Document nN9LZ6nZboDGZzEV7BvNBr3jm

SUMMARY OF COMMENTS AND EPA RESPONSES ON VOLATILE SYNTHETIC ORGANIC CHEMICALS IN DRINKING HATER October 1985 Criteria end Standards Division Office of DrlnXing Hater O.S. Environmental Protection Agency Washington* D-C. 20460 CMA 053063 FCREWLRD this is a conprehensive report providing a sunnary of corronts and EPA's responses on the March 4, 1982 Advanced Notice of Proposed Rulenakiny an volatile synthetic Organic Oiemicals (VOCs) in Drinking Vtetar and the June 12, 1984 Proposed RMCLs for VOCs in Drinking Vfeter. Further discussion of the consents nay be found in the Federal Register Final Rule for VOCS in Drinking Water. Oonirents and EPA's responses on ttetrachloroethylene, from the Advanced Notice of Proposed Rulemaking and the RMCL proposal will be provided in a separate document, after the close of the additional content period. li CMA 053064 $ Il TABLE OF CONTENTS *31 Z. Sunary of Coaments and Responses to the March 4# 1962 Advanced notice of Proposed Rulemaking on Volatile Synthetic Organic Chemicals in Drinking Water ..... .......................... 1-1 A. Significance of Contamination by VOC* ............................... ..... 1-1 B. Approach to Daal with VOCa in Drinking Mater......................................... 1-4 c. What MO. values Should Ba Eatabliahad...................................... X-8 0. Oanotoxic vs. Hongenotoxic Carcinogana ... ........................................ 1-9 B. Baalth Bffacta Criteria Docuaanta ................................................................... 1-11 p. Which Contaminanta should Ba Regulated ........................................................ 1-17 G. Monitoring Requirements ......... .............................................. 1-18 H. Analytical Methods................................................................................ 1-20 1. Analytical Coats of Monitoring ............................................................................ 1-22 J. Total Organic Halogen................................................................................................ 1-23 K. Treatment Technologies ................................................................................................ 1-24 L. Costa of Treatment Technologies....................................................................... 1-25 M. Risk/Benefit Analysis for VOCs ................ 1-26 N. Difficulties of Monitoring Requirements for States.......................... 1-26 O. Home Water Treatment Systems................................................................................. 1-27 P. Strategy for Controlling VOCa ........................................................................... 1-27 Q. Miscellaneous .................................................................. ..... ..................... 1-28 % IX. Summary of Comments and Responses to the June 12, 1984 RMCL Proposal on Technical Issues................................................................................XX-1 A. Trichloroethylene........................................................................................................................ B. 1,1,1-Trichloroethane .............................. ..... .................................... 11-12 C. 1,2-Dichloroethane.......................................................................... 11-22 iii CMA. 053065 I TABLE OF CONTENTS (Continued) D. Vinyl Chloride.............................................................................................................................. I. Benzene.............................................................................................................................. 11-31 F. 1.1-Dichloroethylene.............................................................................................................. G. p-Dichlorobensene ..................................................................,..................................... 11-34 H. Treatment for Control of VOCs............................................................................11-43 I. Coots of Treatment..........................................................................................................11-45 111. Suamisry of Comnsnts and Responses to tho Juno 12. 1984 RMCL Proposal, providing additional dotalla to tho issues discusaod in Appendix A of tho Pinal Rule for RMCLs .... ill-1 A. Strength of Evidence of Carcinogenicity ................................................... 111-1 B. Mouse Liver ..........................................................................................................I1I-3 C. AAD1 Approach....................................................................................................................II1-4 D. RMCLs for Carcinogens at Zero............................................................................II1-8 E. RMCLs for Carcinogens at the Analytical Detection Linlt . . . Ill-15 F. RMCLs for Carcinogens Based on RiskCalculations ................................... XII-15 G. Criteria for Setting RMCLs/MCLs ....................................................................... 111-24 H. Simultaneous Proposal of RMCLs andMCLs ....................................................... 111-26 I. Risk ....................................................................................................................................* III-26 J. RMCLs as Standards..............................................................................................................III-26 K. Total VOCs.......................................................... III-27 L. Other Issues . . ..................................................................................................................111-27 % I * CMA 05306S  I. SUMMARY OF CCMttHTS AMD EPA RESPONSES TO THE MARCH 4, 1962, ADVANCED MOT1C1 OF FROFOSRP RTTT.gxtfTNG OR VOLATILE SYNTHETIC ORGAHIC CHEMICALS XW DRIHXIMG WAT1R A. S1GHIFICAHCE OF CONTAMIKATIOH BY VOCs Issue; What is th significance of contamination by VOCs? Doas tha availabla oeeurranca data and/or haalth affacts data warrant action to liait human exposure to VOCs? 1. Co--snts i The significance of contamination by VOCs was addressed by 66 commenters* Twenty-five coamantsrs fait that naithar tha occurrence data, tha haalth affacts data nor tha conbinad data demonstrate on a national basis, tha significance of VOC contamination in drinking water and, there fore, action to limit human exposure to VOCs is not warranted. Reasons cited by various commenters on tha occurrence of VOCs included such state ments as tha following! * VOC contamination in drinking water is a localised problem, not a widespread national problem; * More information is needed on occurrance and health affacts especially in order to assess the significance of VOC contamination; * State data represented aswrgency spill situations which are not con sidered to be statistically representative of national occurrence; * When present, VOCs usually occur at low part per billion concentrations. At-this level, significant health risk would not be expected. * The results of the Ground Water Supply Survey (GWSS) should be consid ered questionable because the detection limits that were used (i.e-, 0.2 ug/L) are extremely sensitive and can rarely be achieved. * The data concerning the occurrence of VOCs qualitatively indicates their presence in drinking water sources; however, the quantitative reliability and representativeness cannot be determined at the present time because the analytical techniques used to generate such data have not been validated. * Ho real difference in ground water vs. surface water (results) can be shown from the randomized samples. * More than half of the sampling in the drinking water survey was per formed on finished water. Consents on health effects included the following: * The major shortcomings of the available health effects data are that it is not scientifically established at this time and subject to debate among the scientific comminity. Soon commenters felt that 1-1 CMA. 053067 before tta significance of voc contamination can b evaluated, tha national Academy of Sciances (NAS) prisciplaa and tha following iaanas naad to ba reviewed and revised: - Effacts in animals, proparly qualifiad, are applicable to man; Methods do not now exist to establish a threshold for long-tarn affects of toxic agents; - The exposure of experimental animals to toxic agents in high doses is a. necessary and valid method of discovery of possible carcinogenic hazard in man; - Materials should ba assessed in teems of human risk, rather than as "safe" or "unsafe." Some coaamnters also felt that scientific Issues pertaining to NAS vs CAS risk assessment, safety factors (70 kg adult vs. 10 kg child), uncer tainty factors, and fractional dose estimates should be resolved before regulations are set. Since "safe" levels of VOCs cannot be determined from existing health effects data these commenters thus felt that MCLs should not be established. The above commenters eng)hasized the need for more research in the health effects area. Forty-one coventors felt that VOC contamination of water supplies is a significant national problem because of the frequency of occurrence and potential health risk warranting action to limit exposure to VOCs. Their reasoning is based upon the following; * local problems of severe VOC contamination in public water supplies; * State data are more representative than 1FA suggests; * the number of VOCs in drinking water is continually increasing; * VOCs have been demonstrated to cause serious carcinogenic and noncarcinogenie toxic effects including; - carcinogenic effects demonstrated in animal studies and evidence of human carcinogenicity (vinyl chloride); - hepatomas in animals, and in soma cases in humans; - toxicity to the kidneys; - serious effects on the reproductive system; and - depression of the central nervous system. 1-2 CMA 053068 Response{ SPA has considered the above comments in its analysis for determining the significanca of VOC contamination in drinking watars. A discussion of this analysis, which covers most of tha issuas raised in tha above consents, is available in tha Proposal for RMCLs in tha June 12, 1984, Federal Register Notice and in the Response to Cnmant B below. Responses to consents on issues not covered in this Notice are given as follows* Regarding the issue of questionable data near detection limit levels in the GHSS survey, IRA conducted in-house quality control testing to support the validity of this data. IPA, therefore, believes the GWSS forma a reasonable basis for characterising the occurrence of VOCs in ground waters in the O.S. Because of the long holding times, there may have been soma underestimate of the actual occurrence. However, IPA does not believe that this underestimate would be so significant to disqualify this survey as a national estimate. Laboratories generating data in all the surveys were required to undergo a quality assurance program, the data generated is considered reliable within the boundaries of the analysis that was considered. This data is available in the Occurrence Documents for each of the VOCs (Occur rence of Volatile Organic Chemicals in Drinking Hater, name of VOC, SPA, Criteria and Standards Division). Regarding the issue of occurrence in ground water vs. surface water, most VOCs, on the basis of data that are available in the above cited documents, are more likely to occur at levels above 5 ug/L in ground waters than in surface waters. Virtually all persistent occurrences of VOCs above 50 ug/L are expected to occur in ground water. The comment that half of the sampling in the drinking water survey was performed on finished water is incorrect. Host of the occurrence data was based on samples taken from the distribution system. Hith regard to the health effects issues, EPA believes that the NAS principles are accepted in the scientific community and present a scientif ically acceptable basis for establishing health effects numbers. These principles are widely accepted as forming the basis for chemical risk assessment and have been applied by numerous groups over the years. The Office of Science and Technology Policy's recent review of the science and its associated principles for chemical carcinogens (49 FR 21594) listed principles for risk assessment which included the following: - Agents found carcinogenic in animal studies, subject to the con siderations discussed previously, are considered suspect human carcinogens. - it is appropriate to use test doses that generally exceed human exposure levels in order to overcome the inherent insensitivity the traditional design of the long-term animal test. 1-3 CMA 053069 These principles are very similar to those discussed by the NAS. Is addition. IFA's proposed guidelines for carcinogen risk assessment (49 FR 46294) were based upon the same basic principles as outlined above. Regarding other scientific issues such es carcinogen risk assessment, IPA believes that with the publication of IPA's proposed sidelines for carcinogen risk assessment (49 FR 46294), uniform guidelines for risk assessment have been established and have helped to resolve these scientific issues* In reference to other scientific issues such as sefety factors, IPA believes that the science has advanced to the point where relative agreement exists in the scientific comaity cm the calculation of health effects numbers upon which to base regulation* IPA agrees that more research in the health affects area is desirable and will increase our scientific knowledge of the chemicals> however, IPA believes that sufficient data are currently available upon which to base the MCLs. B. APPROACH TO DIAL WITH VOCs IN DRINKING WATIR Issues Which approach should IPA take to deal with VOCa in drinking water? 1. Comments? 117 cements were received that specifically addressed this issue in commenting on either (1) the non-federal regulatory approach, (2) monitoring reflations, or (3) regulations for monitoring and MCLs* Option 1, the non-federal regulatory approach, was favored by 22 coamenters* Several States commuted that recent surveys by IPA and their own sailing did not indicate a major VOC contamination problem within their borders) thus, they felt that national requirements for monitoring and MCLs were not warranted. These States felt that problems could be addressed on a case-by-case basis without federal regulations. One of the States eaphasized that routine, repetitive monitoring requirements mist not be put into regulations because monitoring programs mist be flexible and can best be developed by States and utilities* Option 2, setting monitoring requirements and providing health advi sories for State response as appropriate, was favored by 13 eosnenters* These coamenters generally felt that ground water contamination is a problem in some places that must be addressed butt * contamination was not widespread enough "to require highly formalized and restrictive requirements," * available data are insufficient to determine the scope of the problem, or " only monitoring should be done to determine where problems exist and instead of setting MCLs, guidance should be provided; these commenters generally supported giving States considerable authority for inplementation of the monitoring requirements and for determining appropriate action when contamination was found. 1-4 CMA. 053070 One eowntn stated that thar* should be MCLa aet for the VOCs but not until there la "some agreement among the scientific commmity as to an acceptable and meaningful level of concern." Zn the meantime, this commenter suggested that a monitoring requirement be set at the federal level which would be as flexible as possible such that details of actual monitoring programs could be agreed upon between the States and SPA regional offices. Zn this way/ the monitoring program would address "those communities which are thought to be most vulnerable to contamination." An additional conenter recommended that contaminants be controlled at their source through KPA's existing statutory authority. This commenter stated that MCLs are not appropriate at this time, since "safe" levels of VOCs cannot be determined from existing health-effects data. However/ when the health effects data are evaluated by a recognized independent scientific orgalnzation (l.e., National Academy of Sciences [NAS]), MCLs should be established if a significant health risk exists. This commenter also suggested that national monitoring for specific confound identification should be implemented for all water supplies, preferably using the THM purge and trap procedure (SPA Method 502.1 or equivalent), but requirements for systems serving less than 10,000 people should be at the discretion of the state. The initial monitoring frequency should be similar to the THM rule. Zn addition, at this time, guidance in the form of contamination levels, and action categories for five of the VOCs should be established for all water supplies. (See Table 1 below) TABLE 1 Compound Concentration Levels (ug/L) Categories Vinyl Chloride Trichloroethylene Tetraehloroethylene Carbon Tetrachloride 1,2-Pichloroethane Z >100 >500 >500 >500 >250 XI 10-100 50-500 50-500 50-500 25-250 XXX <10 <50 <50 <50 <25 Category I - high concentrations and consequently greater risks. Immediate action warranted to reduce contaminant level. Category ZZ - intermediate concentration with lower risk. Prompt action warranted to step up surveillance and consider control strategies. Action should reflect whether the concentration is at the higher or lower part of the range* Category III - very low concentration. Little risk associ ated with these concentrations. Only routine monitoring needed. 1-5 CMA 053071 This commenter noted that whan axtanaiva monitoring or installation of treatment systems is necessary, the discharger causing the contamina tion should bear the financial burden of cleanup, not the water utility. However, when the cause of contamination, or the discharger cannot be determined, SPA should use other methods, such as RCRA or Superfund, to provide financial assistance to the water utility* Finally, for the present, health advisories should be used for specific cases of contami nants not previously found in drinking water* One comeantor recoeaended a national monitoring program with State response based upon guidance on health effects and treatment* Without a consensus on safe levels derived from health effects data of the various tOCs, ahlw rnuntir felt that there is no basis for the establishment of hos* This comsenter noted that the monitoring program should be the same for all water supplies, regardless of sixe* The initial monitoring should be done at points in the distribution systems representative of the sources of supply. Thereafter, monitoring should be based upon the initial sample results and the levels of action indicated by the severity of the contami nation in a program commensurate with the characteristics of each water supply system. A comment was received which stated that in the absence of a consensus on the dangers of low levels of VOCs in drinking water, a modified regulatory approach was needed* The approach suggested was as follows: * RMCLs and MCLs should not be developed, except under certain conditions identified below. * The goal of zero cancer risk should be abandoned in favor of a goal of negligible risk. This should be achieved by the establishment of a risk target level (RTX>) of 10~5, in preference to MCLs. * Ho action should be taken unless VOCs occur at this level or above in more than one percent of the public water supplies serving at least one percent of the consuadng public. If it does, the development of MCLs would be warranted. * Since the occurrence data indicate that no action is warranted accord ing to the criteria above, EFA should publish a document containing guidance on health effects, treatment technology, analytical methods, and any other significant considerations. Many cosmenters specifically suggested that the monitoring option would be appropriate if the data on health effects of VOCs is unclear or insufficient, or if the incidence .of contamination is small. These commenters felt that EPA should provide guidance on health effects and treat ment. Humorous commenters pointed out that EPA Health Advisories were very helpful to States and public water systems. Option 3, setting national regulations for monitoring and MCLs, was favored by 82 commenters. numerous commenters stated that MCLs and moni toring requirements should be set for the VOCsi a number of these commenters 1-6 CMA 053072 quAl4.fi.d their iUtunt by saying NCLs should b sst if it is shewn that tha occurxanca of VOCs is widespread and tha haalth affacts data show that VOCs ara a haalth risk. However, most cocisntars fait that sufficiant data wara available showing VOCs to ba a widaspraad problem, that data did show a potantial haalth hazard, and that MCLs wara naadad. ' Tha following ralatad statements wara aadai * Problems with organic chemicals hava baan shown in several Statas and without anforcaabla standards, tha problass will continua to spread; the * While Haalth Advisoriaa (HAS) wara notad to have baan wary uaaful in addressing incidences of VOC contamination, savaral commenters com mented that tha States hava adopted widely varying approaches to dealing with VOCs in drinking water* Sana Statas hava adopted the HAs as anforcaabla standards and consequently public water systems have been forced to sake permanent and costly decisions on tha basis of haalth guidance. * One coaentar felt that national monitoring raquiraaants, HMCL and NCLs should be sat for tha VOCs. This was because contamination was widaspraad and tha haalth affacts data showed a potantial human haalth hazard. * One rn--wantar summarized their argument for NCLs in tha following mannert ~ Contamination of water supplies in tha U.S. with VOCs is indica tive of a national trend. Setting legally anforcaabla national standards will be important in reversing that trend. It will establish a ceiling on how much contamination of drinking water is acceptable and will trigger remedial action in situations where tha ceiling is almost reached or exceeded. - Alternatives involving determination of tha acceptable levels of contaminants by individual statas, based on EPA advisory options, will not ba affective* * It is likely that EPA advisory opinions on haalth affects will ba misinterpreted and misused as demonstrated by many Statas that hava used tha HAS as rigid criteria by which suitability of a water supply is measured. Tha fact that HAs ara developed without consideration for possible carcino genic properties of a compound and with disregard for economic and technological feasibility of achieving them is forgotten. We are batter off with NCLs established in the process involving public participation and intended to ba tha rigid standards by which quality of drinking water is measured. * If left to the Statas, drinking water guidelines will differ from each other. This will laad to confusion and poor public image for State agencies which recommend guidelines less stringent than others. In addition, leaving tha regulatory 1-7 CM* 053073 Activity to States will require acre huun resources in the are* of toxicological evaluation and standard setting. Many States do not have these resources* Thirdly* enforce ment will be very difficult* if not iai>oasible, if neigh boring States have different drinking water standards. Contamination has no boundaries* * In regard to monitoring requirements, cements ranged from suggesting SPA set requirements for very frequent monitoring to a suggestion that SPA should either set minimal requirements or provide guidance to States to set monitoring to address more closely the situation within each State* Sepecific comments are addressed in the discussion of comments on monitoring Response! SPA has considered the above coments in its analysis of approaches for controlling VOCs* Issues regarding health effects* occurrence data and exposure are addressed in the proposal for Recomended Maximum Contaminant Levels for VOCs in the June 12, 1984* Federal Register Notice, issues regarding regulatory approach options and monitoring strategies and EVA's proposed action are addressed in the Federal Register proposal for Maximum Contaminant Levels for VOCs. PA believes that for the eight VOCs and tatrachloroethylene* there is adequate occurrence and potential occurrence in public water systems to justify a national.regulation. SPA has explained elsewhere that these contaminants- are currently found in drinking water systems* often at levels above the RMCLa. It is clear that the Safe Drinking Mater Act requires CPA to set National Primary Drinking Mater Regulations for contaminants that may have an adverse effect on health. Therefore* CPA cannot agree with those commanters who advocate relying on state regulation or combina tions of health advisories and monitoring in lieu of any Federal regulation. However, health advisories and monitoring nay be appropriate for contami nants whose occurrence or potential occurrence is unknown or unclear to the Agency. C. WHAT MCL VALDES SHOULD BE ESTABLISHED Issue! If regulations are determined to be an appropriate approach, what _ MCL values should be established? A total of 14 coamenters addressed this issue* Eleven coomants were received that addressed the risk rate level> four commanters favored a IQ"4 risk rata level, one commenter favored a 10" risk rate level* five coenenters favored a 10"6 risk rate level, and one coanentar favored either a 10"4 or 10" risk rate level depending on economic and technical feasibility. One connenter stated that risk computations are probably the most feasible alternative available for use in establishing acceptable exposure levels of carcinogens, howeveri 1-8 CMA 053074 * the public has a difficult time understanding th concept of risk a awiant unless th regulatory agency makes every sffort to present tbs concept clearly and concisely; * once understood by the public, many people are unwilling to accept any level of risk associated with a drinking water supply; and * the public is sore willing to accept risks as they exercise nore control (i.e., choice) over use or non-use of the substance related to that risk. For example, much of the public will readily accept the risks associated with cigarette snaking or driving without a seat belt since the consuasr is relatively free to decide the respective course of action in these cases* Conversely, fewer customers will accept a risk associated with drinking water, since they are relatively restricted regarding the choice of water consumption in their own residences. Two eomaenters specifically addressed the level of MCLs for VOCs. One comstsnter felt the level for trichloroethylene should be in the range of 50 to 100 ppb. Another ccnnenter grouped the chemicals as follows; * Total chlorinated ethylenes (trichloroethylene, tetrachloroethylene, 1,1-dichloroethylene, cis-1,2-dichloroethylene, trana-1,2-diehloroethylene): 5 to 100 ppb. * Total chlorinated ethanes (1,2-dichloroethane and 1,1,1-trichloroethane)t 5 to 100 ppb* * Total chlorinated benzenes (aonochlorobenzane, dichlorobenzenes and trichlorobenzenes); 5 to 100 ppb. * Vinyl chloride: 1 to 20 ppb. * Benzene: 1 to 20 ppb* * Methylene chloride: 5 to 100 ppb. * Carbon tetrachloride: 5 to 50 ppb. Response; RMCLa have been promulgated, as explained in the preamble accompanying the final rule. KPA has proposed MCLs on the basis of the availability and performance of analytical methods and the availability, performance and costs of technologies to achieve levels as close to the RMCLa as pos sible. A discussion of the rationale used for selecting various MCLs is given id the proposal. GENOTOXIC VS. NONGENOTOXIC CARCINOGENS Issue: Should different risk models or approaches be used for carcinogens that are not genotoxic? What criteria should be used to classify a conpound as "genotoxic" or "n n-gen toxic?* 1-9 CMA 053075 1. Oannents: Seven comrenters addressed the issue of different risk models for genotoxic and non-genotoxic carcinogens. Four comimnters stated that different risk models should be used to account for the differentation of carcinogens recognizing different mechanisms. All of these connenters rejected the GAG risk nodel because it is too conservative in that both the upper and lower bound risks must be taken into account. According to the above connenters, sons of the criteria to classify a caupound as "yenotoxic" include: a reliable, positive demonstration of genotoxicity in appropriate prokaryotic and eukaryotic system in vitro; 0 positive results in studies on binding to DMA; and 4 evidence of biochemical or biologic consequences of DNA damage. One coimenter felt E3>A should continue to use the GAG model for both genotoxic and non-genotoxic carcinogens. Even though knowledge of the carcinogenic nechanism should be a major factor in selecting the most appropriate risk model, this information is generally not availaole for environmental carcinogens. This commter further stated that a distinction between carcinogenic mechanisms is arbitrary because: 4 there is a lack of experimental data establishing a threshold for nonnutagenic carcinogens or showing that the dose-response curve is different in the lower range from that for substances that cause gene mutations, and 4 thresholds ooserved in experiments with an inbred animal population cannot be extrapolated with any degree of certainty to a diverse human population; therefore, no distinction between carcinogenic mechanisms should be made at this time. Response: EPA believes that there is an insufficient scientific basis to dis tinguish classifying chemicals as genotoxic or non-genotoxic carcinogens. The general scientific consensus is that cancer is a multi-stage process involving a variety of events which can include initiation, promotion, and progression. However, the exact nature of the multistage process is not well understood and the available evidence is insufficient to differentiate between carcinogens on the basis of mechanism. This is supported by the Office of science and Technology policy's review of the science and associ ated principles for chemical carcinogens (49 PR 21594). current views on the mechanisms of carcinogenesis were examined and they concluded that "...cancer development is a multistage process that nay involve the genome, both indirectly (frequently termed epigenetic events) and directly, which may include the participation of chemicals or viruses, and which may be nodulated by higher order tunctions, i.e., at the organ and organismic 1-10 CMA 053076 level." In Addition* they stated that "we still laclc an in-dapth under standing of tha mechanisms and stagas of eancar induction and expression." In any event, IPX believes that RMCLs for Known and probable human car cinogens by any mechanism should be sat at zero, as explained in the final rule preamble. HEALTH EFFECTS CRITERIA DOCPHEMTS Issuet Are tha data and conclusions in the Draft Health Effects Criteria Documents scientifically and technically valid? Comments: A total of eight coanenters addressed the Draft Health Effects Criteria Documents. Of the eight eommenters, only four submitted detailed scientific assessments. For the oust part* the eommenters felt the criteria documents were adequate. The following is a summary of the consents and EPA's responses con cerning issues in the Draft Health Effects Criteria Documents. General Comments: 1. Comment: There should be more critical analysis of the data in the Criteria Documents. Response: Since the ANPRM notice in 1982* more critical analysis of the data has been made in the criteria documents, including further analysis of data in response to public cosmwnts, especially on studies used as bases for quantification of toxicological effects. 2. Consent: Better guidance on non-carcinogenic health effects is needed. Response: The quantification of toxicological affects sections in the criteria documents have been revised to give more detailed discussions of the methodology behind the quantification, the studies selected, and the rationale for the selection of studies for quantification. 3. Comment: There is a lack of organization in the discussion of combined effects. Response; Specific sections consolidating this information have been added to the documents. 4. Consent: EPA should publish only one cosprehensive criteria document for agency-wide use. Response: At the time that the regulations development process for the VOCs began, the EPA Health Assessment Documents were not available, nor had they been peer-reviewed externally by the Science Advisory Board (SAB). These documents have been peer-reviewed within the Agency and have now been subjected to external comsMnt through the rulemaking process. 1-11 CMA 053077 5. Comment; Tha document should provide critical analysis of tha indi vidual studias as wall as evaluation of tha data as a whole. Response: Sines tha AHPRM in 1962, tha critaria documents for aach contaminant hava baan ravlsad to includa any avallabia studias with a discussion of additive and synergistic offsets* Howavar, SPA has determined that dua to tha conflicting or weak sciantific evidence on addltivs and synargistic offsets, RMCLs which raflact this avidanca would not ba justifiad. (Saa also rn--ant/Reeponaa --* Ill.K.1) 6. PnssiantT CPA should appoint a panal of racognisad sciantific experts to provide external review of the docuaants. Response; Tha SAB is a panal of racognisad axparts who review critaria docuaants as resourcas penalt. All critaria docuaants are widely raviawad within tha Agency, by consultant scientists, and through public conants. 7. Comment; Toxicology summaries in tha ARPRM are overly brief and si^listlc. Rasponsa; Toxicology summaries in tha RMCX. proposal and discussion of data in tha critaria docuaants ware expanded to includa more details, including discussion of Agency reasons for tha risk assessments used. Consents on tha Carbon Tetrachloride Criteria Document 8. Connant: The Aluaot (1976) study citad is highly incoaplete and should ba interpreted with caution. Response; The revised critaria document indicates the deficiencies in tha Aluaot study* EPA agrees that tha results of this study should ba interpreted with caution. 9. Comment: The discussion on teratogenicity is incomplete and uncritical. Response; The inhalation exposure teratology studias by Schwetz, at al. (1974) and Gilman (1971) ware negative for teratoganesls at high exposure levels. Petotoxicity was observed; however, discussion of these studies was not expanded since they ware not used for quantifi cation of toxicological effects. The statement in tha final paragraph in tha teratogenicity section has baan removed. 