EPA-540/1-86-032 Off'ce of Research and Development Office of Health and Environmental Assessment Environmental Criteria and Assessment Office Cincinnati OH 45268 Superfund vvEPA HEALTH EFFECTS ASSESSMENT FOR 1,1,2,2-TETRACHLOROETHANE ------- EPA/540/1-86-032 September 1984 HEALTH EFFECTS ASSESSMENT FOR 1.1.2.2-TETRACHLOROETHANE U.S. Environmental Protection Agency Office of Research and Development Office of Health and Environmental Assessment Environmental Criteria and Assessment Office Cincinnati, OH 45268 U.S. Environmental Protection Agency Office of Emergency and Remedial Response Office of Solid Waste and Emergency Response Washington, DC 20460 ------- DISCLAIMER This report has been funded wholly or In part by the United States Environmental Protection Agency under Contract No. 68-03-3112 to Syracuse Research Corporation. It has been subject to the Agency's peer and adminis- trative review, and It has been approved for publication as an EPA document. Mention of trade names or commercial products does not constitute endorse- ment or recommendation for use. 11 ------- PREFACE This report summarizes and evaluates Information relevant to a prelimi- nary Interim assessment of adverse health effects assocVated with 1,1,2,2- tetrachloroethane. All estimates of acceptable Intakes and carcinogenic potency presented 1n this document should be considered as preliminary and reflect limited resources allocated to this project. Pertinent toxlcologlc and environmental data were located through on-Hne literature searches of the Chemical Abstracts, TOXLINE, CANCERLINE and the CHEMFATE/DATALOG data bases. The basic literature searched supporting this document 1s current up to September, 1984. Secondary sources of Information have also been relied upon 1n the preparation of this report and represent large-scale health assessment efforts that entail extensive peer and Agency review. The fol- lowing Office of Health and Environmental Assessment (OHEA) sources have been extensively utilized: U.S. EPA. 1980a. Ambient Water Quality Criteria for Chlorinated Ethanes. Environmental Criteria and Assessment Office, Cincinnati, OH. EPA 440/5-80-029. NTIS PB 81-117400. U.S. EPA. 1982a. Revision and update of Hazard profile on 1,1,2,2-tetrachloroethane. Prepared by the Environmental Criteria and Assessment Office, Cincinnati, OH, OHEA for the Office of Solid Waste and Emergency Response, Washington, DC. U.S. EPA. 1982b. Review of Toxlcologlc Data 1n Support of Evalua- tion for Carcinogenic Potential of 1,1,2,2-Tetrachloroethane. Pre- pared by the Carcinogen Assessment Group, OHEA, Washington, DC for the Office of Solid Waste and Emergency Response, Washington, DC. U.S. EPA. 1983b. Health and Environmental Effects Profile for 1,1,2,2-Tetrachloroethane. Prepared by the Envlornmental Criteria and Assessment Office, Cincinnati, OH, OHEA for the Office of Solid Waste and Emergency Response, Washington, DC. The Intent 1n these assessments 1s to suggest acceptable exposure levels whenever sufficient data were available. Values were not derived or larger uncertainty factors were employed when the variable data were limited In scope tending to generate conservative (I.e., protective) estimates. Never- theless, the Interim values presented reflect the relative degree of hazard associated with exposure or risk to the chemlcal(s) addressed. Whenever possible, two categories of values have been estimated for sys- temic toxicants (toxicants for which cancer is not the endpolnt of concern). The