Document K69waKrVGn2nVeXQ1zVLkYVVw

/ / / ( CHEMICAL MANUFACTURERS ASSOCIATION March 30, 1994 Dear Vinyl Chloride Research Coordinators: A calendar to determine your availability to attend the next VCRC meeting is enclosed. A tentative agenda for the meeting also is enclosed. Dr. Greg Bond anticipates sending me the draft scope of work for the epidemiology study by April 7. I will send you the draft as soon as I receive it. Two activities recently have been initiated by EPA and ATSDR. Dr. James Knaak informs me that KKIkJiftft coMissioned Clemment Associates to undertake a risk assessment for vinyl&chlorid#; Dr. Richard Reitz, formerly of Dow Chemical, has developed a physiologically-based pharmacokinetic model for predicting cancer risk from vinyl chloride exposure. An abstract of his model is enclosed. Dr. Knaak has expressed an interest in inviting Dr. Reitz to discuss his model with the VCRC at its next meeting. As EPA's risk assessment activities for vinyl chloride already are underway, I think we should meet with Dr. Reitz as soon as possible and develop a strategy to work with EPA from the beginning to ensure a scientifically sound risk assessment. On March 10, the ATSDR announced various research activities that are underway or ara planned for vinyl chloride*and other chemicals. The enclosed Federal Register notice describes those research activities. The ATSDR has three different options to develop research data as described in the background section of the Federal Register notice. The VCRC commissioned Can-Tox to review the ATSDR profile for vinyl chloride last year and a final report from Can-Tox was issued early this year. This report has not been submitted to ATSDR. I will contact Dr. William Cibulas of ATSDR to discuss various research programs underway or planned as described in T&blee 1 and 2 of'the Federal Register notice. It is important for the vinyl chloride industry to meet with ATSDR and/or EPA to discuss the ATSDR data needs because the ultimate cost of the ATSDR data needs on the industry will be well over $500,000, if the data needs are not minimized. One way or the other, industry ultimately will have to pay for all test costs. We will discuss the enclosed Federal Register notice at our next meeting and decide on a course of action. Please complete your meeting availability calendar and send it to me by fax at 202/887-1237. If you have any questions, please call me at (202) 887-1192. Sincerely, Itcuo Enclosures Hasmukh C. Shah, Ph.D. Manager, Vinyl Chloride Panel BFG 00201 2501 M Street, NW, Washington, DC 20037 Telephone 202-887-1100 Fax 202-887-1237 CHEMICAL MANUFACTURERS ASSOCIATION Vinyl Chloride Panel Vinyl Chloride Research Coordinators Tentative Agenda DATE: TIME: PLACE: TO BE ANNOUNCED TO BE ANNOUNCED CMA Offices 2501 M Street, NW Washington, D.C. 1.0 Approval of February 14, 1994 Record of Meeting 2.0 Discussion of Scope of Work of the Epidemiology Study 3.0 Discussion of Potential Contractors for the Epidemiology Study 4.0 Discussion of Cost Sharing Formula for the Epidemiology Study 5.0 Presentation by Richard Reitz on Predicting Cancer Risk from Vinyl Chloride Exposure with a Physiologically-Based Pharmacokinetic Model - TENTATIVE 6.0 Discussion of Course of Action with EPA on Vinyl Chloride Risk Assessment 7.0 Discussion of ATSDR Research Data Needs for Vinyl Chloride 8.0 Discussion of Course of Action with ATSDR on Its Priority Data Needs 9.0 Financial Statement 10.0 Schedule Date for Next Meeting or Conference Call Subject to Approval Hasmukh C. Shah, Ph.D. Manager, Vinyl Chloride Panel BFG 00202 rdH.Rtitz, MeUri/Hirt V(S17)631-70d9 ttam/94 010:39 AM 22^ SEMINAR TOPIC#! Predicting Cancer Risk from Vinyl Chloride Exposure with a Physiologically-Based Pharmacokinetic Model. Richard H. Reitz McLaren/Hart, ChemRisk Division Physiologically-based pharmacokinetic (PB -PK) models have been proposed as tools for facilitating the extrapolation of animal cancer tests to humans. For instance, several of us (Reitz, Andersen, Gargas, Clevyetiydeveloped a risk assessment for methylene chloride which used PB -PK mbdeling to extrapolate between spedes, across different routes of exposure, arid from high dose to low dose. This risk assessment predicted considerably less risk\to humans than earlier procedures, and the PB -PK risk assessment was consistent with epidemiology studies for methylene chloride (which are generally accepted as negative). si Because the epidemiology studies for methylene chloride are negative (as the PB -PK model predicted they would be), they do not/provide an opportunity for comparing cancer rates in humans with predictions derived from the PB -PK model. However, there is one industrial compound (vinyl chloride, YC) which has been shown to produce measurable increases in thfe incidence of livWahgiosarcoma in both rats and humans. In order to determine whether risk assessments based on PB -PK adjustments of dose adjustments are too conservative, not conservative enough, or about right, we have developed a PB -PK model for VC and predicted the risk to humans based on rat studies. The VC model for rats and humans was developed from several in vivo and in vitro data sets. Both the rat arid human models were then validated with independent studies of Vc metabolism in the appropriate species (i.e. the validation studies were not used in development of the model itself). Then PB -PK model was combined with the multistage model of Crump & Howe (GLOBAL83) to predict the incidence of liver anglosacroma produced in humans. The human studies included more than 12/300 workers exposed to VC occupationally over a period of several decades. The risk assessment based on the PB -PK model predicted considerably less risk than would be calculated by default (nonpharinacokinetic) procedures. However, the incidence of angiosarcoiha actually observed In human subjects was still considerably lower than predicted by the PB -PK/multistage model, suggesting that if the results obtained with VC are typical, risk assessments combining PB -PK and multistage modeling likely overpredict, rather than underpredict, human risk. BFG 00204 11434 Federal Register / Vol. 59. No. 47 / Thursday, March 10, 1994 / Notices DEPARTMENT OF HEALTH AND at any time to conduct research to fiU of science, including risk assessment