10. Comment: The data presented in Table VI-8 on tha results of tha NCI carcinogenesis bloassay in rats are incorrect and should ba recalcu lated or delated. Response; The data are given as presented in tha MCI bioassay report. The influence of mortality on the liver tumor results is discussed in the text of the criteria document. 11. Consent: The daily dose levels given for the Rschenbrenner and Miller (1946) study are incorrect. 1-12 CMA 053078 Response i The correct daily dose levels are now in tha critaria document. 12. CoManti Table VI-11 (on paga VI-29) ia mialoading. Raaponaai All pertinent information on liver laaiona ia elaarly givan in Tabla V-11 in tha final critaria document. Tharafora, EPA doaa not baliava that tha tabla ia aialaading. 13. Coventi Tha Risk Assessment aaction (aaction XX) doaa not provide a critical aaaoaaaant of diffarant atudiaa uaad by CAG and NAS for risk extrapolation* It alao ignoraa aarioua non-carcinoganic offacta. Raaponaai Tha critaria document esphaaizes tha aoat aolid toxicity data with tha aoat aanaitiva andpointa for quantification baaad on noncarcinoganic offacta. Siailaritiaa and dlffarancaa batwaan NAS and CAG riak aaaaaaaanta ara pointed out in tha critaria docunant. However, this coapariaon aay be aoot in that tha Agency riak aaaoaaaant in tha SPA health aaaoaaaant docunant recently approved by tha EPA Science Advisory Board ia that used in tha revised critaria docunant. 14. Commenti Two sections in tha critaria docunant ara Biasing important atudiaa. Responsei Tha discussion of tha Eschenbrenner and Millar (1946) study has bean revised. Tha Sonich, at al. (1981) study is included in the critaria docunant. 15. Comment! Tha 30% inhalation absorption coefficient is inconsistent with tha 40% value used in tha Agency (OHEA) health assessment docunant on carbon tetrachloride. Response! The consent is no longer applicable since only oral dosing studies'ara considered in tha quantification of toxicological affects* Comments on tha Trichloroethylene Critaria Document 16. Comment! Tha section on carcinogenesis should be revised to include tha most recent NCI bioasaay results. Response! nie NTP cancer study with epichlorohydrin-free TCE has been included in tha docunant. 17. Cement; Tha general organization of tha document should be improved. Raaponaai Tha document has been edited. 18. Comment: The document omits recant studies regarding covalent binding of metabolites to DNA, protein, and lipids. Responsei The following references have been added to tha document! DiRenzo, at al., 1982. Microsomal Bioactivation and Covalent Binding of Aliphatic Halides to DNA. Toxicology Letters. 11i243-252> and, Banerjee and Van Duuren, 1978. 1-13 CMA 053079 19. Co--nt: The document omits an important racant study of teratogenicity. Response) The following teratogenicity study has bean added to the document: Dorfmueller, M.A., at al., 1979. evaluation of Teratogen icity and Behavioral Toxicity with Inhalation Exposure of Maternal Rats to Trichloroethylene. Toxicology 14(2):153-166. 20. Cosaent: The section of mategenicity could be expanded to Include a study of sister chromatid exchange. Response: The Gu, at al. (1981). study was not included in the criteria document, but its omission does not affect the qualitative and quantitative conclusions because no clear-cut conclusions were obtained in the study due to exposure to other chemicals which may have affected the results. 21. Comment: An important study (Hards11, at al., 1981) has been omitted from the epidemiology section, and inadequate attention is given to the shortcomings of a "negative study" (Axelson, at al, 1978). Response: The Herdell, at al. (1981) study is not included in the criteria document, but its omission does not affect the qualitative and quantitative conclusions. This is because the epidemiological results are no better than suggestive due to the fact that the subjects were probably exposed to other chemicals. This makes it ispossible to identify the specific causative agent(s). The Axelson, at al. (1978) study is discussed in the Criteria Document with the weaknesses of the study highlighted. The msjor weakness is that there wasn't a sufficient period of time for followup with the subjects in order to see the occurrence of the effects. 22. Comment: How was an absorption factor of 30 percent in the calculation of the adjusted ADI determined? Response t Although the absorption range has been reported in the literature to range between 36 and 75 percent, there are no precise ways for determining this factor. Consequently, EPA used an absorption factor of 30 percent in the calculation as a conservative estimate of absorption over an extended period of exposure. 23. CoMent: The evidence for the carcinogenicity of TCE is questionable and should be reassessed when the (recently completed) RTF bioassay is collated. Response: The Agency, through its Risk Assessment Forum, as discussed in responses to the RMCL Proposal comamnts (see Cosment/Response II.A.4), has concluded that there is sufficient animal evidence to consider TCE an animal carcinogen. The animal evidence includes the RTF bioassay. Cosmante on the Trichloroethylene Health Assessment Document (March 1982) A commenter submitted a review of the Health Assessment Document for Trichloroethylene (March 1982), This document has since been revised and 1-14 CMft. 053080 finalised: however, some of th issues art ati.ll relevant to the final RHCL for trichloroethylene. A summary of the major lssuaa discussed In the riviw follows, with EPA responses pertaining to the current rulemaking (Comments 24 through 29)* 24. Comment: The Implications that low ambient air concentrations of trichloroethylene pose a serious health hazard due to toxic effects on the central nervous system and the cardiovascular system, effects seen at high concentrations, are not supported by the available data. Response: As discussed in the Criteria Document, trichloroethylene at high dose levels produces anesthesia. EPA agrees that the central nervous system effects are seen at high concentrations in animal studies: however, the fact that these effects are seen at high dose levels does not negate their Importance. EPA believes that all effects should be examined and tha RMCL based upon the most sensitive endpoint. For trichloroethylene, the RMCL is based upon tha potential carcinogenicity of the compound. 25. Comment: The claim that teratology studies are inconclusive and do not provide adequate evidence that trichloroethylene may be teratogenic in humans completely Ignores the conclusions reached in the text of the Health Assessment Document that available data indicate no teratologic effect. Resgonse: Baaed on the available data, EPA agrees that trichloro ethylene does not appear to be teratogenic in animals. This conclusion is discussed in the Final Criteria Document where several negative teratology studies are discussed. 26. Comment: The Document fails to recognize the transitory nature of toxic exposure to atmospheric breakdown products. Response: This comment is not applicable to the current rulemaking, as it deals with atmospheric degradation of trichloroethylene while the rulemaking deals with exposure to trichloroethylene in drinking water. 27. Comment: The Document presents a misunderstanding of tha.update, retention and elimination of trichloroethylene and implies it accumu lates in bodily tissue, particularly fat. Response: EPA disagrees with the commenter's conclusion that tri chloroethylene does not accumulate in body tissues. The data indicate that trichloroethylene is distributed in tissues according to their fat content (McConnell, et al., 1975). In addition, trichloroethylene has been reported to cross the placental barrier and has been detected in fetal blood (Beppu, 1968). 28. Comnent: Epidemiology studies, while limited in size, consistently show no increase in liver cancer. Taken as a whole, these studies support the conclusion that trichlorethylene is not a human carcinogen. 1-15 CMA. 053081 Response; KPA does not agree that tha epidemiology atudiaa praaant officiant evidence to concluda that trichloroethylene in not a potential human carcinogen. Thaaa atudiaa rarely involved an unexpoaed group for coaf>ariaon and tha deacription of tha atudiaa uaually did not include tha age and aax distribution of tha workers. Worker exposure to other chemical aubatancaa in thaaa workplace* la another confounding factor that makes it vary difficult to reach firm conclusiona regarding thaaa atudiaa* 29. Comment; Tha preliminary NTP report of tha Carcinogenic Bioaaaay of Trichloroathylana doaa not support the carcinogenicity of pure tri chloroethylene. Response; Tha HTP bioaaaay of trichloroathylana (1982) uaing b6c3f1 ice skewed poaitiva raaulta with liver neoplasms being tha offacta noted* Tha MTP report* in which trichloroathylana was found to be carcinogenic for both aaxaa of nice* is final and haa been accepted by tha HTP Board of Scientific Counselors. This study haa bean considered, along with other relevant data* in tha assessment of the carcinogenicity of tha compound (Sea Comeent/Response - II.A.4 and II.A.8). Consents on tha 1,1,1-Trlchloroethane Health Assessment Document (January 1982) A commentar submitted a review of tha Health Assessment Document for 1 * 1 *1-Trichloroathane (January 1982). This document haa ainca bean revised and finalised; however* some of the issues are still relevant to tha final RMCX, for 1,1 *1-trichloroathane. A summary of the major issues discussed in tha review follows* with SPA responses pertaining to tha currant rule making (Comments 30 through 32). 30. consenti The HAD contains serious misunderstandings of basic and well-recognized physical-chemical factors which influence uptake, storage and excretion of volatile substances. As a result, erroneous conclusions are drawn concerning possible effects of long-term exposure to extremely low environmental levels* Response; These "serious misunderstandings" were not identified, so XPA cannot specifically address them. However* as noted in the final Criteria Document* 1,1 *1-trichloroethane may be absorbed and distrib uted in the body after inhalation or ingestion exposure* with the potential for adverse health effects. Thus, EPA believes that long term exposure to 1*1,1-trichloroethane could result in adverse health effects and is setting the RMd> to prevent their occurrence. 31. Comment; There is unwarranted speculation on a reactive intermediate while available data indicate very limited metabolism of methyl chloroform. Response ; Trichloroethanol and trichloroacetic acid are the primary metabolites of methyl chloroform. Human metabolic profiles after skin application of methyl chloroform indicate both trichloroethanol and trichloroacetic acid in urine. However* most methyl chloroform 1-16 CMA 053082 vu found unchanged in the air* Thus, SPA agrees with the commentar that Halted eetaholisn of nethyl chloroform occurs* 32. Co--nti The HAD selects limited positive autogenic data, while ignoring a large body of negative data. Responsei Mutagenicity testing of methyl chloroform has proven inconclusive. The results show 2 positive studies, 3 negative studies and 1 inconclusive study. 1PA is not considering 1,1,1-trichloroethane to have sufficient evidence of mutagenicity or carcinogenicity in this rulemaking. Position Paper on Water Quality Criteria for Trichloroethylene A cosnenter submitted a review of the Hater Quality Criteria Document for trichloroethylene. The following is a summary of those Issues related to this rulemaking and KFA responses. 33. Comment: The water quality criterion for protection of human health baeed upon cancer is more restrictive than necessary. Since tumors in mice exposed to massive doses of trichloroethylene appear to be induced non-genetlcally, it is appropriate to base the human health criterion for trichloroethylene on non-carcinogenic health concerns. Responses 1PA disagrees that the health-based number for trichloro ethylene should be based on non-carcinogenic effects. As discussed in Co--ent/Response - IZ.A.8, trichloroethylene has been classified as having sufficient evidence of carcinogenicity in animals, and thus the number ahould be based upon carcinogenicity as an endpoint. Comments on the 1,1,1-Trlchloroethane Criteria Document 34. Comment: A potential MCL for 1,1,1-trichloroethane of 1000 ug/L is listed in the Criteria Document, based upon the 1977 NCI bioassay. The Criteria Document does not contain an explanation of how the 1000 ug/L MCL was derived from the toxic effects observed in the bioassay. Responses The RMCL for 1,1,1-trichloroethane is based on an inhalation study and is not-based upon the 1977 NTP bioassay. A discussion of the derivation of the RMCL may be found in the Final Criteria Document for 1,1,1-trichloroethane, as referenced in the federal Register Final Rule for the promulgation of RMCLs. ~ F. WHICH CONTAMINANTS SHOULD BE REGULATED Issues If regulations are determined to be an appropriate approach, for which of the contaminants should regulations be developed7 1. Comments: Eighty-two conmenters were in favor of setting national regulations for VOCs, but did not specifically state which specific VOCs; presumably, these cosnmenters were concerned with the list of six to fourteen VOCs in the ANPRM. 1-17 CMA 053083 Two coventors addressed the specific contaminants for which regula tions should be set. One cosmntsr stated that MCLs should only be estab lished for carbon tetrachloride, trichloroethylene, tetrachloroethylene and vinyl chloride. For non-carcinogens (i.e., 1,1,1-trichloroethane), States should be authorised to require water coopsniss to indicate the concentration of such chenicals in the finished drinking water, the likely risk to the individual at such levels and a list of sites where people can draw drinking water that is free of such chemical coabounds. This commsntsr suggested that this information could be included in the billing statement. One coementer stated that NOa should be established for the voca listed in the AHPRM except for benxene and the chlorinated bensones. Response! PA believes that at this time there is enough informstion available to establish MCLs for 9 of the 14 VOCa considered in the AHVRM. The rationale for the selection of those chemicals proposed to be regulated is presented in the Federal Register Final Rule for the promulgation of RMde. Other VOCs will be considered for regulation at a later date. G. MONITORING REQUIREMENTS* * Issuet What monitoring requirements should be ixq>osed for determining ~ exposure to VOCs? 1. Pmmssnts! Forty-four comenters addressed the issue of monitoring requirements. The commenters' suggestions can be summarized as follows! * Eleven comnenters suggested that federal monitoring requirements be set in such a manner that would allow States to determine the actual sampling requirements for public water systems within their boundaries. These requirements would be set by the State with concurrence by EPA regional offices and would be targeted for public water systems considered to be "vulnerable" to contamination by VOCs. * Ten coamenters recommended that ERA require an initial round of moni toring for all systems to determine the incidence of contamination. One cossMnter felt that a sufficient number of laboratories were available and that the initial round of monitoring should be required to be completed within one year, not three as suggested by BRA. This commenter recommended that the initial round of monitoring should require GC/MS analysis for the 113 "priority pollutants" and the identification of other significant peaks. After the initial round, systems could switch to purge and trap GC if they did not find significant concentrations of non-V0Cs. * Another comnenter recommended that the initial round of monitoring follow the frequency set by the THM regulations and should be at the discretion of the States for systems serving less than 10,000 people. Following the inital sampling, systems would be required to monitor on a frequency based upon the results of the first round of sampling. 1-18 CMA 053084 0 Several consanters recosnended that if no contamination was found, monitoring should ba sat at onca every thraa to five yaars. * Twanty coimnants wars received that statad monitoring frequency should ba sat at laast annually with soma suggasting that quarterly sailing would ba appropriate. One of those coimnentere recoosended the following monitoring requirements* * onca par year for systems not finding VOCs above detection limits in the initial round of sampling; - onca par six months for systems finding VOCs above half the MCL; and - onca par three months for systems finding VOCs at a `level above the MCL, at a concentration above 50 ppb, or at a sum of two or more unregulated organic chemicals above 100 ppb. This commanter suggested that systems should taka a minimum of four sasplas in the distribution system on each sampling day and that sailing requirements should ba for each source. In regard to differentiation of monitoring requirements for surface waters versus ground waters, commenters generally stated that any regula tions should apply to both. However, several of these consenters felt that there may be circumstances that would allow for some distinction such ait * systems located in "remote, mountainous terrain," and * systems on surface waters if MCLs are set around 50 ppb since EPA occurrence data (hots that levels above 1 ppb are seldom found. Four commenters felt that monitoring requirements should be modified based upon the size of the system; one of these especially felt that noncommunity systems should be excluded. One coonenter felt that reduced monitoring requirements are not warranted for VOCs since the discharges from the major VOC sources, industrial discharges and landfills, may fluctuate^widel^. Response; IP* has considered the above comaents in developing the proposed moni toring requirements for VOCs. Proposed monitoring options and the rationale behind them are presented in the Federal Register Proposed Rule for MCLs for VOCs. EPA is soliciting comments to these options. Initial monitoring for the 113 priority pollutants is considered inappropriate at this time. Analysis of all the priority pollutants involves many different analytical methodologies, some of which are more widely used than others. Reliable, analytical capability for VOCs has been established in enough laboratories in the U.S. to support national monitoring. In its proposed monitoring requirements, EPA is recomaending that monitoring include coverage of all VOCs which can be reliably identified 1-19 CMfc 053085 and quantified under tha available analytical methodologies. Monitoring requirements for non-volatile synthetic organic chemicals will be considered in subsequent regulations. H. ABAI.YTICAI. METHODS Issue Are analytical techniques available which can reliably and prac tically be used in Monitoring for TOCs? I. Crwssntat Twenty-three cosMnters addressed the availability of analytical aethods for measurement of VOCs. Most co--enters felt that analytical Methods wers available for naasureaent of VOCs. The ccsmantsrs' suggestions are summarized as follows. Fourteen eoevanters stated that analytical Methods are available to Measure VOCs and eight of these reconaanded the use of BFA Method #502.1 or equivalent. The levels of precision varied among the coamenters regard ing this method. Three coaaenters felt the level of precision would be or - 20%. Another cosswntsr stated the precision level would be + or 10%. Other coomenters felt the inter-laboratory precision at the ppb level would be or - 50% accuracy when considering the precision within laboratories or between laboratories. Five comenters recommended that GC/MS is the most suitably accurate method. One coaaenter felt the precision at the 1 ppb level would be in the range of 1 to 20% and another commenter felt the level of precision would be v or - 10%. nils coementer further stated that the GC/MS method is the most suitable Method in a large sampling program whereas 1PA Method #502.1 and 503.1 are not. Another commenter felt that the GC/MS method could be improved through automation of the analysis. One conentar felt that analytical methods are available to accurately measure these contaminants. However, they have not yet been fully validated in laboratory testing and have not yet had the results published. This commenter stated that "until that effort is complete, any data from those aethods must be considered to have minimal quantitative value. These methods can be improved by completion of the peer review process." Five cossMnters criticized the use of IPA Methods #502.1 and 503*1. Three coamenters stressed the need for adequate peer review and inter laboratory validation of these methods. Two other coamenters questioned the ability of laboratories to test with reliable results at la* concen trations (1 to 5 ppb level). One commenter submitted detailed cosmwnts as to how these analytical methods are not precise, accurate, siqtle or inexpensive. Their evaluation is summarized below: "Method #502.1 was developed at the Organic Analysis Section of BMSL which essentially is a research and development laboratory. The precision and accuracy data for a "single laboratory" (EMSL) suggest that at least 1-20 CMA 053086 ' e "aboratory is what optimistic to expect that any or all other labora tories would be able to employ the method, as currently written, with the same success.a "Section 2.3 of the method indicates that a halogen specific detector is used for measurement. Also, a mass spectrometer may be used in place of the halogen specific detector. It needs to be pointed out that there is a tradeoff which results in different limits of detection. The so-called halogen specific detector is the more sensitive of the two and perhaps allows for low part per billion analyses; however, it lacks the specificity of the mass spectrometer with respect to positive identification. The mass spectrometer, unfortunately, requires more analyte to be present which is reflected in a higher limit of detection. The practical useful range of Method *502.1 is above 10 ug/L and not at low parts per billion levels." "This method has numerous interference problems such as conplex mixtures containing coeluting materials and situations where concentration differences for components are larger than a factor of 10." In addition, this commonter pointed out that, "it is virtually impos sible to establish the presence or quantity of methylene chloride in environmental samples." Most of the cosments for Method #502.1 also apply to Method *503.1. "Bie only differences would be that Method #503.1 uses a photoionization detector instead of a halogen specific detector and the acceptable range for the EMSL certified standard has been raised to or - 20% of the true value." In sum, this coementer questioned "why SPA would propose these methods and solicit comments without providing the necessary supporting data to demonstrate that a particular method is not subject to matrix effects (robustness), has an acceptable level of accuracy (recovery) from the matrix of interest and will generate data with an acceptable and defined level of uncertainty, both within one laboratory (repeatability) and more importantly, between laboratories (reproducibility). Without such data it is iiqsossible to properly evaluate the methods." Response* PA has revised Methods 502.1, 503.1, and 524.1. Additional infor mation on tha precision and accuracy of these methods obtained from an interlaboratory method validation study are given in the Federal Register Proposed Rule for MCLa for VOCs. These methods were tested by 20 labora tories using drinking water spiked with VOCs at various levels. Single operator precision, overall precision, and method accuracy were found to be related to the concentration of the analyte. BPA feels that a require ment that analysis of reference standards agree within + or - 20 percent of the certified values above 10 ug/L is a reasonable criterion that has been successfully applied to its drinking water contract laboratories. (This requirement has been modified in the revised version of Method 502.1 since, originally, the requirement was + or - 10 percent of the certified value.) EPA is presently in the process of gathering information to determine what performance criteria are reasonable at concentrations below 10 ug/L. 1-21 CMA 053087 CPA recognize* that th* Limit* of detection are dependent on th* detection system u**d for th measurement and that thax* ara tradeoffs between tha use of a halogen specific datactor and a aaa* spectrometer. An electrolytic conductivity datactor was u*#d to gather tha information praaantad In Method 502.1. A separata method using'a mass spectrometer as tha detection system has bean developed by CPA. Method 524.1 is a gas chromatography/mass spectrometry (GC/MS) method developed by CMSL in recognition of the fact that the electrolytic conduc tivity and the mass spectrometer detection systems have differences in sensitivity, specificity and that there are specific quality control requirements peculiar to GC/MS methods. Method detection limits (MDLs) are lower for Method 502.1. However. Method 524.1 can measure most voca of interest at or below 1 ug/L. Again, these MDLs are achieved not only by CPA's CMSL laboratory but also by its contract laboratories. Th* section devoted to Interferences provides useful Information on precautionary measures to avoid contamination of sables. This section is devoted to pointing out good laboratory practices in quality control to verify that copounds measured were present in the original saople and are not th* result of saaple contamination. This information is th* result of experience with th* analytical methodology and in no way detracts from the usefulness of th* methodology if the analyst follows the recommendations provided. Concerns expressed by conmenters about Method 503.1 are similar to those already discussed for Method 502.1. This method has been success fully used for th* determination of aromatic co^ounds such as benzene by other laboratories besides CMSL. The revised method provides information on single operator precision, overall precision and method accuracy at various concentration levels. These data were obtained from an inter laboratory method validation study in which 20 contract laboratories participated. Th* statement related to th* decoaposition of aromatic compounds in non-steril* saaple* is followed by the statement that samples can be stabilized by adding a preservative. The revised method recommends th* adjustment of pH to <2 and chilling sables on the day of collection until analysis for preservation. analytical costs or monitoring Issumt What are th* analytical costs associated with monitoring for VOCs? TOX? Coammntet Eleven coamwnters addressed the issue of analytical costs* Eight conmenters estimated th* cost for BPA Methods #502.1 and 503.1. Five conmenters agreed with the cost estimate stated in th* ANPRM to rang* from $100 to $200 per sanqple. Another commenter felt th* cost would be $80 per sample. Two other conmenters believed the estimated costs in th* ANPRM were too low. Their reasoning was that CPA's estimate did not recognize the hidden costs, such as: time required to set up the method, calibrat th* instrument, analyze the EMSL certified standards, determine detection 1-22 CM* 053038 and quantification limits, establish precision and accuracy/ train tech nicians and damonstrate that tha analyst and laboratory are qualified to analyse sables; a conservative estimate of cost per sample would be $500 to $600 Six comments were received concerning the GC/MS analytical method estimated costs* Each commenter'a cost estimate was different, ranging from $75 to $100 per sample to $300 per sasple. Four conentsrs estimated the cost for EPA Method #450.1 (TOE). Two commenters agreed with the cost estimate stated in the AMFJIM of $100 per sa^le. Two other commenters felt the cost would be $120 per sample and $40 per sample, respectively. One commenter stated that ESA's estimated analytical costs are a gross underestimation of actual costs per sa^le for these methods. Responset EPA conducted a survey of analytical costs associated with the analysis of VOCs* The survey included 28 eosmereial laboratories throughout the O.S. The average cost for GC/MS analyses was $197/sa^>le and for GC analyses (Method 502.1 and 503.1) was $187/sa^le. The range of prices quoted was from $50-$300 for GC/MS and $75-500 for GC analyses. These prices are presently being charged by these laboratories and include the `hidden costs-" The prices quoted by the eooawnters appear to be excessr ively high from the information obtained by EPA. TOTAL ORGANIC HALOGEN Issues Should Total Organic Halogen (TOE) be used as a screening mechanism for VOCs? Comments; Of 22 comments received, 12 did not favor using TOE as a screening tool for VOCs. Their reasoning is as followss The lack of specificity would not allow determination of specific cq^ounda without re-analysis. These commenters felt that costs were not that much less expensive than VOC analysis. They felt that more information would be provided to public water systems using VOC analysis instead of TOE. Furthermore, they felt that VOC analysis would be more cost-effective. Several commenters pointed out that VOCs would be masked in TOE analysis in systems using chlorination. Benzene would not be detected by TOE analysis. One commenter submitted detailed comments on the use of TOE. Tha shortcomings cited were: "if TOE (detection limit 5 ppb) is used as a screening method to determine if samples should be analyzed using Method #502.1 (detection limit <10 ppb), the concentration level where one could reliably quantify the data would be approximately 15 ppb. The differences in detection limits for the two methods would limit the usefulness of TOX, as a screen for Method #502.1, to situations where the sum of chlorinated species exceeds 15 `ppb. Furthermore, there are no definitive data to 1-23 CMA. 053089 indicat* that TOX will respond to, or la suitably pracisa or accurata for tba oo^cunds of interest cltad in tha ANPRM. Also, in ordar to usa TOX, th method should apacify just hew tha undissolved solids ara to b* handled." Tan coanaantars fait that TOX should be usad as a screen for VOCs. These commenters pointed out that us* of TOX would avoid us* of tha more ei^aaaiv* analytical aathods that test for a specific list of compounds. TOX would detect all organic halogens, not just those VOCs listed. Once a positive result has been verified, additional testing to dsterain* tha source and nature of the problem could be initiated. It was suggested that XPA should provide either guidance or a standard for TOX as a reference background. These coMsntars fait that TOX would be the aost cost-effective onitoring technique. One coaaenter suggested that TOX should be used in an initial round of aonitorlag of all public water systems and that for those systaas not finding levels above background, TOX Monitoring should be conducted at periodic intervals. On* of tha above coonents received stated that it night be appropriate to us* TOX as a screening analysis. Hcwever, TOX has three major disadvan tages) (1) it does not give readings for Individual compounds; (2) it does not measure non-haloganated VOCs such as benxene (one of the 14 VOCs addressed in the ANPRM); and (3) certain questions remain to be answered about which pollutants are detected with what analytical precision and accuracy. Weapons*: XPA has conducted studies to evaluate the feasibility of using TOX as an Indicator for VOCs and has decided not to us* TOX since it does not measure individual compounds for which the HOI are proposed and it does not measure eonpounds such as benzene. In addition, it would not be costeffective since the individual compounds would have to be analyzed using VOCs analysis in any case to insure the levels are in coop Hanes with the MCL. TREATMENT TECHNOLOGIES Issue: Are treatment technologies generally available to reliably remove VOCs to appropriate levels? Co--*nt i Twelve of the 15 conuwnters felt that treatment technologies were generally available to remove VOCs. Six coamenters favored the use of either SAC or a combination of GAC and aeration on the basis that these are the aost costeffeetive treatment technologies, there is no basis for concern of leaching of any chemical material from SAC, voc concentration can be reduced to 10 ppb or less, and 90% removal with aeration and 99% removal with GAC can be achieved. Some of the above commenters differed on the following two issues: (1) small system feasibility (two commenters said small systems will have no difficulty in operating and installing SAC and/or aeration technologies 1-24 CMA. 053090 and two amid tiara would ba difficulty) and (2) whether or not air pollu tion will ba significant from aaration (ona ccnantar said no air pollution would result, anothar said thera would ba). Five commenters fait that EPA should not raquire a spacific treatment technique* Thay recommended that tha traataant technology ba dacided on a easa-by-casa basis. suggested factors which determine traataant feasibility warat volatility of tha contaainants present, air temperature, price fluc tuations for SAC media, availability of operators, efficacy of aodlficatlon to existing plant facilities, and potential for future contamination. Two of tha above caananters fait that saall systems will have diffi culty In Installing and effectively operating tha available traataant technologies. Ona coaaantar racoaaandad that saall systems should receive preferential traataant such that systems supplying 500 to 1,000 people should ba excluded and systems supplying 5,000 to 10,000 people should use the airiest type of aaration traataant. Three ccaaanters felt that traataant technologies are limited at this tlaa. Ona coaaantar stated that there are aany unanswered questions con cerning tha use of GAC as to tha actual costs, breakthrough of organics in tha bad, and such itaas as frequency of regeneration. Anothar coamantar suggested tha use of either small on-tap watar filtration systems or powdered activated carbon and sand and gravel filtration. However, per formance data indicates that neither traataant Is sufficient to purge VOCs. This comaenter further questioned tha orientation of tha ANFRM's traataant section, in that tha section focuses aore on cost and lass on tha willingness of watar consumers to accept higher watar costs for a greater degree of safety. In addition, this comaenter recomaanded that saall systems ba consolidated In order to handle tha traataant costa. Response; EPA addressed tha above issues In tha Federal Register Proposed Rule for MCLs for VOCs. Although treatment costs per unit volume of water are more expensive for tha smaller systems, EPA believes they are affordable and saall systems have installed these technologies even in the absence of Federal requirements. For very small systems, on-tap filtration devices may offer the best alternative. An approach for how such systems might be used to seat the MCLs is discussed in the propoeal. COSTS OF TREATMENT TECHNOLOGIES Issuei Hhat are the capital and operating costs of available traataant technologies? Are the costa presented in the AMPRM reasonable? CoMentsi One comaenter felt the costs presented In the ANPRM are accurate. However, this commenter expressed concern that there are large uncertain ties due to the fact that there is no history of costs for completed and operating facilities. 