first, the AIS or acceptable intake subchronic, 1s an estimate of an exposure level that would not be expected to cause adverse effects when exposure occurs during a limited time Interval (I.e., for an Interval that does not constitute a significant portion of the lifespan). This type of exposure estimate has not been extensively used or rigorously defined, as previous risk assessment efforts have been primarily directed towards 111 ------- exposures from toxicants 1n ambient air or water where lifetime exposure 1s assumed. Animal data used for AIS estimates generally Include exposures with durations of 30-90 days. Subchronlc human data are rarely available. Reported exposures are usually from chronic occupational exposure situations or from reports of acute accidental exposure. The AIC, acceptable Intake chronic, 1s similar 1n concept to the ADI (acceptable dally Intake). It 1s an estimate of an exposure level that would not be expected to cause adverse effects when exposure occurs for a significant portion of the Hfespan [see U.S. EPA (1980b) for a discussion of this concept]. The AIC 1s route specific and estimates acceptable exposure for a given route with the Implicit assumption that exposure by other routes 1s Insignificant. Composite scores (CSs) for noncardnogens have also been calculated where data permitted. These values are used for ranking reportable quanti- ties; the methodology for their development 1s explained 1n U.S. EPA (1983). For compounds for which there 1s sufficient evidence of cardnogenldty, AIS and AIC values are not derived. For a discussion of risk assessment methodology for carcinogens refer to U.S. EPA (1980b). Since cancer 1s a process that 1s not characterized by a threshold, any exposure contributes an Increment of risk. Consequently, derivation of AIS and AIC values would be Inappropriate. For carcinogens, q-j*s have been computed based on oral and Inhalation data 1f available. 1v ------- ABSTRACT In order to place the risk assessment evaluation 1n proper context, refer to the preface of this document. The preface outlines limitations applicable to all documents of this series as well as the appropriate Inter- pretation and use of the quantitative estimates presented. The Issue of primary concern 1s the carcinogenic potential of 1,1,2,2- tetrachloroethane. Human data addressing this Issue are not available. Limited in vitro mutagenldty data are positive. Only one cancer bloassay has been conducted. In this study 1,1,2,2-tetrachloroethane was not car- cinogenic 1n rats, but was carcinogenic 1n mice by oral exposure. Exposure resulted 1n an Increased Incidence of hepatocellular carcinoma. Using the mouse data, a human q-|* of 0.20 (mg/kg/day)"1 was computed. Data are not available that would allow assessment of the carcinogenic potential of this compound by Inhalation exposure. ------- ACKNOWLEDGEMENTS The Initial draft of this report was prepared by Syracuse Research Corporation under Contract No. 68-03-3112 for EPA's Environmental Criteria and Assessment Office, Cincinnati, OH. Dr. Christopher DeRosa and Karen Blackburn were the Technical Project Honltors and Helen Ball was»the Project Officer. The final documents 1n this series were prepared for the Office of Emergency and Remedial Response, Washington, DC. Scientists from the following U.S. EPA offices provided review comments for this document series: Environmental Criteria and Assessment Office, Cincinnati, OH Carcinogen Assessment Group Office of A1r Quality