Species differences in the disposition of inhaled butadiene

Recent chronic inhalation carcinogenicity studies of butadiene indicated that B6C3F1 mice are more sensitive to the tumorigenic effects of inhaled butadiene than are Sprague-Dawley rats. Tumors in mice included lymphomas, hemangiosarcomas, alveolar/bronchiolar adenomas and carcinomas, and hepatocellular adenomas and carcinomas whereas in rats tumors included mammary tumors, thyroid follicular cell adenomas, uterine tumors, and exocrine pancreatic adenomas. The purpose of this investigation was to determine if there were differences in the uptake and disposition of inhaled butadiene between rats and mice and if these differences were consistent with the differences in the species susceptibility to inhaled butadiene. Male Sprague-Dawley rats and B6C3F1 mice were exposed nose only to concentrations in the range of 0.14 to 13,000 micrograms [14C]butadiene/liter air (0.08 to 7100 ppm; 25 degrees C, 620 torr) for 6 hr. Blood samples were taken during exposure and urine, feces, and expired air were collected for up to 65 hr after exposure. In both rats and mice there was a significant (p less than 0.001) concentration-related decrease in the percentage of butadiene retained at the cessation of a 6-hr exposure with increasing butadiene exposure concentration, suggesting saturable metabolism of this chemical. At all concentrations of butadiene tested, mice retained about 4 to 7 times the amount (mumol/kg body wt) of butadiene and metabolites than did rats. In both species and at all butadiene concentrations tested, urine and exhaled air were the major routes of excretion of 14C, together accounting for 75 to 85% of the total 14C eliminated. In mice, for all concentrations tested, elimination of 14C in urine, feces, and exhaled air increased with increasing butadiene exposure concentration, although the increase was not proportional to exposure concentration. However, exposure of rats to 13,000 micrograms butadiene/liter air resulted in a leveling off in the amount of 14C that was eliminated in urine and a concomitant increase in exhalation of 14CO2. Analysis of blood samples taken during exposure indicated that the blood of mice contained 2 to 5 times the concentration of 1,2-epoxy-3-butene than did the blood of rats. The data from this study indicate that species differences exist in the amount retained and metabolism of inhaled butadiene.