1-25 CMA. 053091 Three coamenters fait the coata praaantad in the AMPDM are too low. Two i n--enters stated that the coata were low by a factor of about two. One co--enter felt the coata for GAC In the AMPRM are 2 to 3 tinea higher than actual costa and that capital expenditures are overstated in Tables IV and V. For example. In the population category of 1,000 to 2,499, capital expenditures of $344,000 are shown, this figure la 7 times higher than their experience Indicates. Complete cost estimates were submitted. One comnantar felt that cost estimates should be co^>ound specific. Detailed cost estimates concerning GAC and Packed Tower Air Stripping were submitted by one eommenter. Response> Based on new Information, SPA has updated capital and operating coats in the Federal Register Proposed Rule for MCLs for VOCs. See the proposal for a discussion of the coata used. M. R1SK/BEMBFIT ANALYSIS FOR VOCS Issuei Should a risk.-benefit analysis be done concerning VOCs in drinking water? Comment! One eommenter addressed this issue and did not favor analysis to be done for any regulation that applies to human health* Response; ZPA presents an analysis of regulatory alternatives in the Federal Register Proposed Rule for MCLs for VOCs. This analysis is conducted in response to Zxecutiva Order Mo. 12291 and discusses risks and costs. The SDWA requires setting RMCLs based upon health effects only and MCLs based upon cost and feasibility factors. M. DIFFICULTIES OF MONITORING REQUIREMENTS FOR STATES Issuei Hill monitoring requirements Impose any difficulties to States and water companies? Co--ants i The two comsenters that addressed this issue felt that any monitoring requirements will create monetary difficulties for their respective States, especially in lieu of federal cutbacks. I-2 CMA 053092 Response : In the proposal of MCLs for VOCs, EPA proposed altarnatlvss for conducting Monitoring over an extended psrlod to mitigate cost ii^acts. EFA solicits contents on those proposals* 0. HOME WATER TREATMENT SYSTEMS Issuet Should EPA encourage the use of hove water treatment systems? Consentsi The two concenters responding to this issue felt that EPA should review and publish information concerning small on-tap water filtration systems. One commenter stated that one water purifier can remove 95% to 100% of 106 organic chemicals. Responsex EPA discusses the use of on-tap filtration systems for removing VOCs in the Federal Register Proposed Rule for MCLs for VOCs. Literature on the performance of these devices is available in the public docket. Also, the following report is available through NTIS. Perry, D.L., j.k. Smith, and S.C. Lynch. 1981. Development of Basic Data and Knowledge Regarding Organic Removal Capabilities of Commer cially Available Home Water Treatment Units Utilising Activated Carbon. Phase 3/Final Report. Performed for Criteria and Standards Division, Office of Drinking water. United States Environmental Protection Agency. P. STRATEGY FOR CONTROLLING VOCs Issue: What strategy should be adopted to control VOCs in drinking water? Comments: Eleven comments were received concerning this issue. Eight conanentars emphasised control of contaminants at their source instead of remedial action, primarily concerning ground water. One commenter proposed a regulatory strategy similar to the possible approaches in the ANPRM which is as follows: * establish a National Drinking Water Quality Assessment Program under Section 1445 of the SDWA to assess the quality of drinking water across the country: * prepare health and technical guidance documents for all of the VOCs found in drinking water for the use of State or local authorities to determine whether they have a contamination problem: 1-27 CMA 053093 * develop a contingency plan whereby the Administrator, under the statutory authority of Section 1431 of the SOMA, would take remedial action if a serious threat to public health is being ignored by the responsible State or local authority; and * reassess the need for national regulations based on data generated from the Drinking Hater Quality Assessment Program or other reliable sources. One cowantar was not in favor of a single NCL value since spills and dumps into surface streams or ground water supplies create extremely atypical transient conditions, This cosmsnter rernwended setting three MCLs, that isi long-term effect MCL; short-term MCL (cover spills); and emergency response MCL (concentration above which the drinking water is iwediately not reco--ended for use). Response; SPA believes that enough information is available to support national regulations requiring monitoring for 9 VOCs at this time by all public drinking water systems and compliance with specific MCLs, Proposed moni toring requirements and MCLs are presented in the Federal Register Prop sed Rule for NOs, SPA is continuing the preparation of health advisories for numerous VOCs found in drinking water. In reference to the coomenter who favored setting three MCLs, the Safe Orlnklng Hater Act specifies that a single MCL be set for chemicals of concern la drinking water. However, by setting health advisories for short- and longer-term exposures, SPA has developed numbers to tske care of emergency and longer-term exposures. Q. MISCELLANEOUS 1. Content; SPA did not address a "cost-cutoff," the point where the cost of improving the water ia higher than the health benefits resulting from the improvement. One coomenter proposed three factors which may help establish cost-cutoffs; public pressure, the cost of l^tortsd water, and tha cost of other residential utilities. Supporting documentation was submitted. Response; SPA does not establish MCLs based on "cost-cutoff" points. However, the SDMA requires setting MCLs based upon cost and feasibility factors, including reasonable costs for public water systems, MCLs are established as close to RMCLs as is feasible taking costs into consideration, A benefit-cost analysis for various regulatory approaches, including "costcutoff" points, is available in the Economic Impact Analysis in the Public Docket for Proposed MCLs for VOCs. 1-28 CMAl 053094 riMMIltl SPA is ignoring the fact that VOCs ara only on* of a*v*ral group* of organic chemicals which contaminate many drinking waters. Furthermore, SPA conductad a biaaad analyaia comparing tha total coat of treatment to only part of th* banafits (ignoring non-volatil* organic*, FCBs, and taata and odor)* SPA ahould avoid a banafit-coat approach to controlling VOCa and adopt a tachnology-basad approach. Response: SPA is developing regulations which will consider other group* of organic chaaicals. Tha extant of secondary benefits in treating to remove VOCs will depend on the technology that is used (different for GAC vs. aeration). If the contaminants of concern can be economically and tachn logically measured, as is th* case for VOCs, SPA is required under tha Safa Drinking Water Act to develop MCLs rather than a treatment regulation. Coement: A major failure of SPA'a risk assessment procedure is th* attempt to use a mathematical exercise as a substitute for sound scientific data (supporting documentation was submitted). Responsei DA's risk assessment procedure Involves a qualitative analysis of th* data to determine the strength of evidence of carcinogenicity and subsequently a quantitative analysis consisting of mathematical extrapo lation, if th* quality of evidence has been determined to be sufficient. BPA believes that all appropriate data should be considered in th* risk assessment process. Comment: The Ground Water Supply Survey (GWSS) is biased in the way the samples were selected. Th* 500 samples should have been randomly selected rather than arbitrarily deciding 200 should be from systems serving under 10,000 people and 300 systems serving greater than 10,000 people. Response: In the GWSS, 500 samples were selected at random following a strati fied community population base to assure national representation of all cownity sixes. CoTMtt OISS study results are probably significantly lower than what is actually present in th* water supplies sagpled because the samples were analyzed 1-2 years after being collected. There are probably a number of false negatives. 1-29 CMA. 053095 Raaponasi Thia problem with th GWSS data was dlacuaaad ia the occurranee asses--ant reports. The national aatlaataa of occurranca for thosa subataaeas for which long holding times la tha GWSS (and othar surveys) laada to a reduction In tha --asured contaminant level ara racognlzad aa poten tially underestimating actual occurranca levels. Co--ant: m naads to do io-dapth atudlas an exposure to VOCa from all routes, taking Into account geographic variations and socioeconomic factors in order to characterize tha significance of axposura to VOCa from drinking water across tha general population. Responsei Tha existing body of data and available resources ara Inadequate to develop national occurranca and axposura data to account for variability among different subpopulations. 1-30 CMA 053096 II. SOMMARY OF COXZNTS AND EPA RESPONSES ON JUNE 12, 1984 RMCL PROPOSAL 0H~TECHMICA1 ISSUES A. TRICHLOROETHYLENE 1. Count! Two i n--nl an selected two studios to cnlculato tho RMCL for tri chloroethylenes Jtismerle and Ebon (1973) and Adaas, et al. (1951). Thay also provldad stop by stop derivations to ealculata tbs RMCL as follows! "For the purpose of risk assessment, a ROIL of 100 ppm Is justlflad. Calling 100 ppa a NOEL Is a sdantlflc judgment reflecting tha fact that 300 ppa for 6 Months was a no-observed-adverse-effect laval (Adaas, at al.. 1959) for four spaclas, whlla taking Into account tha broad ranga over which llvar walght lncraasas wars observed by Klaaarla and Kban (1971) and Adaas. at al. (1951). Zn converting this NOEL based on tha wlstar rat to a dosa expressed In agA9/day, two factors mist be taken into account that are absent fron tha calculation In tha draft criteria docuaant. These are tha ninute oluaa (0.335 1/ain) and tha average body weight of tha sale (0.35 kg) Wlstar rat. These factors are necessary because tha rodent Inhales a greater volume of air par unit of body walght than tha huaan. Adding these factors to tho assumptions used in tha criteria document, the NOEL for the Wlstar rat may be expressed in ag/k9/day as followst 100 ppm x 0.0054 nq/1* x 0.2251/mln`X 480 min/day x 0.3** x 5** 0.35 kg x 7*w 31.2 mgAg/dsy * Conversion factor (1 ppm v/v in air " 0.0054 mg/1 at 25*C and 760 torr) ** Absorption rate Conversion of 5-day to 7-day exposure Thus, using the methodology and the thousand-fold safety factor suggested by EPA, the AADX for man may be computed as followst 31.2 x 70 kg 1,000 x 2 L/day 1*09 mg/L Again using the methodology suggested by EPA, this AADX may be converted Into an RMCL by dividing by 5, on the assumption that drinking water contributes 20 percent of the total dally intake. This results in an RMCL for tri of 0.22 mc/L.* Response! The Adams, at al. (1951) study is a summary of toxicological data and therefore cannot be used for the derivation of an RMCL. There la not enough raw data available from the Adams study to determine its validity. EPA selected the Kimmerle and Eban (1973) study for the calculation as it II-1 053097 Is not a raMty of toxicological data) It la a wall dasigned and wall conducted study and la therefore an acceptable study available to make calculations. Tha EPA and tha commentate' approachaa to calculating tha ADIs are similar, tha major difference being tha doaa conversion from inhalation to ingestion exposure* KFA has used tha approach of Olson and Gahrlng (Olson, K.j., and P.0. Gehring. 1976. Basis for Estimating Accaptabla Levels of Organic Contaminants in Drinking Watar Employing Inhalation Data. Unpub lished report prepared for tha National Acsdemy of Science's Safa Drinking Hater t*rr1 rtsel in which it is believed that the dose for the human would be tha same as it is for the experimental animal because the lung volume to body weight ratio is the same across spades, including nan. Thus, one can substitute tha parameters for tha human into tha equation* It is difficult to find consensus on exactly what values are correct for minute volums and body weight for various strains and species and, thus, EPA believes it is more appropriate to use the Olson and Gehring approach. 2. Comment! It is very difficult to coament on this draft CD since it neglects so many key references that should have been included. A co^arison of the bibliography of the draft HAD with this CD quickly illustrates thst many more references are available than have been used. Response: In response to this comment, EPA reviewed all the references in the draft HAD. EPA added only the reports which were considered relevant in deriving the AADI. Particular attention was directed toward the utilisation of primary references for the assessment of health effects. Secondary references were rarely used. The object of the CD is to assess the health effects information on tri chloroethylene in drinking water for the purpose of proposing an RMCL. To achieve this objective, data on pharmacokinetics, assessment of human exposure, acute and chronic health effects in animals, human health effects (including epidemiology) and mechanisms of toxicity were evaluated. The CD does not present a balanced summary of the data on mutagenesis. Page X-2, Line 16 "Trichloroethylene is mitogenic in bacterial test systems, utilizing liver microsomal fractions for activation." As the CD states, it is not possible to rule out the possibility that pure TCE caused a slight increase in mitant yields in Salmonella. However, it is Important to consider criteria for positive mitagenlc response in this assay. Among the moat commonly accepted requirements for a positive result are a doseresponse relationship, replication of results, exceedance of spontaneous rates by 100% and indications of less than an overwhelming degree of cytotoxicity from the chemical exposure. The reported studies are quite deficient in these respects. Thus, it is appropriate to use them to support contentions of positive mutagenic activity. See de Serres and Shelby, Sciences 203, 563 (1979) for a discussion of recommended criteria II-2 CMA. 053098 for positive responses in Salmonella tests. The Criteria Document suggests that ntagenic responses in bacteria and other orgmniene were dependent on metabolic activation syetana and, thus, atabilizera were not reaponaible for activity seen. However, a clear deeonatratlon of the active role of atabilisere in Salmonella reveralona waa deaonatrated by Shlmada and Williams (1983). Thla should be reflected in the CO. Raeponae: The coMnt relatea to the Suaemry section of the criteria docuaant. section provides pertinent information concerning the health effects of trichloroethylene. Appropriateness or validity of the studies, in this case eutagenesis. Is discussed In the body of the document. The BPA has accepted the conclusions, and thus the criteria, of the Investigators who reported the studies for positive mitagenic responses to the trichloro ethylene sables tested in bacterial, as well as In other test systems. Despite the cosmwnter' s arguments on cononly accepted requirements for aitageniclty findings, we believe there is adequate qualitative evidence of mutagenicity. EPA accepts that the Shimada and Williams study shows that there is a demonstration of the active role of the stabilizers. However, there is evidence that pure TCE is mutagenic (See Greim, et al. 1975, 1977 and Bartsch, et al. 1979). The CD falls to present a balanced summary of the probable mode of carcinogenic action. It is noteworthy that prominent members of the SPA Science Advisory Board, after reviewing the data on trichloroethylene, concluded that it was not appropriate to calculate a unit rlak assessment for trichloroethylene. The mode of toxic action waa most likely non-genetic and the increase in tumors in the mouse was due to repeated tissue injury. The last sentence on page 1-2 needs to be revised or eliminated since it is not consistent with current information. "This intermediate is thought to'be responsible for the mutagenic and carcinogenic potential of trichloroethylene.* There Is now a considerable body of data which indi cates trichloroethylene increases tumors in mice by a non-genetic mechanism. A large number of scientists and several organizations recognize that repeated injury and the reeultant repair can enhance the onset of "normally" occurring tumors. Hepatocellular carcinomas in mice livers are a commonly cited example of a non-genetic mechanism. Hence, the epoxide is not "thought to be responsible for the mutagenic and carcinogenic potential of trichloroethylene," as stated in the CD. Furthermore, the CD should not refer to the current NTP study until the NTP has issued a final report. It has been necessary for NTP to withdraw certain draft reports in order to make significant changes We have also become aware of a very recent paper (attached) by Henschler, Slsasser, Roman and Eder (1984) in which they reported no Increase in tumors in male and female Swisa (ICR/HA) mice given 2400 and 1800 mg/kg daily by gavage in corn oil for two years. II-3 CMA 053099 K8ponw; The sentence, "This intemediate is thought to be responsible for nutagenic and carcinogenic potential of trichloroethylene," has been taken out of context. This sentence provides accurate information if read along with, "However, interaction of the epoxide with the nuclear material - a step towards carcinogenesis - has not been studied." The current NTP study is final and has been accepted by the NTP Board of Scientific Counselors. This study (1984) has been added to the criteria Document. The recently published study by Henschler, et al. (1984) does not offset the conclusion of sufficient animal evidence, wfuch has been obtained with different experimental systems, tor the carcinogenicity of trichloroethylene by the EPA. The NIP studies and the Fukuda study are better tests and outweigh the Henschler study. The Henschler study used mice that are known to be less responsive to hepatocellular carcinomas. Although some Rentiers of the SAB questioned the risk assessment, the SAB as a group accepted the study. The risk assessnent is based on the best available evidence; we recognize there are flaws. However, we are not basing regulation on it. Its information is useful to decisionmakers even with limitations. EPA rejects the distinction between epigenetic/genetic mechanists (See Conrant/Response i.D.l). It is possible that both epigenetic and genetic mechanism are active here; the fact that epigenetic nechanisms occur doesn't preclude the possibility that genetic mechanisms are also oecurriny. Since there appears to be sufficient evidence that TOE is a carcinogen, the exact mechanism is unirportant for purposes of regulation under the SDWA. There certainly is not enough evidence to establish a threshold of carcinogenic etfects from tne data suggesting an epigenetic-mechanism. Conran t; "It has been used in...dry cleaning snops..." TGE has extremely limited use in industrial dry cleaning of shop uniform, gloves and towels, but has no use in retail cleaning machines or coin-operated machines in the U.S. Vhile it nay have had sore experimental use in the early 1930's, it was quickly found to be an unsatisfactory solvent for Personal clothing since it removed colors and damaged certain fabrics and plastics. Response; The EPA accepts the conrant. Comment; "After entering the blood stream, it distributes into various tissues ana organs. The extent of distribution depends largely on the tat content of the organ." This paragraph fails to indicate that a significant portion of ingested trichloroethylene will be rapidly expired unchanged from the lungs. The extent ot distribution of the remaining trichloroethylene depends upon several factors including the fat content of the organs. As written, the reader is led to associate distribution with accumulation (or 11-4 CMA 053100 bioaccusulatlon) and long-term etorege, as la the eaaa with certain large, nonvolatile chlorinated and non-chlorinated aubetancea (l.e., DOT, FCSe, etc.) Thle cannot be the caae for a volatile substance such as trichloro ethylene which has a relatively rapid partitioning into and out of body organs. Responsei The sentence In the Criteria Docueent appropriately discusses the mechanism of transfer of trichloroethylene In body. It has nothing to do with the bioaccusulatlon of trichloroethylene In the body. Bloaccumulatlon of a chemical depends upon the physical and chemical properties, dosing regimen, metabolism and other factors. He agree that a significant portion of Ingested TCt will be expired from the lungs. However, the remaining TCI In the system will be dis tributed as described. "This Intermediate (els 2,2,3-trlchlorooxlrane) is thought to be responsible for the mitagenic and carcinogenic potential of trichloro ethylene." There is not agreement as to what role a potential TCI-epoxlde may play In the toxicity of TCX or whether it even represents an obligate intermediate In the metabolism of TO to the observed excretion products. Miller and Guergerlch (1982, 1983), and Henschler, at al. (1979) have provided substantial evidence that several alternative metabolic schemes for TO exist which do not involve obligatory formation of a TCI-epoxide* It is also noteworthy that in vitro TO-epoxide has been detected In incubation of TO with mouse and rat liver mlerosomes, but not when human microsoaes were used (Miller and Guergerlch 1983). Further, it has been suggested, with a considerable amount of supportive data, that TO may cause tumors in mice as a result of trichloroacetic add-induced prolifera tion of peroxisomes (subcellular organelles primarily involved in fat metabolism) (Elcombe, at al., 1983a, 1983b). This latter mechanism of tumorigenicity would not involve any interaction of TO with DNA (Reddy 1983). The statement should more accurately reflect the available TO metabolism data and not present theories regarding TO tumoriganicity- Reaponsai There is not substantial evidence of alternative metabolic schemes, as suggested by this conaenter, only some evidence to support the hypothesis offered by the commenter* EPA agrees that there are several possible mechanisms for TO metabolism. Several new metabolism studies were noted by the commanters and are discussed in the final criteria document, e.g.. Miller and Guergerlch (1982, 1983), Ilcoube, at al. (1983a, 1983b). SPA also included the Dekant, 1984 study in the criteria document. These studies do not affect EPA's conclusions. Tumorigenicity appears to be one result of the possible mechanisms. Therefore, the above statement in the criteria document has been changed to read, "This intermediate (cis 2,2,3trichlorooxlrane) may be responsible for the.nutsgenic and carcinogenic potential of trichloroethylene." XI-5 CMA. 053101 Conant* "Trichloroethylene was found (to be) carcinogenic in BgCjF^ strain lest however, It was not carcinogenic in Osborne-Mendel rats*" Four other oncogenicity bioassays of TCB are not mentioned* a* Henschler, at al (1980) did an inhalation study using HHRI mica, Syrian hamsters and Wistar rats* So treatment-related tumors wars noted in any sex or species exposed to TCB. An observed increased incidence of lyuphomas in female mice was of viral origin which is endemic in this strain of mouse. b* Fukuda, at al. (1983) did an inhalation study using female ICR mice and Sprague-Oawley rata. An increased incidence (not dose-related) of lung adenocarcinomas was observed in mice, while no tumorigenic response was seen in rats* This strain of mouse has been observed to normally have a high (up to 30%) incidence of benign lung tumors* These results with the ICR mice thus appear to be analogous to the results obtained with the B6C3F1 mouse, in which TCB exposure increased the incidence of a tumor which may already occur at a high incidence in control animals. 1ARC does not consider either lung or liver tumors in mice to be indicative of a carcinogenic risk to man* c. An increased incidence of tumors was not observed in ICR mice receiv ing dermal applications of 1 mgAg TCB 3 times a week for nearly 2 years, nor was TCB found to be an initiator in a skin initiation/ promotion bioassay by Van Duuren, at al* (1979). d. Henschler, at al. (1984) reported no tumor increase in male mice fed 2400 ng/k9/day in corn oil for two years or in female mice fed 1800 mgAg/day for the same period. The mice were XCR/HA Swiss. Responset Trichloroethylene (TCB) appropriately belongs to group B2, indicating that there is sufficient evidence of it producing cancers in animals*' This is the classification for carcinogenicity concluded by a technical panel of BPA's Risk Aseessmsnt Forum (RAF) using the recently Proposed SPA risk assessment guidelines for carcinogens (FR 49 (227)>46294-46301). The RAF considered all four of these studies* Xt has been shown to be carcinogenic in different strains of mica utilizing the inhalation as well as the oral route of exposure. The National Cancer Institute (1976) and the Rational Toxicology Program (1982) conducted two separate studies with TCB contaminated with eplchlorohydrin and with TCB free of epichlorohydrin. In these studies, B^CjF^ mice were used, and the results were unequivocally positive, showing liver neoplasms In the Inhalation study cited, Henschler, et al. (1980) reported dose-related, malignant lymphomas in female mice Tnmri strain) However, the authors downplayed the significance of this observation, indicating that this strain of mice has a high incidence of spontaneous lymphomas* EPA questions this conclusion by the authors as it appears to be speculative. Fukuda, et al. (1983), found pulmonary adeno carcinomas in female ICR mice on exposure to TCB vapor* Although there is an elevated Incidence of lung tumors in this mouse, BPA still believes that the evidence is suggestive, as it does for studies using the B5C3F] II-6 CMA 053102 mouse. The EPA classification schene does give sons weight to studies using species witn normally elevatea incidences of the effect (e.g., the ^C3Fi mouse and liver tumors). Henschler, et al. (1984) tested Swiss (ICR/HA) mice and reported that when the animals were gavaged with TCE in com oil, no statistical differences were observed in the incidence of cancers. The results of this study can be questioned because dosing and the dose levels were changed throughout the experiment. Therefore, it is difficult to assess the actual doses given to the animals. A slight increase in tumors was found in all groups treated with TCE but did not approach statistical significance. The Van Duuren study (1979) with skin applications of TCE in ICE/HA mice does not negate the positive findings with other strains of mice and other routes of exposure. The indicated bioassays in the conrent have been added to the criteria docunent. EPA believes that these data, taken together and despite their weaknesses, support classification in the sufficient evidence category. There is other evidence to support the classification of TCE in group B2. In addition to the long-term bioassays discussed above, TCE has been reported to be weakly nutagenic and to have a low order of binding with DNA. . 9. Garment; This section should include the very relevant information included in papers by Henscnler, et al. (1979), Miller and Guergerich (1982, 1983) and Dekant, et al. (1964) Further, metabolism data for TCE inhaled by rats and mice, with evidence of metabolic saturation in rats, presented by Stott, et al. (1982) was also omitted. Response; These new references have been discussed in the TCE criteria document. 10. Penment: Cwoting from the Criteria Docunent: "From the NAS model, it is estimated that at the 95% confidence limit, consuming two liters of water having trichloroethylene concentrations of 45 ug/L, 45 ug/L or 4.5 ug/L per day over a lifetime would increase the risk of one excess cancer per 10,000, 100,000 or 1,000,000 people exposed, respectively". In reviewing the data on trichloroethylene, rentiers of the EPA Science Advisory Board clearly indicated their lack of confidence in these calcu lations. The use of an inappropriate animal model (the B5C3F1 reuse liver) and the 95% confidence limit are inappropriate. Response; The epa is utilizing state-of-the-art concepts which are consistent with the NAS model in estimating excess cancer risk due to trichloroethyl ne exposure. These concepts include use of the most sensitive animal model and the 95% upper bound with the nultistage model. The above calculations present concentrations ot TCE in drinking water at which appropriate risk can be expected. II-7 CMA 053103 t In 1984* the SAB accepted tha Agency's health assessment document on trichloroethylene, including the risk assessment baaed on mouse liver tueor data and the 95% upper limit with the aultlstage nodal. 11. Conwatt "Baaed on the nechanism of toxicity-speclflcally nitagenesis and carcinogeneaia-trlchloroethylene haa tha potential of being carcinogenic* TCS has been reported to bind with nouse liver DMA in an in vivo experiment The DMA binding and nutagenlcity data do not provide support for the carcinogenicity of TCI. Indeed* these data indicate that TCB is not at all to several known potent carcinogens* The in vivo DMA binding data suggest a vary nlnor degree of DMA alkylation occurs in nice dosed with a high or low dosage of TCB (Stott* at al, 1982)* ana its very weak nutagenlcity suggest that TCB does not increase tuaors via the direct Interaction with genetic naterial bit* rather* increases tuaors via sons nongenetlc nechanism. This statement should be modified to accurately reflect the data. Responsei The SPA disagrees that the DMA binding and nutagenlcity data do not support carcinogenicity. Tha data on TCB need not be slnllar to other potent carcinogens* Tha Office of Science and Technology Policy reviewed current views on the nechanisn of carcinogenesis and concluded that " .cancer development is a oultistage process that nay involve the genome* both Indirectly (frequently termed epigenetic events) and directly* which nay Include the participation of chemicals or viruses* and which may be nodulated by higher order functions, i.e., at the organ and organ!amic level." Thus* it appears that chenicala may act by genetic and nongenetlc mechanisms. EPA concludes that the sentence need not be modified. Many scientists believe that DMA binding and mutagenic responses provide data supporting the carcinogenic potential of compounds. Various mechanisms for carcino genicity have been proposed, and epigenetic and genetic mechanisms are among them* 12. Consent* Data presented by Stott, et al. (1982) regarding the hepatotoxic effects of repeatedly administered TCB was omitted* Response* See Comnent/Response II.A.14 below. 13. Consent* The findings of three oncogenicity studies (see comments on Section 1-2) were omitted. II-8 CMA 053104 Response; See Oximent/Response II.A. 14 belew. 14. QMtunent: Ihe Stott, et al. (1982) reference should be discussed. The extensive hepatic and renal-macronolecular binding data for inhaled (and orally administered-mouae) TCE in rats and mice which was presented in this paper are omitted. Response; These references are included with discussion of the data in the criteria document. 15. Qament; There is insufficient scientific evidence to conclude that trichloro ethylene is a carcinogen and the RMCL should not be set at zero. Response; EPA believes that there are sufficient toxicologic data to conclude that .trichloroethylene is a probable human carcinogen. A repeat'bioassay by the Nd found an increase in hepatocellular carcinomas in both sexes of mice using purified trichloroethylene in com oil, while the initial bioassay using coimercial grade trichloroethylene was also reported to induce hepatocellular carcinomas in male and female mice by oral gavage (see Federal Register Final Rule on RMCLs - Appendix A for a discussion of mxise liver tumors and EPA's response concerning their relationship to huiten cancer risk and see Goment/Response - II.A.8). 