Evaluation of the cancer risk from PAHs by inhalation: Are current methods fit for purpose?

There is ample evidence from occupational studies that exposure to a mixture of Polycyclic Aromatic Hydrocarbons (PAHs) is causally associated with an increased incidence of lung cancers. In both occupational atmospheres and ambient air, PAHs are present as a mixture of many compounds, but the composition of the mixture in ambient air differs from that in the occupational atmosphere, and varies in time and space in ambient air. Estimates of cancer risk for PAH mixtures are based upon unit risks which derive from extrapolation of occupational exposure data or animal model data, and in the case of the WHO use one compound, benzo[a]pyrene as a marker for the entire mixture, irrespective of composition. The U.S. EPA has used an animal exposure study to derive a unit risk for inhalation exposure to benzo[a]pyrene alone, and there have been a number of rankings of relative carcinogenic potency for other PAHs which many studies have used to calculate a cancer risk from the PAHs mixture, frequently incorrectly by adding the estimated relative risks of individual compounds, and applying the total "B[a]P equivalent" to the WHO unit risk, which already applies to the entire mixture. Such studies are often based upon data solely for the historic US EPA group of 16 compounds which do not include many of the apparently more potent carcinogens. There are no data for human cancer risk of individual PAHs, and conflicting evidence of additivity of PAH carcinogenicity in mixtures. This paper finds large divergences between risk estimates deriving from the WHO and U.S. EPA methods, as well as considerable sensitivity to the mixture composition, and assumed PAH relative potencies. Of the two methods, the WHO approach appears more likely to provide reliable risk estimates, but recently proposed mixture-based approaches using in vitro toxicity data may offer some advantages.