Document gb0EjaV1EGQYwR7Z9vvxJ7BoN

PATTON BOGGS. L.L.P. 2550 M STREET. N.W. WASHINGTON, D.C. 20037-1350 (202) 457-6000 WRITER'S DIRECT DIAL April 3, 1996 (202) 457-5270 MEMORANDUM FOR VINYL CHLORIDE PANEL Re; ATSDR Voluntary Research Program 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, III CMA 112986 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 [ATSDR-106] 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 19B0 (Superfund) or CTRCLA, as amended by the Superfund Amendments and Reauthorization Act of 1986 (SARA) (42 U.S.C 9604 (i)), this research program was initiated on October 17,1991. At that time, a list of priority data needs for 38 priority hazardous substances was announced in the Federal Register (56 FR 52178). The list was subsequently revised based on public comments and published in final form on November 16,1992 (57 FR 54150). The 38 substances, each of which is found on ATSDR's list of Priority Hazardous Substances, are aldrin/ dieldrin, arsenic, benzene, beryllium, cadmium, carbon tetrachloride, chloroethane, chloroform, chromium, cyanide, p.p'-DDTDDEJDDD, di(2ethylhexyl) phthalate, lead, mercury, methylene chloride, nickel, polychlorinated biphenyl compounds (PCBs), polycyclic aromatic hydrocarbons (PAHs--includes 15 substances), selenium, tetrachloroethylene. toluene, trichloroethylene, vinyl chloride, and zinc (56 FR 52166. October 17.1991). Priority data needs for 12 additional priority hazardous substances were recently identified and are also being announced in a Federal Register Notice. The 12 substances, each of which is included in ATSDR's List of Priority Hazardous Substances, are chlordane, 1.2-dibromo- 3-chloropropane, di-nbutyl 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 toxapnene. 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 Reseanm Committee (TASARC) comprised of scientists from ATSDR. the National Toxicology Program (NTP), and the Environmental Protection Agency (iPA) 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 researchiias 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 BranchTDlvision 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, end (3) assure the initiation of a research program to address identified data needs associated with the substances.. Before starting such a program. ATSDR will consider recommendations of the Interagency Testing Committee on the type of research that should be done. This committee was established under section 4(e) of the Toxic Substances Control Act of 1976 (TSCA). On October 17,1991. ATSDR announced the identification of the priority data needs for 38 priority hazardous substances (56 FR 52178), requested public comments, and invited private- sector organizations to volunteer to conduct research to address specific priority data needs. On November 16,1992, the agency published a reused list of 117 priority data needs for these priority hazardous substances (57 FR 54150). The major goals of the ATSDR SSARP are (1) to address the substance-specific information needs of the public and scientific community, arH (2) to supply necessary information to improve the database to conduct comprehensive public health assessments of populations living near hazardous waste sites. This program will also provide data that can be generalized to other substances or areas of science, including risk assessment of chemicals, thus creating a sdentific.base for addressing a broader range of data needs. In section 104(i)(5)(D), CERCLA states that it is the sense of Congress that the costa for conducting this research program be borne by the manufacturers and processors of the hazardous substances under TSCA and by registrants under the Federal Insecticide, Fungicide, and Rodentidde Act of 1972 (FIFKA), or by cost recovery from responsible parties under CERCLA. To execute this statutory intent, ATSDR developed a plan whereby parts ofthe SSARP are being conducted via____ regulatory mechanisms (TSCAIFIFRA), private-sector voluntarism, and through the direct use of CERCLA funds. The TASARC, comprised of scientists from ATSDR. NTP, and the EPA has been set up: (1) To advise on the assignment of priorities on mechanisms for addressing data needs; (2) To coordinate knowledge of research activities to avoid duplication of research in other programs and under other authorities; (3) To advise on issues of science related to substance-specific data needs; and (4) To maintain a scheduled forum that provides an overall review of the ATSDR SSARP. The TASARC has met six times since the SSARP began. This Notice is an update on the status of ATSDR's efforts to implement the SSARP, focusing on ongoing activities relevant to test-rule development under TSCA/FTFRA, 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). CMA 112987 Federal Register / Vol. 61, No. 63 / Monday, April 1, 19S6 / Notices 14421 ATSDR believes that these priority data needs will remain on 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 existing database, the agency determines that additional studies are no longer needed. Three recent examples follow. ATSDR in consultation with the TASARC, re evaluated the database for acute inhalation toxicity