Chloroprene: Overview of studies under consideration for the development of an IRIS assessment

Abstract

Beta-chloroprene (C(4)H(5)Cl, chloroprene, 2-chloro-1,3-butadiene, CASRN 126-99-8) is a volatile, flammable liquid monomer utilized primarily in the manufacture of neoprene (polychloroprene) elastomer used in belts, hoses, gloves, wire coatings, and tubing. Absorption into the body occurs primarily via the respiratory system and may occur via the gastrointestinal tract or the skin. Once absorbed, chloroprene is widely distributed as evidenced by effects in several target organs including nose and lung, liver, and skin. Chloroprene metabolism is believed to include cytochrome P450 oxidation to a monoepoxide, hydrolysis by epoxide hydrolases, and glutathione conjugation. Similar to 1,3-butadiene, the epoxide is considered to be the toxic moiety, and species differences in metabolic capacity may influence the severity of effects as well as what tissues are affected. EPA has not previously developed an assessment of chloroprene's potential for human health effects. Existing human epidemiological studies offer little data on noncancer effects, and the associations of exposure with increased cancer (liver and lung) mortality reported are inconclusive. Recent epidemiological studies (submitted for publication) could offer information that may impact chloroprene's health assessment. Multiple-site tumors have been reported in rats and mice exposed to chloroprene by inhalation; nevertheless, there are marked differences in strain sensitivities (i.e., tumors in F344 rats versus no tumors in Wistar rats). Recently developed physiologically based toxicokinetic models may allow for the resolution of species and tissue differences and sensitivities as well as exposure-dose-response relationships relevant to humans. (This presentation does not necessarily reflect EPA policy.).