EPA-540/1-86-053 Environmental Protection Agency A Emergency and Remedial Response Washington DC 20460 Off'ce of Research and Development Office of Health and Environmental Assessment Environmental Criteria and Assessment Office Cincinnati OH 45268 Superfund EPA HEALTH EFFECTS ASSESSMENT FOR HEXACHLOROBUTADIENE Do not remove. This document should be retained in the EPA Region 5 Library Collection. ------- EPA/540/1-86-053 September 1984 HEALTH EFFECTS ASSESSMENT FOR HEXACHLOROBUTADIENE 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 1t 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 associated with hexachlorobutadlene. 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 following Office of Health and Environmental Assessment (OHEA) sources have been extensively utilized: U.S. EPA. 1980a. Ambient Water Quality Criteria for Hexachloro- butadlene. Environmental Criteria and Assessment Office, Cincinnati, OH. EPA-440/5-80-053. NTIS PB 81-117640. U.S. EPA. 1983a. Review of Toxlcologlc Data 1n Support of Evalua- tion for Carcinogenic Potential of Hexachlorobutadlene. Prepared by the Carcinogen Assessment Group, OHEA, Washington, DC 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 1s not the endpolnt of concern). The first, the AIS or acceptable Intake subchronlc, 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 llfespan). This type of exposure estimate has not been extensively used or rigorously defined, as previous risk assessment efforts have been primarily directed towards exposures from toxicants In 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. 111 ------- The AIC, acceptable Intake chronic, Is 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 is insignificant. Composite scores (CSs) for noncarcinogens have also been calculated where data permitted. These values are used for ranking reportable quanti- ties; the methodology for their development is explained In U.S. EPA (1983b). For compounds for which there is sufficient evidence of cardnogenidty, AIS and AIC values are not derived. For a discussion of risk assessment methodology for carcinogens refer to U.S. EPA (1980b). Since cancer is a process that is 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-|*s have been computed based on oral and inhalation data if available. 1v ------- ABSTRACT In order to place the risk assessment evaluation in 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. Hexachlorobutadlene was treated as a carcinogen by U.S. EPA (1980a). Limited data are available concerning the carcinogenicity of this compound. In the only study available, oral exposure to hexachlorobutadlene resulted in Increased incidence of renal tumors in rats at the highest dose level. No human data are available. U.S. EPA (1980a), using the data for both male and female Incidence of renal tubular adenomas and carcinomas in male rats derived a q-j* for oral exposure of 7.75xlO~2 (mg/kg/day)"1. This risk assessment has been extensively peer reviewed. ------- 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 Monitors 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 Air 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 1. ENVIRONMENTAL CHEMISTRY AND FATE 2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . . . 2.1. 2.2. ORAL INHALATION 3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS 3.1. 3.2. 3.3. 3.4. SUBCHRONIC 3.1.1. Oral 3.1.2. Inhalation CHRONIC 3.2.1. Oral 3.2.2. Inhalation , TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS. . . . , 3.3.1. Oral 3.3.2. Inhalation 3.3.3. Other TOXICANT INTERACTIONS 4. CARCINOGENICITY 4.1. 4.2. 4.3. 4.4. 5. REGUL 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 ATORY STANDARDS AND CRITERIA Page 1 , . 