Development of a dermal cancer slope factor for benzo[a]pyrene.
Polycyclic aromatic hydrocarbons (PAHs) are commonly found at environmentally impacted sites in both Canada and the United States, and also occur naturally. Typically, benzo[a]pyrene (B[a]P) is selected as a standard to which the cancer potencies of other carcinogenic PAHs are compared. Cancer potency estimates for B[a]P have been published for the oral and inhalation routes of exposure, however, no such estimate has been established by a regulatory agency for dermal exposure. The main objectives of the current investigation were to: evaluate approaches used to examine the relative carcinogenicity of PAHs; to conduct a review of mammalian dermal carcinogenicity studies for B[a]P; and derive a cancer slope factor for dermal exposure to PAHs using B[a]P as a surrogate for other PAHs. The toxicological database of dermal B[a]P studies was examined for relevant animal bioassays. Seven relevant studies were identified. A cancer slope factor for B[a]P was developed using the benchmark dose approach and the linearized multistage model. The upper 95th CI at the 5% effect level above background incidence was used as the point of departure for low-dose linear extrapolation. An average slope factor of 0.55 (microg/animal day)(-1) was calculated for mice, which was converted to a dose-equivalent slope factor of 25 (mg/kg day)(-1). This latter slope factor is proposed for application to human health risk assessment with no scaling adjustment. Dermal potency equivalency factor values were identified which may be used with other carcinogenic PAH in the calculation of total B[a]P equivalent dermal cancer risk estimates. An identified area for further investigation is the consideration of scaling in extrapolating the calculated dermal cancer slope factor from mice to humans.
Knafla
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Equilibrium Environmental Inc., Suite 609, 815 1st Street SW Calgary, Alta., Canada T2P 1N3.
Phillipps
K A
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Brecher
R W
RW
Petrovic
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Richardson
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M
D000279:Administration, Cutaneous; D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000633:toxicity*; D002274:Carcinogens, Environmental / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008954:Models, Biological; D011084:Polycyclic Aromatic Hydrocarbons / Q000008:administration & dosage / Q000633:toxicity*; D018570:Risk Assessment; D012878:Skin Neoplasms / Q000139:chemically induced*
D002274:Carcinogens, Environmental; D011084:Polycyclic Aromatic Hydrocarbons; D001564:Benzo(a)pyrene