• Under EPA's 1999 Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1999), 1,3-butadiene is characterized as carcinogenic to humans by inhalation. This characterization is supported by the total weight of evidence provided by the following: (1) sufficient evidence from epidemiologic studies of the majority of U.S. workers occupationally exposed to 1,3-butadiene, either to the monomer or to the polymer by inhalation, showing increased lymphohematopoietic cancers and a dose-response relationship for leukemias in polymer workers (see Section II.A.2), (2) sufficient evidence in laboratory animal studies showing that 1,3-butadiene causes tumors at multiple sites in mice and rats by inhalation (see Section II.A.3), and (3) numerous studies consistently demonstrating that 1,3-butadiene is metabolized into genotoxic metabolites by experimental animals and humans (see Section II.A.4). The specific mechanisms of 1,3-butadiene-induced carcinogenesis are unknown however, the scientific evidence strongly suggests that the carcinogenic effects are mediated by genotoxic metabolites of 1,3-butadiene, i.e., the monoepoxide, the diepoxide, and the epoxydiol.
• This may be a synopsis of the full weight-of-evidence narrative.

Inhalation Unit Risk: 3 x 10 ^-5 per µg/m³
Extrapolation Method: Linear extrapolation from LEC01 (0.254 ppm); LEC01 derived from linear relative rate model (RR = 1 + (B)(x)) using lifetable analysis with leukemia incidence data; an adjustment factor of 2 was applied.
Tumor site(s): Hematologic
Tumor type(s): Leukemia (Health Canada, 1998; U.S. EPA, 2002)