A comprehensive evaluation of the carcinogenic potential of middle distillate fuels

Middle distillate fuels (MDFs), which include jet fuel, kerosene, and diese l fuel, are a class of hydrocarbons distilled from crude oil at approximate ly 350-700 degrees F (176-371 degrees C) Although MDFs generally do not con tain appreciable levels of potentially carcinogenic polycyclic aromatic com pounds (PACs), they have produced weak tumorigenic responses in mouse skin characterized by low tumor yield and long latency. Recent studies demonstra ted that the tumorigenic effects of these MDFs were dependent upon chronic dermal irritation. In the absence of skin irritation, tumors did not develo p. Mechanistic studies suggest that straight-run MDFs containing low levels of PACs cause skin tumors through a nongenotoxic mechanism. MDFs cause chroni c skin irritation and injury with repeated application to the skin. They ha ve been found to have little or no activity in the modified Ames mutagenici ty assay, lack tumor initiating activity, and are active skin tumor promote rs. It has been hypothesized that the tumorigenic response to MDFs results from the promotion of preexisting, spontaneously initiated cells. Two recent studies, a one-year tumor promotion study and a two-year skin pa inting study, evaluated the role of skin irritation on the tumorigenic acti vity of MDFs in mice. MDFs were applied in pure and diluted forms to assess the effect of equal weekly doses of irritating and nonirritating test. mat erials. The tumorigenicity of straight-run MDFs correlated to the level of skin irritation. Na significant increase in tumor incidence occurred under conditions that resulted in minimal skin irritation and injury. These studi es indicate that the tumorigenic activity of MDFs containing low levels of PACs is secondary to chronic skin irritation, These materials should not pr esent a carcinogenic hazard in the absence of prolonged skin irritation.