Dosimetry of styrene 7,8-oxide in styrene- and styrene oxide-exposed mice and rats by quantification of haemoglobin adducts

Osterman-Golkar, S.; Christakopoulos, A.; Zorcec, V.; Svensson, K.

Chemico-Biological Interactions 95(1-2): 79-87


ISSN/ISBN: 0009-2797
PMID: 7697755
DOI: 10.1016/0009-2797(94)03348-x
Accession: 008501734

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Rats (Sprague Dawley) and mice (NMRI) were administered nonlabelled or labelled styrene and styrene oxide by i.p. injection. Blood samples were 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. Haemoglobin (Hb) and plasma protein adduct levels were determined by radioactivity measurements or, in the case of adducts to N-terminal valine in Hb, by the so-called N-alkyl Edman procedure. Adducts to N-terminal valine were found to be chemically stable during the life-span of the erythrocytes, whereas adducts to carboxylic acid residues showed a reduced stability. The Hb-adduct levels found after styrene oxide treatment were compatible with a linear dose-response at low doses ( gtoreq 0.4 mmol/kg body weight). At higher doses the detoxification of styrene oxide was overloaded resulting in a higher than proportional increase in adduct levels. Saturation of detoxification of styrene oxide could also explain the non-linear dose-response relationship observed in the mouse following treatment with styrene. Styrene oxide gave 4-7 times higher adduct levels than styrene when administered to the animals at equimolar low concentration. For both compounds, the 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 styrene-exposed animals with adduct levels in styrene-exposed reinforced plastics workers (Christakopoulos et al., Scand. J. Work Environ. Health, 19(4) (1993) 255-263) suggests that styrene is less effective in humans than in mice and rats.