Document oe5BeERwnVqQxQYgmpej8GOng

PATTON BOGGS. L.L.P. 2550 M STREET. N.W. WASHINGTON. D.C. 20037-1350 (202) 457-6000 F*eiiLt. (ZOZ|457-63t5 WRITER'S DIRECT OIA~ April 3. 1996 (202) 457-5270 MEMORANDUM FOR VINYL CHLORIDE PANEL Re: ATSDR Voluntary Research Propram Attached is a notice published earlier this week by the Agency for Toxic Substances and Disease Registry (ATSDR) to update the status of its voluntary research program. The notice reports that the acute inhalation toxicity study of vinyl chloride has been determined no longer to be a data need. It notes that CMA submitted a protocol to address the priority data needs for reproductive and developmental toxicity studies of vinyl chloride by inhalation, and states that ATSDR expects to enter a Memorandum of Understanding with CMA for this study in the near future. Attachment W. Caffey Norman, III 004605.001 14420 Federal Register / Vol. 61, No. 63 / Monday. April 1. 1996 ( Notices DEPARTMENT OF HEALTH AND HUMAN SERVICES Agency For Toxic Substances and Disease Registry (ATSDft-106] 0 Update on the Status of the Superfund Substance-Specific Applied Research Program AGENCY: Agency for Toxic Substances and Disease Registry (ATSDR), Department of Health and Human Services (HHS). action: Notice. SUMMARY: This Notice is an update on the status of ATSDR's continuing effort to implement the Substance-Specific Applied Research Program (SSARP). Authorized by the Comprehensive Environmental Response. Compensation, and Liability Act of 1980 (Superfund) or CERCLA, as amended by the Superfund Amendments and Reauthorization Act of 1986 (SARA) (42 U.S.C. 9604 (l)), this research program was initiated on October 17.1991. At that time, a list of priority data needs for 38 priority hazardous substances was announced in the Federal Register (56 FR 52178). The list was subsequently revised based an public comments and published in final form on November 16,1992 (57 FR 54150). The 38 substances, each of which is found on ATSDR's List of Priority Hazardous Substances, are aldrin/ dieldrin, arsenic, benzene, beryllium, cadmium, carbon tetrachloride, chloroethane, chloroform, chromium, cyanide, p,p`-DDTJDDEJ3DD, di(2etbylhexyl) phthalate. lead, mercury, methylene chloride, nickel, polychlorinated biphenyl compounds (PCBs), polycyclic aromatic hydrocarbons (PAHs--includes 15 substances), selenium, tetrachloroethylene, toluene, trichloroethylene, vinyl chloride, and zinc (56 FR 52166, October 17.1991). Priority data needs for 12 additional priority hazardous substances were recently identified and are also being announced in e Federal Register Notice. The 12 substances, each of which is included in ATSDR's List of Priority Hazardous Substances, are chlordane, 1.2-dibromo- 3-chloropropane, di-nbutyl phthalate, disulfoton, endrin (includes endrin aldehyde), endosulfan (alpha-, beta-, and endosulfan sulfate), beptachlor (includes heptachlor epoxide), hexachlorobutadiene, hexachlorocyclohexane (alpha-, beta-, delta- and gamma-), manganese, methoxychlor, and toxaphene. This Notice also serves as a continuous call for voluntary research proposals. Private-sector organizations may volunteer to conduct research to address specific priority data needs by indicating their interest through submission of a research proposal to ATSDR (see ADDRESSES section of this Notice). A Tri-Agency Superfund Applied Research Committee (TASARC) comprised of scientists from ATSDR. the National Toxicology Program (NTP), and the Environmental Protection Agency (EPA) will review all proposed voluntary research efforts. DATES: ATSDR considers the voluntary research effort to be important to the continuing development of the SSARP. Therefore, the agency strongly encourages private-sector organizations to volunteer at any time to conduct research to address identified data needs unless ATSDR announces that researchhas already been initiated for that specific data need. ADDRESSES: Private-sector organizations interested in volunteering to conduct research may write to Dr. William Cibulas, Chief, Research Implementation BranchTthvision of Toxicology, ATSDR. 1600 Clifton Road. N.E., Mailstop E-29, Atlanta, Georgia 30333. FOR FURTHER INFORMATION CONTACT: Dr. William Cibulas, Chief, Research Implementation Branch. Division of Toxicology, ATSDR. 1600 Clifton Road, N.E., Mailstop E-29, Atlanta, Georgia 30333. telephone 404-639-6306. SUPPLEMENTARY INFORMATION: Background CERCLA as amended by SARA (42 U.S.C 9604(i)) requires that ATSDR (1) jointly with the EPA, develop and prioritize a list of hazardous substances found at National Priorities List (NPL) sites, (2) prepare toxicological-profiles for these substances, and (3) assure the initiation of a research program to address identified data needs associated with the substances.. Before starting such a program, ATSDR will consider recommendations of the Interagency Testing Committee on the type of research that should be done. This committee was established under section 4(e) of the Toxic Substances Control Act of 1976 (TSCA). On October 17,1991, ATSDR announced the identification of the B" y data needs for 38 priority ous substances (56 FR 52178), requested public comments, and invited private- sector organizations to volunteer to conduct research to address specific priority data needs. On November 16,1992, the agency published a revised list of 117 priori data needs for these priority hazardc substances (57 FR 54150). The major goals of the ATSDR SS/ are (1) to address the substance-spec information needs of the public and scientific community, and (2) to sup; necessary information to improve tin database to conduct comprehensive public health assessments of populations living near hazardous