Planning and Standards Office of Solid Waste Office of Toxic Substances Office of Drinking Water Editorial review for the document series was provided by: Judith Olsen and Erma Durden Environmental Criteria and Assessment Office Cincinnati, OH Technical support services for the document series was provided by: Bette Zwayer, Pat Daunt, Karen Mann and Jacky Bohanon Environmental Criteria and Assessment Office Cincinnati, OH v1 ------- TABLE OF CONTENTS Page 1. ENVIRONMENTAL CHEMISTRY AND FATE 1 2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS 3 2.1. ORAL 3 2.2. INHALATION 3 3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS 4 3.1. SUBCHRONIC 4 3.1.1. Oral 4 3.1.2. Inhalation 4 3.2. CHRONIC 5 3.2.1. Oral 5 3.2.2. Inhalation 5 3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS 5 4. 5. 3.4. 3.3.1. Oral 3.3.2. Inhalation TOXICANT INTERACTIONS CARCINOGENICITY 4.1. 4.2. 4.3. 4.4. HUMAN DATA 4.1.1. Oral 4.1.2. Inhalation BIOASSAYS 4.2.1. Oral 4.2.2. Inhalation OTHER RELEVANT DATA WEIGHT OF EVIDENCE REGULATORY STANDARDS AND CRITERIA 5 7 7 8 8 8 8 , 8 8 8 , 8 10 11 V11 ------- TABLE OF CONTENTS (cont.) Page 6. RISK ASSESSMENT 12 6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS) 12 6.2. ACCEPTABLE INTAKE CHRONIC (AIC) 12 6.3. CARCINOGENIC POTENCY (q^) 12 6.3.1. Oral 12 6.3.2. Inhalation 12 7. REFERENCES 13 APPENDIX A: Summary Table for 1,1,2,2-Tetrachloroethane 18 APPENDIX B: Cancer Data Sheet for Derivation of q-|* 19 ------- LIST OF TABLES No. Title -Page 1-1 Selected Physical and Chemical Properties and Half-Lives for 1,1,2,2-Tetrachloroethane 2 3-1 Percentage of Individuals with Hand Tremors with Respect to 1,1,2,2-Tetrachloroethane Exposure 1n Four Different Factories 4-1 Incidence of Tumors 1n Mice Exposed to >90% Pure 1,1,2,2-Tetrachloroethane (in corn oil) by Gavage . . . , 1x ------- LIST OF ABBREVIATIONS ACTH Adrenocort1cotrop1c hormone ADI Acceptable dally Intake AIC Acceptable Intake chronic AIS Acceptable Intake subchronlc bw Body weight CAS Chemical Abstract Service CS Composite score DNA Oeoxyr1bonucle1c add ppm Parts per million rpm Revolutions per minute STEL Short-term exposure limit TLV Threshold limit value TWA Time-weighted average ------- 1. ENVIRONMENTAL CHEMISTRY AND FATE The relevant physical and chemical properties and environmental fate of 1,1,2,2-tetrachloroethane (CAS No. 79-34-5) are given 1n Table 1-1. The half-life for 1,1,2,2-tetrachloroethane In the atmosphere (Table 1-1) 1s based on Us Interaction with OH radicals. Although no estimate of half-life 1s available, the removal of this compound by wet precipitation may play an Important role In removing the compound from air (Callahan et al., 1979). The estimate of half-life for 1,1,2,2-tetrachloroethane 1n aquatic media Is based on the estimated half-life of evaporation of this compound when stirred at 200 rpm 1n still air at 25°C (D1ll1ng, 1977) and the consideration that, In natural aquatic media containing partlculate matter and sediments, an Increase 1n evaporation half-life 1s expected. The half-life of this compound 1n soil could not be located In the available literature. However, by analogy with aquatic media, evaporation 1s expected to be the predominant loss mechanism from the soil surface. In subsurface soil, 1n the absence of significant blodegradatlon (on the basis of lack of blodegradatlon 1n aquatic media) (Tabak et al., 1981), the com- pound Is likely to leach from soil to groundwater (Page, 1981). -1- ------- TABLE 1-1 Selected Physical and