Document zz48rNLRdQM58563roKq4JmV6

e <1 PATTON BOGGS, LL.P. 2350 M STREET, N.W WASHINGTON, D.C. 20037-1350 (202) 457-6000 r.ci.-iLt (202)457-6313 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 CiL ii,-- W. Caffey Norman, III CMA 115429 14420 Federal Register / Vol. 61, No. 63 / Monday, April 1, 1996 / Notices DEPARTMENT OP 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 AQENCY: Agency for Toxic Substances ..wM*' r f *,wrw' Department of Health and Human Services (HHS). ACTON: 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 Reautharization 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 ($6 FR 52178). Hie list was subsequently revised based on public comments and published in final form on November 16,1992 (57 FR 54150). The 38 substance#, 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'-DDTJJDEDDD, di(2ethylhexyl) phtbalate, 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 Research Committee (TASARC) comprised of scientists from ATSDR, the National Toxicology Program (NTP), sM the EnvjiwmfitV':' Pr-Mvaicn Agttuvy {WJ*f n.it jot.,.Dui 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. ADORESSES: Private-sector organizations interested in volunteering to conduct research may write to Dr. William Cibulas, Chief, Research Implementation BranchTDivision oT Toxicology, ATSDR, 1600 Clifton Rood, 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(1)) requires that ATSDR (1) jointly with the EPA, develop and prioritize a list of hazardous substances found at National Priorities List (NPL) sites, (2) prepare toxicological profiles for these substances, and (3) assure the initiation of a research program to address identified data needs associated with the substance#.. 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 revised 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, ar? (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 .dsAAihat-can be iww-rtltted * other substances or areas oi science, mUuchng risk assessment of chemicals, thus creating a sdentific.base for addressing a broader range of data needs. In section 104(l)(S)(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 Rodentidde Act of 1972 (FIFRA), or by cost recovery from responsible parties under CERCLA. To execute this statutory intent, ATSDR developed a plan whereby parts of the SSARP are being conducted via regulatory mechanisms (TSGA/FIFRA). 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/FIFRA, private-sector voluntarism, and the direct use of CERCLA funds. Additional data needs are being addressed through an interagency agreement with NTP, by ATSDR's Great Lakes Human Health Effects Research Program, and other agency programs. To date, a total of 63 research needs associated with 38 ATSDR priority hazardous substances (including 15 polycyclic aromatic hydrocarbons) are being addressed via these mechanisms (Table 1). CMA 116430 Federal / Vol. 61, No. 63 / Monday, April 1, 1996 / Notices 14421 ATSDR believe* that thee* 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 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 e minimal risk level (MRL) for acute oral exposure based on a developmental toxicity study. Although ATSDR believes that additional developmental data would bo useful to more fully characterize the effects and increase the confidence level of the MRL, the agency now believe* that this data is more appropriately classified as a data needrather than a priority data need. Therefore, this priority data need has also bean deleted from the list (Table 1). Similarly, the priority data need for additional acuta oral studies for trichloroethylene has been reclassified as s 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 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 , >-r t!j: J 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 deta needs currently being addressed by TSCA/ FTFRA 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 baaed 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 tasted are yet to he determined. The TASARC has established s 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 (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 MO'1 with GF This *va* the 6ret tan* a private -sector organisation 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 rets," was initiated on February 8,1993. * Project 2, "Metabolite detection as s tool for the determination of naturally occurring aerobic PCB biodegradation," waa 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 bioessayt via the inhalation and dermal routes as data needs for PCBs, agency scientists believe information gained via GE's oral bioasaay (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 bioessay 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 thst the toxicokinetics data (using selected tissues from Project 1) may provide important knowledge about the correlation of health effects with relevant PCB congeners. CMA 115431 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 toxidty 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. Hf.lA I..; fh.; t,'\ U' (*`UCi i. 25-day immunopathology assessment for methylene chloride via oral exposure, a priority data need identified by ATSDR. The agency expects to 0 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, HSIA proposed to first review the existing data for TCT. 