title: Genotoxic effects of bitumen fumes in Big Blue transgenic rat lung.
abstract: Road paving workers are exposed to bitumen fumes (CAS No. 8052-42-4), a complex mixture of volatile compounds and particles containing carcinogenic and non-carcinogenic polycyclic aromatic hydrocarbons. However, epidemiological and experimental animal studies failed to draw unambiguous conclusions concerning their toxicity. In order to gain better insights on their genotoxic potential, we used an experimental design able to generate bitumen fumes at road paving temperature (temperature: 170 degrees C, total particulate matter: 100mg/m3) and perform a nose-only exposure of Big Blue transgenic rodents 6h/day for five consecutive days. The mutagenic properties of bitumen fumes were determined by analyzing the mutation frequency and spectrum of the neutral reporter gene cII inserted into the rodent genome. We previously observed in mouse lung, that bitumen fumes did not induce an increase of cII mutants, a modification of the mutation spectrum, nor the formation of DNA adducts. Since DNA adducts were found in the lungs of rats exposed to asphalt fumes in similar conditions, we decided to carry out an analogous experiment with Big Blue rats. A DNA adduct was detected 3 and 30 days after the end of treatment suggesting that these genetic alterations were quite steady. Thirty days after exposure, the cII mutant frequency was similar in control and exposed rats. In addition, a slight but not significant modification of the mutation spectrum associated with an increase of G:C to T:A and A:T to C:G transversions was noticeable in the treated animals. Then, these data failed to demonstrate a pulmonary mutagenic potential for bitumen fumes generated at road paving temperature in our experimental conditions despite the presence of a DNA adduct. These results may provide information concerning the pulmonary mechanism of action of this aerosol and may contribute to the occupational health hazard assessment.
authors.affiliation: Institut National de Recherche et Sécurité Avenue de Bourgogne, BP 27 54501, Vandoeuvre, Cedex, France.
authors.forename: Marie Claire
authors.initials: MC
authors.lastname: Bottin
authors.forename: Laurent
authors.initials: L
authors.lastname: Gate
authors.forename: Bertrand
authors.initials: B
authors.lastname: Rihn
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Micillino
authors.forename: Monhoven
authors.initials: M
authors.lastname: Nathalie
authors.forename: Aurélie
authors.initials: A
authors.lastname: Martin
authors.forename: Hervé
authors.initials: H
authors.lastname: Nunge
authors.forename: Georges
authors.initials: G
authors.lastname: Morel
authors.forename: Richard
authors.initials: R
authors.lastname: Wrobel
authors.forename: Lucie
authors.initials: L
authors.lastname: Ayi-Fanou
authors.forename: Catherine
authors.initials: C
authors.lastname: Champmartin
authors.forename: Gérard
authors.initials: G
authors.lastname: Keith
authors.forename: Stéphane
authors.initials: S
authors.lastname: Binet
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D020029:Base Pairing; D004247:DNA / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D006838:Hydrocarbons / Q000633:toxicity*; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D014687:Venezuela
chemical_list: D006838:Hydrocarbons; D009153:Mutagens; D011084:Polycyclic Aromatic Hydrocarbons; C006647:asphalt; D004247:DNA