w> sites. This program will also provide data that can be generalized to other substances or areas of science, includ risk assessment of chemicals, thus creating a sdentific-base for addressi: a broader range of data needs. In section 104(i)(S)(D). CERCLA sta that it is the sense of Congress that tht costs for conducting this research program be borne by the manufacture and processors of the hazardous substances under TSCA and by registrants under the Federal Insecticide, Fungicide, and Rodentidc Act of 1972 (F1FRA), or by cost recove from responsible parties under CERCL To execute this statutory intent, ATSC developed a plan whereby parts of the SSARP are being conducted via____ regulatory mechanisms (TSCA/F1FKA) private-sector voluntarism, and throug the direct use of CERCLA funds. The TASARC, comprised of scientist from ATSDR, NTP, and the EPA has been set up: (1) To advise on the assignment of priorities on mechanisms for addressin data needs; (2) To coordinate knowledge of research activities to avoid duplication of research in other programs and unde other authorities; (3) To advise on issues of sci nee related to substance-specific data needs and (4) To maintain a scheduled forum that provides an overall review of the ATSDR SSARP. The TASARC has met six times since the SSARP began. This Notice is an update on the status of ATSDR's efforts to implement the SSARP, focusing on ongoing activities relevant to test-rule development under TSCA/FIFRA, private-sector voluntarism, and the direct use of CERCLA funds. Additional data needs are being addressed through an interagency agreement with NTP, by ATSDR's Great Lakes Human Health Effects Research Program, and other agency programs. To date, a total of 63 research needs associated with 38 ATSDR priority hazardous substances (including 15 polycyclic aromatic hydrocarbons) are being addressed via these mechanisms (Table 1). 004605.002 Federal / Vol. 61, No. 63 / Monday, April 1. 1996 / Notices 14421 AT5DR believes that these priority data needs will remain n the agency's list until ongoing studies to address them have been completed, peerreviewed, and accepted by ATSDR. However, priority data needs could be deleted from the list (Table 1) if upon re-evaluation of the sodsting database, the agency determines that additional studies are no longer needed. Three recent examples follow. ATSDR, in consultation with the TASARC. re evaluated the database for acute inhalation toxicity for vinyl chloride and determined no additional data are needed at this time (Table 1). With regard to the priority data need for oral developmental toxicity studies for tetraduoroethylene (PERC), ATSDR recently re-evaluated the database during the update of the toxicological profile for this substance. ATSDR concluded that the database was sufficient to derive a minimal risk level (MRL) for acute oral exposure based on a developmental toxicity study. Although ATSDR believes that additional developmental data would be useful to more fully characterize the effects and increase the confidence level of the MRL, the agency now believes that this data is more appropriately classified as a data neea rather than a priority data need. Therefore, this priority data need has also been deleted from the list (Table 1). Similarly, the priority data need for additional acute oral studies for trichloroethylene has been reclassified as a data need and thus deleted from the list (Table 1) because an MRL was derived during the updating of the toxicological profile. Conversely, additional priority data needs could be included in the ATSDR list based an assessment by agency programs (See Section F. "Other ATSDR Programs." which discusses exposure subregistries). A. TSCA/FJFRA In developing and implementing the Substance-Specific Applied Research Program. ATSDR, NTP, and EPA have, established procedures to identify priority data needs of mutual interest to Federal programs. These data needs are being addressed through a program of toxicologic testing under TSCA. This research will be conducted according to established TSCA procedures and guidelines. Generally, this testing will address more than one Federal program's need. Following review and endorsement by the TASARC oversight committee during fiscal year (FY) 1993. of the 117 priority data needs for 38 substances, approximately 60 priority data needs were referred to the EPA under TSCA/FIFRA authorities. During 1994, EPA added 11 ATSDR substances (and associated 26 priority data needs) to its master testing list, the first step in test-rule development under TSCA. Section 4 (59 FR11434. March 10,1994). On September 30,1994. EPA published a Federal Register Notice soliciting testing proposals from industry to address the priority data needs identified for ATSDR's priority hazardous substances (59 FR 49934). Although no manufacturers or processors of these substances came forward with testing proposals, several industry groups responded by submitting proposals to address some of the data needs via ATSDR's voluntary research program described in detail in Section B, "Private-Sector Voluntarism." The priority data needs currently being addressed by TSCA/ FIFRA are listed in Table 2. ATSDR shared its priority data needs for these substances with other Federal agencies and programs. On several occasions when ATSDR identified priority data needs far oral exposure, other agencies needed inhalation data. In response, ATSDR is considering proposals to conduct inhalation studies in conjunction with physiologically based pharmacokinetic (PBPK) studies in lieu of oral bioassays. ATSDR expects that inhalation data derived from these studies can be used with PBPK modeling to address its oral toxicity