subregistry of exposed persons. Chlorinated dibenzo-p-dioxins 10A......... Studies via oral (CDDs). exposure designed to assess childhood susceptibility. [[Page 73757]] 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 .............. Filled........ Reference range in humans concentrations (adults) living in serum are near hazardous available (CDC waste sites. 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. 10D......... Exposure levels .............. Filled........ Reference range in children. concentrations in serum are available (CDC 2005). Chloroethane.................. 11A......... Dose-response EPA........... data in animals for acute- and intermediate- duration oral exposures. The subchronic study should include an evaluation of immune and nervous system tissues, and extended reproductive organ histopathology. 11B......... Dose-response EPA........... data in animals for chronic inhalation exposures. The study should include an evaluation of nervous system tissues. 11C......... Potential ATSDR......... candidate for subregistry of exposed persons. Chloroform.................... 12A......... Dose-response .............. Filled........ An MRL was data in animals derived in for ATSDR's 1997 intermediate- updated duration oral toxicological exposure. profile. 12B......... Epidemiologic .............. Filled........ Based on an studies on the evaluation of health effects the data in of chloroform ATSDR's 1997 (Special updated emphasis end toxicological points include profile. ATSDR cancer, will continue neurotoxicity, to evaluate new reproductive data as they and become developmental available to toxicity, determined if hepatotoxicity, additional and renal studies are toxicity). needed. 12C......... Exposure levels .............. Filled........ Reference range in humans concentrations living near in blood are hazardous waste available sites and other (Ashley et al. populations, 1992, 1994; and such as exposed Needham et al. workers. 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 ATSDR......... candidate for subregistry of exposed persons. Chromium...................... 13A......... Dose-response EPA........... 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. 13B......... Multigeneration EPA........... reproductive toxicity study via oral exposure to chromium (III) and (VI). [[Page 73758]] 13C......... Immunotoxicology EPA........... battery of tests following oral exposure to chromium (III) and (VI). 13D......... Prenatal EPA........... developmental toxicity study via oral exposure to chromium (III) and (VI). 13E......... Exposure levels G. Lakes...... Filled........ In addition to in humans the data from living near the Great Lakes hazardous waste Research sites and other Program, populations, reference range such as exposed concentrations workers. in urine are available (Paschal et al. 1998). Also, at least two ATSDR studies that evaluated urine chromium levels and potential adverse health effects are available. Cyanide....................... 14A......... Dose-response EPA........... 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 neuropathologic al end points. 14B......... Prenatal EPA........... developmental toxicity study via oral exposure. 14C......... Evaluation of .............. Filled........ A study the addressing the environmental priority data fate of cyanide need was in soil. 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 ATSDR......... candidate for subregistry of exposed persons. 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 .............. .............. Previously testing battery planned study via oral in the MHPF exposure. Research Program to address this priority data need was canceled. 15E......... Neurotoxicology .............. .............. Previously testing battery planned study via oral in the MHPF exposure. Research Program to address this priority data need was canceled. 15F......... Exposure levels in humans living near hazardous waste sites and other exposed populations, such as exposed workers. 15G......... Potential ATSDR......... candidate for subregistry of exposed persons. [[Page 73759]] 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 ATSDR......... candidate for subregistry of exposed persons. 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 ATSDR......... candidate for subregistry of exposed persons. 1,1-Dichloroethene............ 18A......... Dose-response NTP........... Filled........ Availability of data in animals ongoing NTP for acute- study. duration exposure by the inhalation route. [[Page 73760]] 18B......... Dose-response NTP........... Filled........ Availability of data in animals ongoing NTP for chronic- study. duration exposure by the inhalation route. 