Document mqM92Rjg93852wDkoLg2O7mZ

PATTON BOGGS, L.L.P. 2550 M STREET. N.W. WASHINGTON, D.C. 20037-1350 (202) 437-6000 Facsimile. (SOB) 4S7 63I5 WRITER'S direct DIAL (202) 457-5270 April 3, 1996 " V we -Asie vras MEMORANDUM FOR VfNYCCHLORtPE FANEt"J -tnar .sjouwnorts, ms e- 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. Caffey Norman, III CMA 113302 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 Service* (HUP), 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 (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'-DDT.DDEX>DD, di{2ethylhexyl) pbtbalate, 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-cbloropropane, 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 toxaphene. This Notice also serves as a published a revised list of 117 priority continuous call for voluntary research data needs for these priority hazardous proposals. Private-sector organizations substances (57 FR 54150). may volunteer to conduct research to The major goals of the ATSDR SSARP address specific priority data needs by are (1) to address the substance-specific indicating their interest through information needs of the public and submission of a research proposal to scientific community, and (2) to supply ATSDR (see ADDRESSES section of this necessary information to improve the Notice). A Tri-Agency Superfund database to conduct comprehensive Applied Research Committee (TASARC) public health assessments of comprised of scientists from ATSDR, the National Toxicology Program (NTP), and the Environmental Protection Agency^fEPA) will review all proposed populations living near hazardous wasta sites. This program will also provide data that can be generalized to other substances or areas nf science, inc'udine - risk a^SsfflifeifiSfa'einMs, thus DATES: ATSDR considers the voluntary creating a scientific-base for addressing research effort to be important to the a broader range of data needs. 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. In section 104(i)(3)(D), CERCLA states that it is the sense of Congress that the costs for conducting this research program be borne by the manufacturers and processors of the hazardous substances under TSCA and by registrants under the Federal Insecticide. Fungicide, and Rodentiride ADDRESSES: Private-sector organizations Act of 1972 (FIFRA), or by cost recovery interested in volunteering to conduct from responsible parties under CERCLA. research may write to Dr. William Cibulas, Chief, Research Implementation BranchTbivision of Toxicology, ATSDR, 1600 Clifton Road. N.E., Mailstop E-29, Atlanta, Georgia 30333. To execute this statutory intent, ATSDR developed a plan whereby parts oflhe SSARP are being conducted via regulatory mechanisms (TSCA/FIFRA), private-sactor voluntarism, and through the direct use of CERCLA funds. FOR FURTHER INFORMATION CONTACT: Dr. The TASARC, comprised of scientists William Cibulas, Chief, Research from ATSDR, NIT, and the EPA has Implementation Branch, Division of been set up: Toxicology, ATSDR, 1600 Clifton Road, (1) To advise on the assignment of N.E., Mailstop E-29. Atlanta. Georgia priorities on mechanisms for addressing 30333, telephone 404-639-6306. data needs; SUPPLEMENTARY INFORMATION: Background (2) To coordinate knowledge of research activities to avoid duplication of research in other programs and under CERCLA as amended by SARA (42 other authorities: U.S.C 9604(i)) requires that ATSDR (1) (3) To advise on issues of science jointly with the EPA, develop and related to substance-specific data needs; prioritize s list of hazardous substances and found at National Priorities List (NPL) (4) To maintain a scheduled forum sites, (2) prepare toxicological-profiles that provides an overall review of the for these substances, and (3) assure the ATSDR SSARP. initiation of a research program to The TASARC has met six times since address identified data needs associated the SSARP began. This Notice is an with the substances. Before starting update on the status of ATSDR's efforts such a program, ATSDR will consider to implement the SSARP, focusing on recommendations of the Interagency ongoing activities relevant to test-rule Testing Committee on the type of development under TSCA/FIFRA. research that should he done. This private-sector voluntarism, and the committee was established under direct use of CERCLA funds. section 4(e) of the Toxic Substances Additional data needs are being Control Act of 1976 (TSCA). addressed through an interagency On October 17.1991, ATSDR agreement with NTP, by ATSDR's Great announced the identification of the Lakes Human Health Effects Research priority data needs for 38 priority Program, and other agency programs. To hazardous substances (56 FR 52178), date, a total of 63 research needs requested public comments, and invited associated with 38 ATSDR priority private- sector organizations to hazardous substances (including 15 volunteer to conduct research to address polycyclic aromatic hydrocarbons) are specific priority