3 , . . 3 3 4 4 , . . 4 4 8 . . . 8 8 8 . . . 8 . . . 9 9 9 10 10 . . . 10 10 10 . . . 10 10 . . . 10 10 . . . 13 V11 ------- TABLE OF CONTENTS (cont.) Page 6. RISK ASSESSMENT 14 6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS) 14 6.2. ACCEPTABLE INTAKE CHRONIC (AIC) 14 6.2.1. Inhalation 14 6.3. CARCINOGENIC POTENCY (q^) 14 6.3.1. Oral 14 7. REFERENCES 16 APPENDIX A: Summary Table for Hexachlorobutadlene 21 APPENDIX B: Cancer Data Sheet for Derivation of qj* 22 ------- LIST OF TABLES No. Title Page 3-1 Subchronic Oral Toxldty of Hexachlorobutadlene 5 3-2 Subchronic Inhalation Toxlcity of Hexachlorobutadlene .... 7 4-1 Response to Hexachlorobutadlene Feeding 1n Male and Female Rats 11 6-1 Basis for q-)* for Hexachlorobutadlene 15 1x ------- LIST OF ABBREVIATIONS ADI Acceptable dally Intake AIC Acceptable Intake chronic AIS Acceptable Intake subchronlc BCF B1oconcentrat1on factor bw Body weight CAS Chemical Abstract Service CS Composite score ppm Parts per million TLV Threshold limit value TWA Time-weighted average ------- 1. ENVIRONMENTAL CHEMISTRY AND FATE The relevant physical and chemical properties and environmental fate of hexachlorobutadlene (CAS No. 87-68-3} are as follows: Chemical class: Molecular weight: Vapor pressure: Water solubility: Log octanol/water partition coefficient: BCF: Half-lives 1n water: chlorinated aliphatic hydrocarbon 260.72 0.15 mm Hg at 20°C 2 mg/8. at 20°C 4.78 2.3xl03 29-2300 3-30 days 1n river 3-300 days 1n lakes and groundwater Callahan et al., 1979 Callahan et al., 1979 Banerjee et al., 1980 calculated from the equation of Velth et al., 1979 U.S. EPA, 1980a Zoeteman et al., 1980 No data regarding the half-life of this compound 1n the atmosphere could be located 1n the available literature; however, 1t Is likely that the compound will react with hydroxyl radicals 1n the atmosphere (Singh et al., 1983). In the absence of any rate constant data for this reaction, 1t Is speculated that the half-life of this compound will be several weeks 1n the atmosphere, based on the estimated residence times for the chlorinated ethylenes given by Singh et al. (1981). The half-life of hexachlorobutadlene 1n soils could not be located In the available literature; Based on the expected volatility (Callahan et al., 1979) and blodegradabUHy 1n aquatic media (Mabey et al., 1981), significant volatilization and blodegradatlon may not occur In soils. -1- ------- The compound may, however, be sorbed significantly onto soils containing a high content of organic carbon (U.S. EPA, 1980a). In the absence of significant loss processes, the persistence of hexachlorobutadiene in soil may allow some leaching of the compound into groundwater, particularly from sandy soils. -2- ------- 2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS 2.1. ORAL Pertinent data regarding the absorption of hexachlorobutadlene from the gastrointestinal tract could not be located 1n the available literature. The available toxldty data Indicate that some absorption does occur (Chapter 3) (U.S. EPA, 1980a). 2.2. INHALATION Pertinent data regarding the absorption of Inhaled hexachlorobutadlene could not be located 1n the available literature. -3- ------- 3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS 3.1. SUBCHRONIC 3.1.1. Oral. The subchronlc oral toxldty of hexachlorobutadlene are summarized In Table 3-1. Most of the Information 1s from the Russian literature and 1s available only as abstracts; therefore, H cannot be fully evaluated. Koclba et al. (1971) administered diets resulting In doses of 1, 3, 10, 30, 65 or 100 mg hexachlorobutadiene/kg bw/day to female rats for 30 days. The major hlstopathologlcal change