Chemical Properties and Half-Lives for 1,1,2,2,-Tetrachloroethane Properties Values Reference Chemical class: Molecular weight: Vapor pressure: Water solubility: Octanol/water partition coefficient: BCF: Half-lives 1n A1r: Water: halogenated aliphatic hydrocarbon 167.86 5 mm Hg at 20°C 2900 rng/8. at 20°C 245 8 for blueglll (Lepomls macrochlrus) 1.6 years >1 hour (estimated) NA Verschueren, 1983 Verschueren, 1983 Verschueren, 1983 Banerjee et a!., 1980 U.S. EPA, 1980a Singh et al., 1981 NA NA = Not applicable -2- ------- 2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS 2.1. ORAL Pertinent data regarding the absorption of orally administered 1,1,2,2- tetrachloroethane could not be located 1n the available literature. 2.2. INHALATION Lehmann and Hasegawa (1910) administered 9.1 mg/m3 1,1,2,2-tetra- chloroethane by Inhalation to one rabbit for a period of 3 hours. During this period, 258.3 mg of the 883.3 mg administered was absorbed. Human volunteers absorbed 97% of a single 2.5 mg dose of 1,1,2,2-tetra- chloroethane vapor (Morgan et al., 1970, 1972). One hour later, 3-6% of the administered dose was exhaled. -3- ------- 3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS 3.1. SUBCHRONIC 3.1.1. Oral. Pertinent data regarding the toxldty of orally admin- istered 1,1,2,2-tetrachloroethane could not be located 1n the available literature. 3.1.2. Inhalation. Schmidt et al. (1972) exposed 105 male rats to 1.94 ppm (13.32 mg/m3) 1,1,2,2-tetrachloroethane vapors for 4 hours/day for 265 days. Multiplying 13.32 mg/m3 by the product of 4/24 hours, 7/7 days and the average Inhalation rate for a rat (0.26 mVday), and then dividing by the average weight of a rat (0.35 kg), the exposure level 1s adjusted to a dose of 1.65 mg/kg bw/day. Control rats were exposed only to air. Effects associated with exposure to 1,1,2,2-tetrachloroethane Included Increased white blood cell count, pituitary ACTH and total fat content of the liver, and decreased body weight. Navrotskly et al. (1971) exposed unspecified numbers of rabbits to either 0.3, 1.46 or 14.6 ppm (2.06, 10.03 and 100.25 mg/m3) 1,1,2,2-tetra- chloroethane for 3-4 hours/day for 7-11 months. At 14.6 ppm, liver and kidney degeneration, "altered" blood chemistry and suppressed hemaglutlnin production were observed. Decreased hematocrU, decreased hemoglobin con- tent of red cells, and suppressed hemaglutlnin production were observed at 1.46 ppm, while no effects were seen at 0.3 ppm. Hor1uch1 et al. (1962) exposed a single monkey to 1000-4000 ppm (13,734-27,468 mg/m3) 1,1,2,2-tetrachloroethane for 2 hours/day, 6 days/ week for a total of 190 days. Multiplying 27,468 mg/m3 by the product of 2/24 hours, 6/7 days and the average Inhalation rate for a monkey (1.4 mVday), and then dividing by the average weight of a monkey (3.5 kg), the 4000 ppm exposure level 1s equivalent to a dose of 756 mg/kg bw/day. These -4- ------- Investigators reported signs of'weakness after the seventh exposure, diar- rhea and anorexia after the twelfth exposure, and anesthesia after the fifteenth exposure. Other symptoms reported Include marked vacuollzatlon of the liver and fluctuations In hematocrlt, white blood cell count and red cell hemoglobin content. 3.2. CHRONIC 3.2.1. Oral. Pertinent data regarding the chronic toxldty of orally administered 1,1,2,2-tetrachloroethane could not be located 1n the available literature. 