title: Genotoxicological characterisation of complex mixtures. Genotoxic effects of a complex mixture of perhalogenated hydrocarbons.
abstract: Toxicological and genotoxicological investigation of complex mixtures is one of the main focus of the recent research in toxicology. Testing complex mixtures present a formidable scientific problem since most recently available toxicological data has been obtained from single substance studies and is not simply transferable to mixtures of chemicals. Although there are no special strategies and standard protocols available for determining toxic and genotoxic effects of complex mixtures, the fundamental concepts of evaluation are the same as those for single substances. The focus of interest of the submitted paper is the genotoxicological characterisation of a complex mixture of mostly perhalogenated hydrocarbons which is generated as a waste product from the plasma etching process in the semiconductor industry. By use of several in vitro test systems (comet assay and micronucleus test), the clastogenic potency of the mixture was tested in various human cell types (lymphocytes and normal bronchial epithelial cells) and in rat hepatocytes. Results demonstrated that the complex perhalogenated hydrocarbons mixture causes DNA single-strand breaks and micronuclei formation, and direct concentration-to-effect correlations were proved in all experiments. The presence of an external metabolising system (S9 mix from rat hepatocytes) in human cell culture systems did not cause any change of the observed effects when compared to experiments performed in the absence of the S9 mix. Therefore, we conclude that the mixture acts as direct genotoxicant and that there is no detoxification by the external enzyme system.Further, convincing and reproducible results of the in vitro comet assay and the micronucleus assay in primary human cell cultures indicated these tests may be utilized for the genotoxicological analyses of complex mixtures with concern to human health hazard.
authors.affiliation: Centre of Applied Medical and Human Biological Research, Martin Luther University Halle-Wittenberg, Heinrich-Damerow-Street 1, D-06097, Saale, Halle, Germany.
authors.forename: Peggy
authors.initials: P
authors.lastname: Müller
authors.forename: Thomas
authors.initials: T
authors.lastname: Stock
authors.forename: Siegfried
authors.initials: S
authors.lastname: Bauer
authors.forename: Ilona
authors.initials: I
authors.lastname: Wolff
mesh_terms: D000818:Animals; D001711:Biotransformation; D001980:Bronchi / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects; D004587:Electrophoresis, Agar Gel / Q000379:methods; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D006846:Hydrocarbons, Halogenated / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects*; D015162:Micronucleus Tests / Q000379:methods*; D009153:Mutagens / Q000009:adverse effects / Q000493:pharmacokinetics; D016273:Occupational Exposure; D051381:Rats; D011919:Rats, Inbred Strains; D012680:Sensitivity and Specificity
chemical_list: D002273:Carcinogens; D006846:Hydrocarbons, Halogenated; D009153:Mutagens