data needs. Table 2 includes the priority data needs for three metals, i.e.. beryllium, chromium and mercury. However, the specific forms of the metals to be tested are yet to be determined. The TASARC has established a workgroup to address this issue. The workgroup will also consider the needs of other Federal agencies and EPA programs. The EPA will solicit testing proposals for these three metals at a later date. B. Private-Sector Voluntarism As part of the SSARP, on February 7, 1992, ATSDR initially announced a set of proposed procedures for conducting voluntary research (56 FR 4758). Revisions based on public comments were published on November 16,1992 (57 FR 54160). Private-sector organizations were encouraged to volunteer to conduct research to address these specific priority data needs. ATSDR has been pursuing voluntary research interests with three privatesector organizations: the General Electric Company (GE), the Halogenated Solvents Industry Alliance (HS1A). and the Chemical Manufacturers Association (CMA). Preliminary discussions are being held with a fourth organization, the Shell Oil Company. Through the voluntary research efforts of these organizations, data needs for two classes of substances (PCB compounds and volatile organic compounds) are being addressed (Table 2). To date, two memoranda of understanding (MOU) have been signed by ATSDR and the interested parties. A third MOU is unde development. General Electric Company (GE) On February 8.1995, ATSDR entered into an MOU with GE. This was the first time a private-sector organization volunteered to conduct research to address ATSDR's data needs identified in its SSARP. The MOU with GE covers the following three studies on PCBs: * Project 1. "An assessment of the chronic toxicity and oncogenicity of Aroclor-1016, Aroclor-1242, Aroclor1254, and Aroclor-1260 administered in diet to rats," was initiated on February 8,1993. * Project 2. "Metabolite detection as a tool for the determination of naturally occurring aerobic PCB biodegradation," was initiated on January 2,1995. * Project 3, "PCB congener Analyses,' was initiated on February 8,1993. While the above studies do not address ATSDR's priority data needs for PCBs, the three projects will address some of the agency's data needs for these substances. Specifically, although ATSDR has identified bioassays via the inhalation and dermal routes as data needs for PCBs, agency scientists believe information gained via GHTs oral bioassay (Project 1) is pertinent to understanding the toxidty of PCBs. Furthermore, first-pass metabolism does not appear to play a key role for these substances. Therefore, toxicity information to be obtained from the GE oral bioassay is expected to be relevant to the inhalation and dermal routes. ATSDR has identified PCB degradation in sediment as a data need. Additional environmental fate information is needed to estimate exposure to PCBs under various conditions of environmental release in order to plan and conduct follow-up exposure and health studies. Therefore, Project 2 will address ATSDR's data need for the environmental fate of PCBs Although ATSDR has not identified PCB congener analyses (Project 3) as a data need, agency scientists believe that the toxicokinetics data (using selected tissues from Project 1) may provide important knowledge about the correlation of health effects with relevant PCB congeners. 004605.003 14422 Federal Register / VoL 61, No, 63 / Monday. April 1. 1996 / Notices Halogenated Solvents Industry Alliance Chemical Manufacturers Association broad areas of toxicology and (HS1A) (CMA) environmental health science. Some On April 4,1995, ATSOR entered into an MOU with HS1A covering studies to address three ATSOR priority toxicity data needs ior methylene chloride. The studies consist of acute- and subchronic-duration. and developmental toxicity via oral exposure. The data will be obtained by using PBPK modeling. These studies were initiated on May 23.1995. HSIA has also proposed to conduct a 28-day immunopathology assessment for methylene chloride via oral exposure, a priority data need identified by ATSDR. The agency expects to receive a study protocol from HSIA for peer review in the near future. Currently, HSIA and ATSDR continue to discuss voluntary research efforts for trichloroethylene (TCE) and tetrachloroethylene (PERC). During FY1995, the CMA submitted a study protocol addressing two ATSDR priority data needs for vinyl chloride, specifically, inhalation reproductive and developmental toxicity studies in rats. ATSDR accepted the study protocol as a candidate for voluntary research based on ATSDR peer reviews and CMA's satisfactory response to the peer reviewers' comments. ATSDR expects to finalize an MOU with CMA covering this study in the near future. EPA no longer requires inhalation neurological data for vinyl chloride as originally stated in its solicitation Notice (59 FR 49934. September 30, 1994). Its decision is based on a recent reevaluation of the database. C.CERCLA-Funded Research (Minority Health Professions Foundation Research Program) MHPF members are conducting health studies of minority groups exposed to ATSDR's priority hazardous substances. D. National Toxicology Program (NTP) ATSDR maintains an interagency agreement (LAG) with NTP to conduct toxicologic testing of substances identified at NPL sites. The studies, determine levels of exposure that present a significant risk to humans of acute, subchronic, and chronic health effects. Often these studies include an assessment of the substance's ability to cause cancer, reproductive toxicity, and birth defects. The results of these studies are used by regulatory agencies such as the Food and Drug Administration