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 ATSDR......... candidate for subregistry of exposed persons. 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 G. Lakes...... Filled........ In addition to studies on the the data from health effects the Great Lakes of DDT, DDD, Research and DDE Program, (Special multiple emphasis end studies in points include ATSDR's 2000 immunotoxicity, updated and toxicological reproductive profile are and available. developmental toxicity). 19E......... Exposure levels G. Lakes...... Filled........ In addition to in humans the data from (adults) living the Great Lakes near hazardous Research waste sites and Program, other reference range populations, concentrations such as exposed in serum are workers. 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 .............. Filled........ Reference range in children. concentrations in serum are available (CDC 2005). 19G......... Potential ATSDR......... candidate for subregistry of exposed persons. Di (2-ethylhexyl) phthalate... 20A......... Epidemiologic studies on the health effects of DEHP (Special emphasis end points include cancer). [[Page 73761]] 20B......... Dose-response .............. .............. This research data in animals need remains as for acute- and a priority data intermediate- need because duration oral the previously exposures. The developed MRL subchronic for acute- study should duration (1993 include an toxicological extended profile) was histopathologic withdrawn. evaluation of However, a new the immunologic MRL for and neurologic intermediate- systems. 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 .............. .............. This research reproductive need is toxicity study reassigned as a via oral priority data exposure. 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 .............. Filled........ The existing toxicokinetic database studies provides (Studies adequate designed to information to examine how fill this primates priority data metabolize and need based on distribute DEHP ATSDR's as compared reevaluation of with rodents the published via oral data. exposure). 20E......... Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers. 20F......... Potential ATSDR......... candidate for subregistry of exposed persons. Di-n-butyl phthalate.......... 21A......... Dose-response NTP........... Filled........ Availability of data in animals an NTP study. for acute- duration exposure via the oral route. 21B......... Dose-response data in animals for chronic- duration exposure via the oral route. 21C......... Carcinogenicity studies via oral exposure. 21D......... In vivo MHPF.......... Filled........ Availability of genotoxicity a study in the studies. 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 ATSDR......... candidate for subregistry of exposed persons. Disulfoton.................... 22A......... Immunotoxicology NTP........... Filled........ Availability of testing battery ongoing NTP following oral study. exposure. 22B......... Exposure levels of disulfoton in tissues/ fluids for populations living near hazardous waste sites and other populations, such as exposed workers. 22C......... Disulfoton ATSDR......... should be considered as a potential candidate for a subregistry of exposed persons. [[Page 73762]] Endosulfan ([alpha], [beta], 23A......... Acute-duration and sulfate). 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 ATSDR......... candidate for subregistry of exposed persons. 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 ATSDR......... candidate for subregistry of exposed persons. 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. [[Page 73763]] 25I......... Potential ATSDR......... candidate for subregistry of exposed persons. Heptachlor/heptachlor epoxide. 26A......... Dose-response animal data for acute- and intermediate- duration oral exposures, including immunopathology. 26B......... Multigeneration NTP........... Filled........ Availability of reproductive publication toxicity ``The effects studies via the of perinatal/ oral route of juvenile exposure. heptachlor exposure on adult immune and reproductive system function in rats'' by Smialowicz et al. (2001), Toxicological Sciences 61:164- 175. 26C......... Prenatal .............. Filled........ Based on ATSDR's developmental review of the toxicity literature, studies via the i.e., oral route of Smialowicz et exposure. al. (2001), Toxicological Sciences 61:164- 175 and Moser et al. (2001) Toxicological Sciences 60 (2):315-326. 26D......... Exposure levels .............. Filled........ Reference range in humans concentrations (adults) living in serum are near hazardous available (CDC waste sites and 2005). ATSDR other acknowledges populations, that reference such as exposed concentration workers. 