title: Dosimetry of styrene 7,8-oxide in styrene- and styrene oxide-exposed mice and rats by quantification of haemoglobin adducts.
abstract: 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 (< or = 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.
authors.affiliation: Department of Radiobiology, Arrhenius Laboratories for Natural Sciences, Stockholm University, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Osterman-Golkar
authors.forename: A
authors.initials: A
authors.lastname: Christakopoulos
authors.forename: V
authors.initials: V
authors.lastname: Zorcec
authors.forename: K
authors.initials: K
authors.lastname: Svensson
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D004852:Epoxy Compounds / Q000097:blood* / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006454:Hemoglobins / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D020058:Styrene; D013343:Styrenes / Q000097:blood* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D001798:Blood Proteins; D004852:Epoxy Compounds; D006454:Hemoglobins; D013343:Styrenes; D020058:Styrene; C013690:styrene oxide