and EPA, various environmental and industrial groups, and ATSDR to improve the ability to conduct public health assessments at NPL sites. With regard to TCE, ATSDR has recently reclassified the priority data need for acute oral data to a data need, (see Background section of this Notice). The agency is continuing its discussion with HSIA to assess the possibility of conducting a study or utilizing During FY 1992, ATSDR announced a $4 million cooperative agreement program with the Minority Health Professions Foundation (MHPF) to support substance-specific investigations. This cooperative venture is supported by the direct use of Under this agreement, one toxicity priority data need identified in the SSARP (immunotoxicology study of carbon tetrachloride) is being addressed. An area of ongoing research by the NTP is to study the bioavailability of PCBs in soil, a priority data need for benchmark dose modeling to address this data need. As for immunopathology data, HSIA proposed to first review the existing data for TCE. If the data are inadequate and the methylene chloride CERCLA funds. About $4 million was allocated annually for FYs 1993 to 1995 to continue this research program that ends in September 1997. Currently, 9 priority data needs for 21 ATSDR. Therefore, NTP research may also potentially address this ATSDR priority data need. During FY 1993, the existing LAG was modified to include toxicity studies of immunopathology study mentioned priority hazardous substances ATSDR's priority hazardous substances above has provided meaningful (including 15 PAHs) in the SSARP are via application of structure-activity information, HSIA would then conduct being addressed by the MHPF relationship (SAR) techniques and a similar study for TCE. institutions through this program. Also, PBPK modeling. NIP indicated future Regarding the priority data needs for PERC, HSIA plans to obtain the oral neurotoxicity data called for by the agency by PBPK modeling. The database to be used for modeling will include the HSIA-sponsored inhalation neurotoxicity study recently approved by EPA. EPA and ATSDR scientists recently reviewed and accepted the HSIA-sponsored reproductive toxicity study of PERC via inhalation. HSIA proposed to address ATSDR's priority data need for oral reproductive data using PBPK modeling. As for ATSDR's priority data need for immunopathology data, HSIA would follow the same procedures as for TCE (described above). Finally, with regard to ATSDR's data need for oral developmental toxicity studies for PERC (see Background section of this Notice), ATSDR is continuing its discussion with HSIA to obtain this data via PBPK modeling once the EPA-required inhalation developmental toxicity study has been completed. the MHPF research program will address 13 other substance-specific data needs identified in the ATSDR toxicological profiles concerning exposures and related health effects. To date, more than 20 abstracts have been presented at scientific meetings, 4 manuscripts have been published in peer-reviewed journals, and 7 manuscripts are in preparation. The institutions receiving awards and their respective research projects are listed in Table 2. A not-for-profit 501(c)(3) organization, the MHPF comprises 11 minority health professions schools. Its primary mission is to research the health problems that disproportionately affect poor and minority citizens. The purposes of the ATSDR-MHPF cooperative agreement are (1) to initiate research to address ATSDR-identified data needs for priority hazardous substances, and (2) to enhance existing disciplinary capacities to conduct research in environmental health at MHPF member institutions.` The areas of research at MHPF institutions include those related to plans for SAR modeling for reproductive and immunologic endpoints. ATSDR is continuing to work closely with NTP as the agency has identified many reproductive and immunologic data needs for the 38 priority hazardous substances. As discussed in Section A. "TSCA/FIFRA," ATSDR will consider using PBPK modeling to address data needs when models are well developed and validated. Therefore. ATSDR will continue to work closely with NTP in its efforts to refine the models. E. Great Lakes Human Health Effects Research Program Some of the priority data needs identified in the SSARP have been independently identified as research needs through the ATSDR Great Lakes Human Health Effects Research Program, a separate research program. To date, 12 priority data needs for 19 priority hazardous substances .(including 15 PAHs) identified in the SSARP are being addressed through this program. The institutions receiving 004605.004 Federal Register / Vol- 61. No. 63 / Monday. April 1, 1996 / Notices 14423 awards and their respective studies are 1992. In addition, ATSDR awarded one listed in Table 2. new grant to the Michigan Department The Great Lakes Critical Programs Act of Public Health to design, establish, of 1990 mandated that EPA. in and operate a professi. nally creditable, consultation with ATSDR, prepare a interlaboratory quality assurance/ report that assesses the adverse effects quality control program for the ATSDR of pollutants in the Great lake* system Great Lakes Human Health Effects on the health of individuals in the Great Research Program. Additional funding Lakes states. This report was recently of S3 million and $4 million for FYs transmitted to the Congress by the EPA Administrator. In support of this directive. ATSDR received funds to cany out research. The ATSDR-supported research projects focus on at-risk populations to further define the human health consequences 1994 and 1995, respectively, was allocated to continue support of the 10 research