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 HSIA-sponsored inhalation neurotoxicity study recently approved by EPA. EPA and ATSDR scientists recently reviewed and accepted the HSIA-sponsored reproductive toxicity study of PERC via inhalation. HSIA proposed to address ATSDR's priority data need for oral reproductive data using PBPK modeling. As for ATSDR's priority data need for immunopathology data, HSIA would follow the same procedures as for TCE (described above). Finally, with regard to ATSDR's data need for oral developmental toxicity studies for PERC (see Background section of this Notice), ATSDR is continuing its discussion with HSIA to obtain this data via PBPK modeling once the EPA-required inhalation developmental toxicity study has been completed. Chemical Manufacturers Associate n tCMA) 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 exrwcls t finsJi*e an loOU with LMa covering this study in the near future. EPA no longer requires inhalation neurological uta 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 $4 million cooperative agreement program with tne Minority Health Professions Foundation (MHPF) to support substance-specific investigations. This cooperative venture is supported by the dirsrt use of CERCLA funds. About S4 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 and related health effects. To date, more than 20 abstracts have been presented at scientific meetings, 4 manuscripts have been published in peer-reviewed journals, and 7 manuscripts are in preparation. The institutions receiving awards and their respective research projects are listed in Table 2. A not-for-profit 501(c)(3) organization, the MHPF comprises 11 minority health professions schools. Its primary mission is to research the health problems that disproportionately affect poor and minority citizens. The purposes of the ATSDR-MHPF cooperative agreement are (1) to initiate research to address ATSDR-identified data needs for priority hazardous substances, and (2) to enhance existing disciplinary capacities to conduct research in environmental health at MHPF member institutions ' The areas of research at MHPF institutions include those related to 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 (1AG) 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 scuto.suhduonk, and chronic health effects. Often these studies include an assessment of the substance's ability to cause cancer, reproductive toxicity, and birth defects. Hie 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 (immunotoxicalogy 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, NTT 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. 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 115432 Fedora] 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, ike ATCDK supf :rted reswdh project*-, 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 Lakes contsminants; (4) Investigating the foesibility of establishing registries end surveillance cohorts in the Great Lakes region; end (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 S3 million and 54 million for FYs 1994 and 199S, respectively, wes allocated to continue support of the 10 research projects. During FY 1994, ATSDR held a Great lakes Research Symposium 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, whan 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 snA 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 suhiegistries 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, end 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, end vinyl chloride remain in the candidate pool. They will be considered fo* 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 anti 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 derision will be re-evaluated as more information on the chemicals and exposure sites become available. Finally, the need to collect, evaluate, end 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 extent 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 needa. The agency expects to re evaluate the priority data needs for priority hazardous substances every three years. Dated: March 26,1996. Clair* V. Broome, DeputyAdministrator, Agencyfor Toxic Substances and Disease Rsgittry. Table i.--Substance-Specific Priority Data Needs (PDN) Currently Being addressed Under ATSDR'S Applied Research Programs Substance PDN ID Pro grams <'> Lead ................ 