title: An evaluation of concentrations of styrene-7,8-oxide in rats and humans resulting from exposure to styrene or styrene-7,8-oxide and potential genotoxicity.
abstract: There is potential for oral exposure of humans to styrene (ST) such as from migration of residual levels in polystyrene food containers. After absorption, ST is metabolised to styrene-7,8-oxide (SO), an alkylating epoxide. Hence, a comparison of blood burdens of SO resulting from oral exposures to ST was made with SO burdens possibly warranting genotoxic concern. A validated physiological toxicokinetic model was used for the assessment. Model calculations predicted for exposures to ST that maximum concentrations of SO in venous blood of rats and humans should not exceed 0.33 μg/ml and 0.036 μg/ml, respectively, because of saturation of the SO formation from ST. The daily area under the concentration-time curve of SO in venous blood (AUCSO) was directly proportional to the dose of ST (mg/kg body weight; BW), independent of the exposure route (inhalation or oral exposure). In resting humans, the daily AUCSO was about half that in rats at the same amount of ST/kg BW (calculated up to 100mg ST/kg BW in humans). Taking into account the results of cytogenetic studies in ST-exposed rats, it was deduced that no genotoxic effects of SO are to be expected in ST-exposed humans, at least up to a daily amount of 100mg ST/kg BW, which is equivalent to 100 times the amount originating from the Overall Migration Limit in the EU for ST migrating from food contact plastics. Therefore, no potential genotoxic concern is predicted for ST uptake from food packaging, based on the reported combined measured and modelled data.
authors: Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München, 85764 Neuherberg, Germany. Electronic address: johannes.filser@helmholtz-muenchen.de.
authors: Johannes Georg
authors: JG
authors: Filser
authors: 381 Avenue de Pessicart, F-06100 Nice, France.
authors: Heinz-Peter
authors: HP
authors: Gelbke
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000818:Animals; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D005260:Female; D006801:Humans; D008297:Male; D008958:Models, Molecular; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D020058:Styrene / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D018675:Toxicity Tests
chemical_list: D004852:Epoxy Compounds; D020058:Styrene; C013690:styrene oxide
keywords: Genotoxic risk; Human; Physiological toxicokinetic model; Rat; Styrene; Styrene-7,8-oxide