data needs. On November 16,1992, the agency being addressed via these mechanisms (Table 1). CMAll3303 Federal Bg<nir / Vol. 61. No. 63 / Monday, April l, 1996 / Notices 14421 ATSDR believes that these priority data needs will remain on the agency's list until ongoing studies to address them have Men 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 lhs priority data oeed tor ora* 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 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 needtether 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 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 28 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, several industry groups responded by submitting proposals to address some of ihi, date neJdt 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 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 (HSIA). 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 (Tsble 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 addresrATSDR'n d*tg,ti*ds.ideritified 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 GE's oral bioassay (Project 1) is pertinent to understanding the toxicity 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 113304 14422 Federal Register / Vol, 61, No, 63 / Monday, April 1, 1996 / Notices Halogenated Solvents Industry Alliance (HSIA) 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. HSIA has also proposed to conduct a 28-day iromunopathology assessment rnet^ylf'f'e ihlo1'df " 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, HSLA 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 HSLA 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, HSLA 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. HSLA 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, HSLA 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 HSLA 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 thjs.study.in the near future FTA no TuisgOi ..j inhtk'jon 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 1995 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 ana 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 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 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 sss*wmeri* of the s.'ibstm lity 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. 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 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 CMA 113305 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 dsfi'iB the humcf. health c 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 Lakes contaminants; (4) Investigating the feasibility of establishing registries and surveillance cohorts in the Great Lakes region; and (5) Establishing a chemical mixtures database with emphasis on tissue and blood levels in order to identify new cohorts, conduct surveillance and health effects studies, and establish registries and surveillance cohorts. During FY 1992, ATSDR announced a $2 million grant program to conduct research on the impact on 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 9 institutions originally funded during FY 1992. In addition. ATSDR awarded one new grant to the Michigan Department of Public Health to design, establish, and operate a professionally creditable, interlaboratory quality assurance/ quality control program for the ATSDR Great Lakes Human Health Effects Research Program. Additional funding of $3 million and $4 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 i.1''1 V [.'.iMi'-V-1 in thr 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, and through establishing and using substance-specific subregistries of people within the agency's National Exposure Registry who have potentially been exposed to these substances. The list of 38 priority hazardous substances in the SSARP was forwarded to ATSDR's Exposure and Disease Registry Branch (EDRB), Division of Health Studies, for consideration as potential candidates for subregistries of exposed persons, based on criteria described in 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 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 i'Jt cousidnretiuu diukig 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. The results of the research conducted via the SSARP will be used for public health assessments and to reassess ATSDR's substance-specific priority data needs. The agency expects to re evaluate the priority data needs for priority hazardous substances every three years. Dated: March 26,1996. Claire V. Brooms, 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 PDN description ' Pro grams ) 1A IB 1C Arsenic............. 2A 2B 2C 2D Mercury............ 3A 38 MurhunMir, fnrttiMi nn the naurotoxic affects of lead ................................................................ ............ Analytical methods for tissue levels. Exposure levels in humans living near hazardous waste sites and other populations, such as ex- poeed workers. Comparative toxicokinetic studies to determine if an appropriate animal species can be identified ... Half-lives in surface water, groundwater. Bioavalabillty from son. Exposure levels in humans living near hazardous waste sites and other populations, such as ex- poeed workers Multigeneration reproductive toxicity study via oral exposure..... ............... ......... ................................. Dose-response data in animals for chronic-duration oral exposure.................. -.................................. M M, G M, G E CMA113306 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 PDN ID 3C 3D Vinyl Chloride ... 3E 4A 4B 4C 4D 4E 4F 4G Benzene ........... SA 5B SC 5D 5E Cadmium......... SA SB PTH*............... 7A 7B 7C 7D 7E Chloroform....... 7F 7G<*> 7H) 7I<*> SA 88 8C 8D PAHs............. 9A 9B 9C 9D Trichioro-ethyl- 9E 9F 9G 10A PDN description Pro grams'" Immunotoncofogy battery of tests via oral exposure .,,.......................-.........-..................................... E Exposure levels In humans living near hazardous waste sites and other populations, such as ex- G posed workers. Potential canddtie for subregistry o< exposed persons ............................................................... -...... A, G Dose-response data in animals tar acute-duration inhalation exposure............................................. . Mdtigeneratlon reproductive toxicity study vta inhalation ...............--.................................... -.......... Vcn Dose-response data in animals tar chronic-duration inhalation exposure. Mitigation of vinyl chloride-induced toxicity. 2-spedes developmental toxicity study vta inhalation _....................................... .................................. Vcr> Exposure levels in humans living near riazarckus waste site* and rah.--' pnpztetnm, such a* ex- posed voriuiitv Potential cancRdata tor subregWry o< exposed persons ........................ .................................... .......... A Dose-response data in animals tor acute- and tatermedtate-durabon oral expoatn. Tha subchronic E study should include an extended reproductive organ histopathotogy. 2-specw* developmental toxicity study via oral exposure .............. ............................................. ......... M Neurotoxicctogy battery of tests via oral exposure ....................... ......................................................... E Epidemiologic studes on the health effects of benzene (Special emphasis sndpoints include immunotoxidty). Exposure levels in humans living nsar hazardous waste sites and other populations, such as ex- posed workers. Analytical methods tar biological tissues and fluids and environmental media. Exposue levels in humans living near hazardous waste sites and other populations, such as ex- posed workers. Dose-msponse data in animals tar acute- and inlennertw*a~<kjrtinn oral exposure* ....... ................ G Btodepadabon of PCBa in water btoevailabiity of PCSs in air, water and soA ' Doee-rasponee data tn >014(11010 for acute- and Wermedate-durstton inhalation exposures. The subchronta study should indud* extended reproductive organ histopalhoiogy Epidemiologic studto* on the health effects of PC8e (Spedai enphasi*. endpoints indude G Imrrunotoxidty, gastrointestinal toxidty, liver, kidney, thyroid toxicity, reprodudlve/developmentei - toxidty). Expoeure levels in humans living near hazardous waste sites and other populations, such as sx- G posed worksTM. Potantia) candidate tor subregistry of exposed peraone ..... -...................................... ..................... .... A< Chronic toxicity and oncogeddty via oral expoeure ......................... -.........-................................. -- ,V Aerobic PC8 biodegradation in sediment............_.......................... --- _.............................. ......... V PCB congener analysis.......................................................................................................................... .. V Dose-response data In animals tor tatennedtateduratton oral exposure. Epidemiologic stuefee on the health effects of chtorotorm (Spedai emphasia endpoeits Indude carv car, neurotoxicity, reproductive and developmental toxidty, hepatatoxldty, and renal toxidty) Exposure levels in humans living near hazardous waste sites and other populations, such as ex- paced woken Potential candkisle tor subregistry of exposed persons .................-.................................................... A Dose-response date in animals tor intermedUtte duration oral exposures. The subchronic study M should induds extended reproductive organ histopathotogy and immunopathdogy. 