Biological monitoring of 1,3-butadiene: species differences in haemoglobin binding in rat and mouse.

The adduct formed by the reaction of 1,3-butadiene monoxide, a major metabolite of the mutagen and carcinogen 1,3-butadiene, with the N-terminal valine of haemoglobin was used as a dosimeter for the bioavailability of reactive metabolites. The dose-dependence of adduct formation was studied in female CB6F1 mice and female Wistar rats exposed to 0, 50, 200, 500 or 1300 ppm butadiene in an open inhalation chamber for 6 h per day for five consecutive days. Globin was isolated 18 h after the last exposure, and N-terminal valine was obtained by a modified Edman degradation procedure. Adduct levels were five times higher in mice than in rats (17 and 3.5 nmol/g globin, respectively, at 500 ppm), which may partially explain the greater susceptibility of mice to tumour formation. Adduct levels increased linearly with dose in rats, whereas in mice this slope of the curve became flatter at 500 ppm and increased with higher doses. Similar results were obtained in male and female C3H x 101/EL mice.