Department of Psychology, Wayne State University, Detroit, MI, United States.
Neurotoxicol Teratol. 2013 Jul-Aug;38:29-35. doi: 10.1016/j.ntt.2013.04.002. Epub 2013 Apr 15.
Binge Toluene Exposure in Pregnancy and Pre-weaning Developmental Consequences in Rats. Bowen, S.E. and Hannigan, J.H. The persistent rate of abuse of inhaled organic solvents, especially among women of child-bearing age, raises the risk for teratogenic effects of maternal toluene abuse. In this study, timed-pregnant Sprague Dawley rats were exposed from Gestation Day (GD) 8 to GD20 to 12,000 or 8000 parts per million (ppm) toluene, or 0ppm (controls) for 30min twice daily, 60min total daily exposure. Pups were assessed from postnatal day (PN) 4 to PN21 using a developmental battery measuring growth (i.e., body weight), maturational milestones (e.g., eye opening & incisor eruption), and biobehavioral development (e.g., negative geotaxis & surface righting). Pups exposed in utero to 12,000ppm or 8000ppm toluene weighed significantly less than the non-exposed control pups beginning at PN4 and PN12 (respectively) until PN21. Toluene resulted in significant increases in an index of poor perinatal outcome, specifically a composite of malformations, defined "runting" and neonatal death. No significant delays were observed in reaching maturational milestones. The results reveal that brief, repeated, prenatal exposure to high concentrations of toluene can cause growth retardation and malformations in rats. A comparison of the present, conservative results with findings in previous studies implies that binge patterns of toluene exposure in pregnant rats modeling human solvent abuse can result in developmental and morphological deficits in offspring. These results do not exclude the possibility that maternal toxicity as well as teratogenic effects of toluene may contribute to outcomes. The results suggest that abuse of inhaled organic solvents like toluene may result in similar early developmental outcomes in humans.
孕期大量吸入甲苯和新生大鼠发育前的后果。Bowen,S.E. 和 Hannigan,J.H. 持续滥用吸入性有机溶剂,尤其是在育龄妇女中,增加了母体甲苯滥用的致畸风险。在这项研究中,将受孕的 Sprague Dawley 大鼠从妊娠第 8 天(GD)到第 20 天(GD)暴露于 12000 或 8000ppm 甲苯或 0ppm(对照)中,每天两次,每次 30 分钟,总共 60 分钟。从出生后第 4 天(PN)到第 21 天(PN),通过发育测试来评估幼鼠,包括生长(即体重)、成熟里程碑(例如,睁眼和出牙)和生物行为发育(例如,负趋地性和表面翻正)。与未暴露于甲苯的对照组幼鼠相比,宫内暴露于 12000ppm 或 8000ppm 甲苯的幼鼠从第 4 天(PN)和第 12 天(PN)开始,体重明显减轻,直到第 21 天(PN)。甲苯导致围产期不良结局的指数显著增加,特别是畸形、定义的“发育迟缓”和新生儿死亡的综合指数。在达到成熟里程碑方面没有观察到明显的延迟。结果表明,短暂、反复的产前接触高浓度甲苯可导致大鼠生长迟缓和畸形。与以前的研究结果相比,本研究结果较为保守,这表明在模拟人类溶剂滥用的怀孕大鼠中,甲苯的 binge 暴露模式可能导致后代发育和形态缺陷。这些结果不排除母体毒性以及甲苯的致畸作用可能导致不良后果。结果表明,滥用吸入性有机溶剂,如甲苯,可能导致人类出现类似的早期发育结局。