Cancer risk assessment for oral exposure to PAH mixtures

• Published in: Journal of applied toxicology Vol. 22; no. 1; pp. 73 - 83
• Main Authors: Schneider, K., Roller, M., Kalberlah, F., Schuhmacher-Wolz, U.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-01-2002; Wiley
• Subjects: Administration, Oral; Animals; benzo(a)pyrene; Benzo(a)pyrene - toxicity; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; carcinogenicity; Carcinogens, Environmental - toxicity; Chemical agents; Dose-Response Relationship, Drug; Environmental Exposure - adverse effects; Humans; Medical sciences; Mice; mixture; Models, Biological; Neoplasms - chemically induced; oral cavity; oral exposure; polycyclic aromatic hydrocarbons (PAH); Polycyclic Aromatic Hydrocarbons - toxicity; Rats; Risk Assessment; Tumors; Lung disease; Hydrocarbon; Respiratory disease; Toxicity; Rodentia; Oral administration; Malignant tumor; Polycyclic aromatic compound; Long term; Ingestion; Dose activity relation; Carcinogen; Vertebrata; Mammalia; Mouse; Animal; Risk assessment; Coal tar; Digestive diseases
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.828

Cancer risk estimates for oral uptake of polycyclic aromatic hydrocarbons (PAHs) currently are based on risk estimates for benzo[a]pyrene (BAP). The potency of PAH mixtures often is calculated using relative potency values (BAP equivalency factors). We used recent oral carcinogenicity studies with BAP and coal tar mixtures, as well as older studies for a critical reappraisal of the current practice. A literature survey identified several carcinogenicity studies with oral and dermal exposure and lung implantation that allow a direct comparison of the carcinogenic potency of pure BAP and PAH mixtures. Moreover, when the PAH composition of the mixture has been analysed, prediction of the potency of PAH mixtures by BAP equivalency factors could be compared with the observed PAH potency. The analysis indicates that BAP equivalency factors do not describe adequately the potency of PAH mixtures and lead to underestimations of carcinogenic potency in most cases. Evaluation of several studies with various PAH mixtures revealed that the potency ratio between pure BAP and the PAH mixture in the same assay is highly dependent on the exposure pathway and the target organ, therefore potency estimates for PAH mixtures should be derived separately for oral, dermal and inhalative exposure using data from studies with the relevant pathway. A cancer slope factor for oral PAH exposure was derived based on data from a recent feeding study with coal tar mixtures. By using incidence data for all exposure‐related tumours, a slope factor for humans of 11.5 (human excess risk per oral lifetime exposure with 1 mg BAP kg−1day−1 in a PAH mixture) was obtained. Our analysis led to the conclusion that the contribution of BAP to the carcinogenic potency of the mixture depends on the exposure pathway and type of cancer observed but is relatively constant for various PAH mixtures from industrial sources. Thus, the derived oral slope factor is recommended to be used for the risk assessment of PAH‐contaminated soils. Copyright © 2002 John Wiley & Sons, Ltd.