1A IB 1C Araanic............. 2A 28 2C 20 Mercwy.......... _ 3A 3B Mechanistic studtos on tha neurotoxic eflects of lead........ -............. ................._..... -.......-............ Analytical method tor ttsaue leveto. Exposure levels in humans Iving near hazardous waits Me* and other popUattona, such as ex- poaad workers. Comparative toxiccfcinetic studtos to determine K an appropriate vtimal spades can be identified ... HaIMvee in surface water, groundwater. BioevalaHIty tram toi. Exposure levels in humans living near hazardous waste sites and other popriabona, such as axposed worttats Multigeneralion reproductive toxidty study via oral exposure..................... ............................ ........ Doaa-raaponsa data In animals lor chrodc-duraiion oral exposure_________________ ....-- M M, G M, G E CMA 115433 -l 14424 Federal Regiitsr / Vol. 61, No. 63 I 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 > 3C 30 Vinyl CNoride ... 3E 4A 4B 4C 40 46 4F 40 Benzene .......... SA 58 5C 50 56 Cadmium..... SA SB PCS*......... ..... 7A 7B 7C 70 7E Chloroform ........ 7F 7G<> 7H) 71 w) 8A 68 SC SO PAHs______ 9A 98 9C 90 Tnchloro-ethyl- 9E 9F 90 10A Immunotoxxxilogy battery of tests vie oral exposure _____________________________ ,,____ Exposure levels in humans Rvfng near hazardous waste sites and other populations, such as ex posed workers. PoterttaJ candUtie tor etexegistry ot exposed persons -------------------- ..........------------ .....----------Dose-response dda in animals tar scute-dusflon inhalation exposure..................... -..................... Multigeneration raproducSve toxicity study via tohalatton .... ----- ... ...................... .......... . Dose-response dtu in animals tar chranic-dteafion Inhalation expoetsa. 6 G AG 0<x> ym1 MMgattan ot vinyl chloride Induced totidty. 2-spedee developmental toxicity study via inhalation .............. ..--.................... ...... ........-- V"-' Exposure levels n humans tving near fctardous waste sites and ether populations, such as ex- posed workers Potertaal eanddate tar eubregisky ot exposed persona _.-------- . ----- .. Does response date In anlmala ter acute- and Mermedate-dteatton oral wpoan. The subchronic study should Muds an extended reproductive organ hjetopathotogy. 2-apadee devetapmantaltoxtatly study vta oral exposure --------- ------------------- .---- -- Newotoxiodogy battery of teats vie oral expoeus ------------------------------ ............. .................. ....... Epidemiologic studes on the heaflh effects of benzene (Special emphasis endpoints toefuds A E M E tomuwtoxidty}Expostxe levels in humans living near hazardous waste sites and other populations, such as ax- posed woriwrs. Analytical methods tor biological tissues and lUids and environmental made. Exposure levels to humane living near hazardoua watte sites and ether poptrations, such as ax- posed workers. Doee-reaponee date In animala tor acute- and tarmedate-duation oral axpoauraa .......... ..... ...... Biodegradation ot PC8a in water btoavalafaltty of PC8e In air, water and soil' Doaereaponee <teia In -animal* tar acute- and totermedatedtxation Inhalation exposures. The srtochronta study stadd induds extended reproductive organ histopeiholagy Epidemiologic studes on the health eflecte of PC8s (Speciet emptiest* endpoints Xrtuds SnmuncSoxidty. gastrointestinal toxidty, Ker, kktoey, thyroid toxidty, reprodudtvatdevetopmental -'torddty). G G - Expotwa ieveit to humane fving near hazardous waste sites and ether populations, such as ax- G posed workers. Potential eanddate tor subregistry of exposed persons ........__________ ___ ,,______........______ _ A> Chronic toxicity and oncogenicity vta oral expoaure ____ ........._________--.......... _........... ........... .V Aerobic PCS biodegradation in sediment ___________ --,. ___ _ ___ ____ ______ V PCS congener anetyeie_______ __ __ ____ _________ _______ ____ ......._________ ____ V Does response (tela in animals tar iraatmedate-dureMon ore) exposure. EpWsmiotogte studes on the heath ettects of chloroform (Special emphasis endpoints include cra- car, neuotoxXdty, raproducSve and developmental toxicity, hepatotoxidty, and renal toxicity) Exposure levels in humans living near hazardoua waste sites and other papulations, such as ax- posedworicars Potential canddde tor subregietry of exposed persons .............................. ............ ....................... A Dose-response date in animats tor irtermedate duration oral exposures. Ths wtochronic study M stated indude extended raproducSve organ hjatopaSwtagy and immunopettalogy. 