of HUMAN SERVICES identified data needs, until ATSDR chemicals, thus creating a scientific base announces that research has been for filling a broader range of data needs Agency for Toxic Substances and initiated for a specific data need. CERCLA. in seeds l04(iX5)(D)fe y Disease Registry [ATSOA-7VJ Status of the Superfund Substance* Specific Applied Research Program AGENCY: Agency for Toxic Substances and Disease Registry (ATSDR), Public Health Service (PHS), Department of Health and Human Services (HHS). action: Notice. SUMMARY: This notice provides the status of ATSDR's effort to implement the Agency's Substance-Specific Applied Research Program (SSARP). This research program, authorized by the Comprehensive Environmental Response. Compensation, and Liability Act (CERCLA), as amended by the Superfund Amendments and ADDRESSES: Private sector organizations interested in volunteering to conduct' this type of reeearch may write to Dr. William GbuUs, Chief. Research Implementation Branch, Division of Toxicology. Agency far Toxic Substances and Disease Registry, Mailstop E-29,1600 Clifton Road. NR, Atlanta. Georgia 30333. FOR FURTHER INFORMATION CONTACT: Dc William Qbulas, Chief, Research Implementation Brandi, Division of Toxicology, Agency for Toxic . Substances and Disease Registry, Mailstop E-29,1600 Clifton Road, NE.. Atlanta, Georgia 30333k telephone (404) 639-6306. SUPPLEMENTARY IHFORMATIOWt Pfolijiwmiil stoles that Ms the sense ofCtmgrash thet the costa far conducting torn reeearch program be bone by to* ^MiiUiutw mmd pen re ssinie of hazardous substances under the Toodfe Substances Control Act (TSCA) andby underthe Feder* Insecticide. Fungicide, and Rodanticttie Act (FIFR-raKerby coel recovery free# raepcnsible parties under GgH-f To effect this statutory intent. ATSDR developed a plan whereby parts of the SSARP will be conducted via regulatory mechanisms (TSCA/FIFRA), private sector voluntarism, and the direct use of CERCLA funds. A TW-Agency Superfund Applied Research Committee (TASARQ comprised of scientists from ATSDR, NTP, and the EPA has been set up to: (1) Advise on the assignment of Reauthorization Act (SARA) (42 U.S.C. The Comprehensive Environmental. priorities on mechanisms far filling data 9604 (i)l. was initiated on October 17, Response, Compensation, and Liability needs: (2) coordinate knowledge at 1991. At that time, a list of priority data Act of 1980 (Superfund] or GERCLA, aa research activities to avoid duplication needs for 38 priority hazardous emended by the Superfund of research in other programs and under suhstancceovas announced In the Amendments and Rsauthorizatton Act other authorities: (3) advise on issues of Federal Register (56 FR 52176). The list (SARA) (42 U.S.G 9604(1)), requires that science related to substance-specific was subsequently revised based on ATSDR (1) Jointly with the data needs: and (4) maintain e public comments, and published in Environmental Protection Agency scheduled forum that provides an final farm on November 16,1992 (57 FR (EPA). develop and prioritize a list of overall review of the ATSDR SSARP. S41S0). The 38 suhetonqge, each of which is found on ATSDR's "List ofPriority Hazardous Substances" (56 FR 52166. October 17,1991), are aldrin/dfeldrfn, hazardous substances found at National Priorities List (NFL) sites, (2) prepare toxicological profiles far these mmA (2) maaarm thm fntrtelim of s research program to fill Identified The TASARC has met four times since toe initiation of the SSARP. This notice Enrides the status of ATSDR's efforts to plement the SSARP, focussing on nwgfitnfl activities relevant to test rule arsenic, benzene, beryllium, cadmium, data needs associated with the development under TSCA/FIFRA, carbon tetrachloride* chknoethane. substances. Before starting such e private sector voluntarism, and direct chloroform, chromium, cyanide, p,p'- program, ATSDR will consider use of CERCLA funds. Additional data DDTDDEJ3DD. di(2- [fnmBMTuiiKnn of the Interagency needs are being addressed through an ethylhexyljphthalate, lead, mercury, Testing Committee established uawr interagency agreement with NTP, by methylene chloride, nickel, section 4(e) of rite Toxic Substances ATSDR's Greet Lakes human health polychlorinated biphenyl compounds Control Act on the type of research that effects research program, and other (PCBs), polycyclic aromatic should be done. Agency programs. To date, 59 priority hydrocarbons (PAHs) (includes 15 ^ On October 17.1991, ATSDR data needs associated with 35 ATSDR substances), selenium, announced identification ofthe priority hazardous substances tetrachloroethylene, toluene, priority data needs for 36 priority .. - - (including 15 PAHs) ere being liii lilniiintTijliins ihijlyhbiijdii sad hazardous substance# (56 FR52178), addressed via these mechanisms (Table zinc. This notice also serves ts a continuous call far voluntary research requested publiccomments, and invited 1). private sector organizations tovohmteer to conduct research to fill specific A. TSCA/FIFRA initiatives. ATSDR encourages private priority data needs. On November 16 ' b developing end implementing the sector organizations to volunteer to 1992, the Agency published e revfsed SSARP, ATSDR, NTP. and EPA have conduct research to fill specific priority data needs. A Tri-Agency Superfund Applied Research Committee (TASARQ comprised of scientists from ATSDR, list of 117 priority data needs for these priority hazardous substances (57 FR 54150). The major goals of the ATSDR SSARP established procedures to identify priority data needs of mutual interest to Federal programs. These data needs will be filled through a program of the National Toxicology Program (NT?), axe: (1) To fill the substance-cpedfie toxicological testing under TSCA. This and the Environmental Protection information needs of the public and portion of the research will be Agency (EPA) will review all proposed scientific community, and (2) to sxqjply conducted according to established voluntary research efforts. Information necessary to conduct - TSCA procedures and guidelines. This DATES: ATSDR considers the voluntary comprehensive public health * tmting will fulfill more one Federal research effort to be important to the assessments ofpopulations livingnear . program's need. During FY1993, a continuing development