Comparison of styrene-7,8-oxide adducts formed via reaction with cysteine, N-terminal valine and carboxylic acid residues in human, mouse and rat hemoglobin.
Yeowell-O'Connell-K; Pauwels-W; Severi-M; Jin-Z; Walker-MR; Rappaport-SM; Veulemans-H
Chem-Biol Interact 1997 Aug; 106(1):67-85
The adducts formed by the reaction between styrene-7,8-oxide (96093) (SO) and hemoglobin were investigated. First order elimination rate constants and half lives and second order reaction rate constants for the reaction of SO with the nucleophilic cysteine, N-terminal valine, and carboxylic-acid sites of hemoglobin were determined for human, mouse, and rat blood samples incubated with SO in-vitro. The half lives of SO in mouse and rat blood were about half of that seen in human blood. Marked variations between species were seen in the rate constants for cysteine adducts, whereas the constants for reactions of valine adducts and carboxylic-acid residues were more consistent across species. Each site specific second order rate constant was significantly different across species, except for the rate constant for SO-carboxylic-acid in mice and rats. Studies examining the formation of site specific SO hemoglobin adducts following in-vivo administration of styrene to NMRI-mice (0.86, 1.78, 3.51 or 7.43 millimoles per kilogram (mmol/kg)) and Sprague- Dawley-rats (0.5, 1 or 3mmol/kg) demonstrated that SO-cysteine adducts were present in the highest amounts and valine adducts in the lowest amounts. Site specific estimates of predicted SO blood dose did not demonstrate significantly different values for the adducts in mice; however, the slope based upon SO-cysteine adducts was significantly different from that of the other adducts. For rats, the estimated dose of SO was much lower for carboxylic-acid adducts than for the other adducts. The authors conclude that cysteine and valine, but not carboxylic-acid, hemoglobin adducts should be used as biological markers for styrene exposure.
NIOSH-Publication; NIOSH-Grant; Grants-other; Comparative-toxicology; Styrene-resins; Metabolites; Hemoproteins
Biomedical & Environ Hlth Scis University of California School of Public Health Berkeley, CA 94720
Other Occupational Concerns; Grants-other
University of California Berkeley, Berkeley, California