for vinyl chloride and determined no additional data are needed at this time (Table 1). With regard to the priority data need for oral developmental toxicity studies for tetrachloroethylene (PERC), ATSDR recently re-evaluated the database during the update of the toxicological profile for this substance. ATSDR concluded that the database was sufficient to derive a minimal risk level (MRL) for acute oral exposure based on a developmental toxicity study. Although ATSDR believes that additional developmental data would be useful to more frilly 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 needrather thus a priority data need. Therefore, this priority data need baa 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 Read and thus deleted from the list (Table 1) because an MRL was derived during the updating of the toxicological profile. Conversely, additional priority data needs could be included in the ATSDR list based on assessment by agency programs (See Section F, "Other ATSDR Programs." which discusses exposure subregistries). A. TSCA/FIFRA In developing and implementing the Substance-Specific Applied Research Program, ATSDR, NTP, and EPA have, established procedures to identify priority data needs of mutual interest to Federal programs. These data needs are being addressed through a program of toxicologic testing under TSCA. This research will be conducted according to established TSCA procedures and guidelines. Generally, this testing will address more than one Federal program's need. Following review and endorsement by the TASARC oversight committee during fiscal year (FY) 1993, of the 117 priority data needs for 38 substances, approximately 60 priority data needs were referred to the EPA under TSCA/FIFRA authorities. During 1994, EPA added 11 ATSDR substances (and associated 26 priority data needs) to its master testing list, the first step in test-rule development under TSCA. Section 4 (59 FR 11434, March 10,1994). On September 30,1994, EPA published a Federal Register Notice soliciting testing proposals from industry to address the priority data needs identified for ATSDR's priority hazardous substances (59 FR 49934). Although no manufacturers or processors of these substances came forward with testing proposals, severe! industry groups responded by submitting proposals to address some of the data needs via ATSDR's voluntary research program described in detail in Section B, "Private-Sector Voluntarism." The priority data needs currently being addressed by TSCA/ FIFRA are listed in Table 2. ATSDR shared its priority data needs for these substances with other Federal agencies and programs. On several occasions when ATSDR identified priority data needs for oral exposure, other agencies needed inhalation data. In response, ATSDR is considering proposals to conduct inhalation studios 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 toxidty 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 tasted 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 pert 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 (HSLA), and the Chemical Manufacturers Association (CMA). Preliminary discussions are being held with s fourth organization, the Shell Oil Company. Through the voluntary research efforts of these organizations, data needs for two classes of substances (PCB compounds and volatile organic compounds) are being addressed (Table 2). To date, two memoranda of understanding (MOU) have been signed by ATSDR and the interested parties. A third MOU is under development. General Electric Company (GE) On February 8.1995, ATSDR entered into an MOU with GE. This was the first time a private-sector organization volunteered to conduct research to address ATSDR's data needs identified in its SSARP. The MOU with GE covers the following three studies on PCBs: * Project 1. "An assessment of the chronic toxicity and oncogenicity of Aroclor-1016, Aroclor-1242, Aroclor1254, and Aroclor-1260 administered in diet to rats.'' was initiated on February 8,1993. * Project 2, "Metabolite detection as tool for ths determination of naturally occurring aerobic PCB biodegradation," was initiated on January 2,1995. * Project 3, "PCB congener Analyses,". was initiated on February 6,1993. While the above studies do not address ATSDR's priority data needs for PCBs, the three projects will address soma of the agency's data needs far these substances. Specifically, although ATSDR has identified bioassays via the inhalation and dermal routes as data needs for PCBs, agency scientists believe information gained vis GE's 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. CMA 112988 14422 Federal Register / Vol. 61, No. 63 / Monday, April 1, 1996 / Notices Halogenated Solvents Industry Alliance (HS1A) On April 4,1995, ATSDR entered into an MOU with HSIA covering studies to address three ATSDR priority toxicity data needs for methylene chloride. The studies consist of acute- and subchronic-duration, and developmental toxicity via oral exposure. The data will be obtained by using PBPK modeling. These studies were initiated on May 23,1995. HSLA has also proposed to conduct a 28-day immunopathology assessment for methylene