Asphalt fume dermal carcinogenicity potential: II. Initiation–promotion assay of Type III built-up roofing asphalt

Clark et al. (accepted for publication) reported that a sample of field-matched fume condensate from a Type III built-up roofing asphalt (BURA) resulted in a carcinogenic response in a mouse skin bioassay, with relatively few tumor-bearing animals, long tumor latency and chronic skin irritation. This mouse skin initiation/promotion study was conducted to assess possible mechanisms, i.e., genotoxic initiation vs. tumor promotion subsequent to repeated skin injury and repair. The same Type III BURA fume condensate sample was evaluated in groups of 30 male Crl:CD1® mice by skin application twice per week (total dose of 50 mg/week) for 2 weeks during the initiation phase and for 26 weeks during the promotion phase. Positive control substances were 7,12-dimethylbenz(a)anthracene (DMBA, 50 μg applied once) as an initiator and 12-O-tetradecanoyl-13-acetate (TPA, 5 μg, applied twice weekly) during the promotion phase. During the 6 months of study with the asphalt fume condensate, eight skin masses were observed when tested for initiation, five of which were confirmed microscopically to be benign squamous cell papillomas. Only two papillomas were observed when tested for promotion. There was no apparent relationship between skin irritation and tumor development in this study. These results are more indicative of genotoxicity rather than a non-genotoxic mode of action.