projects. During FY 1994, ATSDR held a Great Lakes Research Symposium in Detroit, Michigan. The proceedings of the symposium will be published in the of exposure to persistently toxic journal of Toxicology and Industrial substances in the Great Lakes basin. The Health in the near future. research activities include but are not limited to the following: (1) Characterizing exposure and determining the profiles and levels of Great Lakes contaminants in biologic tissues and fluids in at-risk populations; (2) Identifying sensitive and specific human reproductive/developmental endpoints and correlating them to exposure to Great Lakes contaminants; (3) Determining the short- and long Other ATSDR Programs In its role as a public health agency addressing environmental health, when appropriate, ATSDR may collect human data to validate substance-specific exposure and toxicity findings. Information on levels of contaminants in humans has been identified and remains as a priority data need for 37 of the 38 priority substances (Table 1). term risk(s) of adverse health effects in ATSDR will obtain this information progeny whose parents were exposed to through exposure and health effects Great Lakes contaminants; studies, and through establishing and (4) Investigating the feasibility of using substance-specific subregistries of establishing registries and surveillance people within the agency's National cohorts in the Great Lakes region; and Exposure Registry who have potentially (5) Establishing a chemical mixtures been exposed to these substances. database with emphasis on tissue and The list of 38 priority hazardous blood levels in order to identify new substances in the SSARP was forwarded cohorts, conduct surveillance and to ATSDR's Exposure and Disease health affects studies, and establish Registry Branch (EDRB), Division of registries and surveillance cohorts. Health Studies, for consideration as During FY1992, ATSDR announced a potential candidates for subregistries of $2 million grant program to conduct exposed persons, based on criteria research on the impact on people's described in its 1988 document, health from eating contaminated fish "Policies and Procedures for from the Groat Lakes region. On Establishing a National Registry of September 30,1992, ATSDR announced `Persons Exposed to Hazardous 9 awards under this program. Substances." In FY 1993, about S3 million was To date. ATSDR has selected benzene, allocated to support the continuation of chromium, and trichloroethylene as the research projects conducted at the 9 primary contaminants to establish institutions originally funded during FY subregistries in the National Exposure Registry. However, aldrin/dieldrin. carbon tetrachloride, chloroethane. chloroform, cyanide, p.p'- DDT. DDE. DDD. di(2-ethylhexyl)phtbalate, mercury, methylene chloride. PAHs. selenium, tetrachloroethylene, and viny chloride remain in the candidate pool. They will be considered for selection as primary contaminants during each selection process (Table 1). Since the publication of the ATSDR March 10,1994, Federal Register Notice (59 FR11434), EDRB has re-evaluated the databases and included nickel. PCBs, toluene, and zinc in the candidate pool for consideration during each selection process (Table 1). However, arsenic, beryllium, cadmium, and lead are not considered to be in the pool of candidate substances for an exposure registry at this time. This decision will be re-evaluated as more information on the chemicals and exposure sites become available. Finally, the need to collect, evaluate, and interpret environmental data from contaminated media around hazardous waste sites remains a priority data need for all 38 priority hazardous substances by ATSDR. However, agency scientists realize that a substantial amount of this information has already been collected through individual State programs and the EPA's CERCLA activities: therefore, ATSDR will evaluate the extant information from these programs to characterize better the need for additional site-specific information. Tire results of the research conducted via the SSARP will be used for public health assessments and to reassess ATSDR's substance-spedfic priority data needs. The agency expects to re evaluate the priority data needs for priority hazardous substances every three years. Dated: March 26.1996. Claire V. Broome, DeputyAdministrator. Agencyfor Toxic Substances and Disease Registry. Table 1 .-Substance-Specific Priority Data needs (PDN) Currently Being Addressed Under ATSDR's Applied Research Programs Substance PDN ID Lead_________ 1A IB 1C Arsenic_______ 2A 2B 2C 20 Mercury______ 3A 3B PDN description " Pro grams'" Mechanistic studies on the neurotonic effect* of lead....... ........ Analytical methods for tissue levels. Exposure levels in humans Bving near hazardous waste sites and other populations, such as axposed workers. Comparative foxicokinetic sturtes to determine it an appropriate animal species can be identified ,, Half-Uvea in surface water, groundwater. BioavaiabBity from sod. Expostae levels in humans living near hazardous waste sites and other populations, such as axposed workers Muttigenenriion reproductive toxicity study via oral exposure .. _______ _____ Doae-response data in animals tor chronic-duration oral exposure____ ____ ____ M M.G M.G E 004605.005 14424 Federal Register / VoL 61, No. 63 / Monday, April 1, 1996 / Notices Table i.--Substance-Specific Priority Data Needs (PDN) currently Being Addressed Under ATSDR'S Applied Research Programs--Continued Substance PON ID PDN description Pro grams"1 3C 30 3E Vnyl Chloride ,, 4A 4B 4C 4D 4E 4F 4G Benzene ---- 5A SB SC SD 5E Cadmium-------- 6A 68 PCBs________ 7A 78 7C 7D 7E Chloroform ,,,,,, 7F 7G> 7H> 7I<*> 6A 88 6C PAHs ..... 