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. 26E......... Exposure levels .............. Filled........ Reference range in children. concentrations in serum are available (CDC 2005). 26F......... Bioavailability from contaminated air, water, and soil and bioaccumulation potential. 26G......... Potential ATSDR......... candidate for subregistry of exposed persons. 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 hexa chloro but adiene 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 ATSDR......... candidate for subregistry of exposed persons. Hexachlorocyclohexane 28A......... Dose-response .............. Filled........ An MRL was ([alpha], [beta] and [gamma]). data for derived in chronic- ATSDR's 1999 duration oral updated exposure. toxicological profile. 28B......... Mechanistic studies on the neurotoxicity, hepatotoxicity, reproductive toxicity, and immunotoxicity of hexachlorocyclo hexane. [[Page 73764]] 28C......... Exposure levels .............. Filled........ Reference range in humans concentrations (adults) living in serum are near hazardous available (CDC waste sites and 2005). ATSDR other acknowledges populations, that reference such as exposed concentration workers. 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. 28D......... Exposure levels .............. Filled........ Reference range in children. concentrations in serum are available (CDC 2005). 28E......... Potential ATSDR......... candidate for subregistry of exposed persons. Lead.......................... 29A......... Mechanistic MHPF.......... Filled........ Multiple studies studies on the (at least 13 neurotoxic publications effects of lead. from the MHPF Research Program + numerous studies in ATSDR's 1999 updated toxicological profile) are available. 29B......... Analytical MHPF.......... Filled........ A publication methods for from the MHPF tissue levels. Research Program and numerous studies in ATSDR's 1999 toxicological profile are available. 29C......... Exposure levels MHPF.......... Filled........ In addition to in humans G. Lakes...... the data from (adults) near Great Lakes hazardous waste Research sites and other Program and populations, MHPF Research such as exposed Program, workers. 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 .............. Filled........ Reference range in children. concentrations in blood and urine are available (CDC 2005). Manganese..................... 30A......... Dose-response MHPF.......... Filled........ Availability of data for acute- EPA........... studies in the and MHPF Research intermediate- Program. 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 hypersensitivit y reactions). 30B......... Toxicokinetic MHPF.......... Filled........ Availability of studies on EPA........... studies in the animals to MHPF Research investigate Program. uptake and absorption, relative uptake of differing manganese compounds, metabolism of manganese, and interaction of manganese with other substances following oral exposure. 30C......... Epidemiological .............. Filled........ Based on an studies on the evaluation of health effects the data in of manganese ATSDR's 2000 (Special updated emphasis end toxicological points include profile. ATSDR neurologic, will continue reproductive, to evaluate new developmental, data as they immunologic, become and cancer). available to determine if additional studies are needed. [[Page 73765]] 30D......... Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers. 30E......... Relative EPA. bioavailability of different manganese compounds and bioavailability of manganese from soil. Mercury....................... 31A......... Multigeneration MHPF.......... Filled........ Availability of reproductive publications toxicity study from the MHPF via oral Research exposure. Program. 31B......... Dose-response .............. Filled........ An MRL was data in animals derived in from chronic- ATSDR's 1999 duration oral updated exposure. toxicological profile. 31C......... Immunotoxicology EPA. battery of tests via oral exposure. 31D......... Exposure levels G. Lakes...... Filled........ In addition to in humans the data from (adults) living the Great Lakes near hazardous Research waste sites and Program, other background populations, levels data are such as exposed available in workers. 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 .............. Filled........ Reference range in children. concentrations in blood and urine are available (CDC 2005). 31F......... Potential ATSDR. candidate for subregistry of exposed persons. Methoxychlor.................. 32A......... Evaluate .............. Filled........ Based on an neurologic evaluation of effects after the data in long-term, low- ATSDR's 2000 level oral updated exposure. 