ofthe SSARP. hazardous waste sites. This program - - subset of the 117 priority data needs for Therefore, the Agmcy encourages also will provide data that can be 38 substances (about 60) was referred to private sector organizations tovolunteer generalized to other substances or areas the EPA undo its authorities following BFG 00205 Federal Register / VoL 59. No. 47 / Thursday, March 10, 1994 / Notices 11435 review and endorsement by the Currently, ATSDR is pursuing minority citizens. The purposes of the TASARC oversight committee. voluntary research interests with two ATSDR-MHPF cooperative agreement 'urrently, 26 priority data needs private sector organizations: the General are: (1) To initiate research to fill jsotiated with 11ATSDR substances Electric Company (GE) and the ATSDR-identified data needs for have been recommended by EPA to be Halogenated Solvents Industry Alliance priority hazardous substances, and (2) to added to its Master TestingXist, Ore first (HSIA). To date, through the voluntary onhanffo <rfrtpg disciplinary capacities step in test rule development under research efforts of GE and HSIA, four to conduct research in environmental TSCA, section 4 (Table 2). Please note priority data needs for two substances health at MHPF member institutions. that although ATSDR has identified are under discussion, potentially The areas of research at MHPF priority data needs for oral exposure to leading to the signing of two institutions include those related to tetrachloroethylene, cyanide, and memorandums of understanding (Table broad areas of toxicology and beryllium. In response to other Federal government agency needs, ATSDR will consider proposals to conduct inhalation studies in conjunction with pharmacokinetic studies for these substances in lieu ofbioassays using oral exposures. It is anticipated that inhalation data derived from these studies can be used, in conjunction with pharmacokinetic modeling, to address ATSDR's oral toxicity data needs. Some of ATSDR's priority hazardous substances will not be added to EPA's Master Testing list because they do not fall within the bounds of TSCA, Section 4 authority. For example, TSCA does not require testing chemicals that are out of production, such as POa. Furthermore, TSCA it not considered the appropriate mechanism for tasting PAH*, because the PAHs are Ire* products ofmultiple industrial processes and, therefore, it is difficult to Identity specific manufacturer*. In addition, TSCA guidelines are not available for some of the ATSDR priority data needs such as the development of analytical methods for cadmium and beryllium, mechanistic studies on the neurotoxic effects of lead, and the mitigation of toxicity ofvinyl chloride. Moreover, some of the ATSDR priority hazardous substances are considered more appropriate for FIFRA 3). During FY1993, ATSDR staff environmental health science. Some of the MHPF member institutions are members met with officials from GE to conducting health studies of minority discuss the Agency's research agenda groups exposed to ATSDR's priority foe PCS*. The Agency has identified hazardous substances. mutual interests In environmental fate testing and human health endpoints assessments and has initiated discussion on these studies with GE. ATSDR met with HSIA D. National Toxicology Program ATSDR "**n**t" an interagency agreement (1AG) with NTP to conduct toxicological testing of substances representatives to discuss the use of identified at NPL sites. The studies determine levels ofexposure that i models to fill priority data needs present a significant ride to humans of for six volatile organic compounds. The acute, subacute, and chronic health Agency selected methylene chloride to effects. Often these studies Include an start using PBPK modeling to address assessment ofthe substance's ability to ATSDR's toxicity priority data needs cause cancer, reproductive toxicity, and because of the extensive database on birth defects. Tan results of these this substance. The toxidty priority data studies an used by regulatory agencies needs for the remaining 5 volatile such as the Food and Drug organic compounds (carbon Administration and the EPA, various tetrachloride. dUoroethahe, chloroform, environmental and industrial groups, tetrechloroethylene, and and ATSDR to Improve the ability to trichloroethylene) may be addressed via conduct public health assessments at voluntary efforts in the future. NPL sites. Under this agreement, one C. CERCLA-Funded Research (Minority Health Professions Foundation Research Program) toxicity priority data need Identified in _ the SSARP (carbon tetrachloride, immunotodcology battery of tests via oral exposure) is currently being During FY 1992, ATSDR announced a addressed. This NTP study was begun S4 Batman cooperative agreement in September 1993 and should be program with tne Minority Health completed in February 1994. Professions Foundation (MHPF) to support substance-specific ' E. Gnat lakes Human Health Effects investigations. This cooperative venture Research Program than TSCA, e.g., arsenic, DDT, and Is supported bythe direct use of Some of the priority date needs aldrin/dieldrin. lbs Office of Pollution, CERCLA funds. During FY 1963, about identified In the SSARP have been Prevention and Toxics (QPPT), EPA* $4 million was allocated to continue Independently identified as research forwarded the data need* for these this research program; no new projects needs through the ATSDR Great Lakes substances to the Office ofPestidda wore initiated. Currently, 9 priority data human health effects research program, Programs for evaluation. needs for 21 priority hazardous a separate rasosreh program. To date, 12 B. Private Sector Voluntarism substances (including 15 PAHs) in the SSARP are being addressed by the priority date needs for 19 priority hazardous substances (including 15 As part ofthe SSARP, ATSDR MHPF institutions through this PAHs) identified in the SSARPire being initially announced a set of proposed program. Also, the MHPF research addressed through this program. The procedures for conducting voluntary program will address 13 other institutions receiving awards and their research on February 7,1992 (56 FR specific data needs identified respective studies are listed in Table 5. 