chloride via oral exposure, a priority data need identified by ATSDR. The agency expects to receive a study protocol from HSIA for peer review in the near future. Currently, HSIA and ATSDR continue to discuss voluntary research efforts for trichloroethylene (TCE) and tetrachloroethylene (PERC). With regard to TCE, ATSDR has recently reclassified the priority data need for acute oral data to a data need. (see Background section of this Notice). The agency is continuing its discussion with HSIA to assess the possibility of conducting a study or utilizing benchmark dose modeling to address this data need. As for immunopathology data, HSLA proposed to first review the existing data for TCE. If the data are inadequate and the methylene chloride immunopathology study mentioned above has provided meaningful information, HSIA would then conduct a similar study for TCE. Regarding the priority data needs for PERC, HSIA plans to obtain the oral neurotoxicity data called for by the agency by PBPK modeling. The database to be used for modeling will include the HSLA-sponsored inhalation neurotoxicity study recently approved by EPA. EPA and ATSDR scientists recently reviewed and accepted the HSLA-sponsored reproductive toxicity study of PERC via inhalation. HSIA proposed to address ATSDR's priority data need for oral reproductive data using PBPK modeling. As for ATSDR's priority data need for immunopathology data. HSIA would follow the same procedures as for TCE (described above). Finally, with regard to ATSDR's data need for oral developmental toxicity studies for PERC (see Background section of this Notice), ATSDR is continuing its discussion with HSIA to obtain this data via PBPK modeling once the EPA-required inhalation developmental toxicity study has been completed. Chemical Manufacturers Association (CMA) During FY 1995, the CMA submitted a study protocol addressing two ATSDR priority data needs for vinyl chloride, specifically, inhalation reproductive and developmental toxicity studies in rats. ATSDR accepted the study protocol as a candidate for voluntary research based on ATSDR peer reviews and CMA's satisfactory response to the peer reviewers' comments. ATSDR expects to finalize an MOU with CMA covering this study in the near future. EPA no longer requires inhalation neurological data for vinyl chloride as originally stated in its solicitation Notice (59 FR 49934, September 30, 1994). Its decision is based on a recent reevaluation of the database. C. CERCLA-Funded Research (Minority Health Professions Foundation Research Program) During FY 1992, ATSDR announced a 54 million cooperative agreement program with the Minority Health Professions Foundation (MHPF) to support substance-specific investigations. This cooperative venture is supported by the direct use of CERCLA funds. About $4 million was allocated annually for FYs 1993 to 199$ to continue this research program that ends in September 1997. Currently, 9 priority data needs for 21 priority hazardous substances (including 15 PAHs) in the SSARP are being addressed by the MHPF institutions through this program. Also, the MHPF research program will address 13 other substance-specific data needs identified in the ATSDR toxicological profiles concerning exposures and related health effects. To date, more than 20 abstracts have been presented at scientific meetings, 4 manuscripts have been published in peer-reviewed journals, and 7 manuscripts are in preparation. The institutions receiving awards and their respective research projects are listed in Table 2. A not-for-profit 501(c)(3) organization, the MHPF comprises 11 minority health professions schools. Its primary mission is to research the health problems that disproportionately afreet poor and minority citizens. The purposes of the ATSDR-MHPF cooperative agreement are (1) to initiate research to address ATSDR-identified data needs for priority hazardous substances, and (2) to enhance existing disciplinary capacities to conduct research in environmental health at MHPF member institutions.' The areas of research at MHPF institutions include those related to broad areas of toxicology and environmental health science. Some MHPF members are conducting health studies of minority groups exposed to ATSDR's priority hazardous substances. D. National Toxicology Program (NTP) ATSDR maintains an intern0sncy agreement (IAG) with NTP to conduct toxicologic testing of substances identified at NPL sites. The studies, determine levels of exposure that present a significant risk to humans of acute, subchronic, and chronic health effects. Often these studies include an assessment of the substance's ability to cause cancer, reproductive toxicity, and birth defects. The results of these studies are used by regulatory agencies such as the Food and Drag Administration and EPA, various environmental and industrial groups, and ATSDR to improve the ability to conduct public health assessments at NPL sites. Under this agreement, one toxicity priority data need identified in the SSARP (immunotoxicology study of carbon tetrachloride) is being addressed. An area of ongoing reseanm by the NTP is to study the bioavailability of ' PCBs in