80 fiA 98 9C 90 Trichloro-ethyl- 9E 9F 9G 1QA Immunnlflgiftrtlngy haftpry nf ImcK via nrol eivprwm . .......................... .... .... E Exposure ieveteto humans living near hazardous waste sites and other populations, sich as ex- G posed workers. Potential can&date tor subregistry o< exposed persons ............ --...... -.......... ---- ----------- AG Dose-response data in animals far acute-duration inhalation exposure------.------------.....--------------- Obi Miitigeneration reproductive toxicity study via inhalation ...... ....... .... ---------------------- Vtn * Dose-<espons data in animals for chronrc-dixation inhalation exposure. Mtigation of vinyl chloride-induoed toxicity. 2-epedes developmental toxicity study via Mutation -------------- ------------ ------------------------ ---- VR> Exposure levels in humans living near hazardous waste sites and other popUations, such as ex- posed workers PUertial candidate tor subregistry of exposed persons --------------------------------------------------------- A Dose-response data in animats for acute- and Wecmerlale-duration oral exposure. The subchronic E study should include an extended reproductive organ histopathotogy. 2-spades developmental toxicity study via oral exposure ----- --- ---------------- -- M Neurotoxicofogy battery of tests via oral exposure ----------- --------- ........................................... E Epidemiologic studies on the health effects of benzene (Special emphasis endpoints indude immunofoxidty). Exposure levels in humans Irving near hazardous waste sites and other populations, such as ex- poeed workers. Analytical methods for biological tissues and fluids and environrnersai media. Exposure levels in humans living near hazardous waste cites and other popUations, such as ex- poeed workers. Dose-response data in animals tor scute- and Mermedtate-duration oral exposures__ ___ G Biodegradation of PCBs in water, btoevailabiUty of PCBs in air, water and soil' Dose-response data in animals for acute- end intermodate-durafon Inhalation exposures. The ttfochronic study should include extended reproductive organ histopsthotogy Epidensofogie states on the health effects of PCBs (Special emphasis endpoints Indude G frnmawtoxidty, gastrointestinal toxicity, liver, kidney, thyroid toxicity, reproductive/developmental tooodty). Exposure levels in humans living near hazardous waste sites and other popUations, such as ex- G poeed workers. Potential candidate for subregistry of exposed persons ,, ._. . A Chronic toxicity and oncogenicity vie oral exposure u .-- -------- - .V Aerobic PC8 biodegradation in sediment PC8 congener . ................ ............... ..... .................... ................... .... V V Dose-response rtata in animals tor Mermetfiale-duration oral exposure. Epidemiologic states on the health effects of chkxolorm (Special emphasis endpoints include can- oar, neurotoxicity, reproductive and developmental toxicity, hepatotoxidty, and renal toxicity) Exposure levels in humans living near hazardous waste sites and other populations, such as ex- poeed workers Potential candidate for subregistry of exposed persons __________ _ A Dose-response data in animals for intermodule duration oral exposures. The subchronic study M should include extended reproductive organ histopathotogy end immunopathology. 2-Species developmental toxicity study via inhalation or oral exposure Mechanistic studies on PAHs, on how mixtures of PAHs can influence the ultimate activation of PAHs, and on how PAHs affect rapidly proliferating tissues Dose-response data in animals for acute- and Intermediate-duration inhalation exposures. The M subchronic study should include extended reproductive organ histopathotogy and frnmunopattiotogy. Epidemtotogic studies on the health effects of PAHs (Special emphasis endpoints include cancer, G dermal, hemoiymphatx:, and hepatic). Exposure levels in humans living near hazardous waste sites and other populations, such as ex- G posed workers. Potential candidate for subregistry of exposed persons .. ____ ____ __ ___ ___ ...___ ___ _ A Dose-response data in animals lor acute- duration oral exposure.__ ________ _____ ____ , On) 10B 10C 10D 10E DDT-------------- 11A 11B 11C 110 11E Neurotoxicofogy battery of tests via the ore) route _ __..._______ _____ ... Immunotoxicofogy battery of tests via the oral route . .... ................ ........................ Eptoemtotog*: studies on the health effects of trichloroethylene (Special emphasis endpoints in- dude cancer, hepatotoxidty, renal toxidty, developmental toxicity, and neurotoxicity). Exposure levels in humans living near hazardous waste sites and other populations, such as ex- posed workers. Dose-response data in animals for chronic-duration oral exposure. Comparative toxiookinetic study (across routes/species). Bioavailability and btoaccumUabon from sofl. Epidemiologic states on the health effects of DOT, ODD and DDE (Special emphasis endpoints include frnmunotoxicity, reproductive and developmental toxidty). Exposure levels in humans living near hazardous waste sites and other populations, such as ex- poeed workers. M v> G G 004605.006 Federal Register / VoL 61, No. 63 / Monday. April 1, 1996 / Notices 14421 Table 1.--Substance-Specific Priority Data Needs (PDN) Currently Being Addressed Under ATSDR's Applied Research Programs--Continued Substance PDN ID PDN description Pro grams"' Chromium 11F 12A 12B 12C 12D 12E Tetrachtoroethylene. 13A 138 13C 13D 13E AJdnfVDieldrin ... 1C 14A 14B 14C 14D Cyanide -......... ISA 15B 15C 15D Carbon Tetrachloride. 15E 16A 16B 16C 16D 16E Beryllium .......__ 17A 17B 17C 17D 17E 17F Toluene____ _ 18A 188 18C 18D 18E IflF Nickel________ 19A 19B . 