3.2.2. Inhalation. The effects associated with occupational exposure to 1,1,2,2-tetrachloroethane by Inhalation or dermal routes are primarily neurological. Grimm et al. (1914) reported that workers who were exposed to 1,1,2,2-tetrachloroethane In a German aircraft factory experienced pain, tremors, headaches, numbness, excessive perspiration and the sensation of "pins and needles" 1n the extremities. Women exposed to 1,1,2,2-tetra- chloroethane 1n a factory that produced artificial pearls experienced paralysis of the Interosseous muscles of the hands and feet, and paralysis of muscles of the eye and jaw (Ler1 and Breltel, 1922). Workers 1n India's bangle Industry were exposed to 9-98 ppm 1,1,2,2-tetrachloroethane and had tremors (35%), vertigo (30.5%), headache (26.6%), abdominal pain (23.7%) and anorexia (22.6%) (Lobo-Mendonca, 1963). As summarized 1n Table 3-1, the percentage of Individuals having hand tremors was correlated to the level of exposure to 1,1,2,2-tetrachloroethane 1n four different plants. 3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS 3.3.1. Oral. Pertinent data regarding the teratogenldty of orally administered 1,1,2,2-tetrachloroethane could not be located 1n the available literature. -5- ------- TABLE 3-1 Percentage of Individuals with Hand Tremors with Respect to 1,1,2,2-Tetrachloroethane Exposure 1n Four Different Factories3 Percent 1,1,2,2-Tetrachloroethaneb (ppm) 50 65 and 98 40 50 and 61 33 ' 40 and 74 14 9 and 17 aSource: Lobo-Mendonca, 1963 ^Values are averages of unspecified numbers of samples -6- ------- 3.3.2. Inhalation. Pertinent data regarding the teratogenldty of Inhaled 1,1,2,2-tetrachloroethane could not be located 1n the available literature. 3.4. TOXICANT INTERACTIONS Pertinent data regarding the Interactions of 1,1,2,2-tetrachloroethane with other toxicants could not be located 1n the available literature. -7- ------- 4. CARCINOGENICITY 4.1. HUMAN DATA 4.1.1. Oral. Pertinent data regarding the cardnogenldty of Ingested 1,1,2,2-tetrachloroethane could not be located 1n the available literature. 4.1.2. Inhalation. Pertinent data regarding the cardnogenldty of Inhaled 1,1,2,2-tetrachloroethane could not be located 1n the available literature. 4.2. BIOASSAYS 4.2.1. Oral. An NCI (1978) bloassay reported that 1,1,2,2-tetrachloro- ethane was carcinogenic In B6C3F, mice but not 1n Osborne-Mendel rats. Groups of 50 males and 50 females of each species were exposed to 1,1,2,2- tetrachloroethane 1n corn oil by gavage for 5 days/week for 78 weeks, and then observed for 12 weeks. No significant Increase 1n any tumor type or total tumors was observed 1n rats exposed by gavage to 1,1,2,2-tetrachloro- ethane at TWA doses of 0, 62 and 108 mg/kg or 0, 43 and 76 mg/kg/males and females, respectively. The results 1n mice are summarized 1n Table 4-1. 4.2.2. Inhalation. Pertinent data regarding the cardnogenldty of Inhaled 1,1,2,2-tetrachloroethane could not be located In the available literature. 4.3. OTHER RELEVANT DATA Brem et al. (1974) reported that 1,1,2,2-tetrachloroethane was mutagenlc to h1st1d1ne-requ1r1ng strains of Salmonella typhlmurlum and preferentially Inhibited the growth of a DNA polymerase-def 1dent strain of Escher1ch1a coll. Callahan et al. (1979) observed mltotlc gene conversion 1n Saccharo- myces cerevlslae strain D7. -8- ------- TABLE 4-1 Incidence of Tumors 1n Mice Exposed to >90% Pure 1,1,2,2-Tetrachloroethane (In corn oil) by Gavage3 Sex H M M Y* F F F Doseb (mg/kg/day) 203 101 0 203 101 0 Duration of Treatment 78 weeks 78 weeks 78 weeks 78 weeks 78 weeks 78 weeks Duration of Study 90 weeks 90 weeks 91 weeks 90 