Comparison of genotoxic potency of styrene 7,8-oxide with radiation and human cancer risk estimation of styrene using the rad-equivalence approach

Abstract

Styrene is suspected to cause lympho-hematopoietic malignancies through the formation of styrene 7,8-oxide. However, we are still unable to calculate the cancer risk for workers exposed to styrene using epidemiological data. The aims of this study were to determine the blood dose after styrene exposure and to compare the genotoxic potency of styrene 7,8-oxide and gamma radiation in order to calculate the cancer risk by means of the rad-equivalence approach. Leucocytes of 20 individuals were exposed to 0, 0.1, 0.2 or 0.3 mM styrene 7,8-oxide (1 h) or 1, 2 or 3 gray (=100, 200, 300 rad) gamma radiation. Genotoxicity was evaluated with the cytokinesis-block micronucleus assay. Comparison of the two slopes of the regression lines between micronuclei and dose revealed a genotoxic potency for styrene 7,8-oxide of 37 rad/mMh, corresponding with a median value derived from mutagenicity studies (1, 37, 208 rad/mMh). At exposure levels of 1 ppm styrene, a blood styrene 7,8-oxide concentration between 0.03 x 10(-)(6) and 0.42 x 10(-)(6) mM is to be expected using data of toxicokinetic models and human exposure studies. With the cancer risk per unit dose of gamma radiation as benchmark, we calculated a lifetime risk of acquiring a fatal lympho-hematopoietic cancer of 0.17 in 10(3) workers (between 0.037 x 10(-)(3) and 5.0 x 10(-)(3)) exposed to 20 ppm styrene during 40 years.