2-Spades developmental toxidty study via inhalation or oral expoaura Mechanistic studies on PAHs, on how mixtures o( PAHs can influence the ultimate activation of PAHs, and on how PAHs affsd rapkty proliferating tissues Dose-response tata in animals tor scute- and intermedtote-duratton inhalation exposures. The M sitochronic study should induds extended reproductive organ histopalhoiogy and immunopaihdogy. Epidemiologic studies on the health effects of PAHs (Special emphasis endpoints indude cancer, G dermal, hemdymphatic, and hepatic). Expoaura levels in humans living near hazardous waste sites and other populations, such as ex- G poaed workers. Potential eandkiate tor subregistry of exposed persons ........................................................................ A Dose-response date in animals for acute- duration oral exposure......................................................... 0) * 106 10C 10D 10E DDT.................. 11A lie 11C 110 11E Neurotoxicdogy battery at tests vis the oral route................................................................................. Immunctoxicoiogy battery of teats via the oral route.............................................................................. Epidemiologic studies on the health effects of trichloroethylene (Special emphasis endpoints inelude cancer, hepatotoxidty, renal toxicity, developmental toxicity, and neurotoxicity). Expoeure levels in humans living near hazardous waste sites and other populations, such as ex- paced workers. Dose-response date in animals tor chronic-duration oral exposure. Comparative toxioddnetic study (across routes/species). Bioavalability and bioaccumulation from soil. Epidemiologic studes on the health effects of DDT, DDD and DDE (Special emphasis endpoints induds immunotoxidty, reproductive and developmental toxicity). Exposure levels in humans living near hazardous waste sites and other populations, such as ax- posed workers. M V<4> G G CMA 113307 Federal Register / 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 Sinstance PDN ID PDN description Pro grams"' 11F Chromium........ 12A 12B 12C 12D 12E Tetrachioroethylene. 13A 138 13C 13D 13E AldrliYDieldrin ... 13F 14A 14B 14C 14D Cyanide ........... ISA 158 15C 15D Carbon Tetrachloride. 15E 16A 16B 16C 16D 16E Beryllium.......... 17A 17B 17C 17D 17E 17F Toluene ........... 18A 188 18C 18D 18E 18F Nickel................ 19A 198 19C 190 19E 19F 19G Methylene Chlo- 20A ride. 208 20C 20D Potential candidate for sUxegistry of exposed persona ..............................................-.......-....._....... Dose-response data m animals for acute-duration exposure to chromium (VI) and (III) via oral ex- posure and for irrtermerSate-duratton exposure to chromium (VI) via oral exposure. Multigeneration reproductive toxicity study via oral expoeue to ehrorrfum (III) and (VI)........... -...... Immunotoxicology battery of tests following oral exposure to chromium (III) and (VI)........... ............ 2-Spedea developmental toxicity study via oral exposure to chromium (III) and (VI) Exposure levels in humans living near hazardous waste sites and other populations, such as ex- pound worttft* Dose-response data in animals for acute-duration oral expoeure, Includng neuropathology and de- meanor, and immunopethology. Multigeneration reproductive toxicity study via oral expoem ............................... ........................... Dose-response data in anirneis for crvonto-dwatlon ora! exposure, induJng nsurcpottoiciuy and demeanor, and immunopethology 2-Species developmental toxicity study via oral axpoaura...................................... ...................... -- Expoeure levels in humans fiving near hazardous waste sites and other populations, such as ex posed workers. Potential candidate for subregistry of exposed persons Dose-response data in animals far Intsrmscfate-dmtfon oral expoem. Bioavallabifity from so*. Exposure levels In humans Rving near hazardous waste sites end other populations, such as ex posed workers. Potential candidate tor sttoreglstry of exposed persons ...... .............. .................................................. Dose-response data In animals for acute- and intermedate-duration exposures via inhalation. The subchronic study should include extended reproductive organ hlstopathology and evaluation of neurobehavioral and neuropsthological endpoints. 2-Species developmental toxicity study via oral exposure................... ................................................ Evaluation of the environmental fata of cyanide In so*....................................................... _............... Expoeure levels In humans lying near hazardous waste sites and other populations, such as expoMd workers. Potential candidate for sttoregistry of exposed persons ................... _.......,,.........--...........-............ Dose-response data In animals for chronic oral exposure. The study should include extended reproductive organ and nervous tissue (and demeanor) hlstopathology. Immunotoxicology battery of tests via oral exposure. Half-life in sod. Exposure levels in humans living near hazardous waste sites and other poputattons. such as ex posed workers. Potential candidate for subregistty of sxpossd persons .......................................................... ............. Dose-response data in animals tor acute- and intermediate-duration inhalation exposures. The subchronic study stxxid include extended reproductive organ hlstopathology. 