4756). It was revised based on public in the ATSDR toxicological profiles The Greet Lakes Critical Programs Act comments and published on November concerning exposures and related health of 1990 mandates EPA, in consultation 16.1992 (57 FR 54160). Ibis voluntary effects. The inkitutions receiving with ATSDR, to prepare a report by research program fills priority data awards and their respective research September 30.1994, that assesses the needs along with other mechanisms protects are listed in Table 4. adverse effects of pollutants in the Great such as test rule development through Tne MHPF, a not-for-profit 501(c)(3) Lakes system on the health of - EPA and CERCLA-funded research. organization, is comprised of 11 individuals in the Great Lakes states. A Private sector organizations were minority health professions schools. Its variety of persistent toxic substances are encouraged to volunteer to conduct primary mission is to research the prevalent in the Grest Lakes, including research to fill these specific priority persistant health problems that PCBe, KIT snd its metabolites, dieldrin, data needs. disproportionately plagua poor and toxaphene, mirex, mercury. HFG 00206 11436 Federal Register / VoL 59, No. 47 / Thursday. March 10. 1994 / Notices benzo(a]pyrene. hexachlordbenzene, furans, dioxins, and lead. Certain priority data need for 37 of the 38 priority substances (Table 1). ATSDR mpqimw products, or occupation can be used to design a rigorous analytic population*--Native Americans, sport will obtain this information through epidemiologic investigation. anglers, fetuses and nursing Infants of exposure and health effects studies, and Epidemiologic studies on several of mothers who consume contaminated through establishing and using ATSDR's 38 priority hazardous Great Lakes fish--have a potentially substance-specific subregistries of substances (such as DDT, PCBs, and higher risk of long-term adverse effects people within the Agency's National PAHs) are being conducted by the resulting from exposure to these Exposure Registry who have potentially ATSDR Great Lakes human health contaminants. been exposed to these substances. effects research program (Table 5). The ATSDR-supported research The list ef38 priority bazardoup TVro epidemiologic studies on lead projects focus on these high-risk substances In the SSARP was forwarded (identified as a data need by ATSDR), populations to try to further define the to ATSDR's Exposure and Disease human health consequences of exposure Registry Branch (EDRB), Division of are also being conducted by the Morehouse School of Medicine and the to these persistently toxic substances. Health Studies, for consideration as King/Drew Medical Center of the The research activities indude, but are potential candidates for subregistries of Charles R- Drew University ofMedicine not limited to: (1) Characterizing exposed persons, based on criteria and Science via the ATSDR--MHPF exposure and determining the profiles described in EDRB's 1988 document, cooperative agreement. ATSDR expects and levels of Great Lakes contaminants "Policies and Procedures for that other substance-specific in biological tissues and fluids in high- Establishing a National Registry of epidemiologic studies, identified as data risk populations; (2) Identifying Persons Exposed to Hazardous needs or priority data needs in the sensitive and specific human Substances.'* To date, ATSDRhas SSARP, may potentially be conducted reproductive/developmental end points selected benzene, chromium, and and correlating them to exposure to trichloroethylene as primary Greet Lakes contaminants; (3) r^T,tTTrnmta to establish subregistries determining the short- and long-term in the National Exposure Registry. riskfs) of adverse health effects in However, aldrin/dleldrin, carbon progeny whose parents were exposed to tetrachloride, chloroethane, chloroform, Great Lakes contaminants; (4) cyanide, p,p'-DDT DDE, DDD, di (2- investigating the feasibility of establishing registries and surveillance ethylhexyl) phthalate, mercury, methylene chloride, PAHs, selenium, 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 FY1992, ATSDR announced a 52 million grant program to conduct research on the impact os human health of contaminated fish consumption in the Great Lakes region. On September 30,1992, ATSDR announced nine awards under this program. In FY 1993, about S3 million was tetradiloroethylene, and vtaylcMeridf remain as a pert of the Candidas poofc They will be considered for selection as primary contaminants during each selection process (Table 1). Finally, arsenic, beryllium, cadmium, lead, nickel, PCBs, toluene, and zinc are not considered to be in the pool of candidate substances for an exposure registry at this time. This dedslon wiff be re-evaluated as more information on the chemicals and exposure sites . become available. With regard to epidemiologic studies, by other Divisions within ATSDR ATSDR acknowledges that the conduct of epidemiologic studies to determine possible linkages between exposure to hazardous substances and human health effects may be accomplished other than by Agency programs, or under other ATSDR- sponsored auspices. Toward that end, try Agency encourages the private sector and other government programs to use ATSDR's priority data needs to plan research activities to identify appropriate populations and conduct studies addressing the specific human health issues. Finally, the collection, evaluation, and interpretation of data from media around hazardous waste sites have been identified as priority data needs for all 38 priority hazardous substances by ATSDR. However, the Agency realizes that a lot allocated to support the continuation of ATSDR believes that for many of the 38 of information has already besot the research projects conducted at the priority hazardous substances, an collected through individual state nine Institutions originally funded extensive amount of animal data, and programs and the EPA's CERCLA during FY 1992. In addition, ATSDR some human data, have already been activities; therefore, ATSDR will awarded one new grant to the Michigan collected: therefore. ATSDR considers it evaluate the extant information from Department of Public Health to design, appropriate, where feasible, to conduct these programs in order to help fill data