observed was degeneration of the renal tubular epithelium at doses of >30 mg/kg bw/day. In the 10 mg/kg bw/day group, there was decreased body weight gain with no pathologic alterations. A marginal change 1n the kidney-to-body weight ratio was observed at 3 mg/kg bw/day and no effects were observed at 1 mg/kg bw/day. Schwetz et al. (1977) administered diets resulting 1n doses of 0.2, 2.0 or 20 mg/kg bw/day to male (groups of 10-12) and female (groups of 24) rats for 140 days. Again, hlstopathologlcal lesions in the -kidneys were the major effects noted, occurring at doses of >2.0 mg/kg bw/day. 3.1.2. Inhalation. The subchronic Inhalation toxiclty of hexachlorobuta- dlene 1s summarized 1n Table 3-2. Gage (1970) exposed groups of four male and four female rats to atmospheres containing 5, 10, 25 or 100 ppm (53, 107, 267 or 1060 mg/m3) hexachlorobutadlene, 6 hours/day, for 12-15 days. A dose of 1060 mg/m3 produced severe toxiclty and death. Renal damage was observed 1n the two highest dose groups, but the only effect observed at an exposure of 107 mg/m3 was a reduced weight gain in the females. No effects were observed at a concentration of 53 mg/m3. -4- ------- TABLE 3-1 Subchronlc Oral Toxlclty of Hexachlorobutadlene* Route Oral (diet) Oral (diet) Species/ Sex rat/F rat/F rat/F rat/F rat/F rat/F rat/N rat/F rat/N No. of Animals 4 4 4 4 4 4 12 24 10 % Hexachlorobutadlene Purity 99 99 99 99 99 99 99 99 99 Dose 1 mg/kg/day 3 mg/kg/day 10 mg/kg/day 30 mg/kg/day 65 mg/kg/day 100 mg/kg/day 0.2 mg/kg/day 0.2 mg/kg/day 2.0 mg/kg/day Duration 30 days 30 days 30 days 30 days 30 days 30 days 148 days 148 days 148 days Observations Reference No effects. Koclba et al., Marginal change In kidney-to-body weight 1971 ratio; no pathologic alterations. Decreased body weight gain; no patho- logic alterations. Renal tubular epithelial degeneration, Individual cell necrosis and regenera- tion, decreased body weight gain; Increase In mean kidney-to-body weight ratio; Increase In hemoglobin concen- tration. No effects among adults or neonates. Schwetz et al., No effects among adults or neonates. 1977 Kidney "roughened,* mottled cortex; rat/N rat/N rat/F Oral Oral rat/NR rat/NR rat/NR rat/NR 20 12 24 NR NR NR NR 99 99 99 2.0 mg/kg/day 20 mg/kg/day 20 mg/kg/day NR NR NR NR 0.0005 mg/kg/day 0.004 mg/kg/day 0.02 mg/kg/day 8.4 mg/kg 100 mg/kg other kidney changes that normally occur appeared to be accentuated. 148 days Accentuation of normal kidney changes; one had renal lesions Identical to those on 20 mg/kg/day; no effects on neonates. 148 days Change In kidney-to-body weight ratio; kidney roughened with mottled cortex; renal tubular dilation and hypertrophy with foci of renal tubular epithelial degeneration and regeneration. 148 days Renal tubular dilation and hypertrophy with foci of renal tubular epithelial degeneration and regeneration; decreased values of body and heart weight, Increased values for relative weight of brain and, kidney; slight decrease In body weight of neonates at time of weaning. 6 months Was at threshold level with respect to toxlclty. 4 months Weakly toxic. 2 months Highly toxic. NR Severe necrotlc nephrosls, as well as NR abnormal changes In the brain, liver and other Internal organs. Poteryaeva, 1973 Dlmltrlenko and Vasllos, 1972 ------- TABLE 3-1 (cont.) Route Oral Oral Oral Species/ No. of X Hexachlorobutadlene Sex Animals Purity dog/NR NR NR dog/NR NR NR guinea NR NR plg/NR Dose 1 mg/kg/day 0.05 mg/kg/day 0.004-2 mg/kg/day Duration Observations 1 6 months Administered to puppies from birth to 6 months. Increased secretion of total N-contalnlng compounds. Increased vol. and total acidity of the gastric juice. 