Hexachlorobutadiene carcinogenicity

Studies in rats indicate that hexachlorobutadiene may increase the risk of kidney cancer if exposures occur for long periods. The International Agency for Research on Cancer (lARC) has determined that hexachlorobutadiene is not classifiable as to its carcinogenicity in humans, but indicated that there was limited evidence that hexachlorobutadiene was carcinogenic in rats. ERA has determined that hexachlorobutadiene is a possible human carcinogen. 

The National Institute for Occupational Safety and Health (NIOSH) classifies hexachlorobutadiene as a potential occupational carcinogen. Because there is potential for effects following contact of the chemical with the skin, measures should be taken to minimize skin exposure. 

Levels of exposure associated with carcinogenic effects (Cancer Effect Levels, CELs) of hexachlorobutadiene are indicated in Table 2-2. Because cancer effects could occur at lower exposure levels. Figures 2-1 and 2-2 also show ranges for the upper bound of estimated excess risks, ranging from a risk of 1 in 10,000 to 1 in 10,000,000 (10 to 10 ), as developed by EPA. 

Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been made for hexachlorobutadiene. An MRL is defined as an estimate of daily human exposure to a substance that is likely to be without an appreciable risk of adverse effects (noncarcinogenic) over a specified duration of exposure. MRLs are derived when reliable and sufficient data exist to identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration within a given route of exposure. MRLs are based on noncancerous health effects only and do not consider carcinogenic effects. MRLs can be derived for acute, intermediate, and chronic duration exposures for inhalation and oral routes. Appropriate methodology does not exist to develop MRLs for dermal exposure. 

No studies were located regarding carcinogenic effects in humans after oral exposure to hexachlorobutadiene. 

Hexachlorobutadiene did not produce skin papillomas, carcinomas, or tumors at distant sites in mice after application of dose levels of 2-6 mg/mouse for 440-594 days (Van Duuren et al. 1979). Data from this exploratory study are not sufficient to rule out carcinogenic effects via dermal exposure. 

The carcinogenic properties of hexachlorobutadiene are proposed to result from binding of the sulfenic acid degradation product or a thioketene intermediate to cellular DNA (Dekant et al. 1990b Henschler and Dekant 1990). Cell necrosis is thought to stimulate replication of cells with altered DNA, enhancing tumorigenesis. 

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. 

IARC. 1979. lARC monographs on the evaluation of the carcinogenic risk of chemicals to humans. Vol. 20 Hexachlorobutadiene. World Health Organization, Lyon, France. 

Ingestion and inhalation of hexachlorobutadiene inhibits cells in the liver and kidney. Animal tests have shown both acute and chronic toxicides. The compound is a suspect human carcinogen. 

Hexachlorobutadiene is on the National Institute for Occupational Safety and Health list of suspected carcinogens because it has the potential to cause kidney and lung cancer. A group of 205 vineyard workers who were exposed seasonally to hexachlorobutadiene (0.8-30mgm in air over the fumigated zones) showed multiple toxic effects contributing to the development of hypotension, cardiac disease, chronic bronchitis, disturbances of nervous function, and chronic hepatitis. 

Hexachlorobutadiene Possible human carcinogen Discharge frrun chemical plants and other industrial activities n.a. 0.6 0.1 0.1 0.6... 

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