GENOTOXICITY AND 28-DAY SUBCHRONIC TOXICITY STUDIES ON TERTIARY AMYL METHYL-ETHER

Tertiary amyl methyl ether (TAME) is an oxygenate with a potential rol e as a component in reformulated gasolines. The genotoxic potential of TAME was assessed in an Ames assay and a mouse micronucleus assay. Th e Ames assay was carried out using five standard salmonella strains an d doses ranging from 100 to 10000 mu g per plate. Tertiary amyl methyl ether was not mutagenic in any of the strains, either with or without metabolic activation. In the micronucleus assay, mice were given a si ngle intraperitoneal injection of TAME at doses of 0.15, 0.375 or 0.75 g kg(-1). Bone marrow samples were collected and evaluated for micron ucleus formation at 24, 48 and 72 h after dosing. No elevation in micr onucleus frequency was observed at any dose or at any of tile collecti on times. Thus, TAME was not clastogenic to mouse bone marrow under th e conditions of this study. Preliminary test data indicated that the a cute oral LD(50) for TAME in Sprague-Dawley rats was ca. 2.1 g kg(-1). In the 28-day subchronic study, Sprague-Dawley rats of both sexes wer e dosed orally with vehicle, 0.125, 0.5 or 1.0 g kg(-1) day(-1) TAME i n corn oil at a dose volume of 2 ml/kg(-1). Dosing continued 7 days a week for a period of 28 days, Deaths of two out of 10 animals in the h igh-dose group (1 g kg(-1) day(-1)) appeared to be compound related. F ood consumption and body weights were reduced in the high-dose male gr oup relative to controls; otherwise, clinical observations were minima l. Dose-related increases in adrenal and kidney weights were observed but no histopathological changes were evident in any of the tissues ex amined. It is concluded that while some evidence of toxicity was obser ved at the highest dose, TAME is of low oral toxicity following repeat ed dosing. The no-observed-effect level (NOEL) for this study was 0.12 5 g kg(-1)day(-1) and the no-observed-adverse-effect level (NOEL) was 0.5 g kg(-1) day(-1).