45 days Administered 1.5-3 months postnatal; Increased total vol., acidity, and amount of HC1 and chloride secreted by the stomach. 7 months 2 mg dose caused a decrease In -SH group cone. In blood plasma without change In blood protein plasma spectrum. Reference Boranova, 1974a.b Kratvltskaya and Boroanova, 1974 Murzakaev, 1965 'Source: U.S. EPA. 1980a NR = Not reported ------- TABLE 3-2 Subchronlc Inhalation Toxlclty of Hexachlorobutadlene* Species/ Sex Rat/NR Hlce/NR Rat/NR Rat/M Rat/F Rat/H Rat/F Rat/M Rat/F No. of Animals NR NR NR 4 4 4 4 4 4 X Hexachlorobutadlene Purity NR NR NR NR NR NR NR NR NR Dose 24 mg/m»-a1r 24 mg/m»-a1r 0.01 imj/m'-alr 25 ppm (267 mg/ra») 25 ppm (267 mg/ma) 100 ppm (1060 mg/m') 100 ppm (1060 mg/m*) 10 or 5 ppm (107 or 53 mg/ma) 10 or 5 ppm (107 or 53 mg/m») Duration 7 months 7 months 6 months (5 hours dally) 15 dally for 6 hours 12 dally for 6 hours 15 dally for 6 hours Observations Reference Caused no alterations. Gulko et al.. 1964 No effects observed Poteryaeva. 1972 Caused respiratory difficulty; Gage, 1970 decreased weight gain and patho- logic Injury to the tubular epithelium of the kidneys. Severe toxlclty Including death. Caused no toxlclty except for retarded weight gain In females at 10 ppm. *Source: U.S. EPA, 19BOa NR = Not reported ------- 3.2. CHRONIC 3.2.1. Oral. Koclba et al. (1977a,b) administered diets resulting in doses of 0, 0.2, 2.0 or 20 mg hexachlorobutadiene/kg bw/day to groups of 40 male and 40 female rats for 22-24 months. In the high dose group, body weight gain In both sexes was depressed. Both relative and absolute kidney weights were Increased in males and relative kidney weight In females. Survival was decreased In the males. Urinary coproporphyrin excretion was significantly Increased 1n male rats by 12 months and in females by 24 months. Histologlcal examination revealed significant abnormalities, including neoplasms (Section 4.2.1.), in the urinary system. The effects of 2.0 mg/kg bw/day were much less severe. Urinary copro- porphyrin excretion was Increased in females after 14 months, and slight hlstofoglcal changes in the kidneys, possibly including renal tubular epithelial hyperplasla, were observed at necropsy. No effects were observed in animals receiving 0.2 mg/kg bw/day. 3.2.2. Inhalation. Pertinent data regarding the chronic inhalation toxicity of hexachlorobutadlene could not be located 1n the available literature. 3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS 3.3.1. Oral. Schwetz et al. (1977) administered diets resulting in doses of 0.2, 2.0 or 20 mg hexachlorobutadlene/kg bw/day for 90 days before mating, 15 days during mating, and throughout gestation and lactation. The only effect on the offspring was a slight decrease in body weight at 21 days postpartum in the high-dose group. No gross malformations were reported and neonatal growth, survival and development were normal in the low- and mid-dose groups. -8- ------- 3.3.2. Inhalation. Pertinent data regarding the teratogenlcity or other reproductive effects of Inhaled hexachlorobutadlene could not be located 1n the available literature. 3.3.3. Other. Female rats were given a single 20 mg/kg subcutaneous Injection of hexachlorobutadlene prior to breeding (Poteryaeva, 1966). Toxic effects reported 1n the dams Included glomerulonephrltis and degen- erative red blood cell changes. An Increase 1n neonatal mortality and depressed pup body weights were reported. A lack of detail In the reporting of experimental design and results, combined with poor control pup survival (79%) make this study difficult to evaluate. In addition, this route of administration has limited relevance to the present assessment. 