19C ISO IflE IflF 18G Methylene Chlo- 2QA ride. 20B 20C 20D Potential candidate lor subregistry o< exposed persons Dose-response data in animals tor acute-duration exposrn to chromium (VI) and (III) via oral ex- posure and tor intermerkate-duration expostxe to chromium (VI) via oral exposure. Mtetigeneration reproductive toxicity study via oral exponae to chromium (111) end (VI). Immunotoxiootogy battery c* tests toBowmg oral exposure to chromium (III) and (VI) 2-Species developmental toxicity study via oral expostae to chromium (III) and (VI) Exposure levels in humans hving near hazardous waste sites and other populations, such as ax- posed workers. Dose-responee data In animals tor acute-duration oral axposue, including neuropathology and de- meanor, and tovnunopethotogy. Muitigeneration reproductive toxicity study via oral exposua Dostnesponse data in animals tor chronic-duration oral axposue. including neuropathology and demeanor, and anmunopathotogy 2-Species developmental toxicity study via oral exposure ,, . __ Exposure levels in humans living near hazardous waste sites and other populations, such as ex- posed workers. Potential candidate for subregistry of exposed persons Dose-response data in animals for intermediate-duration oral exposure. BtoevalabUity tram soil. Exposure levels in humans living near hazardous waste sites end other-populations, such as ex- posed workeis. Potential cartidate for subregistry of exposed persons Dose-response data in animals tor acute- and totermadote-duraiton exposures via inhalation. The subchronic study should include extended reproductive organ histopathotogy and evaluation of neurobehavioral and naurapathotogical endpoints. 2-Species developmental toxicity study via oral exposure Evaluation of the environmental late of cyanide in son ...... ........ ........... Exposure levels in humans Kving near hazardous waste sites and other populations, such as ax- posed workers. Potential randidate far attoragistry of exposed pnrnvH ........ ....................... .............. Dose-response data in animtos tor chronic oral exposure. The study should include extended re- productive organ and nervous tissue (and demeanor) histopathotogy. tmmunotoxicology battery of tests via oral exposure. HaK-Gfe in soO. Exposure levels in humans fiving near hazardous waste sites and other populations, such as ex- posed workers. Potential candidate tor sttoregistry of exposed parsons ...... . ................. Dose-response data in animtos tor acute- and intermediate-duration inhalation exposures. The subchronic study should include extended reproductive organ histopathotogy. 2-Species developmental toxicity study via Inhalation exposure.......................................... Environmental tate in asr. factors sheeting btoavialahility m mk ......... .......... ..... Analytical methods to determine environmental apedation. Immunotoxieoiogy battery of tests totiowing oral expanse .................... ....................... Exposure levels in humans fiving near hazardous waste sites and other populations, such as exposed workers. Dose-response data in animals tor acute- and intermediate-duration oral exposures. The subchronic study should include an extended histopathologic evaluation of the irrenune system. Comparative toxicokinetic studies (Characterization of absorption, rfistributton, and excretion via oral exposure). Neurotaxiootogy battery of tests via oral exposure.............. , , ........................ Mechanism of toluene-induced neurotoxicity. Exposure levels in humans fiving near hazardous waste sites and other populations, such as exposed workers. Potential candidate for subregistry of exposed persons ....... ............. Epidemiologic studtes on the health effects of nickel (Special emphasis endpoints include raproductive toxicity). 2-Species developmental toxicity study via the oral route. Dose-response data in animals tor acute- and intermediate-duration oral exposures. Neurotoxicology battery ot tests via oral exposure. Bioavailability of nickel from soil Exposure levels in humans living near hazardous waste sites and other populations, such as exposed workers. Potential candidate for subregistry ol exposed Demons Dose-response data in animals for acute- and Intermediato-duration oral exposure. The sub-dvon- to study should include extended reproductive organ histopathotogy, neuropathology and demeanor, and tonmunopathaiogy. 2-Spectes developmental taxidty study via the oral route Exposure levels in humans fiving near hazardous waste sites and other populations, such as exposed workers. Potential candttate for subregistry of exposed perxrTM ............. A.G E E E V<oi o<*> A A E E E A NTP A E E E E E E M A"' A< V") A 004605.007 14426 Federal Register / Vol si. No. 63 / Monday. April 1. 1936 / Notices Table 1.--Substance-Specific Priority Data Needs (PDN) Currently Being Addressed Under ATSDR's Applied Research Programs--Continued Substance PDN ID PON description Pro grams4 Zinc--------------- 21A 21B 21C 21D 21E DEHP------------ 22A 226 22C 22D 22E Selenium___ -- 22F 23A 23B 23C 230 23E Chloroethane__ 24A 24B 24C Dose-response data in animals tor acute- and intermediate-duration oral exposures. The aub- chronic study should include an extended histopathologic evaluation ot the immunologic and neurologic systems. Muttigeneretion reproductive toxicity study via oral exposure- Carcinogenicity testing (2-year bioassay) via oral exposure. Exposure levels in humans living near hazardous waste sites and other populations, such as ex posed workers. Potential candidate for stexegistry of exposed persons. Epidemiologic studies on the health effects of DEHP (Special emphasis