Developmental toxicity evaluation of inhaled tertiary amyl methyl ether in mice and rats
Version of Record online: 17 NOV 2003
Copyright © 2003 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 23, Issue 6, pages 387–395, November/December 2003
How to Cite
Welsch, F., Elswick, B., Arden James, R., Marr, M. C., Myers, C. B. and Tyl, R. W. (2003), Developmental toxicity evaluation of inhaled tertiary amyl methyl ether in mice and rats. J. Appl. Toxicol., 23: 387–395. doi: 10.1002/jat.927
- Issue online: 17 NOV 2003
- Version of Record online: 17 NOV 2003
- Manuscript Received: 23 NOV 2002
- Manuscript Accepted: 15 JAN 2002
- American Petroleum Institute
- tertiary amyl methyl ether;
- developmental toxicity
This evaluation was part of a much more comprehensive testing program to characterize the mammalian toxicity potential of the gasoline oxygenator additive tertiary amyl methyl ether (TAME), and was initiated upon a regulatory agency mandate. A developmental toxicity hazard identiﬁcation study was conducted by TAME vapor inhalation exposure in two pregnant rodent species. Timed-pregnant CD®(Sprague-Dawley) rats and CD-1® mice, 25 animals per group, inhaled TAME vapors containing 0, 250, 1500 or 3500 ppm for 6 h a day on gestational days 6–16 (mice) or 6–19 (rats). The developmental toxicity hazard potential was evaluated following the study design draft guidelines and end points proposed by the United States Environmental Protection Agency. Based on maternal body weight changes during pregnancy, the no-observable-adverse-effect level (NOAEL) was 250 ppm for maternal toxicity in rats and 1500 ppm for developmental toxicity in rats using the criterion of near-term fetal body weights. In mice, more profound developmental toxicity was present than in rats, at both 1500 and 3500 ppm. At the highest concentration, mouse litters revealed more late fetal deaths, signiﬁcantly reduced fetal body weights per litter and increased incidences of cleft palate (classiﬁed as an external malformation), as well as enlarged lateral ventricles of the cerebrum (a visceral variation). At 1500 ppm, mouse fetuses also exhibited an increased incidence of cleft palate and the dam body weights were reduced. Therefore, the NOAEL for the mouse maternal and developmental toxicity was 250 ppm under the conditions of this study. Copyright © 2003 John Wiley & Sons, Ltd.