DOSIMETRY OF STYRENE 7,8-OXIDE IN STYRENE-EXPOSED AND STYRENE OXIDE-EXPOSED MICE AND RATS BY QUANTIFICATION OF HEMOGLOBIN ADDUCTS

Rats (Sprague Dawley) and mice (NMRI) were administered nonlabelled or labelled styrene and styrene oxide by i.p. injection. Blood samples w ere collected 6 and 24 h after treatment for studies of dose-response and 6 h to 32 days after treatment for studies of adduct stability. Ha emoglobin (Hb) and plasma protein adduct levels were determined by rad ioactivity measurements or, in the case of adducts to N-terminal valin e in Hb, by the so-called N-alkyl Edman procedure. Adducts to N-termin al valine were found to be chemically stable during the life-span of t he erythrocytes, whereas adducts to carboxylic acid residues showed a reduced stability. The Hb-adduct levels found after styrene oxide trea tment were compatible with a linear dose-response at low doses (less t han or equal to 0.4 mmol/kg body weight). At higher doses the detoxifi cation of styrene oxide was overloaded resulting in a higher than prop ortional increase in adduct levels. Saturation; of detoxification of s tyrene oxide could also explain the non-linear dose-response relations hip observed in the mouse following treatment with styrene. Styrene ox ide gave 4-7 time's higher adduct levels than styrene when administere d to the animals at equimolar low concentration. For both compounds, t he levels of adducts to N-terminal valine were 2-3 times higher in the mouse than in the rat. A comparison of Hb-adduct levels in the styren e-exposed animals with adduct levels in styrene-exposed reinforced pla stics workers (Christakopoulos et al., Scand. J. Work Environ. Health, 19(4) (1993) 255-263) suggests that styrene is less effective in huma ns than in mice and rats.