16. Gomnent: A biological based approach to quantitative risk assessment which consists of establishing an ADI on the basis of the experimentally derived no-oOserved-eftect level with the application of a safety factor should be used. The safety factor should range from 100 to 1000, based upon a consideration of the nechanism of carcinogenesis, the number and type of tumors induced, the spontaneous incidence of the tumor and other factors. For those animal cancer studies which did not employ lower dose levels bo define a NQAEL, the most sensitive cancer response extrapolated linearly down to a dose equaling with a one percent increase above the spontaneous incidence for the particular type of tumor associated with exposure to the chemical should be used. This dose would be comparable to a NQAEL and a safety factor would be applied based on the same considerations outlined above. Response: In regard to die biological-based approach, EPA believes that the primary issue centers on the mechanism(s) of action of the compounds. A 11-9 CMA 053105 great dul of research and discussion has boon forthcoming in racant yaars which addrasaaa tha lssua of differing aachanisaa for carcinogenesis. at the present ties, however SPA neither classifies nor quantitatively characterizes the risk of exposure to compounds for which carcinogenic potential has been Identified on ther basis of their hypothesized mechanlsm(s) of action* As previously discussed* (see CoMent/Response II.A.11) SPA accepts the view of the Office of Science and Technology Policy that chemicals any act by genetic and nongenetic mechanisms. Consideration of the possibility of the existence of differences is incor porated indirectly in the weight of evidence classification scheee for carcinogenic potential recently proposed by the Agency (49 FR 46294)* While data free long tens human epidemiologic or experimental aninal stadias contribute most to the determination of the placement of a reputed carcinogen into one of the five groups* results in short tern studies* sens of which nay give information on potential carcinogenic mechanisms, nay result in the coapound being placed in a cate^ry higher or lower than the longer-term study data would ordinarily suggest* As described elsewhere* a three-tiered approach for the derivation of the RHQaS is being used. This approach is based* to a significant degree, upon the information available on the carcinogenic potential of each of the coopounds for which regulatory action Is being considered. The reader is referred to the Federal Register Final Rule for RMtXa for a detailed discussion of this strategy. Coswentt It is very possible that* particularly in humans, at low dosage levels, the metabolic pathway which leads to the proximate carcinogen is not employed} and therefore, at low concentration levels, trichloroethylene and perhaps other volatile organic chemicals would not be carcinogenic, particularly in humans* (See attached draft paper* "Trichloroethylene: An Update," by Renats Kimbrough, Frank Mitchell and Vernon Houk.) A summary of this paper follows: AUTHORS' ABSTRACT In this paper, recent studies that deal with metabolism and carcinogenicity of trichloroethylene (TCI) are examined. In reviewing the publications on metabolism of TCS, we determined that differences exist in its metabolism. If low doses are compared with high doses in animals, there may also be a dif ference in the metabolism of TCE between different species ~ namely, sice, rats, and humans. TCS has not been shown to be a potent carcinogen in rats, and it only seems to be a potent carcinogen in one specific strain of mice -- namely the B^CjF^ mouse* Epidemiology studies have been rather limited. The number of persons examined so far for chronic toxic effects is small, compared with the enormous size of the work force that is exposed to TCE over prolonged periods. On an empirical basis, the occupational experience with TCE does not suggest that this co>m>ound is a potent carcinogen. The risks associ ated with exposure to trace amounts (parts per billion) of 11-10 053106 CMK TCK concentrations In water appear to be minimal or perhaps negligible. Because there are differences in the Metabolise of TCE, it is i^ortant that theoretical risks attributed to TCI in the past be re-examined. It is highly possible that in humans, the Metabolic pathway leading to the formation of the proximate carcinogen is not activated at low doses where TCK is excreted by first order kinetics. Response; KPA does not agree that trichloroethylene should not be considered a potential human carcinogen for the reasons discussed in the Federal Register Final rule. Kith regard to the nature of the carcinogenic action of trichloroethylene, BFA believes that there is insufficient scientific data to justify classifying chemicals as epigenetic or genetic carcinogens, as discussed in Comnent/Rasponse - IX.A.16 above). 18. CoHtsnts Use of data from all three phases of the HONS survey employed in projecting the national occurrence of TCK in public water supplies had the effect of skewing the projections in a way so that a larger percentage of water supplies were projected to contain seme eeasureable amount of TCK. Responsei In combining the results of all surveys to produce the national estimates, the results for supplies measured in more than one survey, or in the case of the NOMS more than one phase, were averaged so that the results would not be significantly skewed by multiple inclusions of the sane supply. 19. Comment; The TCK occurrence document fails to point out that there is a possibility of the TCK concentrations in sanples Increasing during the holding period due to the biodegradation or reductive dehalogenation of PCX to TCK. Response; FA is unaware of any data that suggests that this had occurred. Since the commenter did not provide any specific data on this point, it is reasonable to assume that this was not the ease. 20. Coement; With reference to the tri, pare and methyl chloroform occurrence documents, it is questionable that any contamination was actually detected in food in the United Kingdom studies where the values obtained approached the limits of detection. 11-11 CMA 053107 Response: The United Kingdom data war* noted becaoee no other food studies were available but were not uaed to project level* of exposure. 21. rosmsnt: In the tri, perc and methyl chloroform occurrence documents, sources of exposure terminology should be defined (e.g., rural/remota, urban/ suburban* source doslnated and msxl wm). Response: These terms were used as presented In Brodzinsky and Singh (1982)) the terms were not further defined in that source* 22. rnsmantt Source-dominated exposures for tri, perc and methyl chloroform appear to be 4 to 5 orders of magnitude lower than those generally recognized as safe for occupational exposure*. Response) The evaluation of human exposure to these chemicals was carried out in order to derive a drinking water level which considers total human exposure. It was not Intended to evaluate safe levels for occupational exposure. 23. Comment: In the tri, perc, and methyl chloroform occurrence documents, a minimum quantification level of 0.5 ug/L was used in combining data from various surveys while each survey had a specific MQL ranging from 0.05 to 5 ug/L. It is not clear whether sources designated as positive were based on the MDL of 0.5 ug/1 or on the MQL of each survey. Response: The column designated "Mo. of positive systems" in the table* pre senting the combined results of all surveys included positives both above and below 0.5 ug/1) the total number of positives below 0.5 ug/L are also detailed in a separate column in those tables. B. 1,1,1-TRICHLOROETHAMB (METHYL CHLOROFORM) * 1. Comment: "Repeated exposure to methyl chloroform has been shown to increase the excretion of metabolites in both animals and man, probably by the mechanism of enzyme induction." Available data indicate that methyl chloroform exposure does not result in enzyme induction* It should be 11-12 CMA 053108 further noted that massive, nonphysiologlcal doses were used In the studies cited in the CD. Responset SPA agrees that the Schumann study cited by the conenter suggests that enzyme Induction does not occur. However, the Platt and Cockrill (1969) study cited in the Criteria Document showed enzyme Induction. Thus, there are conflicting data. In any event, there is not sufficient evidence to draw a definite conclusion, the statement in the Criteria Document reads "probably by the mmchani-- of enzyme induction" which is correct and, therefore, the Criteria Document has not been changed. The significance of the second comment on massive doses is unexplained by the commsnter and IPA is therefore unable to respond. 2. Co--anti Page 1-7, Line 8. "The CAG has calculated an upper limit cancer risk estimate based on the 1983 NCI bioassay ...respectively." This entire paragraph should be deleted, as it was from the final HAD after Science Advisory Board review. No acceptable scientific data are available to calculate such an estimate. Resgonsei As stated in the Criteria Docuaent, this information is included to inform the reader as to the CAG calculations and is not being used to determine the RMCL, which is based on non-carcinogenic effects. IPA believes that, despite the fact that this bloassay is under audit and is being questioned, a risk assessment can be useful as long as the fact that the study is under question is borne in mind. 3 Comment: Page 1*7, Line 21. "Although a number of studies have indicated chronic changes in the heart, nervous reflex activity, respiratory function, and hepatic changes resulting from 'long-term* exposure..." Data do not exist to support the statement that methyl chloroform exposure causes chronic changes in the heart or nervous reflex activity. Such changes, caused by high exposures, have been acute in nature and not chronic. Response! IPA agrees and has deleted the word "chronic" from the text. 4. Consent: Reference to the latest NTF study should be limited to a statement similar to that found on pages VIXX-19. This study has not been reported or peer-reviewed and cannot be used at this time for any purpose. Given the scientific quality of the study, NTP found it necessary to withdraw the draft report Based on the results of audits of this study, a report may never be released. 11-13 CMA 053109 Resgonset Informtion concerning the carcinogenicity results on the NTP repeat draft bioassay in animals is not being considered in determining adverse health effects from methyl chloroform, as the final HTP report is not yet available and is under question. It is not being used to determine the RMCL. Page 1-9, Mae 6 and III-31, Mne 19. "Ingestion of ethanol was shown to increase the hepatotoxicity of methyl chloroform." This statement should be aaplified to indicate the massive doses used to cause the slight effect that was found. Page 111-31, Line 19, also falls to note the massive doses and, in fact, describes the limited effect as "seadily" attained. Responsei The does of ethanol administered was 5 mg/Xg. This dose is now cited in the criteria Document. 6. ent Page III-10, Mne 3 and Page III-11, Mne 1. "These results showed that humans and rata differ in any or all of the parameters of absorption, elimination, or retention" "Coaparison studies of rat and human responses Indicate that both species differ in parameters of absorption, elimination, or retention of methyl chloroform." While these stateamnts are basically true, differences between species appear to be the result of size, rate of respiration and rate of blood circulation. Hence,-data on animals can be realistically extrapolated to humans provided proper adjustments for these differences are made* It is particularly important to note that all species metabolize methyl chloroform to a very limited extent and consist ently excrete a large portion unchanged* Response! SPA agrees with the conentsr that the differences between the species any be the result of size, rate of respiration and rate of blood circulation. BA also agrees that data on animals can be extrapolated to humans. SPA adjusts for size differential and for rate of respiration, but not for rate of blood circulation. 7. Cowenti Page 111-18, Line 19. "...and 130 ppm trichloroethylene, 7 hours/day for 5 days (Stewart, et al,i, 1969)." The reference cited does not appear to be correct since the article does not refer to trichloroethylene. Response! The error in the reference cited (Stewart, et al., 1969) in the criteria document has been changed to provide the correct citation (Swe, et al., 1963). 11-14 CM* 053110 Pag* III-20, Lin* 1. "Krantx, t *1. (1959) estimated th* dosage... halothan*." This entire section fall* to not* on* of th* sort li^ortant a*pet* of th** studies: th* quick and couplet* r*v*rslblllty of th* ffacta without **qu*la*. Response: PA ha* Included th* statement eoncarnlng th* r*vralhlllty of th* effects without sequela* In th* Criteria Document. 9. Conenti Pag* 111-22, Lin* 4. "Impairment of aotor control after exposure t ethyl chiorofor* ha* b**n demonstrated In humane at concentration* as low a* 250 ppm...." This sentence appears to r*f*r to the work of Gamberal* and Bult*ngr*n (1973), who used a very artificial experimental technique In which subjects breathed menthol to cower the odor of methyl chloroform. Furthermore, the subjects wore masks during-th* exposure period. As noted in th* CD, studies don* under more realistic physiological conditions by other Investigators failed to show a similar effect even at 500 ppm and with repeated expoauree. Response! The fact that the technique used methanol and involved maaks does not affect the validity of the study, and the commenter did not show how ERA'S conclusions would be changed* Stewart (1969) found no effects at 500 ppm but Gamberal* found effects at 250 ppm and Salvinl found effects at 450 ppm. Therefore, impaired motor control has been demonstrated at these low levels in some teats, and the statement in the Criteria Document is correct and no change appears necessary. 10. Cosmmnt! Page IIX-24, Lin* 19 and Page vx-1, Lin* 18. "Human autopsy reports have mentioned tissue congestion following deaths due to methyl chloro form, ..." "...an adema typically found in fatalities (sic) result from inhalation of methyl chloroform (Bonventre, at al., 1977 Caplan, at al., 1976)." Congestive changes often accoepany death and are not specific to methyl chloroform. Furthermore, changes of this type after exposure to thousands of parts-per-mllllon have no relationship to exposure at occu pational levels or, particularly, ambient levels. % Response! EPA agrees with the commenter's statement; however, no change Is needed in the statement in the Criteria Document, nils comment does not affect the RMCL. 11-15 CMA 053111 It CcmMnt! Paga XIX-36, summary. "The possibility of increased pneuaotoxicity das to 'additive' exposure to various levels of eethyl chloroform from food and drinking water*..and feces*" The suggestion of paaumotoxlcity due to ingestion of methyl chloroform in water and food is inconsistent with long-term repeated exposure to substantial concentrations of the material* Xt is not a significant concern and should be dismissed. Response! The count refers to pnaumotoxlclty resulting from ingestion of food and water, and the statement has been modified in the CD to indicate that additive effects on pneumotoxicity from exposure to 1,1,1-TC* through these sources cannot be quantified because there is no evidence that pneumotoxicity is or is not consistent with long-term exposure to 1,1,1-TCE* 12* Comment! Page v-1. Last Line and Page V-2, First Line, "...little other toxicological data involving oral ingestion are available." This section should cite Lane, et al* (1982) which appears on Page V-21. Responsei Agree) the Criteria Document has been modified to cite Lane, et al. (1982). 13. Coament: Page V-10, Line 18 and Page V-18, Line 8. "Two lifetime feeding study (sic)... 1983}" and "In the repeat NCI...in those groups." As indi cated previously, the second (NTP) study is not yet reported and is of such doubtful quality that it may never be reported. References to this study need to be deleted. Response! The second NTP study is reported only for the Information of the reader and has not been used to derive the risk calculations or the RMCL* Page V-19, Line 11. "Price, at al. (1978) demonstrated..." All referencee to this unconfirmed report should be deleted. Price also studied methylene chloride at* the same time and found an alleged effect. However, he was not able to reproduce the effect. Neither could Slvak, who also attengted transformation with methylene chloride* Xt can only be concluded that Price's method gives such irreproducible results as to be of dubious value. 11-16 CMA 053112 Rujoniii Price, et el. (1978) is * published study of findings of the experi ments in e scientific journal "In Vitro)" it is not unconfirmed. Price's end Slvak's works on methylene chloride are not at issue here. It is speculation that his study of sethyl chloroform la not reproducible- 15. Count i Page V-19, suMary. The entire summary, which refers to. the unre ported NTP study, must be deleted for the reasons set forth above. Response The information is provided for the purpose of informing the reader an the study and has not been used to derive the risk calculations or the RMCL. 16. P"--nt; Page V-20, Line 14. "...and contained 5.5% or about 50 ppm Inhibitors The sentence is inconsistent; 5.5% is not equivalent to 50 ppm. Response: Agree. The Criteria Document has been corrected. 17. '"""--nt; page VI-4, Last Sentence and Page VZ-5, First Sentence. "Their tests of psyehophysiological function are certainly more sensitive and objective than the indices used in the earlier studies of Torkelson, et al. (1958) and Stewart, et al. (1961, 1969)." Comment has already been made about the artificlalT*exposure technique via masks with menthol used to cover the odor. This alone raises serious questions about this study. Moreover, the most cooprehenslve study is that of Stewart, et al. (1975) conducted for NXOSB. nils report of repeated 7-hour exposures of men and women shewed no objective changes at 500 ppm, although the female subjects did complain of the odor. Response! See Coamwnt/Response - II.B.9 above. 18. Comentt Page VI-12, Line 3. "Collection of data does not appear to have been standardized to avoid bias." This sentence needs to be deleted or an explanation offered for it. Response; Agree. The statement has been deleted. 11-17 053113 19. Comment! 9 VII-1, Lln 4. "...4.5 million art exposed to 1,2 dichloroethane or methyl chloroform (Table VII-1)." There ia no association between 1,2-dichloroathane and methyl chloroform. This sentence should be deleted. Rssponsei Agree. The statement has been deleted. 2. Comment* Page VII-1, last Line, "...exposures to 1,2-dichloroethane do not exceed 5 ppm.." Since the CD addresses methyl chloroform and no relation ship has been established to 1,2-dichloroethane, this sentence should be deleted. Response i Agree. The statement has been deleted. 21. Comment: Page VIli-6, Line 13. "Epidemiological evidence...is worth mention ing." The epidemiological data of Ott, at 1. are of excellent quality and significance. They suggest the lack of effect in humans and should be cited in this paragraph. Response: PA has searched published scientific literature to locate the reference "Ott, et al.," concerning epidemiological studies. The Agency has contacted the coomenter to obtain this specific reference, but the study report has not yet been provided. 22. Comment: Page VIIZ-7, Line 3, VI11-9, Line 5, and VI1I-14, Line 4. "In the second NCI (sic) bioassay study (1983)..." Delete reference to this iaco^lete NTP study as in all previously discussed locations. Response! See previous responses concerning NCI study. 23. Comment! Page VIII-15, Line 3. "There are two shortcomings of this studyi..." The Agency has been supplied extensive information in regard to this study. The observation period was 19 months, not 12 months. Hence, these rats have a longer study period than in any of the other studies. Data have been supplied to the Agency which clearly show that exposure concen trations were adequate to be considered maximum tolerated dose by current definition. 11-18 Cm 053114 Rasponse: The Criteria Document has been changed to note that the observation period was 19 Months. SPA has received no evidence in this record that the concentrations were considered to be at the maxi Him tolerated dose. 24. Cc--nt: If further evidence shows 1,1,1-Trlchloroethane to be a carcinogen, the RMCL should be reproposed at saro. Response: SPA will repropose the RMCL for 1,1,1-trichloroethane, if further evidence is available which would change the classification of the coi^ound based on strength of evidence of carcinogenicity. 25. Caainti The proposed RMCL of 200 ug/1 is too high on the basis that the NTP studies suggest the coapound is a carcinogen, eaerglag evidence that 1,1,1-trichloroethane is an animal teratogen and because the conpound is stabilized with dloxane - a known carcinogen. Responsei The available evidence does not support the rnwinttr'i statement that 1,1,1-trlchloroethane is a carcinogen or an animal teratogen. The MCI has carried out two animal bioassays on the co^ound; in the first bioassay only 3 percent of the animals survived to the end of the experi ment and thus it was concluded that carcinogenicity could not be determined from this study. The results of the second bioassay are presently being audited. The coapound has not been shown to have teratogenic effects in animal studies. IPA recognizes that 1,1,1-trlchloroethane may be stabilized with other conpounda that could contaminate drinking water and is examining each coapound on an individual basis* If a stabilizer is found to be in drinking water and to pose a threat to public health, IPA will propose a standard for that chemical on an individual basis. 26. Coamsnti Attached is a copy of the final report of a lifetime carcinogenicity study in nice entitled "Chlorothene VGx A Chronic Inhalation Toxicity and Oncogenicity Study in Rats and Mice - Part 1. Results of Findings in Mice," by J. F. Quest, L. L. Calhoun and M. J. McKenna, Dow Chemical Coipany. Note that there was no evidence of adverse effect of any kind in mice exposed to 1500 ppm, 6 hours/day, for two years. The following is a summary of the report: Groups of male and female BgCjF.. mice (80/sex/group) were exposed to vapor concentrations of 0, 150, 500, or 1500 ppm 1,1,1-trichloroethane formulation, hereafter referred to as CHLOROTHINI 11-19 CMA. 053115 VG*, for 6 hours/day, 5 days/week for 2 yMrs. Ton aice/sex from each group were predesignated for interim ooeriflcao oftor 6, 12, end 18 month* of exposure. Fifty alc*/*ox froa oach group war* assigned to the study to bo toralnstod oftor 24 months. Foroaotars aoosursd during tho study iacludod aortollty, ln-life clinical signs of toxicity, hematology, clinical chemistry, body weight, organ weights (liver, kidneys, brain, heart, testes), gross pathology, and histopsthology. Inhalation exposure of aale and feaale BgC3P. alee to 1500 ppm or less of CHLOROTHXNE VG vapor for 2 years did not result In any toxic or oncogenic effect considered (hie to the test chemical. Response) f SPA has concluded that there are insufficient data to classify 1,1,1trichloroethane as a probable or possible human carcinogen and thus is regulating the confound as a non-carcinogen* This classification is consistent with the results of the subaitted report in regard to the oncogenicity findings, with regard to chronic toxicity, other studies have demonstrated adverse health effects froa exposure to 1,1,1-trichloroethane and SPA is basing the RMCL upon these effects. 27. Consent! "Calculation* based on toxicological data Indicate that the RMCL for ethyl chloroform should be based on taste and odor rather than toxicity. A no-observed-adverse-effect level for toxicity of methyl chlorofor* has been defined in a 14-week Inhalation study by McNutt, et al. (1975). Mice exposed continuously to 250 ppa experienced only minimal, reversible liver effects. We agree with EPA that this study any appropriately be used to confute an AADI for human exposure. However, 250 ppm should be considered a NOEL, not a LOAEL, because several long-tern studies. Including a life time study, demonstrated NOELs at ouch higher concentrations." Response; EPA does not agree with the cnsmwntsr * s suggestion that the RMCL for aethyl chlorofora should be based on taste and odor rather than toxicity. The RMCL, according to the SDWA, must be based on health considerations only. EPA may set secondary standards based on taste and odor. However, for the purpoee of setting primary standards, an RMCL auat be set for chemicals which aay cause adverse health effects. Methyl chloroform falls in this category. The coamenter agrees with EPA that the McNutt, et ai. (1975) study is an appropriate study upon which to base the AADI. EPA believes that 250 ppm should be considered a LOAEL because exposure at this level resulted in adverse effects) significant changes in the centrilobular hepatocytes of the animals were seen. These changes consisted of vesiculatlon of the rough endoplasmic reticulum with loss of attached polyribosomes, increased smooth endoplasmic reticulum, microbodies and triglyceride droplets. The fact that other studies demonstrated NOAEL* at much higher concentrations does not invalidate the results of the McNutt Study. EPA believes that 11-20 0s3116 this Study clearly demonstrated a LOAZL at 2S0 ppm and thus should b used as tha basis for tbs AADI. Tha conmantar suggested tha following approach for deriving tha RMCL for 1,1,1-txichloroethane, based upon tha McNutt, at al. (1975) study* Xn converting tha NOKL based an tha *~4--1 data to a dose expressed In mgAg/day, tha minute volume (0.05 L/*ia) and average body weight of tha mala (0.025 kg) mouse used by McNutt assertions used In tha criteria document, tha NOSL may be axprassad in mg/kg/day as followsi * Conversion factor (1 ppm v/v in air " 0.0055 mg/L at 2S*C and 760 torr) Absorption rata Thus, using tha methodology and tha thousandfold safety factor. suggested by DA, the AADX may be confuted aa followsi Again using tha methodology suggested toy DA, this AADX may be con verted into an RMCL by dividing by 5. This results In an RMCL for methyl chloroform of 2.1 mg/L. This concentration limit, while sound toxicologically, would in our view need to be lowered in order to be aesthetically acceptable. Response! This approach is basically the same as that used by DA in deriving the RMCL, with the exception of the approach used to convert from lnhalatl n exposure to oral exposure (tha use of tha minute volume and body weight of the animal). The response to comment IX.A.1 above addresses DA's approach in converting exposures. A similar calculation for the RMCL could be made based upon the Quest, at al. (1984) study as followsi 500 ppm x 0.0055 mg/L x 0.05 L/min x 360 nln/day x 0.3 m 0.040 kg mg/Xg/day 11-21 053117 Response i Th eontotar agreed that the McNutt, et *1. study 1* appropriate for deriving as RMCL. EPA's preliminary review of tha Quest, at al. study suggests that thers ara ssvsral unexplained findings in tha study. Thasa findings ara as follows; (1) tha livers of some aala aica in tha 1500 ppm group appaarad to hava davalopad nodulasi (2) tha daath of tha famala mouse (150 ppm) pradasignatad for tha 6-month intarim sacrifica prior to tha schadulad sacrifice; (3) tha daath of several mica (1 mala* 500 ppm; 1 famala, 150 ppm) prior to tha schadulad sacrifica at 12 months; (4) tha gross observations suggastiva of lywphoreticular naoplastic response in all groups of aala mica which tha researchers claimed ware not related to tha chemical exposure; and (5) tha increased incidence of cystitis and dilation of tha renal pelvis in tha 500 ppm group of aala aica which tha researchers claimed ware not related to tha chemical exposure. Thasa unexplained findings, taken as a whole, suggest that there nay ha problems with this study. Thus, EPA believes it is preferable to base tha RMCL upon tha McNutt, at al. study. C. 1,2-DXCHLOROETHAHB (ETHYLENE DICHLORIDE) 1. Comment: After reviewing tha 1,2-Dichloroethane Criteria Document tha commenter came to tha following conclusions; (1) there was undue reliance on Russian literature; (2) toxicity data ara either not germane, inadequate or of questionable quality; (3) tha document overeiqshaslzes literature published prior to- 1971; (4) mutagenicity studies cited are inadequate to draw firm conclusions; (5) evidence for binding to DMA is weak; (6) evaluation of carcinogenicity of EDC must be more balanced; and (7) the estimate of human exposure is overstated. While the OHEA HAD of April 1984 has deficiencies in the commenter's estimation, the HAD should be used as the scientific data base for RMCL development, since it contains discussion of some more recently published pertinent information, which is not contained in the drinking water document Response; We agree with the first six conclusions. Particularly because of the first four conclusions, EPA will use the HAD document as the background document instead of its draft criteria document. Both documents, in EPA's estimation, came to the same conclusions concerning the qualitative assessment of both noncarcinogenic and carcinogenic effect data. EPA will use the OHEA HAD as the background document with inclusion of a revised Quantification of Toxicological Effects (QTE) section which presents the quantitative risk assessment. The OHEA HAD has been received and accepted in substance by the EPA Science Advisory Board. EPA agrees that the improvements indicated by the commenter, specifi cally points 1-4, are in order for the criteria document. Our response recommends use of the OHEA HAD in place of the criteria document as the background document for EDC, particularly because it contains a more 11-22 CMA 053118 complete discussion of tho scientific literature; however, we also not* that ths qualitative assesament conclusions between tha two documents ara the ssm. In tha BAD, *FA concludes that: (1) thara la not undua rallanca of tha Russian lltaratura for aasaaslng health affects, and limitations In tha data on health affects from Russian literature ara acknowledged; (2) tha toxicity data In animals ara of adequate quality to support tha conclusions on health affects, but the htaan toxicity data ara too limited for conclusive assessment of health affects; (3) tha overall literature through 19S3 la considered on tha merit of each study in drawing tha conclusions made, without data of publication being a critical factor In tha assessment; (4) the overall evidence for aitagenldty Is concluded by PA to be adequate support for DC as a weak mitegen; (5) IPA concludes that the evidence for binding of SDC and/or Its metabolites to DMA Is adequate; (6) KPA concludes that Its assessment and conclusions on carcinogenidty, which the BPA Science Advisory Board has accepted, are In order. 2. Cowiant; In the occurrence document for ethylene dichloride, there are Incon sistencies la the treatment of the data. Table 15; R0R8 surface water data shows 22 positive systems, while tha text Indicates that 16 of these positives are below the minimum quantifiable level, defined In Appendix A as "the level below which it cannot be determined whether a VOC Is present and if so, at what concentrations** Thus, Table 15 should Indicate 6 positive systems. Response; The NORS data Indicated'that In 16 of the 22 positives for 1,2dlchloroethane, the contaminant was present above the detection limit of 0.1 ug/L In the GC/MS confirmation analyds but below the minimum quanti fiable concentration range of 0.2-0.4 ug/L in the primary analysis using GC with an electrolysis conductivity detector. 3. Coswent: Review of tha occurrence document reveals inconsistencies In the treatment of data. Ths MORS surface water data shown in Table IS Indicate 22 positive systems, while the test indicates that for this survey, 16 of these "positive* systems were below the minimam quantifiable concentration ("NQC"). Reference to Appendix A of the occurrence document indicates that the MQC is the "level below which it cannot be determined whether a VOC Is present and, if so, at what concentration." Accordingly Table 15 should Indicate only 6 positive systems. Response; The text, perhaps confusing to the cooaenter, is In agreement with Table 15. As noted in the text, 16 of the 22 systems had detectable (but unquantifiable) levels below 0.4 ug/L and two had quantifiable levels below 0.8 ug/L, as Indicated in Table 15. Appendix A and the definition of the MQC is Incorrect to the extent that it precludes Identifying the presence of a contaminant. The NQC Is the level below which an accurate statement cann t be made c ncerning the levels (quantification), but it is often possible to determine that a contaminant is present. 11-23 CMA 053119 4 la the XDC occurrence document, only 9 positive lystoH la 1,059 groun&atar supplies were found for an incidence of 0.8%. This la fairly eloaa to tha 9 positive aystaaa la tha 1,001 groundwater supplies aa shown la Table 22, although It la unclear which groundwater sources ware deleted aa being duplicative. Therefore, the projected national occurrence of KDC la groan<teatar supplies Indicates that 99.7% of groundwater sources contain either no IOC or only levels below 0.5 ug/L. The cooBenter Is correct that, based on the available studies, approx imately 99.7% of supplies with groundwater sources are expected to contain either no 1,2-dlchloroethane or levels below 0.5 ug/L. 5. Cowant: Regarding surface water supplies, the occurrence document Is ouch less clear. After the correction to Table 15 and based on the text. Tables 15*21 Indicate 11 positive sources, l.e., greater than 0.5 ng/L, out of 575 surface water sources, for an occurrence rate of 1.9 percent. Reference to Table 26 shows an entirely different picture. The 575 surfac water sources have decreased to 301 while the number of positive sources, l.e., greater than 0.5 ug/L, has swelled from 11 to 18. The seven sources indicated as being less than 0.5 ug/1 should not be Included In Table 26 at all, since they are below the MQC. Response: A total of 575 systems were samplad during five different surveys. Soma of these systems were saapled multiple times* A total of 301 dlf* farant systems were adequately saspled. KFA agrees that the averaging process moved 7 systems which contained 1,2-dichloroethane into a cate* gory of slightly higher quantity because subsequent analyses, though "negative," had an elevated minimum quantification limit. The averaging methodology Is described on pages A*22 and A*23 of the Occurrence Document and explained In the next comment. 6. Comment: Table 26 shows the 301 supplies and a total of 25 positives, 7 of which were below the common minimum quantifiable concentration of 0.5 ug/L and 18 at or above 0.5 ug/L. The apparent Inconsistency In positives above 0.5 ug/L Is an artifact of the averaging process used where a given supply was sampled in more than one survey with both positive and negative results, where the positive values are lower than the minimum quantifiable concentrations of negative values In other surveys. Zn the case of EDC, several supplies with positives In MORS at values below 0.5 ug/L were averaged with negatives from MORS having a minimum quantifiable concentration of 1.0 ug/L3: In which case the negatives from NORS ware considered to be positives. 11-24 CMA 053120 Response; PA grM> 7. Comment; 9m projected occurrence of KOC la surface watar aooroaa aa Illustrated la Tabla 27 doaa not correspond with Tables 15*21 There are ao Incidents of contamination la system sires 25-3,300, yet Table 27 shows 67 systems la this sire category as containing 0*5-5 ug/L and 67 surface water systems containing 10-20 ug/L ZDC. This Is a totally unreasonable Interpretation of the data* Responsei The data set for KDC was so small that stratification by categories of system sires was statistically 1possible. System sires were collapsed until they were statistically workable, then expanded to the original 11 categories using a simple proportional relationship. This methodology was explained In the appendix of the occurrence document (pages A-23 - A-27 and Appendix B). PA believes that absent a complete data set. It Is incumbent on the Agency to make reasonable estimates of occurrence* Since the IPA believes this methodology is reasonable to derive a stratified population, it is kept In the Occurrence document unchanged. 