establish, and operate a professionally epidemiologic studies an such needs on substance-specific exposures. creditable interlaboratory quality assurance/quality control program for the ATSDR Great Lakes human health effects research program. F. Other A TSDR /tugnunr substances. In response to public comments, the Agency's SSARP will address substance-specific rather than site-specific epidemiologicstudies. The substance-specific studies are rWigw^A to .WwiTirfTM Mihemta. The results of the research conducted via the SSARP will be used for public health ammiTimumts and to reassess ATSDR's substance-specific priority data needs. The Agency expects to re hi itsrale at a public hselth agency specific cause and effect, hi this case, addressing environmental health, ATSDR is not necessarily directed ATSDR may, where appropriate, collect toward populations exposed via the evaluate the priority data noodi far priority hazardous substances every three year*. human data to validate substance- environment at hazardous substance Dated: March 3,1094. spedfic exposure and taxidty findings; release sites, as in a site-specific study. Walter L information on levels of contaminants Instead, any appropriate population of DeputyAdministrator, AgencyforTattle in humans hat been Identified as e suitable exposure via the environment. Substance*endDisease Bepstry. BFG 00207 Federal Register / Vol. 59. No. 47 / Thursday. March 10. 1994 / Notices 11437 table i.--Substance-Specific Priority Data Needs Currently Being Addressed Under ATSDR*s Applied RESEARCH PROGRAMS Substance 10 Priority Data Need Addressed Lead 1A IB 1C Arsenic 2A 2B 2C 20 Mercury ----------------- 3A 38 3C 30 Vinyl CWoride------ \ 3E 4A 4B 4C 4D 4E 4F Mechanistic studes on the neurotoxfc effects of lead Analytical methods tor tissue levels Exposure levels in humans fiving near hazardous waste sites and other populations, such as exposed workers. Comparative toxicofcinetic studas to determine B an appropriate animal species een be identified HalWhes ft surface water, groundwater................ ................ ...................... ............ BioavailabiSty from soil -m--..................--..................... .................................. --.......-- Exposure levels In humans living near hazardous waste sites, and other populations, such as exposed worker*. Mttfgenecation reproductive toxicity study via oral exposure --________ ________________ fftta raiponae data in animate lor dvonfrckaation oral exposure --............. --.......... --. Immunotoxicotoqy battery of tests via oral exposure ...........................-.............. ----------- Exposure levels ft humans frring near hazardous waste sites and other populations, such as exposed workers. Potential candkfata tor subregistry of exposed persona ................. PaaeraMnaed--ftartmatatBearsia rtwtomtohatefteo sapper-- ......... .... M*qi ktefrattoneldnyf dtorirts ftihwrtftdriw , ,, ---------------------------------------- ?spadas dsvatapnanbdtealdtyteJdy vtettetelfftai,, --.... ---- eupmm mm Iff ntmm fctog wr f1 ware dtee and-otere popitetenns, such * y Benzene Cadmium PCBs .... Chloroform__ --. PAHs ... Trichloroethylene .. 4G SA SB SC so 5E 6A 6B 7A 7B 7C 70 ac 80 9A 90 9C. '9D 96 9F 9G 10ft toe toe too PotanUalcancSctaftBtoraubregisay of exposed pereoae_______________ ,______ Onaa raipnnie date in animals tar acute and titermedtela ctmtion oral vpoture. The sttechronie study ahodd indude an axtanctod reproduce* organ hialopatholagy. 2-spedas deveiopmeritMtoidty study via oral axpoaw , ......... ............. Neuwtoarlcctogy battery attests via oral exposure ................ ..................... ......... Epidemiological studte* on the health effects of benzene (Specter emphasis endpoints ft- dudarimmunotoxidlyL Exposure levels ft human* tying near hazardous waste affee and other popoteffons. such as exposed workers. AnaiyBcaf mathoda far biotogicaf Issues and ffuids end erwkonmental meda................ . Exposure levels fit human* iMng near hazardous waste sites and olher populalons, such as exposed workers. Does waponae date in mtinate far acute- and jntemwdBte duration oralexposurea ....... Biodegradation of PCBB in water brcevwtobitoy of PCBs in air, water and aoB Doee-response date in arftnato tor acut^- and fritarmedate'dUrafion Inhalation eipoww. The stfcchrotec stody should ftctude extended rapraductfre organ hrrtopamotog* Epttemtotogfcaf studtee on tfiehadto effected PCBs (Spadal emphasis endpoints include: oi--mpmfrwunnowtox*n--ioc. -ict_yi*i.ygf.asvafntostinal toxicity, Brer, kidney, thyroid toxicity, reproducfrre/devei- 1 Exposure lavela in humans ffvtog near hazardous waste sites and other populations, such as exposed workers. Does response date in anknals ter ftteimedtoteduraffon oral ergweure __________ ___ _ Epfctormoitogfcat afudtea on VreJwaHft effects of clSoroform (Specter emphasis endpoints ln duds: cancer, neurotoxicity, reproductive and dcvetopmeiitaf toxicity, hepetotoxidty, and isnv loucRjfjL Cxpoeure levels to humane Bring near hazardous waste sites and ethsr popdations, such se exposed workers. rom craon vor MDrogtsiry 9 npoMirfww ................................................. .. Dose response date In anfrnato tor Mermedtete durattoo oral exposures. The adachrbnte study should Include extended reproductive organ histopethoiogy and immunopatooiogy. Z-epedea devetopnmitte toxfcffyatudy da tohatetton or oral exposure ...... ,, Mechartsdeatudtes ottPAHs. on how mixtures of PAKs can influence the ultimate active- bon of PAHa, and on how PAHs affed rapldy proMersdng tissues. Brea response date ft araTtttefcr acute-and fttermedatenJuraitan inhalation exposures. Tha sUbchronic study should Indude extended reproductive organ htetopathotogy and tewnmepathotogy. Cpfitonkutogtotestodtos on the iMaffhaffhcte of PAHagpedrtemphaeteeiiiJpuBia include: cancer, dermal, hemdyinjlrate. and hepafic). Exposure tevete in humane living near hazardous waste anas and other populations, such as exposed workers. Potential canddate tor subcagtay of exposed persons ............... ............................. --. DossHaapcriaa data in animate tor acuto-durstfan ore#exposure.................... ............ Msurotoxlcotogybattery of taste via the oraf route -....................... ..................................... InsiMiutuxIcotogy battery ofteste via ffteoraf route ...................... -.................. ................ cptoansoatpCte atudtes on via neann enacte or tncreoroecnyiena {opecai tnpaw enaposvB tnctuos: cancer, naptoowwoiy. war toouesy, oevenpraeraai ouciy, ano neurotoxicity). y y * y y BFG . 00208 11438 Federal Register / Vol. 59, No. 47 / Thursday, March 10, 1994 / Notices Table i.--Substance-Specific Priori Data Needs Currently Being addressed under atsdr's applied Research Programs--Continued Substance DOT___________ Chromium Tetrachtocoethytene AWrinlDteldrin Cyanide ID 10E 11A 11B 11C 110 HE 11F 12A 12B 12C 120 12E 13A 13B 13C 13D 13E 13F 14A 14B 14C 14D ISA 15B ISC 150 Carbon Tetrachloride 15E 16A 16B 16C ISO Beryllium ..... 16E -- 17A 17B 17C 170 17E 17F Toluene ISA Nickel 188 ISC ISO 166 19A 19B 19C 190 196 19F Priority Data Need Addressed Exposure levels in humans fiving near hazardous waste sites and other populations, such as exposed worker*. Dose-response data in animals ter chronic-duration oral exposure-------- -------------------------- Comparative toxiookinetic study (across routes/species) --------------- ---------------- BioavaiiabOty and bioaccumulation from sol------------------------------- ------------ ~~~-----------Epidemiological studtes on the health effeete of DOT, ODD and DDE (Special emphasis endpoints include: immunotoxicity, reproductive and developmental toxicity). Exposure levels In humans irvtng near hazardous waste sites and other populations, such as exposed workers. Potential candklate for subregistry of exposed persons---------------------------------------------Dose-response data in animols tor acute duration exposure to chromium (VI) and (III) via oral exposure and for tntermedtete-dursiioo exposure to chromium (VI) via oral exposure. Muttigeneratton reproductive toxicity study via oral exposure to chromium (III) and (VI)------ Immunotoxicotogy battery oI testa foiowring oral exposure to chromium (III) and (Vi) -- 2-species developmental toxidty study via oral exposure to chromium (III) and (VI) ---- Exposure levels Jn humans Swing near hazardous waste sites and other populations, such as exposed workers. Dose-response data in animats tar acute-duration oral exposure, inducing neuropathology and demeanor, and immunopathology. Muttigeneratton reproductive toxicity study via oral exposu*----- -------- ------- -------------------- Dose-response data in animals tar chronteduration oral exposure, inducing neuropathology and demeanor, and immunopathology. 2-spedes developmental toxidty study via oral exposure---- ----------------- -------- ------- Exposure levels in humans living near hazardous wests shea and other populations, such as exposed workers. Potential candkiate tor subregisby ot exposed peraoos `------- --......--.............................. Dose-response data in animals for intermedtote-duretion oral exposure Btosvailabity from sofl .................... ................................ ........................-- Exposure levels In humans living near hazardous waste sites end other populations, such as exposed workers. . Potential candfoats tor subregistry oI exposed persons____ z.-----------------------------------.-- Dose response data in animals tor acute- and intermodiate duration exposures via inhala tion. The subchronic study should include extended reproductive organ histopathology and evaluation ol neurobehevioral and neuropathological endpoints. 2-species developmental toxicity study via oral exposure -........................................ ............ Evaluation of the environmental tela of cyanide in soil ......--.___ ___ _______________ _ Exposure levels in humans tiving near hazardous waste sites and other populations, such as sxposed workers. Potential eandktata tor subregistry of exposed persons----------------------- -------------------------- Dose-response data in animats tor chronic oral exposure. The study should include ex tended reproductive organ and nervous tissue (and demeanor) histopathology. Immunotoxicotogy battery of teats via oral exposure --,--___ ____ ______ -- -- Half-Me in soB ---............ .................. .......... ..............-------------- -------- ------------------- Exposure levels in humans twing near hazardous waste sites and other populations, such as exposed workers. Potential candkiate tor subregistry of exposed persons__________ _____ _--........................ Dose response deta in animats tor acute- end intermec&ate-duration inhalation exposures. The subchronic study should include extended reproductive organ histopathology. 2-spedes developmental toxidty study via inhalation exposure__ __________ _ Environmental fata in air factors aftocting btoavailabtiRy In air______ ___________ ________ Analytical methods to determine environmental spedation ..------ ------ ------------------------- _ Immunotoxicotogy battery of teats toBowring oral exposure.......... -......,,............... . . .............. Exposure levels in humans Iving near hazardous waste sNet and other populations, such, at exposed workersi Dose response date In animals tor acute- and tatermedteto-duration oral exposures. The subchronic study should indude an extended Nstopatholoflicai evaluation of the Immune system. Comparative toxicokinetie studtes (Characterization of absorption, ,distribution, and excre tion via oral exposure). Neurotoxicology battery of teste via oral exposure '................. '.......-.......... ........... Mechanism of toluene induced neurotoxicity -- -,.....,.......-...................... ....................... Exposure levels In humans Bvtng near hazardous waste sftes and other populationa, such _ as exposed workers. Epidemiological studtes on the health effects of nickel (Special emphasis endpoints include: reproductive toxidty). 2-spectes developmental toxidty study via the oral route........................ ................................ Dose-response date in animals for acute- and Marmedteteduration oral exposures Neurotoxicoiogy battery of tests via oral exposure ---------- ----------...................... --........ BktewBabiWy of nickel from eoB .... ---____ ____ :-------------------- Exposure teveta in humans living near hazardous waste sties and other populations, such as exposed workers. * * * * BFG 00209 Federal Register / VoL 59. No. 47 / Thursday. March 10. 