soil, a priority data need for ATSDR. Therefore, NTP research may also potentially address this ATSDR priority data need. During FY 1993, the existing LAG was modified to include toxicity studies of ATSDR's priority hazardous substances via application of structure-activity relationship (SAR) techniques and PBPK modeling. NTP indicated future plans for SAR modeling for reproductive and immunologic endpoints. ATSDR is continuing to work closely with NTP as the agency has identified many reproductive and immunologic data needs for the 38 priority hazardous substances. As discussed in Section A, "TSCA/FIFRA," ATSDR will consider using PBPK modeling to address data needs when models are well developed and validated. Therefore, ATSDR will continue to work closely with NTP in its efforts to refine the models. E. Great Lakes Human Health Effects Research Program Some of the priority data needs identified in the SSARP have been independently identified as research needs through the ATSDR Great Lakes Human Health Effects Research Program, a separate research program. To date, 12 priority data needs for 19 priority hazardous substances (including 15 PAHs) identified in the SSARP are being addressed through this program. The institutions receiving ,Federal Register / Vol. 61, No. 63 / Monday, April 1 1996 / Notices 14423 awards and their respective studies are listed in Table 2. The Great Lakes Critical Programs Act of 1990 mandated that EPA, in consultation with ATSDR, prepare a report that assesses the adverse effects of pollutants in the Great Lakes system on the health of individuals in the Great Lakes states. This report was recently transmitted to the Congress by the EPA Administrator. In support of this directive. ATSDR received funds to carry out research. The ATSDR-supported research projects focus on at-risk populations to further define the human health consequences of exposure to persistently toxic substances in the Great Lakes basin. The research activities include but are not limited to the following: (1) Characterizing exposure and determining the profiles and levels of Great Lakes contaminants in biologic tissues and fluids in at-risk populations; (2) Identifying sensitive and specific human reproductive/developmental endpoints and correlating them to exposure to Great Lakes contaminants; (3) Determining the short-and long term risk(s) of adverse health effects In progeny whose parents were exposed to Great Lidces contaminants; (4) Investigating the feasibility of establishing registries and surveillance cohorts in the Great Lakes region; and (5) Establishing a chemical mixtures database with emphasis on tissue and blood levels in order to identify new cohorts, conduct surveillance and health effects studies, and establish registries and surveillance cohorts. During FY 1992, ATSDR announced a $2 million grant program to conduct research on the impact on people's health from eating contaminated fish from the Great Lakes region. On September 30,1992, ATSDR announced 9 awards under this program. In FY 1993. about $3 million was allocated to support the continuation of the research projects conducted at the 0 institutions originally funded during FY 1992. In addition. ATSDR awarded one new grant to the Michigan Department of Public Health to design, establish, and operate a professionally creditable, interleboratory quality assurance/ quality control program for the ATSDR Great Lakes Human Health Effects Research Program. Additional funding of S3 million and S4 million for FYs 1994 and 1995. respectively, was allocated to continue support of the 10 research projects. During FY 1994, ATSDR held a Great Lakes Research Symposium in Detroit, Michigan. The proceedings of the symposium will be published in the Journal of Toxicology and Industrial Health in the near future. Other ATSDR Programs In its role as a public health agency addressing environmental health, when appropriate, ATSDR may collect human data to validate substance-specific exposure and toxicity findings. Information on levels of contaminants in humans has been identified and remains as a priority data need for 37 of the 38 priority substances (Table 1). ATSDR will obtain this information through exposure and health effects studies, ana through establishing and using substance-specific subregistries of people within the agency's National Exposure Registry who have potentially been exposed to these substances. The list of 38 priority hazardous substances in the SSARP was forwarded to ATSDR's Exposure and Disease Registry Branch (EDRB), Division of Health Studies, for consideration as potential candidates for subregistries of exposed persons, based on criteria described in its 1988 document, "Policies and Procedures for Establishing a National Registry of Persons Exposed to Hazardous Substances." To date, ATSDR has selected benzene, chromium, and trichloroethylene as primary contaminants to establish subregistries in the National Exposure Registry. However, aldrin/dieldrin, carbon tetrachloride, chloroethane, chloroform, cyanide, p.p'- DDT, DDE, DDD, di(2-ethylhexyl)phthalate, mercury, methylene chloride. PAHs, selenium, tetrachloroethylene, and vinyl