Development of a carcinogenic potency index for dermal exposure to viscous oil products.
Polycyclic aromatic compounds (PACs) present in oil streams and formulated products are important determinants of possible carcinogenicity. Following dermal exposures the transport of the PACs from oil (the carrier) into the skin is a factor that may affect macromolecular (DNA) adduct formation and thus determine carcinogenicity. We have developed a mathematical model, which describes the flux into the skin for a representative carcinogenic PAC, benzo(a)pyrene. The model is based on measurements of the amount of benzo(a)pyrene bound to skin DNA or blood observed in mouse skin painting studies. The degree of adduct formation from a particular oil product, which we term the Bioavailability Index (BI), was shown to be a function of both the viscosity of the oil product, which affected the transport of the PAC through the carrier, and the aromaticity, which affected the partition of PAC between the carrier and the skin. Literature data were analysed from mouse skin painting studies with mineral oils of known carcinogenicity. A linear relationship was shown between the amount of DNA adduct formation, expressed as alkylation frequency, and the arithmetic product of the total (3-6) ring PAC content and the BI, which we have termed the Carcinogenic Potency Index (CPI). Comparison of literature data on DNA alkylation frequencies for oil products and their carcinogenicity indicated that oils giving rise to an alkylation frequency below a certain threshold (ca. 1 adduct in 10(8) nucleotides) are non-carcinogenic to mouse skin. This threshold level can be translated into a value for the CPI, below which the genotoxic carcinogenic risk arising from skin contact with the oil product is considered to be negligible. The CPI for bitumens is well below this value, being both due to the low BI from bitumen, but more so, due to their low PAC content. For some bitumens diluted with solvents, i.e. cutback-bitumens, the CPI may exceed this value, indicating a possible carcinogenic risk for some of the cutback-bitumens. The main determining factor is the PAC content which is principally determined by the nature of the diluent used.
Brandt
H C
HC
Shell International Oil Products BV, Shell Research and Technology Centre, Amsterdam, The Netherlands.
Booth
E D
ED
de Groot
P C
PC
Watson
W P
WP
D000279:Administration, Cutaneous; D000818:Animals; D001564:Benzo(a)pyrene / Q000493:pharmacokinetics*; D001682:Biological Availability; D002273:Carcinogens / Q000493:pharmacokinetics* / Q000633:toxicity; D004247:DNA / Q000378:metabolism; D018736:DNA Adducts; D051379:Mice; D008962:Models, Theoretical; D012869:Skin Absorption / Q000502:physiology*; D012995:Solubility; D014783:Viscosity
D002273:Carcinogens; D018736:DNA Adducts; D001564:Benzo(a)pyrene; D004247:DNA