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 ATSDR. candidate for subregistry of exposed persons. Methylene chloride............ 33A......... Dose-response EPA........... Filled........ ATSDR accepted data in animals Vol Res....... HSIA's toxicity for acute- and study for acute- intermediate- and duration oral intermediate- exposure. The duration subchronic exposure study should duration in include February 1997. extended Also, ATSDR reproductive accepted HSIA's organ immunotoxicity histopathology, study via neuropathology, inhalation in and November 2000 immunopathology. 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 Vol Res....... Filled........ ATSDR accepted developmental HSIA's study in toxicity study February 1997. via the oral route. [[Page 73766]] 33C......... Exposure levels .............. Filled........ Reference range in humans concentrations living near in blood are hazardous waste available sites and other (Ashley et al. populations, 1992, 1994; such as exposed Needham et al. workers. 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. 33D......... Potential ATSDR. candidate for subregistry of exposed persons. Nickel........................ 34A......... Epidemilogic .............. Filled........ Based on at studies on the least two health effects relevant of nickel studies in (Special ATSDR's 1997 emphasis end updated points include toxicological reproductive profile. ATSDR toxicity). will continue to evaluate new data as they become available to determine if additional studies are needed. 34B......... Prenatal EPA........... Filled........ In ATSDR's 1997 development updated toxicity study toxicological via the oral profile, a route. study confirming the results of two previous studies is available. 34C......... Dose-response EPA. data in animals for acute- and intermediate- duration oral exposures. 34D......... Neurotoxicology EPA. battery of tests via oral exposure. 34E......... Bioavailability EPA. of nickel from soil. 34F......... Exposure levels G. Lakes...... Filled........ Based on in humans availability of (adults) living the data from near hazardous the Great Lakes waste sites and Research other Program and an populations, evaluation of such as exposed ATSDR's 1997 workers. updated toxicological profile. 34G......... Potential ATSDR. candidate for subregistry of exposed persons. Pentachlorophenol............. 35A......... Comparative toxicokinetic studies. 35B......... Exposure levels .............. Filled........ Reference range in humans concentrations (adults) living in urine are near hazardous available (CDC waste sites. 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 .............. Filled........ Reference range in children. concentrations in urine are available (CDC 2005). 35D......... Potential ATSDR. candidate for subregistry of exposed persons. Polychlorinated biphenyls 36A......... Dose-response G. Lakes...... .............. Although an MRL (PCBs). data in animals for for acute- and intermediate- intermediate- exposure duration oral duration was exposure. 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. [[Page 73767]] 36C......... Dose-response data in animals for acute- and intermediate- duration inhalation exposures. The subchronic study should include extended reproductive organ histopathology. 36D......... Epidemiologic G. Lakes...... Filled........ In addition to studies on the the data from health effects the Great Lakes of PCBs Research (Special Program, emphasis end multiple points include studies in immunotoxicity, ATSDR's 2000 gastrointestina updated l toxicity, toxicological liver toxicity, profile are kidney available. toxicity, thyroid toxicity, and reproductive/ developmental toxicity). 36E......... Exposure levels G. Lakes...... Filled........ In addition to in humans the data from (adults) living the Great Lakes near hazardous Research waste sites and Program, other background populations, levels data are such as exposed available workers. (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 .............. Filled........ Reference range in children. concentrations in serum are available (CDC 2005). 36G......... Potential ATSDR. candidate for subregistry of exposed persons. 36H \5\..... Chronic toxicity Vol Res....... Filled........ ATSDR accepted and the final oncogenicity report of the via oral GE study in exposure. October 1997. 36I \5\..... Aerobic PCB Vol Res....... Filled........ ATSDR accepted biodegradation the final in sediment. report of the GE study in July 1999. 36J \5\..... PCB congener Vol Res....... Filled........ ATSDR accepted analysis. G. Lakes...... the final report of the GE study in October 1997. Also, data from the Great Lakes Research Program are available. Polycyclic aromatic 37A......... Dose-response MHPF.......... Filled........ MRLs for four hydrocarbons (PAHs) (Includes data in animals PAHs were 15 substances). for derived in intermediate- ATSDR's 1995 duration oral updated exposures. The toxicological subchronic profile. A study should publication include from the MHPF extended Research reproductive Program organ addressing this histopathology priority data and need is immunopathology. available. 37B......... Prenatal MHPF.......... Filled........ Data from the developmental MHPF Research toxicity study Program via inhalation including a or oral publication are exposure. available. 37C......... Mechanistic MHPF.......... Filled........ In addition to studies on publications PAHs, on how from the MHPF mixtures of Research PAHs can Program, influence the studies are ultimate available in activation of ATSDR's 1995 PAHs, and on updated how PAHs affect toxicological rapidly profile. proliferating tissues. 37D......... Dose-response MHPF.......... Filled........ Data from the data in animals MHPF Research for acute- and Program intermediate- including one duration publication are inhalation available. exposures. The subchronic study should include extended reproductive organ histopathology and immunopathology. 37E......... Epidemiologic .............. Filled........ Multiple studies studies on the in ATSDR's 1995 health effects updated of PAHs toxicological (Special profile are emphasis end available. points include ATSDR will cancer, dermal, continue to hemolymphatic, evaluate new and hepatic data as they toxicity). become available to determine if additional studies are needed. [[Page 73768]] 37F......... Exposure levels G. Lakes...... Filled........ Based on data in humans from the Great (adults) living Lakes Research near hazardous Program and an waste sites and evaluation of other the ATSDR 1995 populations, updated such as exposed toxicological workers. 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 .............. Filled........ Reference range in children. concentrations in urine are available (CDC 2005). 37H......... Potential ATSDR. candidate for subregistry of exposed persons. Selenium...................... 38A......... Dose-response EPA. data in animals for acute- duration oral exposure. 38B......... Immunotoxicology EPA. battery of tests via oral exposure. 38C......... Epidemiologic .............. Filled........ Based on an studies on the evaluation of health effects ATSDR's 2001 of selenium updated (Special toxicological emphasis end profile. ATSDR points include will continue cancer, to evaluate new reproductive data as they and become developmental available to toxicity, determine if hepatotoxicity, additional and adverse studies are skin effects). needed. 38D......... Exposure levels G. Lakes...... Filled........ In addition to in humans the data from living near the Great Lakes hazardous waste Research sites and other Program, populations, reference range such as exposed concentrations workers. 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 ATSDR......... candidate for subregistry of exposed persons. 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 ATSDR......... candidate for subregistry of exposed persons. Tetrachloroethylene........... 40A......... Dose-response .............. Filled........ An MRL was data in animals derived in the for acute- ATSDR 1997 duration oral updated exposure, toxicological including profile. neuropathology and demeanor, and immunopathology. [[Page 73769]] 40B......... Multigeneration Vol Res....... .............. HSIA's reproductive inhalation toxicity study study was via oral accepted by exposure. 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 EPA........... HSIA will obtain data in animals Vol Res....... oral data for for intermediate- intermediate- duration duration oral toxicity and exposure, neurotoxicity including by PBPK neuropathology, modeling based and on existing immunopathology. inhalation data. Also, it will conduct an inhalation immunotoxicity study, followed by PBPK modeling to obtain oral data. 40D......... Prenatal Vol Res....... .............. HSIA's developmental developmental toxicity study toxicity study via oral via inhalation exposure. 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 EPA neurotoxicity Vol Res....... study via oral exposure. 40F......... Exposure levels .............. Filled........ Reference range in humans concentrations living near in blood are hazardous waste available sites and other (Ashley et al. populations, 1992, 1994; such as exposed Needham et al. workers. 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. 40G......... Potential ATSDR......... candidate for subregistry of exposed persons. Toluene....................... 