3.4. TOXICANT INTERACTIONS Murzakaev (1967) reported that treatment with hexachlorobutadlene decreased the sulfhydryl content of blood serum and cerebral cortex homo- genate. Mlzyukova et al. (1973) subsequently found that administration of thlols (mercaptlde, cystelne, "unlthlol") 20-30 minutes before a dose of hexachlorobutadlene significantly reduced the resulting toxic effects, as determined by survival rates. -9- ------- 4. CARCINOGENICITY 4.1. HUMAN DATA 4.1.1. Oral. Pertinent data regarding the oral cardnogenlcHy of hexa- chlorobutadlene 1n humans could not be located 1n the available literature. 4.1.2. Inhalation. Pertinent data regarding the cardnogenlcHy of Inhaled hexachlorobutadlene 1n humans could not be located 1n the available literature. 4.2. BIOASSAYS 4.2.1. Oral. Koclba et al. (1977a,b) fed diets resulting 1n doses of 0, 0.2, 2.0 or 20 mg hexachlorobutadiene/kg bw/day to male and female Sprague- Dawley rats for 2 years (Table 4-1). Total tumor Incidences In control and treated groups were similar; however, the Incidence of renal tubular neo- plasms was significantly Increased 1n both sexes at the highest dose level. No other treatment-related tumors were found. 4.2.2. Inhalation. Pertinent data regarding the cardnogenlcHy of Inhaled hexachlorobutadlene 1n experimental animals could not be located in the available literature. 4.3. OTHER RELEVANT DATA Taylor (1978) tested hexachlorobutadlene for mutagenldty in Salmonella typhimurlum TA100, both with and without metabolic activation. The low solubility of hexachlorobutadlene limits the interpretation of this test; however, hexachlorobutadlene did not appear to be mutagenlc 1n this system. 4.4. WEIGHT OF EVIDENCE Data are not available regarding the cardnogenlcHy of hexachlorobuta- dlene 1n humans. The cardnogenldty of this compound has been demonstrated In animals, but only in one strain of rats. Hence, the overall evidence for the cardnogenlcHy In animals is best designated as "limited." Applying -10- ------- TABLE 4-1 Response to Hexachlorobutadlene Feeding In Hale and Female Rats3 Doseb (mg/kg/day) 20.0 2.0 0.2 Control Numbers Hale Rat 9/39 0/40 0/40 1/90 % Response Hale Rat 23 0 0 1.1 Numbers Female Rat 3/40 0/40 0/40 1/90 % Response Female Rat 7.5 0 0 1.1 Observations renal tubular adenocarclnomas; undlfferentlated carcinoma; metastasis to the lung none none nephroblastoma aSource: Kodba et al., 1977a,b bDose administered for 669 days of a 730-day experimental period. ------- the criteria for evaluating the overall weight of evidence for the cardno- genldty to humans proposed by the Carcinogen Assessment Group of the U.S. EPA (Federal Register, 1984), hexachlorobutadlene 1s most appropriately designated a Group C chemical - Possible Human Carcinogen. -12- ------- 5. REGULATORY STANDARDS AND CRITERIA The ACGIH (1980) has recommended a TLV of 0.02 ppm (-0.24 mg/m3), based on the 2-year feeding study by Koclba et al. (1977a,b). The U.S. EPA (1980a) estimated that a concentration of 4.47 yg/8. In ambient water would result 1n an Increased cancer risk of 10~5. -13- ------- 6. RISK ASSESSMENT 6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS) Hexachlorobutadlene is a chemical shown to be carcinogenic 1n male rats and for which a q * has been calculated. It Is Inappropriate, therefore, to calculate an AIS for this chemical. 6.2. ACCEPTABLE INTAKE CHRONIC (AIC) Hexachlorobutadlene 1s a chemical shown to be carcinogenic 1n male rats and for which a q * has been calculated. It Is Inappropriate, therefore, to calculate an AIC for this chemical. 6.2.1. Inhalation. Pertinent data regarding the chronic inhalation toxicity of hexachlorobutadlene could not be located in the available literature. 