2-Species developmental toxicity study via Inhalation axpoaura....................... ................................... Environmental fate in air, factors affecting bioavtalabMty in sir ............................................................ Analytical methods to determine environmental spedattoa Immunotoxicology battery of tests totawing oral exposure.................................................................... Exposure levels in humans Irving near hazardous waste sites and other populations, such as ex posed workers. Dose-response data in animals lor acute- and intermediate-duration oral exposures. The subchronic study should include an extended histopathologic evaluation of the immune system. Comparative toxicokinebc studies (Characterization of absorption, dwtnbubon, and excretion via oral axposm). Neurotoxicology battery of tests via oral exposure.................. ................................................................ Mechanism of toluene-induced nemtoxiclty. Exposure levels in humans living near hazardous waste sites and other populations, such sa ex posed workers. Potential candidate for subragistry of exposed persons ........................................................................ Epidemiologic studtos on the health effects of nickel (Special emphasis endpoints include repro- duettve toxicity). 2-Species developmental toxicity study via the oral route. Dose-response data in animals lor acute- and intermediate-duration oral exposures. Neurotoxicology battery of tests via oral exposure. Bioavailability of nickel from soil. 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 tor acute- and intermediate-duration oral exposure. The sub-chron- ic study should include extended reproductive organ hlstopathology, neuropathology and de meanor, and Immunopethology. 2-Spades developmental toxicity study via the oral route ................................................................... Expoeure levels in humans living near hazardous waste sites and other populations, such as ex posed workers. Potential candidate tor subregistry of exposed parsons ........................................................................ A, G E E e Vi*.*) v*> Off) A A E E E ANTP A E E E E E E M Ai A<n v<**> V(*> A CMA 113308 14426 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 Applied Research Programs--Continued Substance PDN ID PDN description Pro grams <'> Zinc 21A DEHP.... 21B 21C 21D 21E 22A 22B 22C 22D 22E Selenium 22F 23A 238 23C 230 23E Chforoethane .... 24A 248 24C Dose-response data in animals for acute- and intermediate-duration oral exposures. The subchronic study should indude an extended histopathologic evaluation erf the immunologic and neurologic systems. Multigeneration reproductive toxicity study via oral exposure. Carcinogenicity tasting (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 tor subregfs&y of exposed persona. Epidemiologic studies on the health effects erf OEHP (Special amphasis endpoints include cancer). Dose-responae date in animate tor scute- and intermedate-duraiion oral exposures. The subchronic study should include an extended histopathologic evaluation of the Immunologic and neurologic systems. Muftigeiteration reproductive texidty study via oral exposure. Comparative toxiookinetie etudes (Studies designed to examine how primates metabolize and da- tribute DEHP as compared to rodents via oral exposure). Exposure levels in humans living near hazardous waste sites and other populations, such as ex posed workere. Potential candidate tor subragislry of expoeed persons..... ....................................................... ......... Dose-response data in animals for acute-duration oral exposure. Immunotoxicology battery of testa via oral exposure. Epidemiologic studes on the heaRh effects of selenium (Special emphasis endpoints Include can cer, reproductive and developmental toxicity, hepatotoxlcity and advene akin effects). 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 tor acute- and Intermedato-duration oral exposures. The subchronic study should include an evaluation of immune and nervous system tissues, and ex tended reproductive organ histopalhoiogy. Doee-reeponee date in animals tor chronic Inhalation expoews*. The study should Induds an eval uation of nervous system tissues. Potential candidate tor srrfyegistry of axpoaad persona ............................................................... ....... M A> E A A E A ' ATSDR programs for addressing data needs. A-ATSDR Division of Health Studes; E*Envfronmarrfal Protection Agency-TSCA/FIFRA testing; G-Great Lakes Human Health Research Program; M-Minortty Health Professions Foundation Schools; NTP.Naoonal Toxicology Program; VVoluntary research; O-Other. x No longer considered s priority data need based on reoent evaluation of the database by ATSDR. 