1994 / Notices 11439 Table i.--Substance-Specific Priority Data Needs Currently Being Addressed Under ATSDR's applied Research programs--Continued Sttostanoe ID Priority Data Need Addressed Methylene Chloride -- 2QA Zinc----------------- 206 20C 20D 2lA DB-fP - 21B 2TC 21D 22A 22B 22C 220 22E Dose-response data in mala for rate- and intsrmediatetevation oral exposure. The aubchronic study should Include extended reproductive organ histopathology, neuropathology and demeanor, and.irnrnunapathoiogy. 2-specres developments toxicity study via the oral route.................... ----------------------------- Exposure levels in humans Swing near hazardous waste sites and other populations, such as exposed workers. Potential cantSrtnte lor sitoregistry of exposed persona . ---------- ---- Dose-response data-in animals tor ease- and interroedaie-duration oral exposures. The subchronic study should include an extended histoptehotogieal evaluation of the Immunoiogic and ueurotogicai systems. MUtigenaration reproductive toxicity study via oral exposure..................................... .....------ Carcinogenicity testing (2-year bioessay} via oral exposure--------------- ------------- -------- --- Erasure levels in humans Swing near hazardous wests sites and other populations, such as exposed workers. Efridsmiatogia* teteee entire treMh edecte of DBiP (Specif emphasis endpoints sh. elute eanoerR Oeaeee^oiae due In --tefe tar acute- and tatomrergete-tefton end e^oeures. The subehronic ssidy should Muds an extended hietopafhofogleal ewsiuation of the jmmanoto0c and aeurototfc systems. Mitegrereretfcw reproductive toxicity study vfi ocsf axpoeurm ....... .............................. Cornrentitee tartroHnetic tiatas (Studtea dssignad to examine how primates metaboiae slittstitiutePCHP--oorrsreredterottentefecif astpoaurel. f ExpoaUra tevsls In humans toing near hazardous wests she* and other populations, sucn Selenium ...................... 22F 23A 238 23C 230 23E Chkxoethane................ 24A 24B 24C ^_a__ ---------------------- m---------- l Does response date In animate tor,acute-duration oral expoetse -- Immunotoxicoiogy battery of testa via oral exposure ~ Epidemiological studtee on the health effects of setenium (Special emphasis endpoints in- dude: cancer, reproductive end developmental toxicity, hepatotoxicity end adverse skin sheeted Exposure levels in humans Rving near hazardous waste titea and other populations, such m reposed workers. Potential canttidate lor subregistry of exposed persona ---------- --- - Dose-response data In animala tor acute- and intermediate-duration oral exposures. The tttochronic. study should include an evaluation of immune and nervous system (and be- havtor. demeanor) tissues, end extended reproductive organ histopethoioqy. Dose response date In antereIs ta chrome whfatioa exposures. The study should include an svtirehrre of nrevoue system (and bshewot) ti--s Potentialcanddate tee ateegletrycf exposedpersons ------ ------ ^ * * 'These substances are included In the poet ofrcandtaato substances far siixqqfetry development These wtostanoes wSl be considered for se lection as primary contaminants by the Division of Heath Studtes. ATSOft, during eacfr selection process. Table 2.--PRORmr Data needs Being addressed by EPA Rule Making 10 Priority Date Need Mercury .... ......... 3B utynM*....... 3C . Doedeevooee date to enimel* tarcftrantodintion oral exposure Immunotoxicoiogy battery of tests via oral exposure ..........-...... ------...------- --- Benzene -- dSt-v -- _____ SA [imsm fteustapmwtitetQaidty teidy vternNItefli Dneeresnnniis date to enimnls fee tnrenirertife ihrffcxi Orel exposure. The tirfamnic study should include an extended reproductive organ hhtopethology. Trichtoroettiytorre 5C Neurototecofogy battery of tests vis oral exposure ____________ 1QA , Deis response data inanimnls tot areteduration oraf aapoare* ~~ Chromium .. IOC 12A Paso respon--date to anfrels tec enite rttteon eyow--to chtornium(VA and (Up vfa orf exposure. 126 12C Tetrachloroethytene --__ 13A Hitegenewtinn reproductive katetty ttody vtorefe^oauretoshiorTfum (lll>ind (VI}, Immunotoxicoiogy battery of tests following oral exposure to chromium (HI) end Qfl) -- Do-- response date is animals ta acuteduration oral exposure, Induing nnjnpntfiQtojy npdds^fanof. andlmnsfopalho^fifly. ', 13B Multigeneration reproductive toxicity study vis oral exppsute , r------ ---....................... * . * 130 ... ..................pmnrOni xA* ** . " * '* TSCA/RFRA TSCA. TSCA. toga * TBCA'T TSCA. TSCA. TSCA. TSCA. TSCA. TSCA. TSCA. TSCA (inhalation study). TSCA Ortfttion study). TSCA tody). ** pjt.-r, q.p r BFG 00210 11440 Federal Register / VoL 59, No. 47 / Thursday, March 10, 1994 / Notices Table 2.--Priority Data needs Being Addressed by EPA Rule Making--Continued Substance to Cyanide ......___ ________-- ISA 15B 15C Beryttium ...................--...... 17A 17B 17C 17E Toluene ____ _______ ISA 1.88 Methylene Chloride------- - 20A 20B Chloroethane___ --.--..... 24A Priority Data Need TSCA/FIFRA Dose-response data in animals for acute- and intermedais-duration exposures via inhaiatioa The subacute study should Include extended reproductive organ histopathology and evaluation of neurobehevioral and neuropathological onrfooints. 2-$pecies developmental toxicity study via oral exposure --.-------------------------- Evaluation of the environmental fate of cyanide in soH---------------------------------- --- Dose-response data in animals lor acute- and kitermedtote-dumtion inhalation expo- sures. The subchronie study should include extended raprodidive organ histopathology. Environmental late in air; factors affecting btoevailabiWy in air........................---------- Dose response data in animals tor intermecSatedurafan oral exposures. The study should include an extended hfetopathological evaluation of the immune system. Comparative tooucoMnedc etudtos (Characterization of absorption, dtetributkxx, and ex- cretton via ora) exposure!. Dose rawpnmiH data in animats tor totermedate-duration oral exposure. The study should include extended immunopathotogy and neuropathology. 2-species developmental toxicity study via the oral route . -- ........................ ........ Ooee-response data in animals tor acute- and inteemedtete-duration oral exposures. The subchronic study should indude an evaluation of immune and nervous system (and behavior, demeanor) fhsuee. and extended reproductive organ histopathology. . %' ! TSCA TSCA (inhalation study). TSCA. TSCA. TSCA. TSCA. TSCA (inhalation study). TSCA. TSCA. TSCA. TSCA. TSCA. (EPA win only address the immuns system requirement of thte Priority Data Need) Table 3.--priority Data Needs Potentially being aooresseo by voluntary Research Substance ID v' PCBs___________________ 78 7E Methylene chloride ..... .. 20A 206 Priority data need Firm Epidemiological studea on toe health effects of PCBs (Special em phasis endpoints include: krmjnotoxicty. gastrointestinal, tooridty. Kver. kidney, thyfoid, toxicity. raproductive/devetopmentaJ, toxidty). Doee-response data in animate tor acute- and intermedtete-duntion oral exposure. The subchronie study should include extended reproductive organ histopathoiogy. neuropathology and demeanor, and Immunopathotogy. 2-spactea developmental toxicity study via the oral route--------------- General Electric Company. General Electric Company. Halogenated Solvents Industry AlUance. Halogenated Solvents Industry Alliance. Substance Lead Mercury Benzene. PAH* _ Trichloroethylene Table 4.--priority Data Needs Being Addressed by MHPF institutions 10 1A 1C 3A SB Priority data need institution Mechanistic studies on the neurotoxic effects of-toad -- Exposure levels in humane Nvfng near hazardous waste sites and other popteations, such as exposed workers. MuMpeneratton reproductive toxicity study via oral ex posure. 2-species developmental toxicity study via oral expo- Florida A & M University. Texas Southern Universtty. The MngfDrew Medcal Canter of the Charles R. Drew University of Medteine and Science. Morehouse School of Modteina. Tuskegee Universtty. Xavier University. 9A 90 108 Boat response data in'animate tor intermedtete dura tion oral exposures. The subchronie study should kv ckxto extended reproductive organ histopathology and immunopathotogy. Dost response data in animate for acute- and inters medate-duration inhalation exposures. The sttochronfc stody should include extended reproduc tive organ htetopothotogy and Immunopathotogy- Nourotoodcotogy battery of testa via oral exposure Meharry Medcal College. Maharty Medcal College. Texas Southern University. to BFG 00211 Federal Register / Vol. 59, No. 47 / Thursday, March 10, 1994 / Notices 11441. Table 4.--Priority Data Needs Being Addressed by MHPF Institutions---Continued Substance Toluene................. Zinc \ ID 16C 21A Priority data need institution Neurotoxiodogy battery ol tests vie oral exposure ........ Doee-reeponse data In animdB tor acute- and inter- medtotedurstion oral exposures. The subchronie study should Include an extended histopathoiogicaJ evaluation of toe immunologic and neurological sys tems. Texas Southern University. Xavier University. Tuskegee University. Table 5.--Priority Data Needs Being Addressed by the ATSDR Great Lakes Human Health Effects research Program Substance Lead ,, -- ID 1C Mercury-------- _--------- 3A 3D PCBe 3E . ______ 7A 7E 7F PAHi. DDT 9E 9F 11D HE 11F [FR Doc M-65S9 Filed amnacoomstise Priority data need Institution Exposure levels in humans living State University d New York at Buffalo. near hazardous waste sitae and Stats University d New York at Oswego. other populations, such as ex Michigan State University. posed workers. University d Wisconsin--Superior. New York'date Health Department University d Utinois at Chicago. University d ISnois at Urbane-Champaign. Wisconsin Department d Health and Sociat Services. Multigeneration reproductive toxicity State University d New York at Oswego. study via orai exposure. University d Mtoois at Chicago. Exposure, teveis in humans tivtng State University d New York at Buffalo. naar hazardous waste sites end State University d New York at Oswego. other populations, such as ex- Michigan Stats University. posed workers. University d Wisconsin--Siyericr. New York Stats Health Department University d Htinole at Chicago. University d Minds at Urbane-Champaign. Wisconsin Department d Heatto end Sodd Services. Potential candkfcrte lor subregistiy of Wisconsin Departmera d Health and Soda) Service*. exposed persons. Dose response data in animals for University of Wisconsin- Superior. acute and totarmedateduration oral exposures. Epidemiological etudes on toe health Stale University d New York at Buffalo. effects ol PCGe (apodal emphasis Stats University d New York at Oewego. endpoints include: immunotodcity. University d Wisconsin--Superior. gastrointestinal taridty. Nver. kid University d iMnois at Chicago. ney. thyroid toxicity, reproductive/ University d Mtooto at UibarteChampaign. developmental taxidty). Exposure levels in. humans living Stats University of New York at Buffalo. near hazardous wests sties and State University d New York at Oswego. other populations, such as ex Mfchigan State University. posed workers. f Univemtiy d Wisconsin--Superior. V New York date Health DtpartmenL Urtversity of Ittnois at Chicago. University d hftnds at Urbane-Champaign. Wisconsin Department d Health and Soda! Services. Epidemiological etudes on the health Wisconsin Department d Health and Social Services. effects ol PAHs (apodal emphasis enenmdpo.ot-yi-nm-t-s-p4n-in-acAo*lp-u-,d--ae--n:-ac* a*n-ne--cp--earo,cd).ermal, Exposure levels to humans Bving Wisconsin Department of Health end Social Service*. near hazardous waste sties and othsr populations, such as ex posed workers. Epidemiological etudes on the health date University d New York at Buffalo. effecte d DOT.DOO and DDE Stats University d New York at Oswego. (spedd emphaals endpoint* te Mtehfgan Side University. duds: immunotoxlctiy, reproductive University d Mtoois at Chicago. and developmental toxicity). Wisconsin Oeptftmenl of Heatih and Sodal Services. Exposure levels to humans Bving Stats University d New York at Buffalo. - near hazardous waste alias and Stats University d New York at Oswego. other populations, such as ex Michigan State University. posed workers. University of RBnois at Chicago. Wisconsin Department d Healthand Sodal Services. Potential candtoate tor subregistry of Wisconsin Department of Heatih and Social Services. exposed persons. ' B4S am) BFG . 00212