A COMPREHENSIVE EVALUATION OF THE MECHANISM OF SKIN TUMORIGENESIS BY STRAIGHT-RUN AND CRACKED PETROLEUM MIDDLE DISTILLATES

The role of skin irritation and other factors on the tumorigenic activ ity of petroleum middle distillates (PMDs) in mice was examined in a c omprehensive research program. The program culminated in a 2-year derm al carcinogenicity study which compared the effects of equal weekly do ses of irritating and nonirritating PMDs. Modified Ames mutagenicity s tudies and three- to seven-ring polycyclic aromatic compound (PAC) ana lyses indicated that the mutagenic activity of PMDs was correlated to PAC content. In subchronic and subacute studies, PMDs produced marked skin irritation which was ameliorated if the test samples were diluted in mineral oil. The reduction in irritation level was not a result of reduced dermal absorption. Straight-run kerosine (SRK), straight-run gas oil (SRGO), and catalytically cracked light cycle oil (LCO) were e valuated in the dermal carcinogenicity study. Test materials were appl ied either undiluted (2x/week) or as 28.5% (7x/week) or 50% (4x/week) concentrations in mineral oil for a total weekly dose of 100 mu l PMD per animal, All three materials produced moderate to marked skin irrit ation and increased tumor frequency when applied undiluted. When dilut ed, the irritant effects of SRK and SRGO, which contain low levels of PACs, were ameliorated, and there were no significant increases in tum ors relative to controls. LCO, containing 8.7% three- to seven-ring PA Cs, increased tumor frequency when diluted, even when skin irritation was limited. These data indicate that the tumorigenic activity of stra ight-run MDs is likely a consequence of a nongenotoxic process, associ ated with frequent cell damage and repair. PMDs which contain low leve ls of three- to seven-ring PACs are unlikely to cause tumors in the ab sence of prolonged skin irritation, In addition, genotoxic mechanisms may also contribute to tumor formation for other PMDs containing highe r levels of PACs, e.g., products blended with cracked stocks. (C) 1998 Society of Toxicology.