2-Species devetapmsntd toxidty study via InhalaSon or oral exposure Mechanistic studes on PAHs, on taw mtxuxas of PAHs can influence the ultimate activation of PAHs, and on how PAH* aOect rapidy proliferating tissue* Dose-raspons* data in animals tar acute- and intarmedate-duraltan InhalaSon expostess. The M subchronic study stated Induds extended raproducSve organ histopattaiogy and ImmteWpaSiolagy. Epidemiotagic studes on Sw health eflects of PAHs (Special emphasis erxfeaints include cancer, dermal, hemotymphatic. and hepatic). Exposte* level* in humans Rying near hazardous waste sites and other populations, such as ex- posed woriwrs. Pteeraial eanddate tor subregistry of exposed person* ....................,,......................................... Doseresponse data in animats tor acute- duration oral exposure. ...................... _.................... ..... G G A o<*> 108 IOC 100 10E DDT................. 11A 118 11C 110 VIE Neurotoxicology battery ot tests via the oral route.................................... ....................................... Immunotoxtadogy battery of tests vie to* oral route................. ...... .............................................. EptdemidogK dudes an tiie health effects of trichioroethytene (Special amphasia endpoints to- dude cancer, hepatotoxidty. renal toxicty, developmental toxidty. and neurotoxicity). Exposure levels to humans living near hazardous waste sites and other populations, such as ex- posed worker*. Doaereaponee date to animals for chronic-duration oral expoetxe. Comparative toxicakinetic study (across routes/spedes). Bioavalabilty and btaaccumulation from sott. Epidemiologic studes on the health affects of DDT, ODD and ODE (Special emphasis endpoints include toimunotoxidty. reproductive and developmental toxidty). Exposure levels to humans living near hazardous waste sites and other popteations, such as ax- posed woriwrs. M Vw G G CMA 115434 Federal / Vol. 61, No- 63 / Monday. April 1. 1996 / Notice* 14425 table i .--Substance-Specific Probity data needs (PDN) Currently being addressed under ATSDR's Applied research Programs--Continued Substance PDN ID Pro grams <'> 11F Chromium ........ 12A 12B 12C 120 12E Yftiwr,W'* i. ciiiytens. 13* 136 13C 13D 13E AidrirVDieldrin ... 13F 14A 146 14C 140 Cyanide ........... ISA 156 15C ISO Carbon Tetrachloride. 15E ISA 168 ISC 16D 1SE Beryllium_____ 17A 176 17C 17D 17E 17F Toluene .........- ISA 188 ISC 18D 1BE 18F Nickel.............. ISA 196 19C 190 19E 19F 19G Methylene Chto- 20A ride. 206 20C 200 Potential eanddate tor aHregistry of exposed persona -------------------------------------------------------- A, G Doee-tesponae data In animals tor acute-duration expoeure to chromium (VI) and (III) via oral ex- E posire and tor intermedateduatton expoeure to chromium (VI) via oral expoetxe MMUganeraiton reproductive toxicity atudy via oral expoeure to chromium (III) and (VI)..... ............. E immunoioxicotooy battery of taels tolovring oral exposrn to chromium (110 and (VI)------------------- E 2-Spedea developmental toxicity atudy via oral expoeure to chromium (ill) and (VI) Expoeure leveia In humane living near hazardous waste sites and other populations, such as ex- posed workers. Dose-response data in animate tor aciAe-duretton or** exposure, Inctodng neuropathology and de- VI4-3) . meaner, and immunopathotogy. MuNigeneratton reproductive toxicity study via oral expos---------------------- ----------------------- ------ v*>. Doee-rsaponse data in animals tor chronio-dtsation oral mpmn, Inducing neuropathology and demeanor, and Immunopathotogy 2-Species developmental toxidty study via oral exposure-------------------------------- -------------------- Oo) Expoeure levels In humans Bring near hazardous waste sites and ottier popiistfons, such as ex- posed workers. Potential eanddate tor subregistry of exposed persona A Dose-response data in animals (or intermedate-duratton oral expoeure. BtoevalablMty Korn sd. Exposcxe levels In humans Bring near hazardous waste sites and other populations, such as ax- posed workers. Potential eanddate tor subragisty of exposed persons ---------------------------- ---........................... A Dose-response data in animate tor acute- and Intermedate-dcxatton exposures via inhalation. The E subchronic study shotrid Include extended reproductive organ htetopidhotogy and evaluation of nsurobehavtoral and neexopathotogical endpoints. 2-Species developmental toxicity study via oral expoeure------ _ _------------------ ------- E Evaluation of ihe environmental late of cyanide In so>......... - . - ..........---------------- ----- E Exposure levels In humans Bring near hazardous waste sites and other populations, such as ex- poeed workers. Potential eanddate tor sdsegistty of exposed persons ---------- -- ........ ..... -- A Dose-response data in animate tor chronic oral expoeure. The study should Include extended re- productive organ and nervous tissue (and demeanor) histopathoiogy. ImmunotoxicQiagy battery of teste via oral expoeure. NTP Half-Ufa in sol. Expoeure levels in humans Bring near hazardous waste sites and other populations, such as ex- poeed workers. Potential candidate tor sttoragisey of exposed persons .......... ..... .......... ....... .................. ........ A Dose-responae data in animals tor acute- and Intermedtete-duration inhalation exposixes. The E sttochronic study should tocfcde extended reproductive organ histopathoiogy. 2-Species developmental toxicity study via Inhalation exposure ............. --............................. E Environmental late In air factors affecting bioavialabilty in air ... ..... .............. ..................-.... ...... E Analytical methods to determine environmental apecialion. Immunotoxicoiogy battery of taste toloviring oral exposure......................-...............................---- E Exposcxe levels in humans Bring near hazardous waste sites and other populations, such as ex- poeed workers. Dose-responae data In animals tor acute- and intermediate-duration oral exposures. The E subchronic study should Include an extended histopathologic evaluation of the immune system. Comparative toxicokinetic shxAae (Characterization erf absorption, dstribution, and excretion via E oral exposure). Neurotoxkxriogy battery erf tests via oral exposure. ~ ---------------------------- ------ --------------------- M Mechanism of toluene induced neurotoxicity. Exposure levels in humans Bring near hazardous waste sites and other populations, such as ex- posed workers. Potential candUate tor seixegistry of exposed persons ....................-........................ -........... -..... A> Epidemiologic studes on the heiuth effects of nickel (Special emphasis endpoints include repro- ducthre toxicity). 2-Species developmental toxidty study via the oral route. Dose-response data in animals tor acute- and intermediate-duration oral exposures. Necxotoxicotogy battery of tests via oral exposure. Btoavalabttty of nickel from soiL Exposcxe levels in humans Bring near hazardous waste sites and other populations, such as ex- posed workers. Potential candUate tor subregistry of exposed persons ................ .............. .................................... A< Oose-response date in animals tor acute- and intermeciate-duraiion oral exposure. The stto-chron- ic study should include extended reproductive organ histopathoiogy, nauropathology and de- meanor, and Immunopathotogy. 2-Spedas developmental toxicity study via the oral route -..... .......... .... __.................... ....... v> Exposure levels in humans Bring near hazardous waste sites and other populations, such as ex- posed workers. Potential candidate tor sctoregistry.of exposed persons _____ ______ ___ _..-- A CMA115435 14426 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 PDN description Pro gram^1! Zinc.................. 21A D` H' 21B 21C 21D 21E 22A 22B 22C 220 22E Selenium.......... 22F 23A 238 23C 230 Chloroethan* 23E 24A 248 24C Dose-response data In animals tor acute- and toterinadattoduratton oral exposures. The xP chronic study should include an extended lurtrreitv^flP- evaluation ot the immunology neurologic system*. Mutogeneration reproductive toxicity study via oral axposura. Carctooganiclty Mating (2-year bioaaaay) via oral axpoaue. Expoaure tovais in hunans Iving near hazantou* waste sites and other papulations, such as ex posed workers. Potential canddato tor utoregisby of a^waad parsons Epktomtologic studies on to* health affect* of DEHP (Special amphast* #ndpc*nt* include canoer). Does reaponta data to animal* tor acute- and tosofTradtoSa-duatton oral exposure*. The subchronic study should toduda an axtended htatopathoiogic evaluation of Jh* tovnuwiogic and neurologic systems. Mdtigeraration reproductive toxicity study via oral txpoaia*. Comparative toxtooWnedc stud** (StuJes designed to examine tow primes** metabolize and da- tribute DEHP aa oomparad to rodents via oral axpoaura). Expoaure level* in human* Bring near hazardous waste sites and other populations, such ss ex posed worker*. Poterafal canddato tor srtoregistry of exposed parsons --,-- --------------- ------------ ----- -- Dose-response data to animal* lor acute-duration oral axposura. immunotoxicotogy battery of teat* via oral expoaure. Epidemiologic studas on to* heatih affects of selenium (Special emphasis endpoints fnciude can- car. reproductive and devetopmental toxicity, hepatotoxicity and adverse akin affects). Exposure levels In humans living near hazardous waste sites and other popdadons, such ss ex posed worker*. MMiil mwMMb Iw ed mmuH ndraiwt ............................................. Dose-response date to animals tor acute- and IntoimedM* duration oral exposures. The subchronto study should todud* an evalutfton of immune and nervous system tissues, end ex tended reproductive organ histopethoiogy. Dose remora* data to animals tor chronic