8* Cement; In Table 27 of the BDC occurrence document, the same numbers, appear in the columns 0.05-5 and 10-20 up to a system sire of 10,000. This suggests an error in transposing data to the table or an Incorrect modelbeing used. Response: The numbers are correct --- that they are the same is coincident; again, separate estimates were made for the supplies serving 110,000 and >10,000 people. Por the reasons given in consents 7 and 8 above, the estimation of 5.7% of the population being exposed to drinking water containing 0.5-5 ug/L mist be recalculated and the estimates of 143,000 persons being exposed to >5 ug/L must be redone. Response; The responses to consents 7 and 8 answer this consent. Bo change in the estimates is required. 11-25 CMA 053121 10. Cc--nti 1,2-Dichloroethane should not be considered probable human carcinogen based upon deficiencies In th NCI bloassay. In addition, negative rasulta obtalnad by othar rssaarchars naad to bs considered, such as tha potantlal for cross contamination batvaan tha aica gavage stadias bain? coaductad on othar chemicals In tha same rooa. high and aarly aortality In rats and tha praaanca of pnauaonla in both rata and alea* Thara was also a problaa of aarly aortality and low survival In both aala and faaala ales. Tha wa for 1,2-dichloroethane should bs baasd upon an ADI darlvad froa non* carcinogenic data. Besponsa; DA ballavas that thara ara sufflelant toxicological data' to classify 1,2-dichloroathana as a probabla human carcinogen* Tha chaalcal has baan shown to ba carcinogenic in both rats and ales whan administered by gavage. Tha negative carcinogenicity data consists of sawaral Inhalation studies (MCI. 1978; Haltonl. at al., 1980; Thalss, at al., 1977). Sines 1,2* dlchloroathana was shown to ba carclnopanic by tha oral routs, which is tha sans routs by which individuals would ba exposed to tha compound in drinking water, DA ballavas that tha positive oral data should outweigh tha negative inhalation data in tha analysis of tha compound's potential carcinogen!city. With regard to tha MCI bioassay, tha MCI report is final, with tha following conclusions; "Ondar tha conditions of this bioassay thara was a statistically significant assodation between increased dosage and alavatad aortality in both aala and faaala rats and in faaala dee. During tha second year of tha study, aortality rates in tha aala ales ware higher for low dose and untreated control than for high dose alee. Despite this accelerated aortality, positive associations ware established between 1,2-dichloroethane adaini* stratlon and tha incidences of several neoplasms.* These conclusions have baan accepted by IARC and used in their evaluation of tha carcinogenicity of 1,2-dlchloroathana and also by tha SAB in their review of tha Health Aseessaant Document for 1,2*dlchloroethane. Tha daflclancles in tha MCI bioassay cited by tha on--ntar do not appear to have played a role in influencing tha final results. Tha potential for croes-contaalnation with othar chemicals is minimal, as th exposure tha animals received from othar compounds would ba so such lower than tha dose of 1,2-dlchloroathana that it would not negate tha affects noted. Also, tha presence of pneumonia In tha animals would affect tha mortality rate but would not affect tha carcinogenic response. Tha aortality rate of tha animals was noted in tha MCI report but does not Invalidate tha results of the study in any way. As stated in tha report, "Despite this accelerated mortality, positive associations wars established between 1,2-dichloroethane administration and the incidences of several neoplasms." 11-26 CMA 053122 1,2-Dichloroethane has been classified la IPA's Group B2 (probable human carcinogen) and the IARC has classified 1,2-dichloroethane la Group 2B> sufficient evidence of carcinogenicity In animals. Thus, SPA feels that the RMCL should be based upon carcinogenic effects and set at zero, and should not be set using the ADZ. 0. rom CHLORIDE 1. Consent; The animal cancer data Is weak since neither anglosarmess nor hepato cellular cardnoeas are significantly Increased In the low dose groups of the Peron, et al. (1981) study- The only tutors detected at the low dose were liver neoplastic nodules, which have not been proven to be precursors of cancer. Response This study Is not considered to be weak because angiosarcomas/earelnoaas are significantly Increased at aedlua and high doses. In addition, neoplastic nodules are treated as predictive of carcinoses and they were significantly Increased at low doses. The highest dose level used was considered acceptable for assessment of cancer risk because the activation pathways were not saturated, and secondly there was little evidence of chronic toxicity. Since the hitter doses were considered acceptable and since a narked carcinogenic response was seen at these doses, the evidence for carcinogenicity In animals was adequate. The evidence is strengthened further by the marked carcinogenic response noted during Inhalation exposure to a wide range of VC concentrations* 2. Cement: The magnitude of risk is greatly overstated because (1) the use of the upper 95% confidence Interval does not represent a most probable risk, and (2) the coaputer program ignores negative results. Response: The risk is overstated, but IPA is unable to estimate by how much given the cited factors. The methodology used has been peer reviewed and published by the IPA. This methodology has been designed to provide a conservative estimate of risk because of the many unknown factors in the assessment procedure, i,e>, the possibility of unusually ssnsltive sub groups, uncertainty regarding the shape of the dose-response curve at low doses, differences in metabolic pathways affecting responsiveness between human and test animals. The SPA provides the risk assessment for general information for public and Agency use. The RMCL is not based on the risk assessment. 3. Coaswnt: In the study in which VCM was fed to rats In PVC powder, the unexpect edly high incidence of liver cell tumors may be due to unusual sensitivity 11-27 CMA 053123 of the liver as a consequence of an altered metabolic stata caused by ra^wtioa of dally food intaka tlaa to only 4 boora. Response While It can bn poatulatad that sensitivity aay ba altarad by tha feeding regime, thara la no experimental evidence to prora tbla. Until such evidence la provided, it la assumed that sensitivity la noraal in tha experimental animals* 4. Comment! 8Inca both Ferom and Haltool found no obaarmbla affact lamia for exposure to VC and alnea tha no-threahold coocapt baa not boon provan. It aould ba battar to dataralna a MOIL with a aafaty factor to darlm a aafa exposure laval. Response! Saa it-- 5 balow. 5. Co--anti Another eo--antar provided information on additional earelaoganlclty data front Faron and associates where a "no-observed-adverse-effect level" for tuaor Induction In rats was reported. Response! Tha met widely accepted view of carcinogenesis, based on evidence that a single mlecule of a xanoblotlc chesdLcal can react with DUX to genetically altar a call, supports tha no-threshold concept. Moreover, tha bast available apidaBiological and anlnal evidence, especially those studies involving radiation exposure support the no-threshold concept. IPX believes this single contaminant-specific teat showing a threshold is outweighed by the best available scientific evidence on many contaminanta, showing no observable thresholds. In addition, this approach errs on tha sids of safety end protection of public health, given acm degree of scientific uncertainty. In the development of the quantitative estimate of risk, the total number of tumors wars esauaed to be the asms as the number of animals with tumors. This may result in an overly conservative risk sstimste, since some animals aay ham aultipla tumors. Responsei A q* of 2.3 wee derived for female rate based upon the incidences of neoplastic nodules and hspatocsllular carcinomas in the liver plus angiosarcoaae of the lung and liver. For neoplastic nodules alone, the met comas tumor type, the q* was 1.3. Thus, even with the maxima possible 11-28 CMA 053124 incidence of with multiple tumora, tha q* would not bo doeroaood to loao than 1.3. if it la assumed, on tho otbor hand* that oach tumor typo evolves Independently* tho likely numbor of animals with miltlple tumors would bo small enough to result In only a minor decrease la q* below 2.3. The quantitative estimate of risk was based on the best avail able evidence. Milla possible error as discussed above Is undoubtedly small# it is recognised that a more accurate estimate could be made if the tumors present In each individual animal were known. An attempt is* therefore# being medo to obtain this data. However* this data does not affect the conclusion that it is carcinogenic and presents an adverse health effect. 7. Count i In general# the document provides a constant review of the literature through about 1981. More recent documents are omitted and some of the more recent reports nay be of Interest* Response: FA agrees and has discussed the following references Identified by the oonmenter in the Criteria Document: o Hatch# Lein and Stein. o Hansteln, et al. 1961. o Anderson# et aT. 1981. 1981. Knviron. H. Ferspect. Hut. Res. 78:211. Mut. Res. 83:137. o Chinese* et al. 1980. J. Oecup. Mad. 22x677. o Falk* et al. 1981. Hnvlron. H. Ferspect. 41:107. 41:195. All these studies do not affect HFA's findings of adverse health effects. There are sufficient positive mitagenicity data such that these negative studies do not outweigh the overwhelming number of positive studies. 8. C"-->*nt: On Page II-1 it Is stated erroneously that VC dissolved In water rises to the surface because the specific gravity of tha solute is less than that of the solvent. VC escapes from the surface of water because of the concentration gradient present there* not the pull of gravity. Response: PA has removed that statement from the Criteria Document. 9. Conant: *he document contains no details of the "new" risk assessment by CAG which Is necessary in order to comment on the assessment. Response: Details on the CAG risk assessment have been added to the Criteria Docusmnt. However, because the risk assessment is not crucial to the 11-29 CMA. 053125 conclusion that tha contaminant posaa adverse health effects, there la no need for additional comment on this aasssassnt. it is merely provided for ths Agency's and tha public's general information* 10. Co--nantt KPA should not conaidar vinyl chlorida to ba a non-threshold carci nogen* as KPA has supportad this position on tha basis that tha thresholds for carcinogens are net tastshlat and tha nsa of abaanca of avallabia proof aa a reason for acceptance of a theory is not acceptable scientifi cally or philosophically- Vary few cases of cancer would ba averted with a vinyl chlorida regulation and tha saall nt--bar of cases and low occurrence do not justify regulating tha eoapound. If farther consideration showed tha need for a standard* tha RMCL should be baaed upon a 10"5 lifetime risk level. Response KPA baliaves that any exposure to a carcinogen nay present see-- finite risk# since scientists have been unable to axperlwantally verify a threshold for carcinogens, including vinyl chloride. KPA believes that it la better to err on the side of safety in regard to the aachaniaa of action of carcinogens and treat carcinogens as non-threshold contaminants rather then to assume a threshold and perhaps place the public at risk. KPA has 'determined that there are sufficient health effects informa tion and occurrence data to justify regulating vinyl chlorida. Vinyl chloride la a known human carcinogen which has been detected by several States at varloua levels. KPA agrees that the State data are not repre sentative of national occurrence> however* these data indicate that vinyl chlorida is prassnt in a number of drinking water supplies and KPA beliaves that this detection la sufficient to warrant action. In addition* infor mation suggests that vinyl chloride may be found in drinking water ae a breakdown product of trichloroethylene or other chlorinated hydrocarbons under certain conditions. (Parsons* at al.* 1984, Transformation of Tetrachloroethylens and Trichloroethena in Microcosms and Groundwater, j.a.m.W.a.* Vol. 26* Ho. 2; Parsons and Lags* Chlorinated Organics in Si--ilatad Groundwater Environments, J.a.m.W.a.* Vol. 27f Vogel and McCarty* 1985* Biotranaformation of of Tetrachloroethylane to Trichloroethylene, Dichloroethylena* Vinyl chloride and Carbon Dioxide under Msthanogenic Conditions, Applied and Environments1 Microbiology* Volume 49* Ho. 5*) 11. crranti The National Drinking Mater Advisory Council did not recommend regu lating vinyl chloride. Responsei The National Drinking Water Advisory Council has met several times to discuss the VOCa proposal. At the first masting they concluded that due to the low occurrence* an RMCX. should not be set for vinyl chlorida. Bovver* at the second meeting they reversed their initial decision and concluded that an RMCL should be set for vinyl chloride due to the carcino genicity of the eoapound. 11-30 CMA 053126 E BEN2BC 1. Q-iment: One conranter felt that EPA's AADI for benzene was calculated using an extrenely conservative approach based upon (1) the use of 10 ppm as a NQAEL in the Chang study despite the fact that no hemtolog leal toxicity was observed in the 18 workers exposed to 10 to 20 ppm benzene in the study and (2) use of an uncertainty factor of 1,000 despite the fact that the 10 ppm NQAEL reflects hunen data. Response; EPA believes that it is appropriate to use 10 ppm (Chang study) as th NQAEL# as no effects were observed at this level / while cytopenic effects were noted at 20 ppm. EPA further believes that the application of an uncertainty factor of 1000 for the Chang study is appropriate due to deficiencies in the study, these deficiencies include the fact that nany details of the exposure were not provided, an unspecified industrial area was used in the study, and no definition was provided of wsrk exposure concentrations for individual enployees. 2. Ootimentt Use of an uncertainty factor of 10 to account for less than lifetime exposure in the animal study by Wolfe may also be nigh, since the benzene was administered ever 187 days ratner than the 90 days to which an uncer tainty factor of 1U might typically be applied in a study of rats. Responsei The use of an additional factor of 10 in studies that are less than lifetime applies in the case of the wolfe study, since the study was for 187 days, which is only one-quarter of the expected lifetime of the animals. 3. Carmen t; One columnter noted problems with the calculation of the cancer risk estimate for benzene. They felt that the calculation for risk estimates should be decreased by 8%. The following justification was provided: "The first thing that trust be said is that this inhalationderived potency factor (cited in the EPA Criteria Document on Benzene) is outdated. In its nost recent actions regarding the regulation of benzene under the Clean Air Act, EPA has revised this potency factor downward from 0.024/ppm to 0.022/ppm, a reduction of 8% (see 49 Hi at 23488). Even if everything else in EPA's methodology were unobjectionable, this would mean that the benzene concentrations associated with risk levels of 10-6 and 10"5 would have to be increased by 8% to 0.73 ug/L and 7.3 uy/L, respectively." The EPA risk levels of 10"* and lO* are at 0.68 ug/L and 6.8 ug/L, respectiv ly. 11-31 053127 Response t QA agrees with the rro--nt that the risk estimate calculation should bs dsersassd by 8% and this has basn dons by SPA'a Carcinogen Assessment Group (CMS). 4. Cowant* Benzene la not praaant in a sufficient number of drinking vatar auppliaa to charaetarizs it aa a national problea and tha average daily intaka of bansana froa drinking water constitutas a nagliglbla parcantaga of tha total daily vatar intaka froa all sourcaa. Ho justification is found for adapting a drinking vatar standard* Aaapcneat * SPA believes ragulation la appropriate bacausa tha oontaainant has haan found in drinking vatar\ tha occurranea lnforaation auggasta that around 500 public vatar auppliaa vould bs axpactad to contain bansana. Bansana is also classiflad as having suffleiant avidanca as a huaan carclnogsn. In addition, bansana nay bn a oontaainant froa vasts disposal as vail as froa laaklng underground gasoline tanks. KPA believes that a standard for bansana vlll presets unifora action aaong states vhen tha oontaainant is detected and vlll halp prevent future exposure to tha chealcal. 5. Ccaaent: On a vorst case basis, va estimate that approxlaataly 100,000 people nationvlda are exposed to a lifetlne risk of 10"5 as a result of bansana in drinking vatar supplies, and that approxlaataly 2.5 Billion people nationvlda are exposed to a 11 sties risk of 10". This aaounts to 0.036 cancers par year nationvlda. These estimates greatly overstate tha true risk, which is likely to be one to two orders of magnitude lower. Response: KPA is required, under tha Safa Drinking Water Act, to sat RMCLa for those chealeals which aay have an adverse affect on health and to sat tha NCU solely based on health. KPA is regulating such chemicals if they are found or are likely to be found in drinking water. Tha number of cancer cases avoided is not a criteria for setting RMCXa; KPA examines this in tha Kconoalc z^act Analysis for tha MCXa as part of the overall regulatory analysis. 6. Csnt The average daily intake of benzene in drinking vatar represents a nagliglbla percentage of tha total daily intake of benzene froa all sources. The public health iapact of a national priaary drinking vatar ragulation in these circumstances also would be nagliglbla. 11-32 CMA. 053128 toroonwi SPA does not agree with the coMnttr that a primary regulation should not ba sat whan drinking water doas not constituta tha aajor routs of exposure for that chemical. SPA baliavas that all routas of exposure should ba considarsd In tha analysas and a prlaary Tabulation should ba sat whan axpoaura to tha chaaical is shown to rasult In advarss haalth offsets and tha chaaical la known to occur In drinking watar or has tha potential for occurrence in drinking water* t. 1,1-PICHLQB01TBM1 1 CMUtl One eoaaanter responded to tha question of whether or not 1,1-dlchloroathylene is a carcinogen. Tha coaaantar stated that tha toxicological evidence doas not warrant classification as a carcinogen. Tha ooBsnter presented an option by which an ADZ and AADI for 1,1-dlchloroethylene can ba darived, than, in turn, used to develop tha fUtCL for this substance. Tha option is based upon data gathered in two studies in rats, one via Inhalation at exposure levels of 25 or 75 ppm (Ra^>y, a al. 1977, McKenna, at al. 1980) and one via drinking watar at nominal dosae of 50, 100 or 200 mg/L (Raspy, at al. 1977, Quast, at al. 1983). 25 ppm was considered by tha investigators to ba a LOAEL in tha former study and at 50 ppm in tha drinking watar study* Using tha T,OAEL of 25 ppm from tha inhalation study, tha rplanter suggested an ADI of 0*68 mg/day and an AADZ of 0.068 mg/L, if 20* contribution from drinking watar ware assumed. Response: FA agrees that tha toxicological evidence doas not warrant classifi cation of this chemical as a carcinogen. SPA has classified 1,1-dichloroathylana In KPA's Group C ("possible" human carcinogen) baaad upon tha mutagenic potential of tha coepound, tha results of mouse and rat inhalation data and tha eospounds's structural similarity to vinyl chloride. For derivation of an ADZ for noncarcinoganie affects, tha Agency used tha data from the drinking watar study. Tha drinking watar study is used instead of tha air study, as drinking watar studies are generally more appropriate for calculating drinking watar ADZs. In this case, a drinking watar study la available and tha LOAEL from this stu4y is vary close to tha TtOAITi from tha air study. Using tha Agency's calculations, tha ADZ was derived at 0.7 mg/day which yielded an AADZ of 0.070 mg/L, assuming a 20% contribution from drinking water. This AADZ is essentially identical to tha co--enter's AADZ. 2. Co--nti * occurrence data shows 1,1-dichloroethylene to be tha least common (considering 1,1,1-trichloroethane, methylene chloride and 1,1-dichloro- ethylane) of these three conpounds in drinking water. Therefore, questions may be raised concerning the need for an RMCL for this co^ound. 11-33 CMA 053129 Response* KPA did not propose an RMCL for methylene chloride (dichloromethane) la this phase of th Ravisad Ragulatlona die to problems with tha quality of tha avallabia occuxranca Information aad lasufflclaot toxicological Information. This eo^ound will ba coasldarad la a latar phaaa of tha Revised Regulation. An RMCL was proposed for 1,1,1-trlchloroethane basad upon nou-careinogenic offsets boeausa quaatlons wars raised concerning tha latest bioassay data oa tbs co^ouad. fba RMCL is basad upon tha most carraat valid data for tha compound. Aa RMCL was proposed for 1,1-dichloroethylene basad upon tha compound's possible carcinogenic affects and non carciaoganlc affects. G. P-DlCHLOROBiaiZUtt 1. Cc--ent* the refaraaca to Girard, at al. (1969) should ba deleted or Modified to accomodate for tha possible coincident exposure to other coapounds. Responset Tha suanary reference (Page 1-2) to tha Girard study has beea codified to add a sentence reading* "In three of those gases, it is likely that the individuals were exposed to other cospounds as well. Thus, fros this study it Is not possible to state with any degree of certainty that there is a link between DCS exposure and the disease state.* 2* rrxeinti The discussion of anesla following DCB exposure should note that the observed cases of aneaia were induced only after large exposures and were reversible. Response* The 8u--ary reference to this effect (page 1-3) has been Modified to include the following sentence* "These cases reflect exposure to signifi cant --scuts of the agent* When exposure was curtailed, there appeared to be recovery." Co--enter clains that the Sunaary statement which states that granulo cytopenia is a precursor to leukenla (page 1-5) Is unsound and suggests that this relationship is entirely speculative. They provide undocumented information to substantiate their belief* Response* Since, at the aoaent, EPA does not have the primary references to support the statement in the Criteria Document, it has been removed from the document. 11-34 CMA 053130 4. Count* The rn-- nt si addreaaes the action In th document that states that ths -- tolsratsd doss (NTD) nay not havs bssn reached In the bloassay with o-OCB. The conentdrs assert that the NTP Board of Scien tific Counselors# in Its public review of the bloassay# felt that the dosing regimen was adequate# tesgonaei The purported view of the Board of Scientific Counselors has not been docoNnted as being other than that which appears In the draft report# The draft report states that the MTD say not have been utilised. The ODW Health Effects criteria Document will be Modified to neks It clear that it Is the HTP's draft report opinion that was described In the docuaent# and when a final report on the bioassay becoaes available# any change In opinion will be duly noted# The coaenter Mentions that the docuaent should be altered to reflect the existence of teratogenicity studies for o- and p-OCB that Were conducted by the Chlorobenzene Producers' Association. Responses These studies have been aoquired froa the Office of Toxic Substances and are described In detail in the Pinal Health Effects Criteria Document. 6# Cotents The conoenter refers to the Summary statement (page 1-1) that suggests that increasing use of o- and p-DCB as deodorizers will lead to increasing aaounts being present in waters In the future. Responses As the ccsoenter points out, these chemicals have been used for this purpose for aany years#' and yet# the concentrations found in waters have been snail. The sentence in the docuaent has been aodlfled to reads "The use of o- and p-DCB as deodorizers in industrial wastewaters and toilet bowl waters would suggest that there is a potential for these substances to be found in water# particularly surface, around the country." 7. Comment: One comenter criticised the derivation of the RMCL for p-diehlorobenzene based on data identifying the HOAEL from a subchronic study stating that the exposure duration is too short for defining a "safe" level for possible lifetime exposure. Their concern was based upon two sources of information: (1) NAS's reiteration of an ADZ of 0.0134 mgAg/day and (2) the report about the threshold odor concentration of 0.03 mg/L. 11-35 CMA 053131 Rssponas; Tha Agency feels that tha us* of tha particular study daacrlhad was appropriate for tha generation of tha ADI, AADX and tha RNCL for p-dlchlorobenxene. To accosnodats for tha possibility that offsets aay ba soon after lifetime exposure at doses that la tha subchronic study ware without effect, aa extra uncertainty factor of 10 was applied to tha data. Tha Agency disagrees that tha IM (1983) reassessment of aa ADI, ate. for p-dlehlorobanseae la tha correct one. Their assesmesnt was based upon the 1956 Hollingsworth study which employed three garage doses, each an order of magnitude apart. Tha 90-day study which tha Agency saployed in deriving the SMCL used fire treatment dosee, over a narrower range. In the Agency's judgmsnt, this study better defined tha highest BOAEL. It Is agreed that if p-dlchlorobenxane actually were present In the drinking water at levels near the RMCL, the water would not be aesthetically pleasing to the consumer. At this time, however, CPA's first priority is to sst revised primary drinking water regulations; secondary drinking water regulations will be updated later. 8. rc--isntt * There is no need for an RNCX for p-dlchlorobenzene because the compound is not generally present In drinking water at significant coacentratlon levels or at levels to which significant populations are exposed, even if the compound was detected In drinking water, the proposed RNCX, Is far In excaas of any concentration level at which the command has been found in drinking watsr. Thus, there is no need for the costly monitoring and recordkeeping requirements to be imposed as pert of a national standard. Bssponss: SPA agrees that the frequency and levels of detected contaminants are quite low, however, since the contaminant nay have an adverse effect on health and has been detected in drinking water, SPA believes that a standard is appropriate and consistent with Congressional intent. In addition, it may now be occurring at hispier levela la systems that were ' not sailed by SPA or the States; It mey also occur st higher levels in the future* CPA rejects the notion that a contaminant must be datactad at levela which ere likaly to cauaa adverse health affects before s regulation is justified. The SDWA endorses s protective philosophy which SPA Is Implementing through regulation of contaminants such as p-dlchlorobazene. 9. Comment t The NOMS survey, GWSS, and MSP surveys used for closure estimates of pDCB wore not mads available for outside review or coewnt; It Is therefore Impossible to evaluate the accuracy of EPA's exposure estimates. Response; All EPA surveys were available for outside review end coewnt before the proposed rule and were included in the rulemaking record available to 11-36 CM& 053132 the public. Mit In addition, tha data from these survays hava baan summarized in tha individual Occurranca docum--ts on aach chaaical. 10. Co--sntt Tha following co--anta wara --da concerning apacific atudiaa eitad in tha draft Criteria Docu--ntt On paga 1-4, line 6, tha doaa reported for tha Varshavskaya study should be 3,220 mgAg* At line 10, tha reference to 2 cc/n3 is an inappropriate description of at--spheric concentration. It would be --re appropriate to refer to mg/L or mg/m3 The description of the Varshavskaya study at V-10 and V-11 should state data in ter-- of mgAg rather than mg/L* Table VIII-1 should be revised to reflect that the U>so* for the Varshavskaya study wars stated in agAg* The Burstone (1965) citation is not lieted aacng the refer--eas. It is, therefore, l^ossible to evaluate the dale that tissue DFN, TPN, glucosa-6-phosphate --d alkaline phosphatase activity is indicative of carcinogenicity. The description of the Guerin --d Curzln (1961) data at V-58 should be supplemented with tha scores for control nice. Response; All of the above cited studies have be-- raaoved from tha Final Criteria Document for the following re--onsi Tha Burstone (1965) study inadequately supports the claim that enzymes assessed in the Varshavskaya study are Indicative of carcinogenesis; the Guerin and Curzin (1961) study is a short-term skin test which does not adequately characterize the carcinogenic pot--tial of dichlorobenzene, end; there is inadequate infor--tion in the Varshavskaya study to convert LD5QS mgAg*from mg/L to elimination of the-- studies does not affect the conclusions in the Criteria Document. REVim Of p-DICHLOROBEHZENg HEALTH ASSESSMENT DOCOMBMT A com--nter submitted a detailed review of the Health Assessment Docu--nt for chlorinated benzenes (Bxternal Ravi-- Draft, May 1, 1984). ' This docu--nt has since been revised end finalized; however, sc-- of the issues are still relev--t to the fina1 RMCL for p-dichlorobenzene A sum--ry of the issues relev--t to the curr--t rulemaking --d SPA responses follows. (Co--ants 11 through 29) 11. <---ntt Bach of the chlorobenzenes is quite distinct from other chlorobenzenes in use, in --viron--ntal properties --d effects --d in toxicologic effects. 11-37 053133 Any ** several Response1 at of these chemicals must clearly diffsrantlata among the that have baan considered In tha SPA draft. SPA agraaa and tha Criteria Document for o-dichlorobenzena, m-dichloro banaana and p-dichlorobenzene conaidara each of tha iaoaara aa a diati.nct ccapound. 12. Comot: It la an error to contend that all ohlorobenaenaa bioaccumulate in ani--i and human tiaauaa fron anbiant air, water and food. SPA cannot conclude that tha lower ehlorobanaanaa accumulate and paraiat on tha baaia of partition ooaffieianta. Tha SPA Draft ahould Halt its conelualona to thoaa ehlorobanaanaa that are praaant. Raaponaa Tha Criteria Document atatas that tha ortho- and para-dichlorobanaanaa have baan shown to ba quite lipophilic, and can be expected to bioeccumulata in tiaauaa with high fat content during prolonged, continuous exposure para-Oichlorobenxena has baan detected in huaen adipose tissue and all three iaoaara have baan detected in blood. Tha Criteria Docuaant only addresses tha dichlorobenzenes and thus does not address tha relative persistence of all the chlorinated bansenes. 13. Commentt Several specific coaaents were provided concerning production data from the chlorinated bansenes such aa incorrect descriptions of the pro duction of the compounds and probleaa with tables. Responsei These coaaents are not directly applicable to tha RMO. proposal. The discussion in the Criteria Docuaant on production data states, "only two U.S. eoapanias produce s-dichlorobenxana and in 1974, 31,000 pounds wars i^orted." 14. CcManti Tha environmental Transport and Fata chapter overlook# Monsanto data on bioaccuaulation and photogradation. In addition, tha chapter postulates that chlorinated compounds are likely to be resistant to biotransformatlon. This is not demonstrated in the data which show lower chlorobenzenes exhib iting relatively rapid biotranaformatlon. Raaponaat Tha focus of the Criteria Document is upon the health effect# of the dichlorobenzenes and thus only minimal data on the environmental transport and fata were included in the document. The Criteria Document did not discuss anvironmsntal biotranaformation of the chlorinated benzenes. 11-38 CMA 053134 15 Oommnt: Throughout tl ecological effects section, the report states that chlorobenzenes are toxic or have adverse effects on reproduction of invertebrates ana tish. host chemicals have these properties at sone concentration. No attenpt was made to put the toxic effects in perspective. Response; These coments are not applicable, as the criteria Document discusses health effects in animals and humans and not ecological effects. 16. Oonrent: Detailed concents were provided on nonochlorobenzene. Response; These contents are not applicable as the Criteria Document deals with the dichlorobenzenes and not the nonochlorobenzenes. 