Welsch Frank, Elswick Barbara, James R Arden, Marr Melissa C, Myers Christina B, Tyl Rochelle W
CIIT Centers for Health Research, 6 Davis Drive (PO Box 12137), Research Triangle Park, NC 27709-2137, USA.
J Appl Toxicol. 2003 Nov-Dec;23(6):387-95. doi: 10.1002/jat.927.
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.
该评估是一项更为全面的测试计划的一部分，旨在确定汽油含氧化合物添加剂叔戊基甲基醚（TAME）对哺乳动物的潜在毒性，且该评估是应监管机构要求启动的。通过对两种怀孕啮齿动物物种进行TAME蒸汽吸入暴露，开展了一项发育毒性危害识别研究。妊娠第6至16天（小鼠）或第6至19天（大鼠），每组25只定时怀孕的CD（斯普拉格-道利）大鼠和CD-1小鼠，每天吸入含0、250、1500或3500 ppm的TAME蒸汽6小时。按照美国环境保护局提出的研究设计草案指南和终点指标，对发育毒性危害潜力进行了评估。根据孕期母体体重变化，以近期胎儿体重为标准，大鼠母体毒性的无可见不良作用水平（NOAEL）为250 ppm，大鼠发育毒性的NOAEL为1500 ppm。在小鼠中，1500 ppm和3500 ppm时均出现了比大鼠更严重的发育毒性。在最高浓度下，小鼠窝显示出更多晚期胎儿死亡、每窝胎儿体重显著降低、腭裂发生率增加（归类为外部畸形）以及大脑侧脑室扩大（一种内脏变异）。在1500 ppm时，小鼠胎儿也出现腭裂发生率增加且母体体重减轻的情况。因此，在本研究条件下，小鼠母体和发育毒性的NOAEL为250 ppm。