chloride remain in the candidate pool. They will be considered fo- selection ss 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 site* remains a priority data need for all 38 priority hazardous substanbaa by ATSDR. However, agency scientists realize that a substantial amount of this information has already been collected through individual State programs and the EPA`a CERQLA activities; therefore, ATSDR will evaluate the extant information from these programs to characterize better the need for additional site-specific information. The results of the research conducted via the SSARP will be used for public health assessments and to reassess ATSDR's substance-specific priority data needs. The agency experts to re evaluate the priority data needs for priority hazardous substances every three years. Dsted: March 28. IMS. Clairs 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 2D Mercury............ 3A 3B PDN description * Pro grams <'i MpChanleMr itudws On the nnqrotOI>>C nt lead..... ................ ....... Analytical methods for tissue levee. Exposure levels in humans living near hazartkx* waste sites and other populations, such as ax- posad workers. Comparative toxicokinetic studies to determine it an appropriate animal species can be identified ... Half-lives in surface water, groundwater. Bioevaiability from soil. Exposure levels in humans living near hazardous waste sites and other papulations, such as ex- posed workers Multigeneralion reprcx>jctive toxicity study via oral exposure.......... .............. ...................................... Dose-response data In animals for chronic-diration oral exposure....................................................... M M, G M, G E CMA 112990 14424 Federal Register / Vol. 61, No. 63 / Monday, April 1, 1996 / Notices Table 1 .--Substance-Specific Priority Data needs (PDN) Currently Being Addressed Under ATSDR's Appued Research Programs--Continued Substance PDN ID PDN description Pro grams'" 3C 3D Vinyl Chioode ... 3E 4A 48 4C 4D 4E 4F 4G Benzene ........... SA 56 SC 50 5E Cadmium......... SA 66 pr-Hn 7A 7B 7C 7D 7E Chloroform........ 7F 70 > THW 7|a) 8A SB 8C 8D PAH*............. 9A 96 9C 90 9E 9F Trichioro-ethyl- 9G IDA 106 IX 10D 10E DDT.................. 11A 116 11C 11D 11E Immunotoxicotofly battery of tests via oral exposure.....................................--.................... -.......... E Exposure levels in humans living near hazardous waste sites and other populations, such as ax G posed workers. Potential candkteto tor subregistry of exposed persons ..................--...................... ...------------- - A. G Dose-response data in animats tor acuta-dtfaMon toholeticn exposure....................... .............. ......... O'*) MUbgeneration reproductive toxicity study via tohalatton .................................................. ............... .. VCD ' Does response data in animals tor chrento-dtntion Inhalation exposure. Mitigation of vinyl chloride-induced toxicity. 2-spede* developmental toxicity study via Inhalation.... ................................. .................................. ... VCD Exposure levels to humana living naar fezardoua wasta alias and olhar populations, such as ax- poaed woridft Potertlal candidata tor subregistry of txpoeed persons . ... --... A Dosa-responss dtoa to animals tor scuta- and Wermedato-durafion oral axpoatae. Ths subchronic E study shodd toduds an sxtsndsd reproductive organ Nstopathotogy. 2-spedee developmental toxidty study via oral exposure------ --- --....... _______ ,,____ M Neurotoxicology bsttery of testa via oral expoeure --------- -------------- --------------------- ------------------ E Epidsmtotogic eludes on the health effects of banzana (Special amphasis endpoints toduds imnMxaoxidty). Exposure levels to humane Hying near hazardous wasta allaa and olhar populations. such as ax- posed workers. Analytical msihotta tor biotogical tissuee end fluids and anvironmaraal metfla. Exponas levels in humans living naar hazardous waste sites wid other popdationa, such as ex- posed workers. Dose-rtnpnnse <kta in animsls tor scute- end Irtarmedete-duration oral expat*--___ Q Btodapadatton of PCB* to water bioavalabllty of PC8s to air, water and aoi ' Doee-fMponae dria to arimata tor acuta- and totermsdate-duntton Inhalation axposuraa. The subchronic study should include extended' reproductive organ histopathology Epidsmtotogic studes on the health affects of PCS* (Special emphasis endpoints Indude G krantoototocty, gastrointestinal taxidly, Iver, kidney, thyroid toxidty, raproitoctivw'developmerato - tcnddly). Exposure levels to humans living near hazardous wasta sites and dher populations, such as ax- G posed workers. iMivtsftrtA W fufrwgtatfy r* pwn ........................ ........... ......... ............. A' Chronic toxidty and oncogenicity via oral exposure--------....------------------- -- ----------................. ...... .. V v pnp analysis............. .............. ................................................. ........ . v Dote response data to enimeli tor totermedate-duratton oral exposure. Epidemiologic studes on the health affects of chloroform (Special emphasis aottootot* toduds cam oar. neurotoxicity, reproductive and developmental toxidty, hepatotoxidty, and renal toxidty) Expoaura levels to humans living near hazardous waste sitae and other populations, such as ax- posadwarkers - Potential canddata tor subragisiry of exposed persons _______ ...--....................... ............. ............ A Doae-rasponse data to animals tor totermedate duration oral exposures. The sifcchronie study M should toduds extended reproductive organ histopathology and immunapethology. 2-Species developmental toxidty study via inhalation or oral exposure Mechanistic etudes on PAHs. on how mixtins of PAHs can Influence the ultimate activation of PAHs. and on how PAHs affect rapidy proliferating tisaues Dosmrespanae data to animals for acute- and totermadate-duraifon inhalation expoaura*. The M sifcchronic study should include extended reproductive organ histopathology and immunopathdogy. Epidemiologic studies on the health effects of PAHs (Special emphasis endpoints toduds canoar, G dermal, hamofyitphatic. and hepatic). Exposure levels in humans living naar hazardous wasta sites and olhar populations, such as ex- G poeedwarttere. Potential candidate tor subregistry of exposed pereons ........................................................................ A Dos* response data to animals for acute- duration oral exposure. ..................................................... o> Neurotoxiootogy battery of tests via the oral route............................. ................................................... Immunotoxjcoiogy battery of tests via ths oral route.............................................................................. Epidemiologic studies on the health eflaote of trichloroethylene (Special emphasis enctooints in- dude cancer, hepatotoxidty, renal toxidty, developmental toxicity, and neurotoxicity). Exposure levels to humans living near hazardous waste sites and olhar populations, such as ax- pasad workers. Dose-response data in animals tor chronic-duration oral exposure. Comparative toxioddnetie study (across routas/species). BioavalabilHy and btoaocvnulation from soil. Epidemiologic studes on the health effects of DDT, DDD and DDE (Special emphasis endpoints include immundoxidty, reproductive and developmental toxicity). Expoatae levels in humans living near hazardous waste sites and other populations, such as ax- posed workers. M v<> G G CMA 112991 Federal / Vol. 61. No. 63 / Monday, April 1, 1996 / Notices 14425 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*11 11F Chromium........ 12A 12B 12C 12D 12E TetracMoroethylene. 13A 13B 13C 130 13E AkJnrVDieldrin ... 13F 14A 14B 14C 14D Cyanide ........... ISA 15B ISC 15D Carbon Tatrachloride. 1SE ISA 16B 16C 16D 16E Bsrylliixn.......... 17A 17B 17C 170 17E 17F Toluene ........... 18A 188 18C 18D 18E 18F Nickel............... 19A 19B 19C 190 19E 19F 19G Methylene Chto- 20A ride. 200 20C 20D Potential candidate lor aubregittry of exposed persons _______,,_____________ _________ _____ Doss-resporw* data in animals tor acute-duration exposure lo chromium (VI) and (III) via oral ax- poets* and tor lntemttdat*dundton exposure to chromium (VI) via oral exposure Muftigwisration reproductive toxicity study via oral exposire to chromium (III) and (VI)................... Immunotaxwdogy battery ot tests tolowtng oral exposure to chromium (III) and (VI)...... ................. 2-Species developmental toxidty study via oral exposure to chromium (III) and (VI) Exposure levels in human* fang near hazardous waste sites and other populations, sttoh as ex- posed workers. Dose response data in animals tor acute-duration oral axpoeue, todudng neuropathology and de- meanor, and Immunopethology. MUtigeneration reproductive toxicity study via oral exposure ------------------ ------- ------------- Doe^raaponse data to animal* for chronfo-duratfon oral exposure, todudng neuropathology and dam--nor, and immunopalhciogy Exposure levels in humane lying near hazardous waste Sites and other populations, such ** ex- posed worker*. Potential canddats tor tttoragistry of exposed persons Dose-response data in animals tor intarmadate-duration oral axpostn. Bioavatabfflty toom ao*. Exposure levels in humane Rving near hazardous waste sites and other population*, such as ax- poeed workers. Potential candidate tor subregistry of exposed persona ....------------------ ------ ------- -------- ---------- Dose rssponie data In enimele tor acute- and intarmadate-dixation axpostxaa via inhalation. The sttochronic study should include extended roprodudlv* organ Netopattnlogy and evaluaiion ol neurobehavioral end rwxopatiiotogical ent^oMs. 2-Speoie* devslopmentai toxidty study via oral expoeue ----- --___ -- -------------- Evaluation ot the environmental tats ol cyanide in sol______ _ ,,,,............... .............. Expoetae levels In humane King near hazardous waste the* and dher popdstions, such as ex- poeed workers. Potential candidate tor artragistiy of exposed persona .. ------- -------------------- Dose-response data to animals tor chronic oral exposure. The study should Include extended re- productive organ and nervous tissue (and demeanor) Natopathoiogy. Immunotoxiooiogy bsttsry ol tost* via oral axpoatxs. Hatf-MS to soi. Expoaura lavals in human* fang new hazardous waste ahes and other popdstions, such as sx- posed workers. Potential candidate for eubregMy of exposed persons ,,,,,,________________ _________ _______ Dose-response data in animals tor acute- end iraermadata-duration inhalation exposures. The eitochronic study shodd todude extended reproductive organ histopelhotogy. 