METABOLISM OF 1,3-BUTADIENE - INHALATION PHARMACOKINETICS AND TISSUE DOSIMETRY OF BUTADIENE EPOXIDES IN RATS AND MICE

Significant species differences exist in the susceptibility to butadie ne (BD)-induced cancer in rats and mice, and metabolism is likely a cr itical determinant for species sensitivity. This study measured the in vivo concentrations of, (1) BD in blood; (2) epoxybutene (EB) and die poxybutane (DEB) in blood, lung and liver; and (3) glutathione (GSH) i n lung and liver of male B6C3F(1) mice and Sprague-Dawley rats during and after 6-h exposure to 62.5, 625, 1250, and 8000 (rat only) ppm ED. Mice had higher concentrations of EB and DEB in blood and tissues tha n did rats, DEB could not be detected in blood or tissues of rats, and the greatest depletion of GSH occurred in the lungs of mice. During e xposure, the peak concentrations of EB in mice compared with rats were 4- to 8-fold higher in blood, 13- to 15-fold higher in lung, and 5- t o 8-fold higher in liver. These data suggest that higher levels of BD epoxides in blood and tissues of mice compared with rats may explain, in part, the greater sensitivity of mice than rats to BD-induced carci nogenicity.