6.3. CARCINOGENIC POTENCY (q^) 6.3.1. Oral. Koclba et al. (1977a,b) demonstrated the Induction of renal tubular adenomas and carcinomas in rats. The U.S. EPA (1980a), using the tumor incidence in male rats and a linearized multistage model (Table 6-1), has derived a human q * of 7.75xlO~2 (mg/kg bw/day)"1. -14- ------- TABLE 6-1 Basis for q-j* for Hexachlorobutadlene* Dose (mg/kg bw/day) Incidence (No. Responding/No. Tested) 0.0 0.2 2.0 20.0 Duration of Experiment = 730 days Length of Treatment = 669 days Llfespan of Animals = 730 days Average Weight = 0.610 kg 1/90 0/40 0/40 9/39 ^Source: U.S. EPA, 1980a -15- ------- 7. REFERENCES AC6IH (American Conference on Governmental Industrial Hyg1en1sts). 1980. Documentation of the Threshold Limit Values. 4th ed. (Includes Supple- mental Documentation, 1981, 1982, 1983). Cincinnati, OH. Banerjee, S., S.H. Yalkowsky and S.C. Valvan. 1980. Water solubility and octanol/water partition coefficient of organlcs. Limitations of the sol- ubility-partition coefficient correlation. Environ. Sc1. Techno!. 14: 1227-1229. Boranova, T.I. 1974a. Nitrogen releasing function of the stomach 1n onco- genesls under the effect of hexachlorobutadlene. Eksp. Issled. Khlm. B1ol. (no vol.): 198. (Cited 1n U.S. EPA, 1980a) Boranova, T.I. 1974b. Effect of hexachlorobutadlene on the secretory func- tion of the stomach of puppies of various ages. Protsessy Obmena Veshchestv S-kh. Zhlvotn. Uslovlyakh Normy Vozdelstv. Vysokochast. Elektromagn. Pol. (no vol.): 83. (Cited 1n U.S. EPA, 1980a) Callahan, M.A., M.W. Sllmak, N.W. Gabel, et al. 1979. Water-Related Environmental Fate of 129 Priority Pollutants. Vol. II. U.S. EPA, Office of Water Planning and Standards, Office of Water and Waste Management, Washington, DC. EPA-440/4-79-029b. -16- ------- D1m1tr1enko, V.D. and A.F. Vasllos. 1972. Kidney damage during experi- mental acute poisoning with hexachlorobutadlene. Zdravookhranenle 15-11. (CHed in U.S. EPA, 1980a) Federal Register. 1984. Environmental Protection Agency. Proposed guide- lines for carcinogenic risk assessment. 49 FR 46294-46299. Gage, J.C. 1970. The subacute Inhalation toxldty of 109 Industrial chem- icals. Br. J. Ind. Med. 27: 1. (CHed 1n U.S. EPA, 1980a) Gulko, A.G., N.I. Zlmlna and 1.6. ShroH. 1964. lexicological study of the Insecticide hexachlorobutadlene. Vopr. G1g1eny 1. Sanlt. Ozderovl. Uneshn. Sredy, Kishinev, Sb. (no vol.): 128. (CHed 1n U.S. EPA, 1980a) Koclba, R.J., P.J. Gehrlng, C.G. Humlston and G.L. Sparschu. 1971. Tox1- cologlc study of female rats administered hexachlorobutadlene or hexachloro- benzene for 30 days. Dow Chemical Company, Midland, Michigan. (CHed In U.S. EPA, 1980a) Koclba, R.J., D.G. Keyes, G.C. Jersey, et al. 1977a. Results of a two-year chronic toxlclty study with hexachlorobutadlene In rats. Am. Ind. Hyg. Assoc. 38: 589. (CHed 1n U.S. EPA, 1980a) Koclba, R.J., B.A. Schwetz, D.G. Keyes, et al. 1977b. Chronic toxlclty and reproduction studies of hexachlorobutadlene 1n rats. Environ. Health Perspect. 21: 49-53. (CHed In U.S. EPA, 1980a) -17- ------- KratvHskaya, P.A. and T.I. Boroanova. 1974. Secretory function of the stomach in pups from 1.5-3 months of age under the effect of hexachloro- butadlene. Eksp. Issled. Kh1m. Blol. (no vol.): 207. (Cited In U.S. EPA, 1980a) Mlzyukova, I.G., et al. 1973. Relation between the structure of detoxify- ing action of several thlols and amines during hexachlorobutadlene poison- Ing. Fizlol. Aktlv. Veshchestva. 5: 22. (Cited In U.S. EPA, 1980a) Mabey, W.R., J.H. Smith, R.T. Podoll, et al. 1981. Aquatic Fate Process Data for Organic Priority Pollutants. U.S. EPA, Monitoring and Data Support Division, Office of Water Regulations and Standards, Washington, DC. EPA-440/4-81-014. Murzakaev, F.G. 1965. Effect of small hexachlorobutadlene doses on some biochemical and 1mmunob1olog1cal Indexes. G1g. Tr. Prog. Zabol. 