"INTRODUCTION AND BACKGROUND The American Petroleum Institute (API) has expressed a need to obtain information regarding the uptake and biological disposition of inhaled gasoline components. Previous long-term inhalation exposures of rats and mice to 67.292 and 2050 ppm of completely volatilized gasoline (McFarland et al.@ 1984) resulted in early-occurring (first observed after 3 months of exposure) progressive renal tubular disease and late-occurring (after 24 months of exposure) primary renal neoplasms in male F344 rats and increased incidence of hepatocellular tumors in female B6C3F1 mice. Gasoline includes five major classes of compounds: linear alkanes@ branched alkanes@ olefins@ alicyclics (cycloalkanes) and aromatic compounds. Table 1 lists the major compounds found in gasoline (MacFarland et al.@ 1984). Pitts er al. (1983) used oral dosing of male F344 rats to various subfractions of gasoline to determine if the nephrotoxicity could be attributed to any one class of compounds. They found that branched alkanes (2@3@4- and 2@2@4-trimethylpentane) and cycloalkanes were the most nephrotoxic. Further studies with branched chain alkanes (Short er al.@ 1986; Kloss er al.@ 19867) suggest that metabolites of these compounds bind to serum proteins and that the resulting complexes are responsible for the observed nephrotoxicity. Studies at Lovelace ITRI under the technical proposal ""Studies on the Absorption of Inhaied Hydrocarbon Vapors"" were designed to determine if there are significant differences in the uptake of hydrocarbon vapors having different chemical structures. A final report describing those studies was accepted by API in November@ 1987. Significant differences in dose@ on a per kilogram body weight basis@ were observed for different hydrocarbons inhaled at the same vapor concentrations (Dahl er al.@ 1987; Dahl et al.@ 1988). Because branching appears to be critical to the toxic effect of saturated hydrocarbons on male rat kidneys@ n-octane and 2@2@4-trimethylpentane (isooctane) were chosen as test compounds in an API-funded project ""Studies on Tissue Equilibria and Excretion Routes of Inhaled Hydrocarbon Vapors and Their Metabolites."" An earlier study by pitts et al. (1983) showed that n-octane administration does not lead to male rat nephropathy@ while isooctane administrations does. Our project was designed to measure rates of metabolism and elimination (by different routes) for each of the test compounds to determine if differences in these parameters might help account for differences in toxicity. Excretory patterns and blood distribution and retention patterns for inhaled hydrocarbons and their metabolites were assessed and are described in this report."
API PUBL 36-31430-1989 history
1989API PUBL 36-31430-1989 STUDIES ON THE ABSORPTION@ TISSUE EQUILIBRIA AND EXCRETION ROUTES OF INHALED HYDROCARBON VAPORS AND THEIR METABOLITES