tohalatnn exposures. The study should toduds an eval uation of nervous system tissues. Potential candidate lor sitoreglstry of exposed person* --__ _ --,,--...... ............. . .. M ' A<~< E A A E' A 1ATSDR program* tor addressing data need*. A-ATSDR DMaton of Health Stud**; EEnvironro*r*ai Protection Agency-TSCA/FIFRA toning; G-Great Lake* Human Health Raeeareh Program; MMtoor*y Health Profession* Fottodation Schools; NTP-Naforal Toxicology Proyam; V-Voluntory research; OeOtoar. *No longer considered a priority data need based on recent evaluation ot the database by ATSDR. The** substances have been Included In the pool of canddato sitoatanoea tor subragistry development sine* the publlcatton of the Federal Register node* on March 10.IBM (50 FR 11434)7 4 Potentially to be adekassed by ATSDR** Voftsitery Raeeareh Program. Deta to be obtained by PBPtCmodalng. initiation of immunopMhotogy study ponding submission snd peer review of study protoooL 'Data to be obtained from a combined 2-generation reproduction and devetopmental toxicity study in rats. Not a priority data need. Table 2.--Groups Addressing ATSDR priority data Needs (PDN) ATSDR Program ' Finn, institution, agency, or Coneortiun SUtetane* PON ID Voluntarism ........................... Minority Health Professions Foundation Schools. ' Great Lakes Human Health Research Program. QhMltil U^HiHlinn iwvUiM _________________ General Electric Company ._-- ___ ...,,____-...... Hatoganated Solvent* industry tiwn ........................... Florida ASM IMvaraNy .................... .................... The Ktog/Drew Madtoai Canter of to* Chariaa R. Drew Ud- vanity of Madeira and Sdanoa. Mehairy Madcal Cotiega ................ .............. .................... Morehouse School of Madeira__________ _____________ Texas Southern University.................................................. * Tuakegae Univaratiy---------- --------------------------------------Xavier University _____ _____ ,, ......__ _____ Michigan Slate Univaratiy , ......--, ..... ..... * Vinyl ChLvVUi PCS* W1 fUMJ-LH.UI---f-D---O---T---J--y---W----f--W--- a t.Ah j,,i . * '- t ten ................ .................... Lead------------------------------- PAH* ........ .................. ... Lead ................... ................. 1 aid - ~ ............. Tttohtoroatoytera ...... Tduara............... ................ Mareuy _______ _________ Ztoc------- ..... .......... .. Benzene _________________ Ztoc_______________ __ ...... (.esri ....................................... Marotry . ___ ___ ___ PCBs------------------------------ 46.4E 70, 7H. 71 IOC 13A. 138 20A.20B 1A 1C 9A.9D 1C 1A 106 18C 3A 21A 56 21A 1C 30 7F CMA 115436 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, mettuboo, agency, or Consortium StDManoe PDN ID TftrA/FIFRA National Toxicology Program . New York State Health Department ................................ State University of New York at Oewego ............. .............. University of Illinois at Chicago ............................... ..... . University of Illinois at UrbanaChampeign......... -- University ol Wisconsin--St^erior......................... ............. Wisconsin Department of Heath and Social Services * Environmental Protection Agency ------______ ____ National Institute of Environmental Heath Sciences........... DDT____________________ Lead .........-......................... Mercury --........ .----------PC8a----------------- -----------Itad |rT______ __________ Merctsy ----..... ------ PC8e _ ----------------- DDT--------------- --------------- Lead -- ----------------- Merctry .-- PCSe DOT-----Lead _ Mercury .......--...---- --............ -------- ------- PCSe----------------------------DDT____________________ Lead - ----------- Merctry--------- --------- ------- PCSe................................... Lead.................................... Mercury--- ----------------------- PCSe -------------- Lead -- ------------------- Merasy .......... ................ PCSe...................... ............ PAHs nnr ------ -- ................ ....... . - Meretsy ... ------------------ Benzene --------- . - Benzene ------ Chromasn____ _____ --- Chromium --------- --------- - Chromium ---- ---------- Cyanide------------ -------------- Cyanide . .-- -- Cyanide-------------- ------ Beryllium...........---------------- BeryOum ---------------- ----- -- BeryHum --------------........ Betyium....... ....................... Toluene .......... --............ Toluene ............................... DEHP___________________ Carbon Tetrachlcrtde --------- no, he 1C 30 7F 1C 30 7E.7F 110,11E 1C 3A.3D 7E-. 7F 110,11E 1C 3A.30 7E.7F 110,11E 1C 30 7E, 7F 1C 30 7A, 7E, 7F 1C 30, 3E 7F 9E.9F 110,11E, 1.1 F 3B 3C SA 5C 12A 12B 12C 15A 15B ISC 17A 17B 17C 17E ISA 1SB 22D 24A 168 (FR Doc. 06-7852 Filed 3-20-96; 8:43 m| UM OOOC 41U-70-8 CMA 115437