17. foment: The description of the Hawkins, et al. (1980) rat study reveals that the data do not support the conclusion drawn by EPA. The Agency cannot conclude that "1,4-dichlorobenzene appears to be well absorbed," on the basis of a study in which no quantitative measures of absorption were attenpted. Response: 0?A agrees; however, the Criteria Document does not include this conclusion. The Hawkins, et al. study described the tissue distribution of p-dichlorobenzene in aduTtTenale rats following inhalation, oral or subcutaneous exposure. This study showed that mast of the activity (91-97%) was eliminated in the urine within five days after cessation of exposure, while smell amounts were found in the feces and expired air. About 50-60 percent was excreted in the bile during the first two days, siegesting reabsorption in the enterohepatic circulation. EPA agrees that it is not possible to conclude that the conpound was "well absorbed" on the basis of this study alone, since there have not been studies reported which determine the percentage of a dose of dichloro benzene absorbed following oral or inhalation exposure, EPA is basing its assured absorption of p-dichlorobenzene (100% from oral exposure and 60% from inhalation exposure) upon the absorption characteristics of benzene and the smaller chlorinated ethanes and ethylenes (Astrand, 1975; Dallas, et al., 1983). This is reasonable based upon the similar molecular weights oT the conpounds and the fact that there does not appear to be any reason why the absorption characteristics would be markedly different between benzene and these conpounds. CMA. 053135 18 It should bs observed thst ths metabolism data generated by dosing ths animals with dichlorobsnzsnss in oil uy haws bssn affsctsd by ths hiels. Studios haws shown that oil affacts metabolism. Response* ths coamenter did not cits any studios or saplain how oil sight haws affsctsd sstaboliss or SPA'S conclusions. Therefore, SPA cannot fully address ths eomsant. However, SPA is basing its conclusions on sstaboliss on studies in which p-dichlorobenxane was admin1starsd through inhalation, oral and subcutaneous exposure. SPA is unaware of any studies suggesting that oil has affsctsd the results of studios on dichlorobansenej howawar, since SPA is not relying totally on corn oil studies, the conclusions would not change swan if this wars shown to be the ease* 19. It should also be notad that, like aonochlorobensene. diehlorobenssnes do not bioeoeumulste but are instead rapidly biotransforned and alininatad (Hawkins, at el.. 1980). Response* .20 There haws not bssn studiss reported which determine the percentage of a dose of dichlorobensene absorbed following oral or inhalation exposure. (See Consnt/ltssponss 16. shows.) However, p-dichlorobenxone has bssn shown to accumulate in huaen blood and adipose tissue (Norite and Ohi, 1975) Dowty, etal., 1975). Mention of the lethality of darmally applied 1,2-dichlorobenzene in the Reidel (1941) study is not meaningful without a description of the methodology, the dose applied and the degree of lethality. Without such information, thera ara too many unknowns to conclude anything substantive about the study. .21 Die Reidel (1941) study is not discussed in the final Criteria Document since darmally applied 1,2-dlchlorobenzene is not directly relevant to ths possible health affects of ths compound through drinking water. it* It is stated that 1,2-dlchlorobenzene is sera active In its liver toxicity and protein binding than la 1,4-dichlorobenzene. However, the last line of the Summary discusses this activity for 1,4-dlchlorobenzene only, suggesting that 1,4-dichlorobenzene is quite active, while 1,2* dichlorobenzene is lass so. In fact. Tables 8-4 and 8-5 show -that neither coiqxsund is very active* 11-40 CMA 053X36 RM0DM> Thia coaaint addraaaaa tha relative liver toxicity and protein binding of 1,2-dichlorobenzene (tha ortho-isomer) versus 1,4-dichlorobenzene (tha para-isomer). For tha purpoaa of thia rulemaking, only p-diehlorobenzene ia balng addraaaad and thua tha relevant iaaua la tha livar toxicity and protaln binding of tha para-laonar. p-Dlchlorobensene haa baan shown to axhlbit biatologieal alternatives in tha livar In rata by gavaga (BattelleColumbus# 1978a# bi 1980a# b) and hiatopathological changaa in tha livar in inhalation atudiaa (Hollingsworth, at al., 1956)* Tha (uaaary of apldaaiologic data notaa that tha data ara inaofficiant to avaluata dose-response relationships. Thia conclusion auggaata that tha apldaaiologic data ara aufficiant to avaluata ganaral toxicologic ralationaipa. In fact# tha data ara lialtad to caaa atudiaa in which axpoauraa wara aixad with othar chemicals. It la thua uncertain whether tha effacta noted wara related to dichlorobanzana exposure. Response t SPA agreea that tha human data' ara limited to caaa atudiaa in which othar chamicala may have baan involved. Thua# SPA ia not baaing tha RMCL upon human data but ia baaing it upon animal data. 23. Cnimantt Tha alleged aaaoclationa between dichlorobenzenea and blood-forming tiaaua toxicity and between 1,2-dichlorobenzene and chromoaomal alterations in humane oust be questioned on several grounds. First# there is no valid experimental evidence that chlorobenzenes have nitagenic/clastogenic activity in test systems relevant to mammals. Indeed, a bona narrow chromosomal taat in rats was negative. Second# tha activities described ara those expected for benzene which may have been a factor in many of these observations. Third, the recent NTP subchronic and chronic test in two species failed to demonstrate effects on the blood-forming tissues. Response* *FA agreea that exposure to p-dichlorobenzsna has not been shown to result in blood-forming tissue toxicity and thua livar toxicity and not blood-forming toxicity was used as the endpoint in the derivation of the RMCL. With regard to the association between p-dichlorobenzene and chromosomal alterations in humans# the data Indicate that p^dichloroben- cene is mutagenic in certain of the test systems# such as its ability to interact with and damage bacterial DNA in the X. coll differential toxicity assay system. published. No evidence of mutagenic activity in animals has been 24. Comment: Table 8-5 claims that the Doosnjaz (1946) inhalation study used a dose of 1()5 mg/m3 of 1,4-dichlorobenzene. Such a high concentration would be almost impossible to generate in an inhalation chamber. 11-41 CM7V 053137 t Response This coseent ia not relevant aa tha Dceenjax (1946) atudy la not discussed In tha final Criteria Document. 25. Ccaaient; Tha obaervatlon that tha dlchlorobanaanea have net baan extensively studied for autagenic activity ia inaccurate, m overlooked tha unsched uled DMA aynthaaia aaaay and tha call tranefcreation aaaay partoread by Williams, at al. All testa reported that tha dlchlorobanaanea vara without autogenic activity. Response) 26. Tha Mutagenicity data on p-dlehlorobanseue has shown mixed results, dMonatratad aa followst p-Dichlorobenzene has baan shown to induce abnormal aitotlc division in plants and to increase tha frequency of bach nutation in tha fungus, Aspergillus nidulana (Prasad and Pramer, 1968; Prasad, 1970). Tha cospound was not nutagenic whan tasted in a culture of histidine-requiring eutanta of Saleonalla typhieuriun or in tha I. coll WP2 system (Anderson, at al., 1972) Anderson, 1976) Siaeon, at al., 1979). p-Dichlorobenxene has not'baan shewn to be autaganic in animals (Anderson, at al., 1976) Anderson and Hodge, 1976). > Coneant) Tha CPA Draft contends that tha MTP rat study on 1,2-dichlorobenzane was not conducted at an appropriately high dose level (120 mgAg) and that tha bioaasay may not have baan sufficiently sensitive to detect potential carcinogenicity. This la not a supportable contention since tha HTP Board of Scientific Counselors indicated that tha dose selection was appropriate. Response; This coaesnt is not relevant since the draft report of the results of the NTP studies with 1,4-dichlorobenzene (pars-) has not bean made available as yet* SPA will not make a final assessmsnt of tha compound's carcinogenic potential until tha results of the study become available. 27. moments The BPA draft notes that no data on reproductive or teratogenic effects were available for review. Xt should note that teratogenicity studies on nonochlorobenxene, 1,2-dlchlorobenxene and 1,4-dichlorobencene have been performed by the Chlorobenzene Prograe*Paael and the results have been submitted to the epa Test Rules Developasnt Branch. Response) SPA has cited several teratogenicity studies in the final Criteria Document (Hodge, et al., 1977; Hayes, at al., 1985) Hayes, et al.( 1982). XX-42 CMA. 053138 Qjuuent: The EPA draft should be revised to delete repeated references to bioaccunulation as there are no available data that denonstrate bioaccuitulation in human tissues. Response; p-Dichlorobenr**"* has been shown to accunulate in human blood and adipose tissue (see Cbnsent/Response 18, above). 29. Oocrent; Specific comrents were submitted on the trichlorobenzene, tetrachlorobenzene, pentachlorobenzene and hexachlorobenzene chapters. Response; These consents are not relevant to this rulemaking since they do not discuss p-dichlorobenzene. H. TREATMENT FCR CONTROL OF VDCS These consents are being addressed here as a courtesy to those who consented and as a further explanation of the basis for EPA's proposed MCLs. Pinal consents and responses will be provided when the MCL is pronulgatsd. I. Consent; A treatment device, consisting of a conbination of ozone and ultra violet light, will significantly reduce concentrations of voCs. (Oonsenter provided promotional raterial on the device.) Response; This raterial does not directly inpact the RMCL and thus will not be addressed in this package. EPA will consider this material with the MCL proposal-consents. 2. Consent; Granular activated carbon (GAC) units or systems using reverse osmosis and activated carbon are effective point-of-use devices and should be considered generally available technology (GAT) by EPA. Point-of-use treatment presents a cost-effective and reliable alternative to central water treatnent for removal of VDCs in drinking water. Response; EPA agrees with this consent and is considering authorizing point-ofuse treatment devices under certain circumstances. See the Fed ral Register MQ, Proposal for a further discussion of this issue. 11-43 CHA 05313s 3 rnmnsnt! VOCs should be controlled at th source, not at tha tap. Thar* are problems with various treatment techniques for removing vocsj GAC only weakly removes VOCs and air stripping of VOCa is unfeasible. Response! DA agrees that VOCs should be controlled at the source and is working through a variety of programs to control their releases. However, because they are not always controlled at the source, drinking water systems must treat the water they serve. GAC is effective for the removal of all vocs to low levels except vinyl chloride. Aeration is also an effective treatment method. 4. Comment! HVA should provide performance standards to meet the statutory requirements of the SOMA, allowing utilities in cooperation with the primary agency to select the most effective treatment process. Treatment techniques are extremely site specific and effectiveness is dependant on numerous factors. Response! The definition of "performance standards" is unclear, but IRA is setting MCLe to meet the requirements of the SOKA. DA agrees that the effectiveness of treatment techniques is dependent on numerous factors. DA does not intend to require any system to use special treatment tech* niques to control VOCsi systems may select treatment techniques that are efficient at the specific site. 5. Comment; The level of contaminant removal should be a function of the costeffectiveness of the removal technology. Increments of VOC removal should be compared to incremental increases in treatment cost for setting the MCL. Response! DA agrees that the level of contaminant removal should be a function 'of the cost-effectiveness of the removal technology and has examined incremental increases in treatment costa for setting the MCLs (see the Federal Register MCL proposal). 6. Comment! A limit of technology or limit of detection approach to setting the MCLs should be used, not an approach based on quantitative risk assessment. GAC can bring the concentration of most VOCa down to 0.1 ppb or the limit of detection and thus technology availability is not a limiting factor in setting the MCLs. 11-44 CMA 053140 Resgonsei PA agrees that a limit of technology or detection approach should ha oaad to sat tha MCLs and baa applied this approach In tha analysis (saa tha Psdsral Register MCL Proposal). KPA also agrees that technology availability Is not a Halting factor In sotting tha MCLs. 7. Oosmti Biological degradation, osonatlon and raversa osaosla arc practical and cost-effective taehnologlas for VOC raaoval. Responsei SPA faals that lnsufficiant data ara available to analyse tha tech nologies of biological degradation, osonatlon and reverse osmosis for practical application and cost-effectiveness. The current literature does not support tha claim that these taehnologlas ara practical and cost-effective. Thera are indications that natural biological activity ay convert one VOC to another (i.e., trichloroethylene to vinyl chloride) which aust be considered in an evaluation of biological degradation as a treatment technology* X. COSTS OF TREATMENT Those coomsnts ara being addressed here as a courtesy to thoss who comanted and as a further explanation of tha basis for IPA's proposed MCLs. Pinal cossMnts and responses will be provided when the MCL is promulgatsd. 1 Consents Operating and maintenance costs, as well as capital cost, should be compered in any table coshering costs of alternative treatment methodol ogies. This appears to be missing in Table 0 In tha June 12 PR Notice. Responses SPA agrees that operating and maintenance coats should be factored in an analysis of treatment methodologies, nils was included In Table 8 (p. 24349) la the calculation of unit cost (cents per X gallons) even though the annual operating and maintenance costs were not presented In the table* 2. Comments ' The estimates of cost of GAC and aeration should be substantially higher than those developed by SPA and presented in the Paderal Reqister Notice, 11-45 053141 There are several reasons for the differences In coat. For aeration, tha coat for buildings and pua^ing facilitiaa war* added to tha commenter's coat, bat were not oaad in developing SPA'a coat* The operating and mainte nance coat la vary aanaitiva to tha electric potter rate. The commenter's rata la $.10 per KWH while SPA uaed a rate of $.07 par KNH. Tha coamenter included the coot of replacing tha wall ptu^a which may not alwaya be neceaaary and waa not included by SPA. In addition, the commenter's deaign ia baaed on treating average daily flow, bat actual flowa era one-third of thia. This reaulta in tha capital portion of the rata appearing three tinea higher than if deaign flow ia uaed ia the danoninator. For GAC, tha coenanter1 a deaign ia baaed on treating average daily flowa, but actual flowa are approximately one-third of thia. The commentar's equipment coata are high compared to SPA*a eatiaatea. One major expense in the rnmntir'i ayatem ia a backwash recycling ayatom, while the SPA coat eatianta aaoumed discharge to a aewer. SPA faala that thia recycling system ia probably not coat-affective considering that backwash occurs for 10-15 minutes every 39 days. The electric power cost assumption uaed by the eommanter-is $.10/KWH versus $.07/XHB uaed fay SPA. The eommanter assumes a GAC cost of $.40 per pound versus $.50 per pound assumed by SPA. In addition, the eommanter shows coat for replacing well pump and motor. SPA's costa do not Include thia assuaptlon, since existing well pumps and motors would likely be suitable. Comment! Cost of treatment nay coma down due to development of new technologies and increased utilisation of existing techniques. Response: SPA agrees that there is a logical basis to the assertion that costs of contaminant removal may come down due to development of new technologies* However, there is no direct evidence to support this conclusion and SPA mist consider the current costs of technology in the development of MCLs. % 11-46 CMA. 053142 ZZI gCHHanv Qf COWgMTS AMD EPA RESPONSES TO THE JUNE 12/ 1984 RMCL PROPOSAL! ADDITIOHAL TECHNICAL ISSOXS A. STRENGTH OF EVIDENCE OF CARCINOGENICITY 1. CJ--ntt 0A *1101114 not refer to a substance as "almost" an IARC Group 2B and usa as a baala for regulation. In addition, if aajor new data hava baan developed ainea tha last IARC review and SPA raelasslflas a substance, the evidence and reclassification should be reviewed by SPA*a Science Advisory Board. Response BPA's Science Advisory Board reviews najor new information on chem icals and has reviewed IRA's classification of several of the VOCs based on carcinogenicity. SPA agrees that a substance should be placed into an IARC category baaed upon the best available scientific information. 2. Cumnantt Distinguishing between carcinogens on the basis of mechanism is not warranted by the scientific information at this time. This is demonstrated in the following attached article# Frederica Perera. The Genotoxic/Epigenetic Distinction) Relevance to Cancer Policy. Environmental Research, Volume 34, 1983. A summary of this article followsi AUTHOR'S ABSTRACT: Should federal agencies use separate, less stringent guidelines for regulating epigenetic or nongenotoxic carcinogens on the assustption that thresholds are likely to exist for these agents? This article reviews recent Initiatives by the Environmental Protection Agency that either propose or informally adopt this approach in light of responses from the scientific coaminity and a review of the recent literature. Relevant background is pro vided by current research concerning the role of chromosomal damage and oncogene activation in carcinogenesis along with findings that classical promoters or "epigenetic" agents can induce both DBA damage and chromosomal rearrangements. The con clusion is that such a revision of cancer policy la not now supported by available scientific data concerning chemical carcinogenesis. "Genotoxic" may be broadly defined as "having the potential to cause a heritable change in the structure or sequence of the genetic material at the level of the nucleic acid, the gene, or the chromosome. A distinction can be made between "direct" genotoxicity (in which the parent cocpound or its metabolite Interacts with the genetic material) and "indirect" genotoxicity (in which the actual damage is inflicted by a reactive agent or IZZ-1 CMA 053143 factor induced by the genotoxin). "Epigenetic" nay be equated with "nonyenotoxic." AMPLIFICATION: Attenpts ts distinguish types of carcinogens have important implications for regulation of these agents. The concept of a clear distinction between epigenetic and genotoxic agents could affect the interpretation of experimental data with these resultss 1) Reconsideration of linear extrapolation of dose response curves# and new enphasis on thresholds and "hockey-stick type" curves. 2) Strengthening the idea of reversibility of activity below a certain threshold level# because of the nechanisms of epigenetic activity (tissue injury# imtunosupptessive effects, etc.) 3) Reinterpreting curves an the basis that "the carcino genic effect in experimental animals was likely to be secondary to physiological effects triggered only at high levels." Proponents of the distinction have classified neny inportant chemicals as epigenetic. These include asbestos# the insecti cide permethrin# formaldehyde# diethyl stilbestrol (DBS), and others. With regard to.its effect on regulation# the arguments for and against the distinction cane to a head in the Oomtents on the Draft Carcinogen Assessnent Group Proposal (EPA, 1982). "Vhile there was sore qualified support, the rejority were negative on the yenotoxic-epigenetic regulatory distinction." A large body of specific information is cited to show that the distinction should not be used in developing regulations. With regard to the mechanism of carcinogenic action# the genotoxic and epigenetic rechanisre are not mutually exclusive. "It ray be preferable# therefore, to think of the carcinogenic process as comprising three general stages--initiation# promo tion# and progression--each involving a variety of mechanisms# both genetic and non-gene tic." Response: EPA agrees with the substance and conclusions of this article that there is insufficient scientific basis to distinguish classifying chemicals as yenotoxic or non-genotoxic carcinogens. As explained in the final rule preamble, EPA is classifying chemicals according to the strength of evidence of carcinoyenicity and is not classifying chemicals according to mechanism. (See Cbiment/Response - I.D.l). III-2 CMA 053144 B M0P51 LIVE* TOMORS 1* CB>inti Mouse liver tumor data arc inadequate to serve as tha basis for a meaningful quantification of huaan cancar risk* Tha rsport by tha International Ixpert Advisory CoMlttae to tha nutrition Foundation antitlad Tha Rslavanea of Mouaa livar Hepatoma to Huaan Carcinogenic Risk" confiras this visa. Tha following is a suaaaxy of this raportt Tha complexity and difficulty of idantifying and classifying livar tuaors in nica ara clsarly displayed* Those Conors occur in several forma, both benign and malignant, with various sub divisions* Classification depends largely on morphology. Functional criteria also apply, including affects on enzyme reaction and other chemical reactions* Types of biological behavior used as criteria include invasions of adjoining tissues, aetastases, and growth of transplants* Tha report enunerates factors affecting the incidence of ttaors* These include genetic factors (with wide variations among strains), dietary and related factors, sex and sax related conditions, and age. In one instance, a laboratory-to-laboratory variation was reported for spontaneous hepatomas in the sane strain of nice* One special difficulty with the use of nice in assays is the large number of spontaneous neoplasms observed. Morphological differences between spontaneous and induced neoplasms occur in soma cases and not in others* The variation of types of spon taneous tumors occurring in different strains of mice is co^lex. with respect to tests on suspected carcinogens, one instance is reported in which different agents produced quite different distributions of the various type of tumors* A broader view is provided by the National Cancer Institute Bioassay results for 85 chemical agents. A tablulation shows the occurrence of cancer types (liver and non-liver) for differ ent sexes and for different animal species (mice and rats). The occurrences for different chemicals ara widely distributed between cancer types and between species* They are less widely distributed for sex, within each species* These considerations lead to a cautious conception of regulation. "From a regulatory point of view, caution is necessary in making judgments based upon tuaor pathogenesis alone, since we do not have a full understanding of carcinogenic mechanisms." Patently genotoxic chemicals should be strictly regulated* "Less concern is werranted in the case of chemical induction of tuaors only in mouse liver, particularly if the tumors are benign neoplasms, that are associated only with high exposure levels that produce additions! biological effects such as chronic tissue injury." IXX-3 CMA 053145 % However, a sore conservative course would be warranted when additional toxicological data suggest an increased potential for hunen risk. Response: EPA's policy regarding mouse liver tumors and their relation to human cancer risk is discussed in the Federal Register Final Rule (Appendix A). ERA agrees with the report that ''caution is necessary in making judgments based upon tunor pathogenesis alone, since we do not have a full under standing of carcinogenic mechanisms." EPA also agrees that less concern is warranted where a chemical induces tumors only in souse livers and that a sore conservative course is justified when other toxicological data suggest carcinogenicity. ' 2. Ctamnent: The work of Roe and others (Proc. Nutr. Soc. 40:57, 1981) demon strated that libitum feeding substantially affects the hormonal status of rodents and produces nighly statistically significant effects on sur vival and on several varieties of spontaneous tumors. In one instance the crude incidence of SPP mice with liver tumors was reduced from 14% in males fed ad libitum to 2% when fed on restricted diets. Lung, pituitary and lymph or thynus tumors were correspondingly reduced. Therefore, liver tumors in imle mice who have a substantial spontaneous incidence of such tumors should not be the sole basis for assessing potential carcinogenicity. Response: This concent concerns the weight of evidence issue on mouse liver tumors, including conditions under which mouse liver tumors along with any other evidence for carcinogenicity are interpreted as either sufficient or limited evidence for carcinogenicity, as discussed in EPA's Proposed Guidelines for Carcinogen Risk Assessment (49 FR 46294). In such a case, EPA looks carefully at short-term test results and does not rely only on liver tumors in mice with spontaneous incidence of such tumors. The concenter cites evidence for reduced formation of spontaneous tumors in mice fed restricted diets as opposed to ad libitum diets. EPA agrees that caloric intake could play a role in the occurrence of tuners. However, the Agency does not believe that there are sufficient data at this time to incorporate this parameter into the Agency Guidelines for Carcinogenic Risk Assessment, since ad libitum feeding is the usual procedure in carcino genicity studies, arS3 until mote data consisting of conparisons with ad libitur and restricted feeding become available for consideration, EPA will continue to weigh evidence for carcinogenicity as stated in the guidelines mentioned above. C. AADI APHtCACH 1. Cbnrent: The development of RMCLs for non-carcinogens based upon human epidem iology or animal studies to determine the "no ffect" levels for chronic II1-4 CMA 053146 t There li however, a constant need to review and revise the no-obaarvedadverse-effect level (MOAXL) for each co^ound regulated. Responsei XPA agrees that the MOAXLs for each eo^ound regulated should be up dated as new information becomes available and SPA plans to continually review the scientific literature and update the umbers, as needed. 2. Coswan 11 Me can certainly agree that for compounds where human ingestion atudiaa have been used to determine the MOAXL, the use of an uncertainty factor of 10 may be well justified. There is, however, significant ques tion as to the need for a safety factor of 100 where long-term animal studies have been used and of 1,000 where inadequate animal studies were used as the basis for determining the MOAXL* Responses XPA bases its uncertainty factors upon the MAX guidelines (Drinking Mater and Health, Vol. I, 1977) which state that an uncertainty factor of 10 should be used with valid results from studies on prolonged ingestion by man; an uncertainty factor of 100 should be used with valid results of long-term feeding studies on experimental animals in the absence of human studies; an uncertainty factor of 1,000 should be used with scanty results on experimental animals. XPA believes that these uncertainty factors have been protective in the past and adequately account for uncertainties in the data. According to the NAS, "When the quality and quantity of data are high the uncertainty factor is low and when data are inadequate or equivocal, the uncertainty factor must be larger." (Drinking Mater and Health, Vol. X, 1977, p. 804.) 3. Comment: In deriving RMCLs, XPA should consider all potsntial routes of human exposure to volatile organics via drinking water, and routinely include these factors in their calculations of AADXs. Baaed upon Dr. Brown's paper, an additional reduction of at least 50% after the 80% reduction recommended by the MAS, would appear to be indicated. The following is a summary of Dr. Brown's paper (Brown, at al. 1984 The Role of Skin Absorption as a Route of Kxpoeure for Volatile Organic Compounds [VOCa] in Drinking Mater. American Journal of Public Health, Volume 74, Ho. 5); Contaminants in drinking water`may operate through avenues other than ingestion, in particular through skin absorption. The authors analyze literature data on skin absorption for aqueous solutions of ethylbenzene, styrene, toluene, and xylene. They uae Pick's Law to extrapolate absorption rates to the low levels which could be present environmentally. III-5 CMA 053147 The authors proceed to calculate total quantities of the hydro* ffgrKffnf absorbed from very dilute solutions by adults and child ren under various assumed conditions of exposure (in bathing and swimming). oalng these results together with reasonable estiaates of drinking water ingested* they calculate that absorption can account for 29*91 percent of the total hydrocarbon trane* ferred. (The high figure Is extreme* being based on laeersion of a seall child for 1 hour.) Responsei SPA agrees that all sources of human closure to VOCs should be con* aidered in the calculation of AADls. However* SPA believes that an 80% redaction Is sufficient to account for other sources of exposure, includ ing inhalation end darnel exposure. IPA does not believe that an addi tional redaction of at least 50% after the 80% reduction Is warranted. 4. Conwsnti Per VOCs, by definition* air will be the prieary source and even that source is ainiscule by co^arison with the waterborne source* even where air pollution is high. At the highest contamination site recently reported for aethyl chloroform in the air (H.B* Singh* et al.* Environ. 8ci. 8 Tech. 16t872* 1982) the concentration averaged 4 ug/a3. If that concen tration (i.e., 4 ug/m3) were inhaled for 24 hours a day it would still represent under 5% of an RMO. calculated for drinking water as the sole source of this material. For the occupationally-exposed working population this RMCL represents less than 0.003% of the TLV and is insignificant. Response EPA does not believe that the RMCLs should be set based upon a com parison with the 3Z.VS, for the two values are set based upon totally different factors. RMCXa are designed to be protective of the entire population over a lifetime exposure while TLVs are occupational standards designed to be protective for a particular subset of the population (workers) over a specified time period (5-day work week). 5. Comment! The application of the 100-fold factor to the highest no-adverseeffect dose measured in animal studies to establish ADXs for humans was one of the key steps in deriving food tolerances. The expert cosaittees of the FAO/WHO believed that a steadfast* indiscriminate use of the 100fold factor would not provide due consideration to species* strain* and sax differences among animals, to variations in susceptibility among exposed individuals and inadequate human and animal data* among others and, therefore* recommended the employment of a range of safety factors depending on the quality and nature of the data under review* Responsei PA agrees that a steadfast. Indiscriminate use of the 100-fold uncer tainty factor is not warranted. EPA believes that a range of uncertainty IZX-4 CMA 053148 factors, depending on tha quality and quantity of tba data, should ba applied. I urga tha EPA to re-evaluate Its ason practice of uslnq safaty factors of 10, 100, and 1,000 steadfastly and should consider tha Incor poration of appropriate safaty factors based on FAO/WHO recosmendations. Such an approach would reduce the arbitrary nature of safety factors thereby lending sore scientific support to tha AADXs derivation process. Response! EPA accepts tha recoeeandationa of the MAS Safe Drinking water Cniai ittaa (Drinking Water and Health, Pol. I, 1977) and applies uncertainty factors of 10, 100, and 1,000 as the data indicate. However, XPA will apply other uncertainty factors if the data suggest an intermediate uncer tainty factor nay be more appropriate. 7. CDMinti I believe that the literature contains sufficient information, al though not precise, for the ERA to assess the contribution of inhalation exposure and, possibly, oral exposure for some contaminants instead of reducing the AADIs by an arbitrary 80* or 99% to establish RNCLs and MCLs. Resgonsei EPA agrees that for. certain contaminants, information is available on the contribution from inhalation exposure. When data are available and reliable, EPA believes it is appropriate to factor this into the ADI. However, EPA does not believe that sufficient data are aveilable on all the V0Cs at this time, and thus believes that it is appropriate to reduce the AADIs by a set value for these co^ounds. 8. Co--nt A study suggests that petroleum-product vapor buildup in the bathroom resulting from volatilisation as one takes a shower may be sufficiently high so as to cause or contribute to mucous membrane irritation. The predicted bathroom air concentrations are consistent with those measured in gasolinecontaminated homes whose residents have complained of headaches and eye, nose and throat irritations. Response! EPA agrees that volatilisation is one route for inhalation exposure to VOCs. 9. Coaanent: For acute exposure, the use of low level chemically contaminated water for showering purposes can generate vapor in the confined area of the bathroom at levels sufficient to cause or contribute to mucous tissue III-7 CMA 053149 irritation conronly reported in affected hones. High temperatures and humidity may also contribute to these effects especially in the bathroom. For chronic exposure, the use of chemically contaminated water at EPA reconrended guidelines for all purposes in an affected hone may result in inhalation, oral, and dermal exposures leading to emulative doses exceedirq EPA's reconrended total daily body burdens for an adult and a child. Response: EPA does not agree that emulative doses exceeding the ADZ caanonly occur in hones. However, there is undoubtedly sons exposure through showering and EPA believes that by reducing the ADI by 80% to account for exposures from inhalation, oral ana dermal exposure, the public should be sufficiently protected against all routes of exposure. 10. Concent: "Non-carcinogens" will have RMCLs chosen by using safety factors applied to a NQAEL. He question the adequacy of such safety factors in certain circumstances, since risk analysis is being applied to "carcino gens" , why is a similar approach not taken towards the "non-carcinogens"? Response: EPA believes that it is appropriate to assume a threshold approach for non-carcinogens and to calculate the RMCLs using safety factors applied to a NUAEL. This approach is reconrended by the National Academy of Sciences (Drinking Hater and Health, Vol. 3, 1980) and by numerous other scientific organizations. EPA is not using risk analysis to set the RMCLs for carcinogens. D. RMCLS FCR CPRCINOGEtS AT ZERO 1. CDirrent: Althougn the health effects work groups studying the drinking water problem believed there was sufficient data to cause concern, every group qualified its recoamndation by saying, variously, that the data were limited, more studies were needed, and that the difference between genotcatic and nongenotoxic carcinogens should be addressed by EPA. until such questions are resolved by further information, we believe the RMCLs should not be set unduly low and certainly not at the zero level. Response: EPA believes that there are sufficient data available to make a judg ment on the carcinogenic and non-carcinogenic effects of the nine VOCs. Additional research will add to current knowledge on these chemicals; however, EPA Delieves that the current data show sufficient reason for concern over the adverse health effects of the chemicals, (See the RMCL Proposal tor a discussion of the adverse health effects of the VOCs and Cbnnent/Response - i.D.l for a discussion of genotoxic versus non-genotoxic carcinogens.) III-8 CMA 053150 2t If you aut develop RMCLa, non* of than should bo 0. Tho word "non" would bo proforablo to using "0". it would bo even bottor to adopt a polity which would oay "It ia tho goal of all watar supplier* and regula tors that thara bo no contaminants in tho drinking water. ' Responsei 1 Tho cowont does not identify why this ioouo is important or haw it should offset tho MCL. Tha SOW* roquiros that RMCLa bo ostablishod and states that an ma is a health goal* *PA roeognisos that "non" is equivalent to "zero" and has chosen to us* tho word "saro". While it is ideal that thara bo no contasdnants in drinking watar* goes contaminants have thresholds for adverse health offsets* and it is important to sot RMCLa that rofloct thos* edworso health affect levels* Csrcinogans will havo RHCLs of sero. 3* Common t Section 1412(b)(1)(B) of tho Safa Drinking Water Act roquiros tha Administrator to detormin* the lowest level at which health offsets may occur, plus a margin of safety* in establishing RMCLa* This requirement mandates a risk assessment method, sotting RHCLs at soro or at analytical dotoetion limits would fail to fulfill this statutory requirement. Rssona*t FA does not agree that tho SDWA mandates a risk assessment method. Using a risk assessment method to set a risk level and tho RMCL would not fulfill tha statutory mandate that RMCLa ore to be set to prevent adverse health affects with a margin of safety* Tha risk calculations consider levels at which a specified concentration of a chemical results ia a certain axeess cancer risk in the population. These risk calculations do not consider the no-effect level with a margin of safety. Rather, they approve of some risk and some projected level of occurrence of the adverse effect* RNOs are by definition based on health and safety considerations, but this approach is not based on such considerations. Most oospounds have a concentration benaath which health risks ora not identified. As a result, selection of saro for an RMCL would not provide significant addi tional protection of health beyond that provided by a highar* finite*, level* Response t PA disagrees. EPA believes that chemicals which or* known and probable human carcinogens should be classed along with other carcinogens which are believed to have no threshold and thus have no safe level of exposure. As such, selection of zero as an RMCL does provide additional protection beyond that provided by a higher, finite level* III-9 CMA. 053151 5 Qxncent: Settiny RMCLs at zero would also present a misleading picture to the public, since most of the compounds for which RMCLs are currently proposed are also ingested daily via inhalation* food intake* or smoking. Attempts to reduoe concentrations to zero would not necessarily reduce daily expo sure to any given compound. Response: EPA agrees that mast of the conpounds for rtiich RMCLs are proposed are also ingested daily to some extent via inhalation* food intake or sacking. However* EPA believes that it Is appropriate to reduce the intake ot potential human carcinogens via drinking water as it should ultinetely lead to an overall reduction in the daily exposure to a compound. 