Characterization of hemoglobin adduct formation in mice and rats after administration of [ 14C]butadiene or [ 14C]isoprene

Abstract

Occupational exposures to 1,3-butadiene or isoprene occur through their use in the manufacture of rubber and other related polymer products. The purpose of this study was to determine if butadiene or isoprene administration would result in the formation of adducts with blood hemoglobin (Hb), and if such adducts can be used as a measure of previous exposure(s). Male B6C3F 1 mice and male Sprague-Dawley rats were injected intraperitoneally with 1, 10, 100, or 1000 μmol [ 14C]-butadiene or 0.3, 3.0, 300, 1000, or 3000 μmol [ 14C]isoprene per kilogram body weight. Animals were killed 24 hr later. Globin was isolated from blood samples and was analyzed for 14C by liquid scintillation spectroscopy. Hb adduct formation was linearly related to administered doses up to 100 μmol [ 14C]butadiene or 500 μmol [ 14C]isoprene per kilogram body weight for mice and rats, respectively. For [ 14C]butadiene, the efficiency of Hb adduct formation in mice and rats within the linear response range was 0.177±0.003 and 0.407±0.019 (pmol of 14C-adducts/mg globin)/(μmol of retained [ 14C]butadiene/kg body wt), respectively ( x ± SE; n = 18 ). For [ 14C]isoprene, these values for mice and rats were 0.158±0.035 and 0.079±0.016 (pmol of 14C-adducts/mg globin)/(μmol of retained [ 14C]isoprene/kg body wt), respectively (mean ± SE; n = 12). Hb adducts also accumulated linearly after repeated daily administration of 100 μmol [ 14C]butadiene or 500 μmol [ 14C]isoprene per kilogram body wt to mice and rats, respectively, for 3 days. [ 14C]Butadiene-derived Hb adducts in blood showed lifetimes of ∼24 and ∼65 days for mice and rats, respectively, which correlate with the reported lifetimes for red blood cells in these rodent species. Thus, levels of butadiene- or isoprene-derived adducts on Hb in circulating blood may be a useful measure of prior repeated exposures to these compounds.