Multiple organ carcinogenicity of inhaled chloroprene (2-chloro-1,3-butadiene) in F344/N rats and B6C3F(1) mice and comparison of dose-response with 1,3-butadiene in mice

Chloroprene (2-chloro-1,3-butadiene) is a high production chemical used alm ost exclusively in the production of polychloroprene (neoprene) elastomer. Because of its structural similarity to 1,3-butadiene, a trans-species carc inogen, inhalation studies were performed with chloroprene to evaluate its carcinogenic potential in rats and mice. Groups of 50 male and female F344/ N rats and 50 male and female B6C3F(1) mice were exposed to 0, 12.8, 32 or 80 p.p.m. chloroprene (6 h/day, 5 days/week) for 2 years. Under these condi tions, chloroprene was carcinogenic to the oral cavity, thyroid gland, lung , kidney and mammary gland of rats, and to the lung, circulatory system (he mangiomas and hemangiosarcomas), Harderian gland, kidney, forestomach, live r, mammary gland, skin, mesentery and Zymbal's gland of mice. Survival adju sted tumor rates in mice were fit to a Weibull model for estimation of the shape of the dose-response curves, estimation of ED10 values (the estimated exposure concentration associated with an increased cancer risk of 10%) an d comparison of these parameters with those for 1,3-butadiene. Butadiene ha s been identified as a potent carcinogen in mice and has been associated wi th increased risk of lymphatic and hematopoietic cancer in exposed workers. Shape parameter values for most of the neoplastic effects of chloroprene a nd 1,3-butadiene were consistent with linear or supralinear responses in th e area near the lowest tested exposures. The most potent carcinogenic effec t of 1,3-butadiene was the induction of lung neoplasms in female mice, whic h had an ED10 value of 0.3 p.p.m. Since the ED10 value for that same respon se in chloroprene exposed mice was also 0.3 p.p.m., we conclude that the ca rcinogenic potency of chloroprene in mice is similar to that of 1,3-butadie ne. Cancer potency of chloroprene is greater in the mouse lung than in the rat lung, but greater in the rat kidney than in the mouse kidney and nearly equivalent in the mammary gland of each species.