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Genotoxicity and twenty-eight-day subchronic toxicity studies on tertiary amyl methyl ether

✍ Scribed by Wayne C. Daughtrey; Michael G. Bird


Book ID
102872469
Publisher
John Wiley and Sons
Year
1995
Tongue
English
Weight
614 KB
Volume
15
Category
Article
ISSN
0260-437X

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✦ Synopsis


Abstract

Tertiary amyl methyl ether (TAME) is an oxygenate with a potential role as a component in reformulated gasolines. The genotoxic potential of TAME was assessed in an Ames assay and a mouse micronucleus assay. The Ames assay was carried out using five standard salmonella strains and doses ranging from 100 to 10000 μg 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 single 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 micronucleus formation at 24, 48 and 72 h after dosing. No elevation in micronucleus frequency was observed at any dose or at any of the collection times. Thus, TAME was not clastogenic to mouse bone marrow under the conditions of this study. Preliminary test data indicated that the acute 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 were dosed orally with vehicle, 0.125, 0.5 or 1.0 g kg^−1^ day^−1^ TAME in 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 high‐dose group (1 g kg^−1^ day^−1^) appeared to be compound related. Food consumption and body weights were reduced in the high‐dose male group relative to controls; otherwise, clinical observations were minimal. Dose‐related increases in adrenal and kidney weights were observed but no histopathological changes were evident in any of the tissues examined. It is concluded that while some evidence of toxicity was observed at the highest dose, TAME is of low oral toxicity following repeated dosing. The no‐observed‐effect level (NOEL) for this study was 0.125 g kg^−1^ day^−1^ and the no‐observed‐adverse‐effect level (NOAEL) was 0.5 g kg^−1^ day^−1^.