3 These substances have bean included in the pool of candidate aubstancea tor subregistry development since the publication of the Federal Register notice on March 10,1994 (58 FR 11434L 4 Potentially to be addressed by ATSDR's VoArti/y Research Program. 4 Data to be obtained by PBPK modeing. * Initiation of immunopathotogy study pending submission and peer review of study protooot. 7 Data to be obtained from a combined 2-generation reproduction and developmental toxicity study in rats. Not a priority date need. Table 2.--Groups Addressing ATSDR priority data needs (PDN) ATSDR Program Firm, institution, agency, or Consortium StiManoe PDN ID Voluntarism............................. Minority Health Professions Foundation Schools. Grsat Lakes Human Health Research Program. Chemical Manufacture's Association _____ ... .......... General Electric Company..................................................... Hatogenaled Solvents Industry Alliance ............................... Florida ASM Univarefty .......................... ....... .......... Vinyl Chlnriftn .................. PCBn ..... ........ ........................ Trichloroethylene................... Trtrachtoroethylene............... Methylene chloride.............. .. 1 mmti ...... ......................... 4B, 4E 7G, 7H, 71 IOC 13A, 138 20A.20B 1A The King/Drew Medea! Center of the Charles R. Drew Univarsity of MecScme and Sdenoe. Meharry Medcal College ....................................................... Mprahouta School of Modem*............................... ............ Texas Southern University......... ............... .....................f.r..... Tuskegee University............................................................... Xavw Unfo*f*fty ..................... ......... ......... ........................... Michigan State University.................... -.............................. Lead -.................................... PAHs...................................... 1 ad .................................. 1 ond .................................. Trichloroethylene................... Toluene .................................. Mercury ............................... Zinc......................................... BAruami .... ........*................... Zinc.... ........... ......................... Lead ...................................... 1C 9A.9D 1C 1A 108 18C 3A 21A 5B 21A 1C Mercury ................................ .. 3D PC8a...................................... 7F CMA113309 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 Substance PDN ID National Toxicology Program . Naur Ynrfc Atata r\*paftm#nt .... .................. ftfctta l JntvAnktty rtf Naur Ynric at ......................... University ot IHinoto id Chicago........ ...................... . University of Illinois at Urtn*Champeign...... ............ University of Wisconsin--Sumrior............................ Wisconsin Department of Health and Soda) Services----- ........................ ....................................... Environmental Protection Agency.................... ..................... National Institute of Environmental Health Sciences........... DDT ........................... Lead .......................... Mercury....................... PC8e......................... \ aari ..................... Mercuy ....................... PCBs ........ .................... -- DDT........ ........................ 11D, 11E 1C 3D 7F 1C 3D 7E.7F iid, iie l aari 1C Merctay ............ ............... 3A.30 PCBs....... ....................... 7E.7F DDT-------------- -- ------ 11D. 11E Lead...... .................... 1C Memf; ..................... 3A, 3D PCBS............... -........ 7E, 7F DDT_________ _____ 11D, 11E .......................... 1C Mercury __ --------- 3D PCBs ........-................. 7E. 7F Lead .......................... 1C 3D P\ fCffBi s................................................... 7A. 7E, 7F 1C Mercury__............ ............... 3D, 3E PCBs.............. ...................... 7F PAHs__________ _______ 9E.BF DDT--------------- -------------- 11D, 11E, 11F Mercury............... ................. 38 Mercury...... .....-................... 3C Benzene --...................-- 5A Benzene .----- ------------ -- 5C Chromium............................ - 12A ChroiT*um .............................. 12B Chromium ............................. 12C Cyanide----------- ---------------- 15A Cyanide............ .................... 15B Cyanide .................................. 15C Beryllium ........................ -...... 17A Beryllium................................ 17B Beryfflwn................................ 17C BeryMum................................ 17E Toluene ................................. 18A Toluene ................................. 188 DEHP.................................... 22D Chkxoethane......................... 24A Carbon Tetrachloride ............ 168 [FR Doc. 96-7852 Filed 3-29-96; 8:45 am) 0ILUMQ COOf 41U-70-P CMA 113310