9: 50-53. (Cited In U.S. EPA, 1980a) Murzakaev, F.G. 1967. Effect of small doses of hexachlorobutadlene on activity of the central nervous system and morphological changes 1n the organism of animals Intoxicated with It. Gig. Tr. Prog. Zabol. 11: 23-28. (Translation) (Cited 1n U.S. EPA, 1980a) Poteryaeva, G.E. 1966. Effect of hexachlorobutadlene on the offspring of Albino rats. Gig. SanH. 31: 33. (Cited 1n U.S. EPA, 1980a) -18- ------- Poteryaeva, G.E. 1972. Substantiating the maximum permissible concentra- tion of hexachlorobutadlene 1n the air of Industrial premises. 61g. SanH. 37: 32-36. (Cited 1n U.S. EPA, 1980a) Poteryaeva, G.E. 1973. Toxldty of hexachlorobutadlene during entry Into the organism through the gastrointestinal tract. G1g. Tr. 9: 98-100. (Cited 1n U.S. EPA, 1980a) Schwetz, B.A., F.A. Smith, C.G. Humlston, J.F. Quast and R.J. Kociba. 1977. Results of a reproduction study in rats fed diets containing hexachlorobuta- dlene. Toxlcol. Appl. Pharmacol. 42: 387-398. (Cited 1n U.S. EPA, 1980a) Singh, H.B., L.J. Salas, A.J. Smith and H. Sh1ge1sh1. 1981. Measurements of some potentially hazardous organic chemicals in urban environments. Atmos. Environ. 15: 601-612. - Singh, H.8., L.J. Sales, R. Stiles and H. Shigaishi. 1983. Measurements of hazardous chemicals in the ambient atmosphere. Prepared by SRI Inter- national, Menlo Park, CA. EPA 600/3-83-002. NTIS PB 83-156935. Taylor, G. 1978. Personal communication. Natl. Inst. Occup. Safety Health. (Cited in U.S. EPA, 1980a) U.S. EPA. 1980a. Ambient Water Quality Criteria for Hexachlorobutadlene. Environmental Criteria and Assessment Office, Cincinnati, OH. EPA-440/5- 80-053. NTIS PB 81-117640. -19- ------- U.S. EPA. 19805. Guidelines and Methodology Used 1n the Preparation of Health Effects Assessment Chapters of the Consent Decree Water Quality Criteria. Federal Register. 45: 79347-79357. U.S. EPA. 1983a. Review of Toxlcologlc Data 1n Support of Evaluation for Carcinogenic Potential of: Hexachlorobutadlene. Prepared by Carcinogen Assessment Group, OHEA, Washington, DC for the Office of Solid Waste and Emergency Response, Washington, DC. U.S. EPA. 1983b. 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. Velth, G.D., D.L. DeFoe and 8.V. Bergstedt. 1979. Measuring and estimating the bloconcentratlon factor of chemicals In fish. J. F1sh. Res. Board Can. 36: 1040-1048. Zoeteman, B.C.J., K. Harmsen, J.B.H.J. Llnders, C.F.H. Morra and W. Slooff. 1980. Persistent organic pollutants 1n river water and groundwater of The Netherlands. Chemosphere. 9: 231-249. -20- ------- APPENDIX A Summary Table for Hexachlorobutadlene Carcinogenic Potency Species Experimental Effect qi* Dose/Exposure Reference ^ Inhalation ND i Oral rat 0, 0.2, 2.0 or renal tumors 7.75x10 2 Koclba et al., 20 mg/kg bw/day (mg/kg but/day)'1 1971; U.S. EPA, 1980a ND = Not derived ------- APPENDIX B Cancer Data Sheet for Derivation of q-|* Compound: hexachlorobutadlene Reference: Koclba et al., 1977a,b Species, Strain, Sex: rat, Sprague-Dawley, male Body weight: 0.610 kg (measured) Length of exposure (le) = 669 days Length of experiment (Le) = 730 days Llfespan of animal (L) = 730 days Tumor site and type: kidney tubules, adenomas and carcinomas Route, vehicle: oral, diet Incidence Transformed Dose* (mg/kg/day) No. Responding/No. Tested or Examined 0 1/90 0.18 0/40 1.83 0/40 18.33 9/39 transformed dose expanded for treatment on 669 of 730-day experimental period. Unadjusted q-|* from study = 1.598xlO~2 (mg/kg/day)"1 Human q-j* = 7.75xlO~2 (mg/kg/day)'1 -22- ------- |