6. Oamrent: If the EPA sets RMCLs at zero for each carcinogen* then they provide no information and guidance. The potency of carcinogens varies ten mil lion fold to one from agents like saccharin and 1,1,1-trichloroethane to agents like aflatoxin Bi and dioxin. Surely Conyress did not mean that EPA set the same level for saccharin as for dioxin. Response: The goal of RMCLs is not to provide information and guidance; it is to set a health goal for the MCL rulemaking. EPA has considered strength of evidence in setting the final RMCLs for carcinogens so that the RMCLs for chemicals with sufficient evidence of carcinogenicity are set at zero and tne RMCLs for cneimcals with equivocal evidence of carcinogenicity are set at a non-zero level. Thus* chemical potency is considered in the evaluation of the strength of evidence. 7. Consent: It is currently inpossible to label any mterial as definitely not a carcinogen* since a test with inproved sensitivity or better experimental design may subsequently show that the material is carcinogenic. Indeed such a case is quoted within tnis notice of proposed ruleneking. Response: The Agency agrees. EPA classifies chemicals according to the weight of evidence of carcinogenicity at the current tine. The Agency recognizes that new data may become available in the future which would result in the reclassification of the chemical and in such a case* EPA would repropose the standard for that chemical. 8. Oonwent: The use of zero for an RMCL is essentially based on the belief in a linear dose-response curve at low doses -- so that any amount of material might cause some irreparable damage. However* choosing zero RMCL as a III-10 CMA 053152 policy decision denies the possibility that ths doee-response relationship Is not linear, as is plauslbls and psrhaps Uksly with some Materials. Thus an automatic choice of ssro for ths RMCL of any "carcinogen" prevents the use of other infornation which nay be available. Response m believes that it is appropriate to follow a conservative approach, in order to be protective of honsn health# and believes# based on best scientific judgment and review of nany cancer studies# that the doseresponse curve is probably linear at low doses* IFA does not agree that by setting an UNO. at aero# other infornation on the chemical nay not be used. The Agency is aware that evidence of non-linear dose-response curves nay bacons available and will consider any such evidence when it becomes available. 9. Conaanti Zt seems odd that a material which has been shown to provoke a car cinogenic response should be specially singled out for having a aero RMCL. There are other responses which could also be irreversible and caused by very low doses (l.e., have no threshold) -- especially in certain groups of sensitive individuals. Mich less is known about the wtagenic and teratogenic effects of most materials# for exanple# especially at low doses, and low doses of sons materials ni^it have feto-toxie or neurologi cal effects, especially if they bioaccunulate. Response SPA considers all effects (including mutagenicity and teratogenicity) in the analysis of the chemicals and has set RMCLs of sero for those chemicals showing a carcinogenic response since this response has not been shown to exhibit a threshold. Mutagenicity is factored into ths classifi cation of the chemical for carcinogenicity, according to the SPA Proposed Guidelines for Carcinogen Risk Assessment and can result in a chemical being classified in a different category than it would have been had the mutagenicity data not have been available. The SPA Proposed Guidelines for the Health Assessment of Suspect Developmental Toxicants (49 PR 46325) considers teratogenicity to be a threshold effect and proposes that a safety factor approach be used to assess developmental toxicants. The rnmmmntsr does not explain how this conant should affect HPA's decision making for these VOCs. 10. CMBt> The proposal appears to assume, even if not explicitly stating so, that achieving a xero level of these pollutants in our water supplies will achieve a xero level of risk. This is not true. He know that the pollutants currently exiat in at least some supplies, and so aome action would be required to reduce their levels. Associated with any such actions will be concomitant risks. Thus, for exa^le, adding aeration stages or activated charcoal filters to water supplies will have some effect on the levels of bacteria within the water supplies -- possibly leading to increased risk. Even the construction of such filters or III-11 CMA. 053153 ration plant* has associated with it a risk. Such offacts hava to ba considered -- or at least shown negligible -- in setting the RMCL so as to hare negligible adverse health effects. Response SPA bas propoeed RMCLa at aero as a health goal and recognises that it is not possible to achieve "aero* level of these pollutants in our water supplies, or in society generally. There will be other risks fron VOC control in drinking water, for enaaple fron aeration or transfer of VOCs fron water to granular activated carbon. However, those risks and risks fron bacteria in water supplies are already regulated to protect health! VOCs in drinking water are not. Thus. SPA does not believe that an RMCL of sero will achieve a sero level of risk* 11. CnieMnti Setting the RMCLs to sero is foolish. It eay also be dangerous. Sons eaterials (e.g.. seleniua la a possible candidate) nay be both car cinogenic and also essential components of a human's diet. If the aajor source of such a notarial is water, and it is also possible to reduce the level in water to lew levels, then an RMO. of sero will be elachievous. Response* FA agrees that it nay not be appropriate to set RMCLs at sero for those compounds which are essential elements. However, this is not the case for any of the nine VOCs in the proposal. 12. CoMent! He favor a new MCL when considering the significance of the Woburn study by the Harvard School of Public Health. follows* A sunnary of this study The authors performed a health survey in Woburn, Massachusetts, in 1982-1983. The objective was to investigate health hazard* associated with contamination of certain wells in the city's water supply. The najor finding was "a consistent pattern of positive associa tions between availability of water fron wells 6 and 8 and the incidence of childhood leukemia, perinatal deaths, and sene classes of birth defects and childhood disorders." The population surveyed for leukemia comprised 4.978 children (in 1982). Children with leukenia had an average 21.1 percent of their yearly water supply coning from wells 6 and H, coopered with an expected availability of 9.5 percent* The pattern of incidence of leukemia was as follows* III-12 CM* 05315* "K Period of Observation Cases observed; Cases expected*; 1969-1979 12 5.3 1980-1983 4 2.3 Prom a satchsd population of Woburn children The easociation with use of water frow wells 6 and Hi) is signif icant. Other conditions associated with water froai the oestsBinated wells ware perinatsl deaths and sobs classes of birth defects There was no evidence of association for spontaneous abortions or low birthrate. Among the observed group of children, there were no denonatrable associations between well water use or place of residence and anemia, diabetes, heart/blood pressure disorders, learning dis abilities and other disorders. However, elevated risks for the expoeed groups were found for lung/respiratory, kidney/urinary, allergy/skin and neurologic/sensory disorders* No analyses for water contentnanta were reported in the study. However, the following data are available froB another source; Contaminants in Wells C and H in 1979 Response* Chlorofora Trichloroethylene Tetrachloroethylene Trichlorotrifluoroethane Dlchloroethylens Dlchlorotrifluoroethane 1,1,1-Trichloroethane Dibroaochloramethane Arsenic ppb 1.1 - 11.8 63 - 267 9.0 - 20.8 22 - 23 28 <5 0.6 - 2.1 2.(> 2 The water analysis data froa the Woburn study identifies trichloro ethylene as the prinaxy agent of concern. EFA believes that there are sufficient toxicologic data to consider trichloroethylene to be a probable huaan carcinogen, as discussed in the Pederal Register Final Rule. How ever, the data froa the Woburn study are not conclusive and thus this data will not be factored into the analysis of the carcinogenicity of trichloroethylene. 13. Comment; The Safe Drinking Water Act does not require that RMCLa be set at zero. Although the House Couaittee suggested that an RMCL should be set at zero where there is no safe threshold for a contaminant, it did not III-13. CMA 053155 stats that "safe" naans entirely fre* of risk. To ths contrary, tha Housa Report uaaa relative tanas in dascribing what is intended by tha *adaquata margin of safety" provision. Consequently# undar tha Safa Drinking Water Act# tha prasanca of a carcinogen at vary lw levels does not naan that tha drinking watar is "unsafe. SPA has intarpratad tha tarn "safaty" and tha concept of "margin of aafaty" as not requiring tha elimination of all risk under tha other regulatory programs. As there is no legal requirement that SPA sat RMCLs at taro for carcinogens# SPA should use tha "significant risk" approach to sat SMCLo. Tha Safa Drinking Water Act does not provide a "relative standard of safety" approach to setting RMCLs. Section 1412(b)(1)(B) states that "each such recommended maximum contaminant level shall be sat at a level at which, in tha Administrator's judgment based on such report# no human or anticipated adverse affects on the health of parsons occur# and which allows an adequate margin of safaty." Tha statute itself states that IPA shall determine tha level which meats these criteria# including allowing for an adequate margin of safety. It is clear that sero for carcinogens best meets these criteria. This position is most consistent with Congressional intent and with the most explicit statement given to IPA# i.e.# that where there is no safe threshold for a contaminant# the RMCL should be set at aero. In the opinion of the Agency# there is no safe threshold for carcinogens# i.e.# every level of exposure to a carcinogen presents some degree of risk and thus the RMCLs should be set at sero. Commentt RMCLs should not be set at sero, as zero level RMCLs are not in accord with the views of Federal agencies on risk assessment. For exasple# in considering regulatory action under the Toxic Substances Control Act# risks in the range of 10~6 to 10~* have been regarded as insignificant by IPA. The Nuclear Regulatory Comsission has adopted a policy designed to limit carcinogenic radioactive exposures to risk which would be reasonable when compared to risks posed to society fay day-to-day living and fay cosparable technologies. Other advisory groups and everts also agree with a risk approach. Responsei IPA acknowledges that other Federal agencies and offices within IPA have used a risk approach to setting regulations. However# IPA does not believe that a risk approach for carcinogens is appropriate under the Safe Drinking Hater Act. The Safe Drinking Water Act has its own legis lative history and statutory language which clearly states that if a threshold cannot be demonstrated for a chemical, then the RMCL should be set at zero. IPA believes that the direct language of the legislative history and statute is preferable over Interpretations inported from other statutes. IXI-14 CMA 053156  B. RMCLa FOE CARCINOPVMS AT THE ANALYTICAL DETECTIOH LIMIT 1. Coenanti Risk My be defined as exposure at a concentration level which cauaea toxicity* The fact that a chaaical aubetance can ba detected at a vary low level, such aa ita *liait of detection," doaa not nacaaaarily mean that the chaaical substance rapraaanta a riak at that concantration. Responsei SPA agrees that the fact that a chaaical can ba datactad at a cartain leval doaa net nacaaaarily aaan that the chaaical rapraaanta a riak at that concentration. SPA haa not aet the Rims baaed upon the analytical detection lialta. EPA haa aat the RMCLa for known and probable hoaan carcinogens at aero baaed upon the EDNA, which etatea that Rims arc to ba aat at a level at which no known adverse or anticipated adverse health affects occur# with a Mrgin of safety, for non-carcinolens, IPA haa determined RMCLa based upon conventional toxicological principles which asauna a threshold of affect. F. RHCLe FOR CARCINOGENS BASED OH RISK CALCPLATI0W8 1. Co--nti As is noted in various places in the proposed rulemaking# EPA'a Car cinogen Assessment Group (CAG) uses a 95 percent upper-confidence bound on a linearized Multistage nodal to assess cancer risks. This is a highly conservative anthod which typically overestieatea actual cancer risks significantly ReSonset EPA agrees that the 95 percent upper confidence Unit on the linear ized multistage model is a conservative Mthod which can overestiMte actual cancer risks. However, it is not possible to state the extent to which the actual cancer risks whould be overestimated. 2. rnMintt In addition to the biological uncertainties in interspeciea mg>arisons, there are also severe uncertainties in MtheMtical extrapolation from high-to-low dose risks in the test species themselves. With respect to carcinogenesis# there are several dose-dependent differences which current MtheMtical models do not take into consideration. Responsei EPA agrees that there are many uncertainties in MtheMtical extrapo lation. However# EPA has not based the RMCLa for known or probable human carcinogens upon risk models. IXI-15 CMA. 053157 3. CggMttti The risk uuifMnt model currently esployed uses only on* p*rt of available dates tumor incidence. Other relevant date, such aa pharmaco kinetics , co^arative metabolism, and coveting risks should, as Mechan ises become sere understood, be evaluated and appropriately reflected in risk characterisation. Current sod*Is, while based on "informed logic," are not biologically validated, leading to potential differences between extrapolated results and observed results that differ by orders of Magni tude. responsei The risk assessment aodels are not being used to set the HHCLs for known or probsble huaen carcinogens. SPA agrees that the current aodels are not biologically validated. However, to wait for such validation in the face of sufficient evidence to indicate that there aay be adverse affects on health is inconsistent with the Act. Current nodals represent the best asthods currently available to evaluate cancer risk. 4. Ci,a>nti For clearly identified carcinogens, a variety of aodels exist, of approximately equal validity, with which aaxtnM likelihood estiaates of carcinogenic risk can and should be made. responset SPA agrees that there are a variety of aodels with which aariwun like lihood estiaates of carcinogenic risk can be aade. The Agency employ* a variety of models to estimate carcinogenic risk, emphasizing the linearized multistage aodel, as this nodal is presently believed to be the most biologically plausible of the various risk models. The reason why the linearized multistage aodel is considered to be the most biologically plausible is that this aodel has been used to support the somatic mutation hypothesis of carcinogenesis (Armitage and Doll, 1954; Wittamore, 1978; Wittemora and Keller, 1978). This aodel is consistent with linearity dose-response evidence and the fact that carcinogenicity progresses through a number of stages (HAS, 1977). 5. Cuanenti The range of additional lifetime risks cooaonly referenced by regula tory bodies and experts lies in the range of 10"4 to 10". Legislative precedent focuses on the higher end of the rang*. EPA and other regula tory agencies historically have developed such ad hoc thresholds for carcinogenic risk. In addition to these precedents, numerous outside cooaentatora have recommended threshold values of acceptable risk. Al though these sources do not provide the Agency with a single unique recom mendation, they agree on the general range of such risk values. HI-16 CMA. 053158 Response) SPA agrMt that tha range of lifetime risk commonly referenced by regulatory bodlas and experts liaa in tha ran9a of 10"* to 10"8. However, SPA baliavas that tha RMCLa for cospounds with aufficiant evidence of carci009anicity should ba sat at zero, not basad upon risk calculations. SPA doaa usa such risk estimates for contaainanta which prasant known or antieipatad non-cancer affacts but also haws equivocal evidence of carcino genicity as a aaans of accounting for this equivocal avidanca. 6. Coaaant: Arbitrary selection of one quantitative risk asseswent nodal, say tha aost consarvativa, is unjustified scientifically and is contrary to racent legal precedent which ruled against the exclusive usa of extreaa risk nodaling procedures, ha racoaaand tha use of several applicable aodals to represent tha range of estiasted risk. Tha foilwing aodals aarit consideration) Logit, probit, anltistaga, Weibull and aultihit. Response1 SPA's CAS, in tha derivation of nuabers basad upon risk aodals, uses several aodals to derive risk. CAS e^hasises tha Multistage nodal as tha aost biologically plausible nodal, but does derive nuabers based on other Models. Tha exposure levels should ba extrapolated from tha saall laboratory aniaal to nan using at least two extrapolation Methods. Tha first is on a agAg body waight basis which ignores any influence of astabolic rata and suggests that tha toxic affect is a direct function of the aaount of coapound prasant in a unit body waight. Tha second nethod for dose rata extrapolation includes a consideration of aatabolie rata and can ba basad on a direct cooparison of aatabolie rata or one of tha indirect indicators of aatabolie rata such as body surface area. We racoaaand at least these two Methods in order to bettor define tha likely range of risk by using all tha available infornation. Ijesgonaei extrapolations froa aniaals to huaana could also bo doaa on tha basis of relative weights rather than surface areas. Tha latter approach, used hare, has aora basis in human pharmacological responses) it is not clear which of tha two approaches is aora appropriate for carcinogens. In tha absence of information on this point, it saeas appropriate to usa tha aost generally accepted method, which also is aora consarvativa* 8. Comment1 Unless there is information to tha contrary, all aodals provide risk estimates with an equal probability of being correct. A process that tak s into consideration all of this information is one in which the geometric mean of all of the risk estimates is obtained. This is a rational and III-17 CMA 053159  systematic method which is recommended to develop an estimate of the central tendency of the likely risk that ia neither arbitrarily conserva tive nor arbitrarily liberal* Response* KPk examinee each chemical on a caae-by-caaa basis and for those iceia where a valid study by the appropriate route is available, a risk estimate is determined using the aultistage model* For other chemicals where several studies by the appropriate route are available and all have been determined to be of equal validity, SFA will use the geometric mean of all these studies using the aultistage model, this was the ease for carbon tetrachloride where the geometric mean of four studies was used to determine the cancer risk. * The stronger and more reliable the evidence, the less risk one takes. If the evidence is weak and does not appear to support a strong ease for adverse effects in man, then the higher the estimated risk one is likely to find acceptable. Response! EFA agrees with this coament and has followed this philosophy by set ting the RMCLs for known or probable human carcinogens at sero (allwing less risk) and setting the MCLs for those conpounds with less evidence of carcinogenicity at a finite level (allwing more risk). 10. Comment! The conaanter does not endorse "risk assessment" as a regulation setting tool at this time. Despite its analytical elegance, risk assess ment is laden with uncertainties -- soma of which are addressed in the proposed rule -- and these require value judgments by the analyst. Response t SPA agrees that it is not appropriate to use risk assessment for set ting regulations for all chemicals. RMCLs for chemicals with "sufficient" evidence for human carcinogenicity have been set at sero and not based upon risk calculations* SPA also agrees that risk assessment has many uncertainties associated with it which require value judgments by the analyst. 11. Comment! If the notion of acceptable risk were accepted, it would be necessary to sat risk at a level of magnitude higher than 1 in 100,000, in order to take into account the effects of a carcinogen in combination with other chemicals present in drinking water. Ill-18 GWA 0531SO iMJOBMt la tha past# regulations haw generally bean set la tha gaaaral rang* of 10"* to 10"*. Horavtr, XPA has not aalactad an "acceptable" risk lewl as tha basis for all Tabulations* 12. Comment* A ona la a allllon par ysar risk lswl is also saaa to ba raasonabla whan we look at tha txoa legislative requirement that tha lawl ba sat at a lawl that no adwrsa haalth offsets ba obsarwd with a sultabla margin of safety (warding not exact). Ms suggest that this ba iatarpratad using tha languaga eowonly used by aadieal aaa and others at that tine, and not by tha aora precise language of risk analysts who wst assuse that any thing poses a risk awn at aaall doses* tha key hare is 'obsarwd* haalth affects* The lawl at which an epidealologleal study can just detect a risk# in fawrabla circumstances * is about O.lt annual risk (5% of canc r incidence). This could ba called a Ho Iffact Lswl in Man* and 1 in 106 annual risk giws a 3 orders of magnitude safaty factor -- more than often demanded* Responset Tha SDHA specifies that tha RMCLs are to ba sat at a lawl *at which# no known or anticipated adwrsa effects on tha haalth of parsons occur and which allows an adequate margin of safety*" SPA does not bellow that a risk lawl Is consistent with tha legialatiw mandats* since a risk lawl corresponds to a concentration where affects occur# and not to tha no affect lawl with an adequate margin of safaty. 13* Cowant For the "non-carcinogens," it is possible to assume a toxicological modal (e.g.* the probit - log (dose) model which assumes a lognormal distribution of thresholds in tha population) and estimate tha risks from the various lewis of materials obtained after applying tha safety factors. Why has this not bean done# in order to shew that tha non-carcinogens are to ba regulated as mich (or as little) as tha "carcinogens" (see below section G)? Tha absence of a calculation or tha absence of data does not iaply tha absence of risk) Tha potential utility of dose-response extrapolation methodology for noncareinoganic human risk assessment does exist but has bean found to ba of limited wlua for contaminants in drinking water* Tbe models used to estimate risk require lifetime feeding studies which use appropriate numbers of animals of each sax and demonstrate soma dose response* As noted above# this type of information is not now available for many of the contaminants of drinking water. While both tha risk estimate and ADZ approach require soma degree of value judgment# it is tha belief of the SPA that the ADI methodology is the most useful for noncareinoganic hazards given the general deficiencies in available data* In situations for which high-quality toxicological data are available, tha risk estimate approach III-19 CMA 053161  would be appropriate for the uitiiMnt of noncarcinogenic hazards* Consequently, In tha absanca of such data tha application of safaty factors to no-obsarved-effeet levels that have baan darivad from laboratory animal toxicity data is tha nest faasibla and currantly acceptable method for tha 'determination of human axposura Units to noncarcinogenic environmental contaminants. 14. taanti Whan information is available other doee response relationships should be considered. The information here will necessarily be indirect, for as mist be aaphasised. there is no data which can prove the abeenee of a threshold for any type of health effect at sufficiently lew doees. This might change at some future time whan KVWUf possible northsnl am for ANY effect can be elucidated, but currently, even whan thresholds are apparent at sons dose levels, one cannot deny the possibility of same other mechan ism operating down to very low doses. Response s *PA agrees that it is not possible to prove tha abaanca or presence of a threshold at sufficiently low doses. Thus, KFA is foilwing a con servative philosophy and assuming a nonthreshold philosophy for carcinogens at low doses. 15. Coamant: The KPA has not considered risk in context, nor realised that to carry useful risk analysis and assessment ALL effects of actions mist be factored in, not just a single effect of that action. A summary of four articles which were provided on tha subject of risk assessment followst 1) Richard Wilson. Comentaryt Risks and Their Acceptability. Science, Technolooy and Human Values. Volume 9, Issue 2, 1964. Risks are ever-present and necessary. In the conduct of their lives, people are continually forced to trade off risks* Their perceptions lead them to overstate many risks while Ignoring others of much greater magnitude. for an objective evaluation, hazards may be quantified and ranked in terms of deaths produced per year of exposure* Using this measure, risks above some boundary in the neighbor hood of one in one million, or 10"*, are generally considered acceptable. Many common causes (all industrial work, traffic accidents, etc.) create risks which are far higher. "Moat occupational risks of 10~Vyear are usually ignored." Legal indecision over the regulation of saccharin as a car cinogen suggests that the average ingestion of saccharin leads to a risk which is near tha borderline of acceptability. This estimated value is 2 X 10~*/year> III-20 CMA. 053162 The economic risk of hazards is also evaluated by a method which calculates tha coat par fatality averted lulled by various sociatal activities* 2) I.A. Crouch, R. Wilson and C. Zaisa. Tha Risks of Drinking Watar. Watar Rasourcas Research, Volume 19, Ho* 6, 1983* AUTHORS' ABSTRACT! Kxpoaures to the low lavals of organic compounds found in drinking watar night causa a variety of health affects, cancer being one of great concern* Tha estimation of eancar risk is uncertain, which nay in part explain why cancer risk is not properly considered in establishing drinking watar standards* Currant standards for a given chanical or class of chenieals do not account for tha presence of other pollu tants, chanicals which have not been tasted in long tarn oral bioaasays are generally ignored, and the uncertainties of risk calculations are not explicitly considered* To batter quantify risks fron drinking waters, we apply procedures which incorporate neasures of uncertainty into the risk calculation and consider all chanicals included in a water analysis* This procedure is denonstrated by calculating risks for several U*S* water supplies. Our results show that sons night pose noderately hi^i risks* 3) Bdmind Crouch and Richard Wilson* Regulation of Carcinogens, Risk Analysis. Voluna 1, Nwber 1, 1981. AUTHORS' ABSTRACT! We propose a procedure, suitable for regulatory use, for estinating individual and societal risks of carcinogenic materials by using information on interspecies cospariaons of carcinogenic potency* The consistent treatment of uncertain ties allows evaluation of confidence limits and hence regula tory measures of risk which incorporate safety factors and incentives for better information* Numerical enables are given, together with discussion of the treatment of undetec ted carcinogens* Applications of the procedure to setting priorities for carcinogenicity testing and to product substi tution are mentioned* 4) Lauren Zeise, Richard Wilson and Bdmind Crouch. Use of Acute Toxicity to Bstimate Carcinogenic Risk. To be published in Risk Analysis* AUTHORS' ABSTRACT: Data on the effects of human exposure to carcinogens are limited, so that estimation of the risks of carcinogens must be obtained indirectly. Current risk estimates are generally based on lifetime animal bioassaya which are 111-21 CMA 053163 expensive and which take more than two years to conplete. M here shew how data on acute toxicity can be used to make a preliminary estimate of carcinogenic risk and give an idea of the uncertainty in that risk estimate. Die esti mates obtained are biased upwards, and so are useful for setting interim standards and determining whether further study is worthwhile. A general scheae which incorporates the use of such estimates is outlined, and it is shown by exaaple how adoption of the procedures suggested could have prevented regulatory hiatus in the past* Response: EPA has examined the data presented on risk assessment and agrees that risk assessnent is a useful tool in the health assessment of chemi cals present in the environment. However, EPA does not agree that the RMCLs should be set for all chemicals using risk assessnent. For those chemicals which are potential human carcinogens, EPA believes that an RMCX of zero is most consistent with the legislative nendate of the SERA. Article #4 presents a schene by which data on acute toxicity can be used to neke a preliminary estimate of carcinogenic risk. This approach appears to be worth further investigation; however, EPA does not believe that this approach should be incorporated into the nethodology for screening chemicals for carcinogenicity at the present time. The main drawback is that this approach further conpounds the uncertainty of risk by adding one more conversion to the chain of conversions and projections already used. In addition, the authors noted several glaring exceptions to the predicted behavior of the chemicals. These exceptions need fur ther investigation before this method can be fully accepted. Ooncent: It is important that risk assessment is used in a way that is unbiased and accepted from a toxicological perspective. In using the multistage model, I think that there are certain things that we feel should be pro posed for guidance before we would use that model and the procedure. For exanple, if the agent was shown to cause either a benign or malignant tumor, and if this was found to be in a does dependent manner, and if the study was deemed acceptable by a peer review committee, that would be the first basic criterion. Response; EPA agrees that risk assessment should be used in an unbiased and toxicologically acceptable manner. EPA bases its risk assessment upon studies which it deems to be acceptable, i.e., those studies which show benign or malignant furors in a dose-dependent manner and which have been carried out in a scientifically acceptable manner. The studies and resulting risk levels are reviewed by the SAB. III-22 CMA 053164 17. comment: If the carcinogenic effect occurred only at the highest dose of several, dose levels* or it was not significant at the lower levels* then i would recommend that further toxicologic studies be carried out to ensure that the reason why the toxicologic effect was occurring wasn*t because of son* type of dose-dependent kinetics* whereby saturation was occurring and detoxification mechanisms ray have been overwhelmed. Response: EPA agrees that in the situation described above * it is desirable that further studies be carried out to confirm the toxicologic effect. However, EPA does not agree that further studies should be required before the original study could be used for risk assessment purposes. Since the original study did show an effect at a dose level * even if the reason for that effect was due to saturation or another mechanism* EPA believes that that study should be considered* only with all other relevant data* in the risk assessment process. See also the Response to Comment 18 below. 18. Oonment: If something is shown to be a carcinogen but it occurred because of the saturation pnenonenon, that would be the basis for not using quantitativ risk assessment. Response: EPA disagrees. If a compound is shorn to be a potential human carcin ogen* regardless of the mechanism, which induces the carcinogenicity* EPA believes that it is appropriate to perform a risk assessment. However* as previously discussed, EPA is not setting the RMCLs for potential human carcinogens based upon risk levels but is setting the RMCLs at zero. 19. Comment: Something should be considered a carcinogen if it was positive in one animal species and positive in a yenotoxic screen. On the other hand* if it was carcinogenic in the long-term bioassay but negative in a genotoxic screen* I would not recommend its use in quantitative risk assessment using the multistage model. However, I would still recommend using quanti tative risk assessment* out I would use a less conservative model* typically a tolerance distribution model. Response: EPA follows the criteria outlined in EPA's proposed Guidelines for Carcinogen Risk Assessment in order to determine whether a compound should be considered a carcinogen. Those criteria are discussed in 49 FR 46300* Nov. 23, 1984. EPA does not agree that different risk models should be used depending on the strength ot evidence of carcinogenicity for the compound as th re is no rational basis for choosing one risk iiodel ov r another with regard III-23 CMA 053165 to strength of evidence. EPA believes that it ia appropriate to do risk calculations using several, nodela, but the multistage model ia esphasized aa thia ia the most biologically plausible aodel. 