Overview of the acute, subchronic, reproductive, developmental and genetic toxicology of β-chloroprene

Abstract β-Chloroprene (CD), the 2-chloro derivative of 1,3-butadiene, is used for the manufacture of the synthetic rubber, polychloroprene. Acute inhalation studies show that CD is lethal to Crl:CD® rats at >2300 p.p.m. (4 h); the primary target organ effects were pulmonary hemorrhage and edema, and hepatic necrosis. In 2- and 4-week inhalation studies in Fischer 344 (F344) and Wistar rats, early deaths occurred at 500 and ≥161 p.p.m., respectively. Organ system injury was found in the nose (degeneration/metaplasia of olfactory epithelium), liver (centrilobular necrosis), and blood (decreased red blood cell count in F344 rats only). In a 90-day inhalation study with F344 rats, degeneration/metaplasia of the olfactory epithelium and reduced nonprotein sulfhydryl content of lungs and liver were found in animals exposed to 80 p.p.m., and anemia, hepatocellular necrosis, and forestomach inflammation were observed at 200 p.p.m. In a 90-day study with B6C3F1 mice, CD caused deaths at 200 p.p.m., the highest concentration tested, and epithelial hyperplasia of the forestomach at 80 p.p.m. Other than a slight ( 0 generation exposed to 100 p.p.m., and in the F 1 offspring at 33 and 100 p.p.m.; no effects on reproductive parameters or histopathology were found. CD is nonmutagenic in standard plate incorporation bacterial reverse mutation assays (Ames assays) but positive using direct gas-phase incubation methods. Bacterial mutagenicity (primarily base pair substitution) was either negative or weakly positive when freshly prepared CD was tested. Mutagenicity increased markedly with time, presumably from CD dimer formation, and also by addition of liver S9 metabolic activation system. In vivo micronucleus, chromosome aberration and sister chromatid exchange studies in mice showed no structural chromosomal damage. Overall, the pathological effects in the liver and nose dominate the subchronic toxicity of CD. The genotoxicity of CD is inconsistent and requires further study.