Assessment of the carcinogenic potential of automotive gasoline in humans based on mechanistic evidence

• An evaluation of automotive gasoline mechanistic hazard was conducted. • Observational studies of exposed workers showed elevated genetic damage. • Overall, no consistent genotoxic activity was found in animals or human cell lines. • Genotoxic activity is attributed to a complex exposure environment, not gasoline. Liquid gasoline (CAS 86290-81-5) is produced by the fractional distillation of crude oil, and mainly consists of volatile organic compounds; finished automotive gasoline products may also include various additives. The objective of this study was to review mechanistic data including mutagenicity and genotoxicity, along with indications suggestive of immunosuppressive and/or epigenetic activity pertaining to carcinogenicity in humans potentially exposed to automotive gasoline. Six reliable observational studies of fuel station attendants occupationally exposed to gasoline showed a significantly elevated frequency of genetic damage in workers compared to controls and two reliable studies showed no evidence of genetic damage. Fuel station attendants were exposed to a poorly characterized, complex mixture of chemicals, including automotive fuel, diesel, and gasoline engine exhaust. In contrast, animal model and human cell line studies, with a better characterized exposure, did not produce consistent evidence of genotoxic activity. A substantial body of mechanistic data in exposed humans was available; however, limitations in study design and methodological reliability prevented conclusions on whether occupational gasoline exposure leads to immunosuppressive or epigenetic changes. This analysis indicates that the genotoxic activity observed in occupationally-exposed human subjects likely results from the complex environmental exposure that occurs in fuel stations, and cannot be directly attributed to automotive gasoline