weeks 90 weeks 91 weeks Tumor Type hepatocellular carcinoma hepatocellular carcinoma hepatocellular carcinoma hepatocellular carcinoma hepatocellular carcinoma hepatocellular carcinoma Tumor Incidence (p Value)c 44/49 (p<0.001) 13/50 (NR)d 1/18 (p<0.001) 43/47 (p<0.001) 30/48 (p<0.001) 0/20 (p<0.001) ^Source: NCI, 1978 bTWA dose reflecting 5/7 days per week treatment cp levels for the Fisher Exact test and Cochran-Armltage tests are given when <0.05 dp = 0.033 when compared with pooled vehicle controls ------- 4.4. WEIGHT OF EVIDENCE Pertinent data regarding the cardnogenlcHy of 1,1,2,2-tetrachloro- ethane 1n humans could not be located 1n the available literature. In the NCI (1978) bloassay, the chemical was found to be associated with hepato- cellular carcinoma 1n mice, but the validity of liver tumors In mice as an Indicator of the potential of a chemical to cause human cancer Is not universally accepted. The evidence, therefore, that 1,1,2,2-tetrachloro- ethane 1s an animal carcinogen 1s best considered to be limited. Applying the criteria proposed by the Carcinogen Assessment Group of the U.S. EPA (Federal Register, 1984) for the overall weight of evidence for human car- dnogenlcHy, 1,1,2,2-tetrachloroethane 1s most appropriately classified In Group C - Possible Human Carcinogen. -10- ------- 5. REGULATORY STANDARDS AND CRITERIA The OSHA standard for 1,1,2,2-tetrachloroethane 1n the workplace Is 5 ppm (35 mg/m3) with the designation that dermal exposure may be a signifi- cant route of absorption (Code of Federal Regulations, 1981). However, NIOSH (1976) and AC6IH (1983) recommend a TWA of 1 ppm (7 mg/m3) for occupational exposure to 1,1,2,2-tetrachloroethane. ACGIH (1983) also recommends a STEL of 5 ppm (35 mg/m3). The ACGIH values were established to prevent "serious intoxication and nervous, hepatic, and gastrointestinal effects" (ACGIH, 1980). Hygenlc standards for permissible levels of 1,1,2,2-tetrachloroethane in the working environment of various countries are 7 mg/m3 in the Federal Republic of Germany, 10 mg/m3 1n the Democratic Republic of Germany and 5 mg/m3 (maximum permissible concentration) in the USSR (U.S. EPA, 1983b). For ingestlon of 1,1,2,2-tetrachloroethane, the U.S. EPA (1980a) recom- mends a criterion of 1.7 yg/8. for drinking water. This value was based on the NCI (1978) cancer data, using the linear multistage model to estimate the level of 1,1,2,2-tetrachloroethane associated with a 10~5 risk of cancer. -11- ------- 6. RISK ASSESSMENT 6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS) 1,1,2,2-Tetrachloroethane 1s a chemical for which there 1s limited evi- dence for cardnogenldty In animals but for which data are sufficient for computing a q,*. It 1s, therefore, Inappropriate to calculate an oral or Inhalation AIS for 1,1,2,2-tetrachloroethane. 6.2. ACCEPTABLE INTAKE CHRONIC (AIC) 1,1,2,2-Tetrachloroethane Is a chemical for which there 1s limited evi- dence for cardnogenldty 1n animals but for which data are sufficient for computing a q *. It Is, therefore, Inappropriate to calculate an oral or Inhalation AIC for 1,1,2,2-tetrachloroethane. 6.3. CARCINOGENIC POTENCY (q^) 6.3.1. Oral. Using the data on female mice from the NCI (1978) bloassay, U.S. EPA (1980a) derived a carcinogenic potency factor, q * of 0.20 (mg/kg/day)"1. The data base used 1n the computation of this q * 1s presented 1n Appendix B. 6.3.2. Inhalation. The lack of data regarding the cardnogenldty of Inhaled 1,1,2,2-tetrachloroethane precludes assessment of carcinogenic risk. -12- ------- 8. REFERENCES ACGIH (American Conference of Governmental Industrial Hyg1en1sts). 