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HEXACHLOROBUTADIENE 66 2. HEALTH EFFECTS hazardous waste sites; therefore, additional short-term animal studies by oral routes may be useful to more thoroughly assess the potential human health risk. Intermediate-Duration Exposure. No data are available on the effects of hexachlorobutadiene in humans after intermediate-duration inhalation, oral, or dermal exposures. In animals, data on inhalation exposure are limited to one developmental toxicity study in rats in which maternal body weights were reduced at a concentration (15 ppm) that was also fetotoxic (Saillenfait et al. 1989). Oral studies revealed kidney damage in female mice at dose levels of 0.2 mg/kg/day (NTP 1991; Yang et al. 1989). This LOAEL was used to derive an intermediate-duration oral MRL of 0.0002 mg/kg/day . Liver damage was evident in male rats at dose levels of 6.3 mg/kg/day but not at dose levels of 2.5 mg/kg/day for 13 weeks (Harleman and Seinen 1979). Treatment-related histopathological hepatic lesions were not seen in females. Some serum biochemical parameters (aspartate aminotransferase and total bilirubin), were increased at doses of 20 mg/kg/day for 4 weeks (Jonker et al. 1993b). No data are available on the effects of hexachlorobutadiene in animals after intermediate-duration dermal exposure. Inhalation exposure to vaporous hexachlorobutadiene can occur when this material is exposed to the environment. Studies of toxicity from material absorbed through the lungs are justified. Chronic-Duration Exposure and Cancer. Data in humans are limited to one study that reported increases in serum bile acids in workers chronically exposed to vapors of hexachlorobutadiene (0.005-0.02 ppm). Because workers were also potentially exposed to other chemicals (carbon tetrachloride and perchloroethylene), these effects cannot be attributed to hexachlorobutadiene exposure alone. No studies are available on the effects of hexachlorobutadiene in humans after oral or dermal exposure. In animals, a chronic-duration oral rat study showed that the kidney was the target organ following chronic exposure to hexachlorobutadiene. Kidney damage as well as evidence of impaired kidney function were evident in female rats at dose levels of 2 mg/kg/day, but not at 0.2 mg/kg/day (Kociba et al. 1977a). Since the intermediate-duration oral MRL is protective against affects on the kidney following lifetime exposure, a chronic MRL was not derived. Data are not available to derive a
HEXACHLOROBUTADIENE 67 2. HEALTH EFFECTS chronic inhalation MRL. This data need can be evaluated after the results of the suggested acute- and intermediate-duration research becomes available. No epidemiological studies of hexachlorobutadiene are available. The occurrence of renal tumors after chronic oral exposure in rats suggests carcinogenicity may be an area of concern following occupational exposure to hexachlorobutadiene and long-term exposures from waste sites. Genotoxicity. No information is available on the genotoxic effects of hexachlorobutadiene in humans. Following exposure to hexachlorobutadiene, results were negative in in vivo rat and Drosophila tests that evaluated gene mutation and chromosomal damage (NIOSH 1981). The results were negative in in vitro tests evaluating gene mutation (De Meester et al. 1980; Haworth et al. 1983; Reichert et al. 1983; Vamvakas et al. 1988a) and DNA repair in Salmonella tests (with and without metabolic activation), and positive in mammalian assay systems using Syrian hamster cells (Schiffmann et al. 1984); the overall results were not consistent. Studies of hexachlorobutadiene metabolites have indicated that some of the cysteine derived metabolites are mutagenic while others are not (Wild et al. 1986). Additional studies of the genotoxicity of intermediary metabolites are needed. Reproductive Toxicity. No data are available on the reproductive toxicity of hexachlorobutadiene in humans. Hexachlorobutadiene did not cause adverse reproductive effects in mice or rats after inhalation or oral exposures, even at dose levels causing kidney and liver damage (Harleman and Seinen 1979; Kociba et al. 1977a; NIOSH 1981; NTP 1991; Saillenfait et al. 1989; Schwetz et al. 1977). No data are available on the reproductive toxicity of hexachlorobutadiene after dermal exposure. Based on existing data in animals, it does not appear that exposure to the compound would pose any significant risk to human reproduction. Developmental Toxicity. No studies were located regarding developmental effects in humans. Inhalation and oral studies in rat pups revealed that hexachlorobutadiene is fetotoxic, but not embryotoxic or teratogenic, at dose levels that are also maternally toxic (Harleman and Seinen 1979; Saillenfait et al. 1989; Schwetz et al. 1977). Additional oral studies in another species would be useful in clarifying the apparent lack of significant effects of hexachlorobutadiene on development. Systemic toxicity studies in rabbits suggest there is potential for dermal absorption to
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TOXICOLOGICAL PROFILE FOR HEXACHLOR
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HEXACHLOROBUTADIENE iii UPDATE STAT
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HEXACHLOROBUTADIENE 2 1.1 WHAT IS H
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HEXACHLOROBUTADIENE 4 1. PUBLIC HEA
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HEXACHLOROBUTADIENE 6 1. PUBLIC HEA
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HEXACHLOROBUTADIENE 9 2.1 INTRODUCT
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HEXACHLOROBUTADIENE 11 2. HEALTH EF
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FIGURE 2-1 Levels of Significant Ex
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HEXACHLOROBUTADIENE 116 8. REFERENC
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HEXACHLOROBUTADIENE 130 9. GLOSSARY
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HEXACHLOROBUTADIENE 132 9. GLOSSARY
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HEXACHLOROBUTADIENE A-l Chapter 1 P
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HEXACHLOROBUTADIENE A-5 APPENDIX A
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