41A......... Dose-response .............. Filled........ Availability of data in animals MRLs for acute- for acute- and and intermediate- intermediate- duration oral exposure exposures. The durations in subchronic ATSDR's 2000 study should updated include an toxicological extended profile. histopathologic evaluation of the immune system. 41B......... Comparative .............. Filled........ Based on toxicokinetic evaluation of studies the data in (Characterizati ATSDR's 2000 on of updated absorption, toxicological distribution, profile. and excretion via oral exposure). 41C......... Neurotoxicology EPA........... A publication battery of MHPF.......... for acute tests via oral exposure but exposure. 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 .............. Filled........ Multiple studies toluene-induced in ATSDR's 1994 neurotoxicity. and 2000 updated toxicological profiles are available. [[Page 73770]] 41E......... Exposure levels .............. Filled........ Reference range in humans concentrations living near in blood are hazardous waste available sites and other (Ashley et al. populations, 1992, 1994; such as exposed Needham et al. workers. 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 ATSDR......... candidate for subregistry of exposed persons. 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 ATSDR......... candidate for subregistry of exposed persons. Trichloroethylene............. 43A......... Dose-response .............. Filled........ An MRL was data in animals derived in for acute- ATSDR's 1997 duration oral updated exposure. toxicological profile. 43B......... Neurotoxicology EPA .............. A publication battery of MHPF.......... for acute tests via the Vol Res....... exposure but oral route. 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 Vol Res....... .............. HSIA has battery of completed an tests via oral inhalation route. immunotoxicity study which is undergoing ATSDR peer review. HSIA will obtain oral data via PBPK modeling based on the inhalation data. 43D......... Prenatal Vol Res....... .............. ATSDR has developmental accepted HSIA's toxicity study final report via oral for an exposure. 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 EPA neurotoxicity Vol Res....... study via oral exposure. 43F......... Epidemiologic .............. Filled........ Based on studies on the evaluation of health effects the data in of ATSDR's 1997 trichloroethyle updated ne (Special toxicological emphasis end profile. ATSDR points include will continue cancer, to evaluate new hepatotoxicity, data as they renal toxicity, become developmental available to toxicity, and determine if neurotoxicity). additional studies are needed. [[Page 73771]] 43G......... Exposure levels .............. Filled........ Reference range in humans concentrations living near in blood are hazardous waste available sites and other (Ashley et al. populations, 1992, 1994; such as exposed Needham et al. workers. 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. Vinyl chloride................ 44A......... Dose-response .............. Filled........ An MRL was data in animals derived in for acute- ATSDR's 1997 duration updated inhalation toxicological exposure. profile. 44B......... Multigeneration Vol Res....... Filled........ ATSDR accepted reproductive the final toxicity study report of ACC's via inhalation. study in November 2000. 44C......... Dose-response data in animals for chronic- duration inhalation exposure. 44D......... Mitigation of vinyl chloride- induced toxicity. 44E......... Prenatal Vol Res....... Filled........ ATSDR accepted developmental the final toxicity study report of ACC's via inhalation. study in November 2000. 44F......... Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers. 44G......... Potential ATSDR. candidate for subregistry of exposed persons. 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 neurodevelopmen tal end points following oral exposure. 45E......... Exposure levels in humans living near hazardous waste sites. 45F......... Exposure levels in children. 45G......... Potential ATSDR. candidate for subregistry of exposed persons. Zinc.......................... 46A......... Dose-response MHPF.......... Filled........ Availability of data in animals ongoing studies for acute- and in the MHPF intermediate- Research duration oral Program. exposures. The subchronic study should include an extended histopathologic evaluation of the immunologic and neurologic systems. 46B......... Multigeneration MHPF.......... Filled........ Availability of reproductive ongoing studies toxicity study in the MHPF via oral Research exposure. Program. 