2-Spedee developmental toxicity study vie tohalallon exposixe_____ ______ ____ ____ _ Environmental late in air; (actors affecting bioevialabitty in air ...................................... ---............. Analytical methods to determine ermronmental spedation. Immunotoxiooiogy battery of teats toffowing oral exposixe....................... ................... _................ Exposure levels in humane fang new hazardous waste sitae and other populations, such as ax- poeed workers. Dose-response data in animals tor acute- and intermeckate-durstjon oral exposures. The subchronic study should indude an extended histopathologic evaluation of the immune system. Comparativa toxtookinetlc studa* (Characterization ol absorption, attribution, and excretion via oral exposure). Neurotoxicotogy battery ol tests via oral exposure. ......................._____________ __ ____ Mechanism of tdutneinduced neurotoxicity. Exposixe lavals in humans fang new hazardous waste shea and other populations, such as ex- posed worker*. Potential candidate tor subrsgistry of exposed person* ........................ ......................................._...... EpMamiotogtc studs* on the health effects d nickel (Special emphasis endpoints include rapro- ducthre toxidty). 2-Spades developments! toxidty study via the oral route. Dose-response data in animal* tor acute- and intermediate-duration oral exposures. Neurotoxicology battery of testa via oral exposure. BtoavailabWty ol nickel from soi. Exposure lavals in humans living near hazardous wads sites and other populations, such as ax- posed worker*. Potential canddat* tor subrsgistry ol exposed persona ................... .................................................... Dose-response data in animals for scute- and intermediate-duration oral expoaura. The stto-chroo- ic study should include extended reproductive organ histopathoiogy, neuropathology and de- meanor, and immunopathdogy. 2-Spedes developmental toxicity study via the oral route -................................................................. Exposure level* in humans fang near hazardous waste sites and other papulations, such as sx- posed workers. Potential candtoata tor sdxegtetiy of exposed persons ....................................................................... A. G E E E v<**> Ob) A A E E E A NTP A E E E E E E M A< A< V<j v<*> A * CMA 112992 14426 Federal Register / Vol. 81, 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 PDN ID PDN description Pro grams >>> Zinc................... 21A 21B 21C 21D 21E DEHP................ 22A 228 22C 22D 22E Selenium.......... 22F 23A 238 23C 230 23E Chtoroethane .... 24A 248 24C Dose-response data in animals lor scuts- and intermadiateduration oral exposures. The xi> chronic study should include an extended histopathologic evaluation of the immunologic and neurologic systems. Muttigenemtion reproductive toxicity study via oral exposure. Carcinogenicity testing (2-year bioassay) via oral exposure. Expoeura levels in humans living near hazardous waste sites and other popdations. such as ax- posed workers. Potential candkJate for sitoregislry of expoead persona. Epriamioiogic studies on the health effects of DEHP (Special emphasis endpoints include cancer). Doee-responae data in animals tar acute- and mtermadate-duraUon oral exposure*. The subchronic study should include an extended histopathologic evaluation of the immunologic and neurologic system*. Multigeneration reproductive toxicity study via oral exposure. Comparative todockinetic shales (Studes designed to examine how primates metabolize end ds- tribute DEHP as compared to rodents via oral exposure). Exposure levels in humans living near hazardoua waste sites end other popUatione. such as ax- posed workers. Potential candidate tar eubragiatry ot expoead persona________ ________ ..._______________ _ Doee-responae data in animals for acute-duration oral expoeura. Immunotoxicotogy battery of teats via oral axposura. Epidemiologic itudss on the health affects of selenium (Spade) emphasis endpoints indude cam car, reproductive and developmental toxicity, hepatotoxidty and advene skin effects). Exposure levels in humans living near hazardous waste alias and other populations, such as ex- posed workers. Potential candktsle tor subregistry ( exposed persons ______ _____ ,,...____ _____ ,,___ Doee-responae data in animals tor acute- and tatermadata-dMltan oral exposures. The subchronic study should include an evaluation of immune and nervous system tissues, and ex- landed reprortodive organ hjetopathotogy. Dose-response data in animals tar chronic Inhalation axpoauraa. Tha study staid include an aval- uatkm o( nervous system tissues. Potential candidate tor eubragiatry of exposed parsons __________ _______ ______...