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-'LUrM D= GASOL= f 65-21 supersnaosed old raz nepnrauathv an tha z_axziazion. deveionmant, and progression of renal neoplasia induced by unleaded gazotj.. _ Thus the UAM revtev concluded that: "The chronic inhalation scudv demonstrated chat unlea"L. gasoline Inhalation produced acuza, subchronic and chronic tonicity in the kidneys of mala rats. SL=LLzanaously, there was the development of preneoplastic lesions and ultimately the appearance of adenomxx ` and adenocarcinomas in these male rats. The link hacvaen acute - _ -�- and chroaxc toxicity and r-Arcinogenicity is not clear. nor can it _ �_ - (be) date=inad from the dors generated in this bioaxxay. Al- though the pattern of acura and chronic nou-neoplastic toxic lesions is somewhat unique for gasoline-related hydrocarbons, the r�t morphological appearance of the preneoplastic and neoplastic lesions is similar to that produced by a number of renal carcino- gens." 65.3.1.2 Mutagenicity In general, studies of unleaded gasoline have shown no genoroxi:city. Uatleadad gasoline failad to induce his} mutanrs in the Ames Salmonella plate or suspension assays performed with and without metabolic activation by roc liver microsomes (2303) . In cycogenecte sttadias, no chromosomal abnatuaLit3es were seen in the bone marrow of rats created intraperttansally with unleaded gasoline (2303.2304) , nor vera sister chromatid exchanges increased in human lymphoblasts trsacad In A=:z (2301) . When unleaded gazolina Baan tested in the L5178Y mouse Lymphoma assay (2303) and is a simLlar anuay employing a huum lymphoblastoid line (2301) . n® incrsaso in mutation frmquour-7 V= abaorvad in either system. A dons-related increauo in unschedulod DEQ sjnthQzXz (GIDS) wao obsorved in rat hepacocyzes trenced is Xj= with 0.05 to 0.100 (v/v) ganolin®, whoresa thsso doses were t=ic in both nousra and human hepatocyte cultures (7302) . Weak UDS activity wads observed in heptacoeyzes isolated from male and female mice treated 12 ' hours prev'Lously by gastric intubation -with 2 g unleaded- gasoline/kg (2302) . 65.3.1.3 Teracogentcizy, Embryotoxicity and Reproductive Effects Unleaded gasoline did not induce dominant Lathai muratlosts in ` sperm calls of CD-1 male mice (2300) . The mice were exposed to geso- ;� Lina vapors for 6 hours per day, five days per week for eight weeks prior to mating with untreated females. Doses of 400 ppm and 1600 pp= L did not cause any significant, reduction in the fertility of the treated males, nor was any significant increase in pre- or post-implaataclon Loss of embryos noted. It should be noted. however, that deaths amongst the males occurred during the treatment period; the cause and 4' significance are unknown. lr 6/87 L