20. Cements In a atody involving a summation of the literature, X have found that sex-specific occurrences are known for over 200 different pollutants and drugs, and that with respect to the hiaan, about 2 dozen sex-specific responses occur. So it is not oncossson in aniaal studies to find that the agent causes cancer or aoaa adverse effect just in one sex. X do not believe that a study shouldn't be used for quantitative risk assessnant because the effect only occurs in one sex. Response! ' DA agrees and considers studies in which effects are seen in only one sex for risk assessnant purposes. G. CRITERIA TOR SKTTIBG BMCLs/MCLs 1. Comment! In general, prioritization involves aa initial deteraiaatlon that a cogpound poses a "significant" health or environnental riak. For regula tion of drinking water, significance should be judged froa analyses and interpretation of data on both occurrence and exposure. Response KVA prioritizes cheaicals for regulation based upon the analytical ability to detect a contaainant, the potential health risk and the occur rence or potential for occurrence in drinking water. EPA believes that those substances of greatest concern generally should be regulated first but a preventive approach should be taken so that substances which present a risk or potential risk in drinking water are regulated. SPA should consider regulating cheaicals which fit into one of the following categoriesi 1) present in 8-10% of randoady selected water supplies. 2) found in 25 or wore instances of contamination. Response t KVA has set criteria for selection of contaminants for regulation (see RMCL Proposal). However, EVA does not feel that it is appropriate to set a numerical cutoff level based upon percent occurrence in drinking water for deciding whether a compound should be regulated. Many factors enter into the decision on regulation,' such as potential for occurrence in drinking water and these factors oust be considered in total before a III-24 CMA 053166 is aids. In addition, thi suggested critiris would not b* pre ventive* potintillly significant health risk would haws to occur bsfors regulation was appropriate. SPA intends to apply the 8DHA in a protective fashion. Coement* RHCLs and subsequent national primary drinking water regulations should be promulgated only when two conditions are net* 1) the contaminant is present in drinking water at a level which, on the basis of epidemiological or toxicological data, may reasonably be expected to have an adverse effect on human health* and 2) The contaminant is present at such a level in a significant number of drinking water supplies nationwide, so that SPA can fairly conclude that the problem is not limited, end localised in nature. In deciding whether the foregoing conditions are mat, SPA also should consider what percentage the average daily intake of the co^ound in drinking water constitutes of the total daily intake of the compound from all sources. Response* SPA does not agree with the coonenter that a contaminant should only be regulated if it is found at levels in drinking water whit* pose a health hasard, on a nationwide basis. SPA believes that a preventive epproach is consistent with the Safe Drinking Hater Act and contaminants should be regulated if they are found to cause adverse health effects, even at levels below that normally found in drinking water. If SPA were to wait to regu late until contaminants were found at levels in drinking water resulting in adverse health effects, public health would not be protected* SPA elso feels that regulation should not wait until a problem goes from localized to nationwide. National primary drinking water regulations should serve the purpose of preventing contamination on a nationwide scale and this can only be acconplished by setting RHCLs and MCLs for those chemicals known to occur in drinking water even on a regional basis, or which have the potential for occurrence in drinking water. However, SPA believes this criteria is mat for VOCs as a group. VOCs have been detected at levels that are believed to pose significant risk and they have been detected in a number of drinking water systems across the nation. In regard to the comment that SPA should also consider what percentage the average daily intake of the compound in drinking water constitutes of the total daily intake from all sources, SPA does not believe that this criteria should be considered in deciding whether or not to regulate. A cospound could be present in drinking water and result in adverse health effects and etill constitute a small percentage of the total daily intake, e.g., carcinogens. In these situations, SPA feels that it is appropriate to regulate the chemical in order to protect the public against possible toxic effects throu^i drinking water. The other sources of exposure to the chemical, such as air or food, should be regulated under the appropriate statute for that particular medium. II1-25 CMA 053167 SIMOLTMUOOS PROPOSAL OF RMCLa AMD MCL* 1. Co--nti It is realised that the statutory language of the SDWA (1412) antici pates the proposal of an MCL on the date an RMCL la promulgated. The Inherent delay la this two-step process tends to encourage state and local regulatory bodies to discount coats and feasibility whan addressing water quality issues* One way to alleviate this problem without being in deroga tion of the statute is to issue an advance notice of proposed raise*ting (Aim) for the NCL whidi specifically takes costs Into consideration, at the sane tine RMCL goals are aanmneed. Response t SPA believes that the issuance of an Aim for the MCIs at the sane tine that RMCL* are proposed would add an additional step to the already lengthy and tias-consuning process* By proposing MCL* at the sane tine the RMCL* are promulgated, the public has an opportunity to eaanant on the MCL* before they are finalized and 1PA believes that this process is sufficient without adding an additional Aim. X* RISK ASSR38MHHT 1. Cogenti In aekaowled^Mnt of the lack of convincing evidence for thresholds for carcinogens, including those which do not act directly on the genome, 08TP rejected the us* of the Mo Observed Adverse effect Level (NOARL)/ Safety Factor approach in carcinogen risk assessment. Response! BFA agrees with the OSTF review of chemical carcinogens and does not us* the MOAEL/safety factor approach in carcinogen risk assessment. J. RMCL* AS 8TAMDAKDS 1* Commenti The case for practical as opposed to theoretical or "ideal" RMCL* is , strengthened further when it ia recognized that State and local entities us* federal recommendations to determine appropriate regulatory response. Nonbinding federal drinking water advisories. Suggested Mo Adverse Response Levels (SNARLs), have been used as cleanup standards in several states including Florida and Michigan. Response IFA recognizes that non-binding Federal drinking water advisories have been used a* cleanup standards in several States* However, RMCL* and other drinking water advisories are not intended for use in this manner and BFA III-26 CMA. 053168 does not encourage or endorse the adoption of guidance aa standards tv Statss or othor localss. K. TOTAL VOCs 1. Comsnt; neither a total VOC Tabulation nor "supporting guidance" is justifiad at this time. Tba Haltad data that ara available indicata that only a saall fraction of drinking water systaas have aora than ana TOC prasant in measurable quantitias. Moreover, as EFA itsalf reoognlsas, tha sciantifio evidence as to whathar haalth affacts from expoeura to drinking watar containing aora than ona TOC ara additive, synergistic or antago nistic is weak and often conflicting* Xn addition, type and degree of toxicity ara known to vary substantially aaong TOCs* A total TOC standard, to be naaningful, would hare to taka into account tha specific TOCs that will be prasant in watar and tha type of toxicity associated with each of these expounds, both singly and in combination. Response SPA agrees with tha cosmenter that a regulation for total TOCs is not justifiad at thka time due to tha conflicting scientific evidence and tha varying toxicity data anong TOCs* In addition, as a natter of priority ERA is attsaptlng to regulate aa nany TOCs as possible which eat its criteria for regulation. DA nay reassess addltivar and syner gistic affacts at a later data. L. OTHER ISSPXS 1. Coment; Currant RCRA regulations do not allow groundwater as sailed, analysed, and reported under RCRA, to deteriorate below primary drinking water standards. Whan the goals of the proposed regulations bacons incorporated into these standards, they will have a profound affect on the discharge and groundwater nonltoring policies at nany of our plant sites and on tha cost of operating such plants* Response The RHCLs are strictly health-based goals and are not equivalent to primary drinking water regulations* The MCLs, when promulgated, may be incorporated into the RCRA regulations for groundwater* If that action is taken, there will be an opportunity to address the i^acts of that regulation through notice and cowment procedures* 2. Comment; We agree with tha HAS principle (Drinking Water and Health, Volume I) that states human exposure to carcinogens should be addressed in terms of risk rather than safe or non-safe. III-27 CMA 053169 Bmpcbwi SPA also agrees with the MAS that human axpoaura to carcinogens should ba addraaaad in terms of ralativa risk. However, tha RMCLs ara to ba aat at a lavsl at which adverse haalth affacta will not ba seen, with a margin of safety, and SPA believes that taro boat fulfills this statutory requirement. SPA doas not baliava that tha MAS intandad this principle to ba interpreted to aaan that RMCLs should ba sat at eanear risk levels. 3. riswti SPA should provide- national guidance lavaIs for tha primacy agency to implement for thosa VOCs whara tha quality of evidence oooearning tha compound's potantial to eausa eanear in aithar animals or humsns is inadequate. This guidance should ba published, along with remanended response actions gaarad to tha level of eontaaination encountered. A low concentration that represents vary little, if any, risk would require only ainor action or no action. Bigh concentration would require iaandiata action to reduce tha leval of eontaaination. Coapounda between a high and low concentration would require increased aonitoring and consideration of other alternatives, according to tha severity of the eontaaination. Mesponsei SPA is providing guidance levels for short-taxm exposure to regulat d cospoonds in drinking water and short-term and long-term exposure to unreg ulated ca^ounds in drinking water (Health Advisories), these guidance levels will ba provided to interested Agencies for their use in contamina tion situations. 4. roiaaantt One approach to regulation could ba structured around types of chemi cals instead of individual ones. Such an approach would involve setting a group MCL and regulating specific chemicals within each group aa the health data becoaaa available. Theee groups should consist of chemicals with similar structures and should include' at least two chemicals which have extensive toxicity teats, the groups should be constructed so that every chemical would fit into at least one group. Such a group might consist of halogenated hydrocarbons without double bonds. Tha numerical value of the group MCL should be baaed on the highest toxicity of the chemicals within tha group which have been tested for toxicity. In the absence of data, EPA should assums the worst in order to be safe. Response PA believes that chemicals should ba examlned on a caaa-by-caaa basis to dstermina if it is appropriate to set MCLs for a group or for the individual coapounda. In the case of the trihalosmthanea, SPA determined that a group MCL was appropriate. For the VOCa, SPA believes that regula tion should be done on an individual chemical basis, as it is not possible to extrapolate the toxicity results from one chemical to anothar. 111-28 CMA. 053170 ** SPA ziMdi to devise a scheme for regulating potentially dangerous which hat* baan datactad in drinking watar bat which have bean under-researched or not invaatigatad at all. Response: SPA doaa not baliava that ragalation by group would be an appropriate raaponaa for thoaa chanicala which have not baan invaatigatad or underraaaarcbad. Regulation fay group ia an appropriate raaponaa whan the tox icity of the chanicala have baan invaatigatad and they have baan ahown to resemble each other toxicologically. For thoaa ehanicala which have not baan invaatigatad. further raaearch to document the toxicity of the chemi cal ia required. 6. CoMent: If the Agency paraiata in ita currant approach for aetting HCLa baaed on quantitative rink aaaaaanant. however, wa strongly urge adoption of the following recoanandation. Instead of any of the population incremental risk levels which are presented in the proposal (49 Pad. Rag. 24334), SPA should designate one excess case in 107 people as the maximum allowabl risk associated with drinking water. Salient reasons for such a protect ive stance are (1). the involuntary and universal nature of human consump tion of drinking water, (2) the legitimate expectations fay the public that drinking water quality should be carefully guarded fay government, and (3) the aaau^tion of at least additive risks from numerous co^ounds to which people are simultaneously and sequentially exposed. Response; SPA is not proposing to set MCXs based upon quantitative risk assessment. 7. Comment: These regulations will result in the downstream consumer bearing the continuing cost of cleanup while the discharger may still release waste into the drinking water supply. Response: PA believes that other EPA and State programs, such as the NPDSS pro gram and Superfund program, will help control the release of wastes into water sources which may ultimately be used for drinking water purposes. In addition, there are often common law and tort remedies available to prevent such activities where they can be identified. SPA believes the discharger should bear the cost of cleanup and is working through these programs and others to ensure that the responsible parties clean up their wastes. III-29 CMA. 053171 8. COMMOtS Basically, we propose that drinking water regulation consist of thraa atepat 1) A regulatory risk celling for contaminants in drinking water would be eatabllahed to aaaure drinking water quality. Contaainanta would be prioritized for regulation agalnat thin rink celling to aaaure that thoee contaainanta which poae the greateat national rlak in drinking water are regulated flrat* 2) Tlminaaenilail Maxlwia Contaalnant Levels (RNCLs) would be aet at practicable levels below rink cellinga eonalderlng their broad uae In other regulatory app11catlona He believe that a defenalble annual threahold for cancer rlak la la the region of W*s to 10*6. 3) Maximum Contaalnant Lavela (MCLs) would be developed eaaentlally at the same tlae aa RMCXe, and aet aa eloae to RMCLs aa feasible, taking Into conaldaratlon the coata related to drinking water applications. Slnultaneoua iaauanee of MCXn and RMCLe la daalrable to elnlnlze confualon between goala and enforceable atenderda. Response: SPA doea not believe that a regulatory riak celling should be eatabliahed for contaainanta in drinking water. ERA prlorltlzee contaainanta for regulation baaed upon: (1) the occurrence of the chealcal In drinking wateri (2) the potential for occurrence of the chealcal In drinking water, and (3) the health effacta of the contaalnant. KPA believes that this aethod of prioritization ensures that those eheaicals which present the greatest potential for adverse effects In drinking water are regulated first. Comments (2) and (3) are addresaed elaowhere in this docuaent. 9. Conmmnt: Mutagenicity and teratogenicity should be considered in addition to carcinogenicity in regulating VOCs. We agree that regulation of contami nants should be federal to ensure uniformity and thus equity across states* Response: KPA agrees that mutagenicity and teratogenicity should be considered ' In regulating VOCs. KPA examines all of the available data and calculates a number based upon the most sensitive endpoint. 10. Coament t KPA, rather than defining only one standard, should define levels which would correspond to increasing seriousness of contaminant problems and needed remedial action. The following model is suggested: 111-30 CM* 053172 IA Health Hi> Chemical Concentration Contamination Problem of Immediate Concern Contaalnatlon Problem of Intermediate Significance Adequate Margin of Safety for Long Sun T X 0 0 Beaponaei SPA, according to the Safe Drinking Mater Act, aust eet a single standard (MCL) for each eo^ound that It has determined mill result In adverse health effects* Thus, sliding standards or a series of levels are not an appropriate response according to the legislative mandate* How ver, SPA does aet nonregulatoxy health effects guidance (Heelth Advisories) for different durations of exposure for chemicals In drinking water* 11. Comment: At the time of the ANPR, several survey of drinking water supplies to document the extent of contamination by various compounds and to allow prioritization of regulatory needs* Since the information In this proposed rulemaking is based upon the same data seta as those cited in the ANPR, it is clear that the Agency has not responded to these recommendations for a survey in spite of the two year lapse between the ANPR and this proposal. Response: Several EPA surveys have airwady been conducted* These data form the basis of occurrence/exposure estimates. Survey designs, sailing and quality assurance procedures have been reviewed by government work groups, as well as by Independent contractors* The regulatory decisions on Indi vidual chemicals are made based mi the fact that these contaminants occur in drinking water or are likely to occur. The occurrence document provides both the raw data and national estimates* These documents have also undergone review by scientific personnel outside the originating office. 12. Cement: The balancing of costs and benefits is an essential part of cleanup under CBRCLA. As noted by Senator Stafford during debate on the billt III-31 CMA 053173 The relationship between the coats and the benefits of a par ticular response action ars an essential part of both the \n>m^ contingency plan to be developed under Section 105 and the selection of reasdial and response actions under Section 104..." (Congressional Record* Movamber 24, 1980). Ideally, the balancing would include a consideration of scientific judg- aent concerning the hazard, the need to protect exposed papulations, and the availability of technologies. Any arbitrary standard, such as an RMCL equalling sero, would appear to be in direct opposition to the goals of Response* SPA believes that RMCLs set at sero for potential hnasn carcinogens fulfill the aandate of the Safe Drinking Water Act. RMCLs are not set under the statutory authority of CERCLA and thus ara not set balancing costs and benefits. Any use of RMCLs under CSROA would be subject to notice and consent through revisions to the Rational Contingency Plan or nterra removal or renedial actions and are not the subject of this ruleasking. 13. Cnanant* Of the aany saapling and analytical deficiencies confounding the in terpretation of the existing data, one of the aost scientifically troublesons is the statistical treatments used. There is no indication that any sophisticated analyses capable of discerning significant differences were used. Response* Data fron randoa and nonrandom segaents of the Ground Water Supply Survey were subjected to statistical tests to discern differences. The findings ara presented in the occurrence documents for individual chemicals. 14. Consiant* We believe that the full reports of the appropriate surveys should be available for review. The occurrence data should be correlated to the size of the water systems and statistically meaningful population exposures generated for each compound. Response* The findings and raw occurrence data from the surveys were placed in the occurrence documents for the individual contaminants. In addition, several of the occurrence surveys have been reported in peer-reviewed literature. Occurrence data ara correlated to site of the water systems and population exposures that were generated. $ IIX-32 CMA 053174 15 it* Thla proposal completely leaves oat tha helomethanes, chloroform, bromoform and others. Why? They ara volatile. Oiloroform la synthetic (it }-a producad by tha action of chlorlna on organic aattar In chlorina tion planta). indeed, tha aalactlon aathod Cor tha VOCa aantlonad In thla propoaad rulemaking la illogical# for It baa no relation to poaaible health rlaka which la preauaably what tha whole propoaal la about. It la livortaat to go after tha large rlaka and leave tha small risks until later# and If tha reduction of tha large rlak reducea the aaall onaa alao# ao aaeh tha batter. DA addraaaad tha trihalomethanes In ita Pinal Rule for tha promulga tion of an NCI. for trlhalonethanaa (44 PR 68624). In tha NCI. promulgation package# tha health rlaka of diloroform and other trihalnmathanaa ara dlacuaaad. DA agraaa that it la Important to regulate tha large rlaka firat and leave tha amallar rlaka until later. Thla la tha reaeon why an NCL for tha trlhalonethanaa waa promulgated eeveral yaara ago# before tha other VOCa. Other volatile organiea will be conaldered for reviaed rule making In the future. 16. Coenentt Continuing purault of establishment of HNX* repreaenta the expenditure of tine and raaourcea on a program directed at managing rlaka at levels far below what DA haa deemed negligible. Reanonae* DA la required# under the Safe Drinking Water Act# to aet RMCLa and MCLa for all coq?ouada that may have an adveree effect upon the health of peraona. DA la alao regulating thoee contamlnanta that appear In drinking water or are likely to appear. Therefore, DA cannot aay theae rlaka are negligible. of RMCLa. DA la following the legialatlve mandate In the eatabliahment 17. Content i DA la proponing .RMCLa for aeveral VOCa baaed upon cancer atudiea in which VOCa were administered to rata and mice In corn oil (NCI# 1976) ... Dae of auch atudiea la wholly inappropriate for aeaeaelng cancer rlaka that night reault from the preaence of VOCa In drinking water. Recent atudiea (SRI for DA) auggert that the corn oil vehicle nay have promoted the tttora found In MCI chloroform bloaaaaye. % DA'a reliance on data obtained from atudiea that do not admlnlater the VOCa to animals In drinking water are totally unreasonable as a basis for setting a zero RMCL. III-33 CMA. 053175 Response The overal1 finding that chloroform, for instance, la probably carcinogenic for humans la baaad upon several diffarant aata of data, tha mooaa liver response via corn oil gavage being only one of these. The positive long-term bioassay data include tha foliating (although other poeltlve, single dose and negative studies also exist)* Gevage Oil Drinking Mater Toothpaste or oilArachls Savage use, male female + liver v liver not tested v kidney - net tested similarly rat, male female + kidney + kidney - kidney not tested The uncertainty regarding-the possible influence of corn oil upon the tusorigenic responses in the mouse bioassays certainly does not negate the positive finding in the souse, nor does it render the overall con clusion of "probably carcinogenicity in humans" for chloroform invalid. While sans uncertainty remains about the influence of com oil on liver tumors in the BgCjF-t mouse, the interpretative significance of the dose delivery vehicle can be explained by consideration of two sets of factors 1) The appearance of kidney tumors in male rats in both the corn oil (NCI) and drinking water (IPA/SRI) studies speaks to the reproducibility of the results regardless of carrier vehicle* 2) A pharmacokinetic analysis shows that differences in dosing regimens result in variations in- absorption patterns, peak blood and tissue levels, and percent of dose metabolised. The absorption patterns for chloroform have been shown to differ depending upon whether the carrier vehicle is corn oil or water. Also, the rate and possibly the extent of absorption is probably diminished by the com oil, not increased. However, in the carcinogen bioessaya the chloro form administered in corn oil as a single bolus would result in considerably higher peak blood and target tissue levels than those resulting from the multiple intermittent doses due to the drinking water.regime. Therefore, the failure to obtain a positive response in the drinking water study (female mouse) may well be a result of the particular phar macokinetic considerations with or without influence from corn oil itself. The present knowledge of chloroform metabollma and related acute toxicity suggests several general cellular mechanisms that may lead to a carcinogenic effect. Bach of these mechanisms is supported by experimental data. III-34 CMA. 053176 Available information concerning the metabolic pathway of VOCa includ ing chlorofoxa in rata and mice suggests that thoaa may not ba appropriata animal aodala froa which to axtrapolata data to humans. There ia evidence of apaolaa variations in tha metabolism of VOCa batwaan rodanta, rata, aica, and tha non-human primates. Haaoonaai Sxperlmentsl data for chloroform ahow no diffaranoa ia abaorptlon charactariatica among species, including man* Thara ara known qualitative diffarancaa among apaelaa with ragard to matabolic pathwaya or metabolic profiles* Mataboliam of chloroform producaa phoagana and other putative reac tive matabolitaa that covalently bind extensively to cellular lipida and protaina, and alao minimally to OKA* Organ localization and binding intanaity parallela acuta cellular toxicity in liver and kidney of experi mental animala, i.e., in mica, covalent binding of chloroform matabolitaa in both liver and kidney haa bean damonatratad to ba proportional to tha dome. Thia ia noteworthy ainca tha liver and kidneya ara target organa of carcinogenicity. The irrevaraible binding of the reactive chloroform matabolitaa to cellular oacroooleculea la generally believed to ba raaponaible not only for hepatic and renal damage from chloroform, but alao tha careinogmnic response, although the machaniam for the latter haa not bean elucidated* It ia true that even within a apeciea there ara atrain and aax differencaa for the susceptibility to liver and kidney toxicity to a fixed doae of chloroform. The human population enco^aaeea a full range of genetic variability in contract to the inbrad etraine of laboratory animala, and hence a carcinogenic reaponaa obeervmd in only certain apeciea, etraina or aaxaa in laboratory animala may ba expreaeed in the human counterpart. Coanaant} The NCI cancer atudiea upon which IPA raliaa ware never intended t ba other than preliminary taata to identify ehemicala which needed to be atudled more intenaely. The animala in the NCI atudy had their daily doaee adalaietared by gavage, which ia believed to induce a cancer reaponaa aignificantly different than that obtained when a teat compound ia adminiatered through drinking water. Response SPA agrpea that the HCX atudiea were carried out aa preliminary taata. However, SPA believea that tha NCI atudiea preaent information which mint be conaldered along with all other data on the chemical in order to make a Judgment on the carcinogenicity of tha ehemicala. SPA uaea oral gavaga atudiea to aaaeaa carcinogenicity in the ab sence of drinking weter atudiea. SPA doee not agree that these atudiea alweya induce a response different than that obtained through drinking III-3S CMA 053177 < weter exposure and believes that oral gavage studies present a valid method of toxicological analysis. (Sos Comment/Response - III.L. 17 abovo). 2. Co--nt Tbs promulgation of tbs propoeed RMCLs as a final nils sxcsada EPA's statutory authority undsr tbs SOMA, sines Section 1412(s) of tbs Aet requirss kpa to arrange with tbs HAS or otbsr indspsndsnt sciontiflc organisation to study tbs potsntial bsaltb offsets of contaminants in drinking watsr Ssetion 1412 of tbs Safs Drinking Water Act provides that tbs Admini strator shall establish Revised Drinking Water Regulations incorporating Maxi-- Contaminant Levels (MCLs). Such regulations are to be developed after consultation with the national Acade^r of Sciences (HAS) and propa gation of RMCLs. Under section 1412(e), the Administrator is required to arrange with the HAS for a study to determine appropriate RMCLs. Ibis study is to contain (1) evaluations of relevant publications, (2) a state ment of methodologies, (3) a statement of methodologies for estimating the margin of safety, (4) proposals for RMCXs, (5) a list of contaminants whose levels cannot be determined, and (4) recovended studies and teat protocols for future research. The HAS was also to consider morbidity and mortality data, the existence of susceptible groups in the papulation, synergistic effects, total contamination from all media sources, and total body burden. The HAS report was to provide proposals for RMCLs which EPA would then be required to publish within 10 days (Section 1412(b)(1)(A)). The MAS responded by providing a comprehensive study of the health effects of drinking water contaminants on June 20, 1977. Subsequent re ports were provided in 1980, 1982 and 1983* The study represented an exhaustive effort and, for most of the contaminants it addressed, provided most of the data necessary to determine RMCLs. The items HAS omitted ware proposed RMCLs and the list of contaminants that could not be measured. It is clear that the MAS substantially complied with the statutory directive. HAS has provided the Agency with significant data and mch f the information that would be necessary to determine RMCLs* For this reason, we believe that HAS' omission did not excuse the Agency from the responsibility of proposing and promulgating RMCLs. Rather, the HAS omission merely excused EPA from meeting the statutory deadlines for proposing and promulgating RMCLs and Revised Regulations. Since 1977, EPA ' has completed sufficient data gathering to initiate rulemaking on the Revised Regulations. There is no legitimate argument that HAS' failure to provide RMOn precludes promulgation of RMCLs or the Revised Regulations. The statute contemplated that EPA would propose and promulgate RMCLs based on the study supplied by HAS. The RMCLs were merely one part of the study that Congress directed HAS to provide. To preclude the Agency from promilgating Revised Regulations -- a major feature of the Act -- because of the minor failure of the NAS is totally inconsistent with the statute. XIX-34 CMA 053178 a jIs n. 21. CmMBtl The granular activated carbon in existing filter bed* at water treatment pleats -- e technology likely considered by IRA to be the best available technology for reducing the levels of VOCs in drinking water -- My present its own health problems. Bacteria and pathogenic nicroorganlsns attached to GAC particles can contaminate treated water. fifESfgy IPA recognises that activated carbon may protect urgnnlmu against disinfection* However, there have been no documented outbreaks associ ated with microbiological growth on SAC. Sufficient poet-chlorination would control microbiological growth and protect public health against microbiological outbreaks. 22. COMSnti The NAS principles from Drinking Water and Health* Volume I, 1977, most be carefully considered In U$it of the available data as regards the VOCs* Response FA believes that the NAS principles are valid. These general prin ciples are In agreement with the Office of Science and Technology Policy's review of chemical carcinogens (49 PR 21594) and with the NPA Guidelines for chemical carcinogens. 23. Comment! There are problems with reproductlblllty of the GH8S data. Thirtysaven supplies ware resampled and 25 of the positive sables did not recur. Response! Follow-up analyses on GWSS sampling sites have Indicated that individual wells serving a comannlty may be contaminated while those in adjacent well fields are not. The apparent negatives detected upon resampling of systems Initially found to be positive has been ascribed to differential pumping rates for Individual wells and changes in samp ling locations rather than error in Initial chemical analysis. 24. CQMgnti There are problems with precision in the GWSS study. Forty-three of 99 positive staples were < 1 ppb. The analytical variability of less than 5 ppb Is 100%. This leaves open the possibility of false positives. Response! The possibility of false positives was. not a problem with the GWSS; the chemicals were detected in the analysis. The quantitation of the 111-37 CMA. 053179 4# rtrl t1 la tarn* of/the exact levaia datected, la another issue not addressed la this comment. ( 25. Ceawsntt 8tate data were used which ware often collected la response to emergency spills and, ` that'afoife, c,:lT hot representative of stateside concentrations. Wsapooaai DA agrees. For that r*onc state data ware not used to project national occurrence. 26. CoMfiti The statistics,used in interpreting data la the GWB8 are cptot to question. The study used only the highest concentration reported at a given wier supply In their statistical variation ignoring the analytical and actual variability. Resgonaet Only aha sa^le was collected for each water supply during the GwsSi thus there was. only one data point for each water supply. only concentration available In their statistics. SPA used the ' 27. Comments Data contained In occurrence documents Indicate that the vast najority (> 95%) of public water systans are either not contaminated or contain levels below the limit of detection. is not a major public health problem. Exposure at these levels Responses SPA believes that a sufficient number of public water supplies have bean shown to be contaminated with VOGs to warrant action In this eras. The SODA does not require that "a major-public health problem" be demon strated before regulation! In fact, the 8DMA is a preventive statute In which the approach la to arr on the aids of safaty. 26. Coamanti Data caviled In the occurrence documents have not received any Independent scientific review. Responset The documents have been widely reviewed within SPA, Including the Office of Air and Radiation and the Office of Drinking Water staff and are open to public comment. 111-38 CMA 053180