title: Styrene-7,8-oxide burden in ventilated, perfused lungs of mice and rats exposed to vaporous styrene.
abstract: Styrene (ST) is an important industrial chemical. In long-term inhalation studies, ST-induced lung tumors in mice but not in rats. To test the hypothesis that the lung burden by the reactive metabolite styrene-7,8-oxide (SO) would be most relevant for the species-specific tumorigenicity, we investigated the SO burden in isolated lungs of male Sprague-Dawley rats and in-situ prepared lungs of male B6C3F1 mice ventilated with air containing vaporous ST and perfused with a modified Krebs-Henseleit buffer (37 degrees C). Styrene vapor concentrations were determined in air samples collected in the immediate vicinity of the trachea. They were almost constant during each experiment. Styrene exposures ranged from 50 to 980 ppm (rats) and from 40 to 410 ppm (mice). SO was quantified from the effluent perfusate. Lungs of both species metabolized ST to SO. After a mathematical translation of the ex-vivo data to ventilation and perfusion conditions as they are occurring in vivo, a species comparison was carried out. At ST concentrations of up to 410 ppm, mean SO levels in mouse lungs ranged up to 0.45 nmol/g lung, about 2 times higher than in rat lungs at equal conditions of ST exposure. We conclude that the species difference in the SO lung burden is too small to consider the genotoxicity of SO as sufficient for explaining the fact that only mice developed lung tumors when exposed to ST. Another cause is considered as driving force for lung tumor development in the mouse.
authors.affiliation: Institute of Toxicology, GSF-National Research Center for Environment and Health, D-85764 Neuherberg, Germany.
authors.forename: Christiana
authors.initials: C
authors.lastname: Hofmann
authors.forename: Christian
authors.initials: C
authors.lastname: Pütz
authors.forename: Brigitte
authors.initials: B
authors.lastname: Semder
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Faller
authors.forename: György A
authors.initials: GA
authors.lastname: Csanády
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Filser
mesh_terms: D000280:Administration, Inhalation; D000395:Air Pollutants, Occupational / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004350:Drug Residues; D004852:Epoxy Compounds / Q000493:pharmacokinetics* / Q000633:toxicity; D005740:Gases; D066298:In Vitro Techniques; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial; D020058:Styrene / Q000493:pharmacokinetics* / Q000633:toxicity
chemical_list: D000395:Air Pollutants, Occupational; D004852:Epoxy Compounds; D005740:Gases; D020058:Styrene; C013690:styrene oxide