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- UTMD= C,ASOL= ' b5-21 j - SUperz.,aased old rat nephropathy on the 3 n7 ziazian. develommanz. and ?rogression of ranal neoplasia induced by unleaded gasoli:._. Thus the UAREP review concluded that: "The chronic inhalation studv demo narrated that unleadec. 3asoline inhalation produced acute. subchronic and chronic toxicLL7 in the kidneys of male rats. Si=LLtaneously, there was the developmenr i of preneoplastic lesions and ultimately the appearance of adeinomaa ocarcinom s and adenas in these male rats. The Link between acute 1 and chronic toxicity and carcinogenicity is not clear, nor can it (be) detarminad from the data generated is this bioassay. AI- though the patrarn of acute and chronic non-neoplastic toxic lesions is somewhat unique for gasoline-related hydrocarbons, the {' ;. morphological appearanca of the preneoplastic and neoplastic lesions is similar to that producad by a number of renal carcina- i 65.3'.1.2 Mutagenicity In general, studies of unleaded gasoline have shown no ganotoxTaity. Unleaded gasoline failad to induce his mutancz in the Ames WIMILIA6 plate or suspension assays perforated with and without ._ metabolic activation by rac liver microsomes (2303) . In cytogenetic studies, no chrosrosomaL abnormalitias were seen in the bona marrow of rats traace'd inErapezritonaally with unleaded gasoline (2303.2304). nor were sister chromatid exchanges increased in human lymphobLasts treated Sa V_1=2 (2301). When unleaded gasoline was tested in the L5178Y mouse N_ lymphoma assay (2303) and in a similar assay employing a. human l hoblastoid Zine . ymP (2301). no increase is mutation frequency was . observed in either systas. A dose-reLatad increase in umschadmLed MM • • synthesis (UDS) was observed in rat hepatocytes treated _An VISIM with 0.05 to 0.105 (v/v) gasoline, whereas these doses were toxic in both souse and human hepatocyra cultures (2302). Weak UDS activity was ` observed in haparacytes isolated £roe male and female twice treated 12 hours previously by gastric iatubacion with 2 g unleaded gasoline/kg (2302) . y 65.3.1.3 Teratogenicity. Fmbryotoxicity and Reproductive Effects i E1 Unleaded gasoline did not caduca dominant lethal mutations is sperm cells of cD-1 male mics (2300) . The mice were exposed to gaso- line vapors for 6 hours per day, five days per week for eight wooks i • prior to mating with uatreatad females. Doses of 400 ppm and 1600 ppa �L did noc cause any significant raduccion in the ferzilitT of the treated males. nor was any siguifiaant increase in pre- or post-implantation loss of embryos noted. It should be noted, however. that deaths amangst the males occurred during the treacmenu: period; the cause and ' }� significance are urdmown. i i 6/87 �r yF