1980. Documentation of the Threshold Limit Values, 4th ed. (Includes Supplemental Documentation, 1981, 1982, 1983). Cincinnati, OH. p. 390. ACGIH (American Conference of Governmental Industrial Hyglenlsts). 1983. Threshold Limit Values for Chemical Substances and Physical Agencts 1n the Workroom Environment with Intended. Changes for 1983-84. Cincinnati, OH. p. 32. Banerjee, S., S.H. Yalkowsky and S.C. Valvan. 1980. Water solubility and octanol/water partition coefficients of organlcs. Limitations of the solu- bility partition coefficient correlation. Environ. Sc1. Technol. 14: 1227-1229. Brem, H., et al. 1974. The mutagenlcHy and DNA-mod1fy1ng effect of halo- alkanes. Cancer Res. 34: 2576. (Cited 1n U.S. EPA, 1982a) Callahan, M.A., M.W. SUmak, N.W. Gabel, et al. 1979. Water-Related Envi- ronmental Fate of 129 Priority Pollutants. Vol. II. Office of Water Plan- ning and Standards, Office of Water and Waste Management, U.S. EPA, Wash- ington, DC. EPA-440/4-79-029b. (Cited 1n U.S. EPA, 1982a) Code of Federal Regulations. 1981. OSHA Safety and Health Standards. (29 CFR 1910.1000). -13- ------- Dining, W.L. 1977. Interphase transfer processes. II. Evaporation rates of chloromethanes, ethanes, ethylenes, propanes, and propylenes from dilute aqueous solutions. Comparison with theoretical predictions. Environ. Scl. Techno!. 11: 405-409. Federal Register. 1984. Environmental Protection Agency. Proposed guidelines for carcinogenic risk assessment. Federal Register 49:46294-46299. Grimm, V., A. Heffter and G. Joachimoglu. 1914. Industrial Intoxication 1n airplane manufacturing. Vierteljahresschr Gerichtl. Med. Oeff. Sani- taetswes. 48: 161-204. (Ger.) (Cited 1n NIOSH, 1976) Horiuchi, K., S. Horiguchi, K. Hashimoto, K. Kadowakl, K. Aratake. 1962. Studies on the Industrial tetrachloroethane poisoning (2). Osaka City Med. J. 8: 29-38. (Cited in NIOSH, 1976) Lehmann, K.B. and Hasegawa. 1910. Absorption on chlorinated hydrocarbon compounds from air in animals and man. Chloroform, carbon tetrachloride, tetrachloroethane. Arch. Hyg. 72: 327-342. (Cited 1n NIOSH, 1976) Ler1, A. and Breltel. 1922. Chronic polyneurltls. Tetrachloroethane induced polyneurltls in pearl workers. Bull. Mem. Soc. Med. Hosp. Paris. 46: 1406-1412. (Cited in NIOSH, 1976) Lobo-Mendonca, R. 1963. Tetrachloroethane - A survey. Br. J. Ind. Med. 20: 50-56. (Cited in NIOSH, 1976) -14- ------- Morgan, A., et al. 1970. The excretion 1n breath of some aliphatic halo- genated hydrocarbons following administration by Inhalation. Ann. Occup. Hyg. 13: 219. (CHed In U.S. EPA, 1980a) Morgan, A., et al. 1972. Absorption of halogenated hydrocarbons and their excretion 1n breath using chlor1ne-38 tracer techniques. Ann. Occup. Hyg. 15: 273. (Cited 1n U.S. EPA, 1980a) Navrotskly, V.K., L.M. Kashln, I.L. Kullnskaya, et al. 1971. Comparative assessment of the toxldty of a number of Industrial poisons when Inhaled 1n low concentrations for prolonged periods. Trudy S'ezda Glgenlstov Ukranl- so1. 8: 224-226. (Rus.) (CHed 1n NIOSH, 1976) NCI (National Cancer Institute). 1978. Bloassay of 1,1,2,2-tetrachloro- ethane for possible cardnogenlclty. NCI Cardnogenesls Tech. Rep. Ser. No. 27. p. 45. [Also'publ. as DHHS (NIH) PB-277-453]. (CHed In U.S. EPA, 1982b) NIOSH (National Institute for Occupational Safety and Health). 