___ _ M A> E A A E A ' ATSDR program lor addressing data nssda. A-ATSDR Division of Health Studies; E-Emrironmata) Protection Ageney-TSCA/FIFRA testing; G-Grest Lakes Human Health Research Program; M-Minority Health Proleesions Foundation Schools; NTP-Na$onal Toxicology Prorasm; V-Voluntary research; O-Other. 1 No longer considered a priority data naed baaed on recant evaluation of the database by ATSDR. 'These substances have been included In the pool of canddate substances lor si&egiatry development since the publication of the Federal Register notice on March 10,1994 (59 FR 11434)7 4 Potentially to be addressed by ATSDR** Voluntary Research Program. * Data to be obtained by PBPK modeling. * Initiation of immunopafoology study pending submission and peer review of study protocol. 7 Bats to bs obtained from a combined 2-generation reproduction and developmental toxicity study m rats. * Not a priority data need. Table 2.--Groups Addressing ATSDR priority Data Needs (PDN) ATSDR Program Firm, institution, agency, or Consortium Substanos PDN ID Voluntarism............................. Minority Health Profession# Foundation Schools. Great Lakes Human Health Research Program. Chemical Manufacturers Association General Fleelric Company.................... ................... Haloqanatad Solvents Industry Altianra Florida ASM University ................. ............... ....................... The King/Draw Medtasi Center of the Charles R. Draw Univarsity of Medtone and Science. Mehany Madcal Cottage .................................................... uonhQuue Sdita nt Medcine............................................. Texas Southern University................................................ .. m- Tuskegee University............................................................... Xavier University ........... ....................................... ......... .. Michigan State University................,,.................................... Vinyl Chinriri* ... ............... PCRa TftatfQfpvihylAM .................... Tetrechloroelhylena _________ Methylene chloride.............. Lead ................. ..................... 4B, 4E 7G 7H 71 IOC 13A, 138 20A.208 1A Lead ....................................... 1C PAHS 1 .............................. Lead ....................................... Trichloroethylene................... Toluene .................................. M*miry ...... .... ...... Zinc..... -..........,,.................... Zinc.... ........... ....................... t ear! ............................................ 9A, BP 1C 1A 108 ISC 3A 21A SB 21A 1C Mercury ...... ........................... 3D PCBs ...................................... 7F ' | I | i CMA 112993 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 Substarae PON ID TSCA/FIFRA............................ National Toxicology Program . New York State Health Department...................................... State University ot New York at Buffalo .................-............ State University of New York at Oswego -----------------------University of IKnots at Chicago ................ ................ ............ University ol IKrais at Urbane-Champaign-------- -------------University of Wisconsin--Superior.......................... .............. Wisconsin Department ol Health and Soda! Services------Environmental Protection Agency______----__________ -- National Institute o< Environmental Health Sciences............ DDT____ ________________ Lead --.......... ..................... Mercury___ ______________ PCSs..................................... Lead................. .................. Mercury ......... ....................... PCfle DDT Lead____ Msrctay--- ----------------------- PCBa------------------------------DDT--------------------- ------- - Lead Mercury . ----------- PCBe .................. DDT ... ----------- Lead------------------------------Mercury----------- --------------- PCSs........ ...................... Lead........ ..............-............. Mercury ............... ................. PCSs____________ ___ -..... Lead............. ...................... Meretry ........... ..................... PCSs____________________ PAHs nrYr -----............... Mercwy.......... --,,--........ Mercury........... ..................... 6tni((W Benzene ___ ... Chromium ....................... .. Chromium------------------------- Chromium ------------ .....------- Cyanide------ ----------Cyanide-------,------ ------- Cyanide .................. .. Beryllium........................ .. Beryllium --............................ Beryllium..... .......................... BeryKum..... .......................... Toluene.... ............................ Toluene ................................. DEHP .................................... CWoroethene------------------ ... Carbon Tetrachloride ............ IlD, TIE 1C 3D 7F 1C 3D 7E.7F 11D, 11E 1C 3A.3D 7E.7F 11D, 11E 1C 3A. 30 7E.7F 110,11E 1C 3D 7E, 7F 1C 3D 7A, 7E, 7F 1C 30. 3E 7F BE, BF 11D, 11E, 11F 36 3C 5A SC 12A 12B 12C ISA 15S 15C 17A 17B 17C 17E ISA 18B 22D 24A 166 (FR Doc. 96--7852 Filed 3-29-96; 8:43 im) BILLMO OOOC 41U-70-P CMA112994