46C......... Carcinogenicity testing (2-year bioassay) via oral exposure. 46D......... Exposure levels .............. .............. This priority in humans data need, living near previously hazardous waste anticipated to sites and other be addressed populations, under the such as exposed voluntary workers. research program, is not being investigated under any of the ATSDR research programs. [[Page 73772]] 46E......... Potential ATSDR. candidate for subregistry of exposed persons. ---------------------------------------------------------------------------------------------------------------- \1\ Priority data need identification number. \2\ 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. \3\ PDN can be filled or remain unchanged based on reevaluation of the database using criteria developed by ATSDR. \4\ 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. \5\ Not a priority data need. Table 2.--Groups Which Are Addressing/Have Addressed ATSDR's Substance-Specific Priority Data Needs (PDNs) ---------------------------------------------------------------------------------------------------------------- Firm, institution, Program agency, or consortium Substance PDN ID ---------------------------------------------------------------------------------------------------------------- Voluntarism....................... American Chemistry Vinyl chloride...... 44B, 44E Council. General Electric PCBs................ 36H*, 36I*, 36J* Company. Halogenated Solvents Methylene chloride.. 33A, 33B Industry Alliance, Inc. Tetrachloroethylene. 40B, 40C, 40D, 40E Trichloroethylene... 43B, 43C, 43D, 43E Minority Health Professions Florida A & M Lead................ 29A Foundation. University. The King/Drew Medical Lead................ 29B, 29C Center of the Charles R. Drew University of Medicine and Science. Meharry Medical PAHs................ 37A, 37B, 37C, 37D College. Morehouse School of Lead................ 29C Medicine. Texas Southern Di-n-butyl phthalate 21D University. Lead................ 29A Toluene............. 41C Trichloroethylene... 43B Tuskegee University.. Chlordane........... 9A Mercury............. 31A Zinc................ 46A, 46B Xavier University.... Manganese........... 30A, 30B Zinc................ 46A Great Lakes Human Health Effects Michigan State DDT/DDE............. 19D, 19E Research Program. University. Lead................ 29C Mercury............. 31D PCBs................ 36D, 36E, 36J* Selenium............ 38D New York State Health DDT/DDE............. 19E Department. Lead................ 29C Mercury............. 31D PCBs................ 36D, 36E, 36J* State University of PCBs................ 36E New York at Albany. State University of DDT/DDE............. 19D, 19E New York at Buffalo. Lead................ 29C Mercury............. 31D PCBs................ 36D, 36E, 36J* State University of DDT/DDE............. 19D, 19E New York at Oswego. Lead................ 29C Mercury............. 31D PCBs................ 36D, 36E, 36J* University of DDT/DDE............. 19D, 19E Illinois at Chicago. [[Page 73773]] Lead................ 29C Mercury............. 31D PCBs................ 36D, 36E, 36J* University of DDT/DDE............. 19D, 19E Illinois at Urbana- Champaign. Lead................ 29C Mercury............. 31D PCBs................ 36D, 36E, 36J* University of DDT/DDE............. 19D, 19E Wisconsin-Milwaukee. Lead................ 29C Mercury............. 31D PCBs................ 36A, 36D, 36E, 36J* Selenium............ 38D Wisconsin Department Arsenic............. 2D of Health and Social Services--5 State Consortium. Cadmium............. 7B Chromium............ 13E DDT/DDE............. 19D, 19E Lead................ 29C Mercury............. 31D Nickel.............. 34F PAHs................ 37F PCBs................ 36D, 36E, 36J* Environmental Protection Agency EPA/ATSDR Test Rule.. Benzene............. 4A, 4B, 4C TSCA/FIFRA. Chloroethane........ 11A, 11B Cyanide (hydrogen 14A, 14B cyanide and sodium cyanide). Methylene chloride.. 33A Tetrachloroethylene. 40C, 40E Toluene............. 41C Trichloroethylene... 43B, 43E Metals Testing Task Arsenic............. 2A, 2B, 2C Force (TASARC). 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 tetrachloride 8B Environmental Health Sciences. 1,1-dichloroethene.. 18A, 18B Di-n-butyl phthalate 21A Disulfoton.......... 22A Heptachlor.......... 26B ---------------------------------------------------------------------------------------------------------------- * Not priority data needs. Editorial Note: FR Doc. 05-23361 was originally published at page 71506 in the issue of Tuesday, November 29, 2005. The corrected document is republished in its entirety, due to printing errors. [FR Doc. R5-23361 Filed 12-12-05; 8:45 am] BILLING CODE 1505-01-D