1976. Cri- teria for a Recommended Standard...Occupational Exposure to 1,1,2,2-Tetra- chloroethane. U.S. DHEW, PHS, CDC, Rockvllle, MD. Publ. No. 77-121. Page, G.W. 1981. Comparison of groundwater and surface water for patterns and levels of contamination by toxic substances. Environ. Sc1. Techno!. 15: 1475-1480. -15- ------- Schmidt, P., S. B1nnew1es, R. Gohlke and R. Rothe. 1972. Subacute action of low concentrations of chlorinated ethanes on rats with and without addi- tional ethanol treatment. I. Biochemical and toxlcometrlc aspects, especi- ally results 1n subacute and chronic toxldty studies with 1,1,2,2-tetra- chloroethane. Int. Arch. Arbeltsmed. 30: 283-298. (Ger.) (Cited 1n NIOSH, 1976) Singh, H.B., L.J. Salas, A.J. Smith and H. Sh1ge1sh1. 1981. Measurements of some potentially hazardous organic chemicals 1n urban environments. Atmos. Environ. 15: 601-612. Tabak, H.H., S.A. Quare, C.J. Mashnl and E.F. Baoth. 1981. B1odegradab1l- 1ty studies with organic priority pollutant compounds. J. Water Pollut. Control Fed. 53: 1513-1518. U.S. EPA. 1980a. Ambient Water Quality Criteria for Chlorinated Ethanes. Environmental Criteria and Assessment Office, Cincinnati, OH. EPA 440/5-80-029. NTIS PB 81-117400. U.S. EPA. 1980b. Guidelines and Methodology Used In the Preparation of Health Effects Assessment Chapters of the Consent Decree Water Quality Cri- teria. Federal Register. 45:79347-79357. U.S. EPA. 1982a. Revision and update of hazard profile on 1,1,2,2-tetra- chloroethane. Prepared by the Environmental Criteria and Assessment Office, Cincinnati, OH, OHEA for the Office of Solid Waste and Emergency Response, Washington, DC. -16- ------- U.S. EPA. 1982b. Review of Toxlcologlc Data In Support of Evaluation for Carcinogenic Potential of 1,1,2,2-Tetrachloroethane. Prepared by the Car- cinogen Assessment Group, OHEA, Washington, DC for the Office of Solid Waste and Emergency Response, Washlngon, DC. U.S. EPA. 1983a. Methodology and Guidelines for Reportable Quantity Deter- minations Based on Chronic Toxldty Data. Prepared by the Environmental Criteria and Assessment Office, Cincinnati, OH, OHEA for the Office of Solid Waste and Emergency Response, Washington, DC. U.S. EPA. 1983b. Health and Environmental Effects Profile for 1,1,2,2- Tetrachloroethane. Prepared by the Environmental Criteria and Assessment Office, Cincinnati, OH, OHEA for the Office of Solid Waste and Emergency Response, Washington, DC. Verschueren, K. 1983. Handbook of Environmental Data on Organic Chemistry, 2nd ed. Van Nostrand Relnhold Co., New York. p. 1310. -17- ------- I CO APPENDIX A Summary Table for 1,1,2,2-Tetrachloroethane Carcinogenic Potency Inhalation Oral Species female B6C3F-| mice Experimental Dose/Exposure 1 vg/mVday Effect hepatocellular carcinoma qi* ND 0.20 (mg/kg/day) a Reference NCI, 1978; U.S. EPA, 1980a ND = Not derived ------- APPENDIX B Cancer Data Sheet for Derivation of q-|* Compound: 1,1,2,2-Tetrachloroethane Reference: NCI, 1978 Species, Strain, Sex: Mice, B6C3F-|, F Body weight: 0.030 kg (measured) Length of exposure (le) = 546 days Length of experiment {Le) = 637 days Llfespan of animal (L) = 637 days Tumor site and type: Hver, hepatocellular carcinoma Route, vehicle: oral, gavage Experimental Doses or Exposures (mg/kg/day) 0 101 203 Transformed Dose (mg/kg/day )t 0 86.571 174.000 Incidence No. Responding/No. or Examined 0/20 30/48 43/47 Tested "•"Adjusted to reflect treatment on 5 days/week and exposure for 546 days of 637 day experimental period. Unadjusted q-|* from study = 1.5181003xlO~2 (mg/kg/day)~l Human q-j* = 0.20 (mg/kg/day)'1 -19- ------- |