endpoints include cancer). Dose-response data in animals tor acute- and intennedtete-duration oral exposures. The subchronic study should include an extended histopathologic evaluation of the immunologic and neurologic systems. Multigeneration reproductive toxicity study via oral exposure. Comparative tonookinetic studies (Studies designed to examine how primates metabolize end cfc- trtoute DEHP as compared to rodents via oral exposure). Exposure levels in humans living near hazardous waste sites and other populations, such as ex posed workers. Potential candidate for subregistry of exposed persons ___ ___ ____ _ Dose^esponse data in animals for acuteduration oral exposure, knmunotoxiootogy battery of tests via oral exposure. Epidemiologic studes on the health effects of eetoniixn (Special emphasis endpoints indude can cer, reproductive end developmental taxidty. hepatotoxidty and adverse skin effects). Exposure levels In humans living near hazardous waste sites and other populations, such as ex posed workers. Potential candidate tor subregistry of exposed persons Dose-response date in animals tor acute- and Mermedtote-duration oral exposures. The subchronic study shoted stcfude an evaluation of immune and nervots system tissues, and ax- tended reproductive organ histspathotogy. Dose-responsa data in animals for chronic inhalation exposures. The study should incfude an eval uation of nervous system tissues. Potential candidate for subregistry of exposed persons _ . ______ ............... M AW E A A E A 1ATSDR programs for addressing data naads. A-ATSDR Division of Health Studies; EErtvironmerxal Protection Agency-TSCA/FlFRA testing GGreat Lakes Human Health Research Program; M-Minority Health Professions Foundation Schools; NTP-NaSonaf Toxicology Program; V-Voluntary research; O-Other. *No longer considered e prfodty data need based on reoent evaluation of the database by ATSDR. 3 These substances have been included in the pool ot candidate substances tor subregistry development since the publication of the Federal REGISTER notice on Match 10,1994 (58 FR 11434). 4 Potentially to be addressed by ATSOFTs Voluntary Research Program. 6 Data to be obtained by PBPK modeling. Initiation of immunopathotogy study pending submission and peer review of study protocol. 7 Data to be obtained from a combined 2-generation reproduction and developmental toxicity study in rets. Not a priority data need. Table 2.--Groups addressing ATSDR Priority Data needs (PDN) ATSDR Program Firm, institution, agency, or Consortium SUastanoe PON ID Voluntarism _______ _ Chemical Manufacturers Association _____ ______ __ General Electric Company___________________________ Halogenatod Solvents industry AHianoe ,, ... ____ ... Vinyl Chloride _______ __ ,, PCBs __________ Trichloroethylene Tetrechtoroefhyleoe 48.4E 7G, 7H, 71 toe 13A. 138 Minority Health Professions Florida A ft M UnivTMty .......... ... Methylene chloride... ............ 20A.206 1 uH 1A Foundation Schools. The King/Drew Medical Center of the Charles R. Drew Uni- Lead varsity of Medicine and Science. 1C Meherry Mecfcal College____._____ _____________ .__ __ Morehouse School of Medicine .. .............. ............ ........ Texas Southern University ___ ____ __ ____ ______ ._____ * PAHs _ . Lead Lead .......................... ........... Trichloroethylene ... ........... 9A.9D 1C 1A 106 ' Tuskegee University .................. ........ ..... ............. . Toluene kiUmiry _________ _ 18C 3A Xavier University____ Zinc-------------------------------- 21A Rmimm 58 Great Lakes Human Health Research Program. Zinc _ __ ,, 21A Michigan State University ----------- ----------- .---------------- 1 Mrt ______ 1C Mercury ...... ........................ 30 * PCBs___ ________ 7F 004605-008 Federal Register / VoL 61, No. 63 / Monday, April 1. 1996 / Notices 14427 Table 2.--Groups addressing ATSDR Priority Data Needs (PDN)--Continued ATSDR Program Firm, institution, agency, or Consortium Substanoe PDN ID # TSCA/FIFRA National Toxicology Program . New York State Health Department .. .... State University of New York at Buffalo ............................. State Unwiw^ity of New York at Oswego ...... ............. * University of Illinois at Chicago____________________ ,i__ University of Illinois at Urtena-Champaign_________ University of Wisconsin--Si^mrior .......... ............... Wisconsin Department of Health and Social Services____ Environmental Protection Agency ....... .......... National Institute of Environmental Health Sciences___,,,,,, DDT----------_------------------- Lead ............ .................. Mercury PC8s _ _____ Lead _____________________ Mercury _______________ PCSs ______ DDT | eerl ........ Merouy PCBs _ DDT_____________________ Lead _______ _TM_________ Merouy PCBs ............. DDT _ ----------- Lead ................. .................. Mercury . _ ____ PCBs ---------------------------- Lead________ ____________ Mercury . PCBs .................. .......... ___ Lead .____________________ Mercury PC8s PAHs ____________________ nrrr Mercury ___________ Benzene Benzene Chromium________ _ Chromium_______ ________ Chromium _______________ Cyanide Cyanide _________________ Cyanide . ___ _______ Beryttum________ Beryfiium____ __ __________ BeryHium _________________ Beryllium _____ ___ Toluene . __ __ ___ Toluene _________ ________ DEHP........... . . ___ .. Chloroethane..... ................... Carbon Tetrachloride _ 110.11E 1C 30 7F 1C 30 7E.7F 11D, 11E 1C 3A.3D 7E.7F 11D, 11E 1C 3A.3D 7E.7F 11D, 11E 1C 3D 7E. 7F 1C 3D 7A, 7E. 7F 1C 3D.3E 7F E,F im up up 38 3C 5A 5C 12A 12B 12C ISA 1SB ISC 17A 17B 17C 17E ISA 188 22D 24A 16B (FR Doc. 96-7852 Filed 3-29-06; 8:45 ami MUJNG OOOE SISS-TO-P 004605.009