Abuse pattern of gestational toluene exposure and early postnatal development in rats
Abuse pattern of gestational toluene exposure and early postnatal development in rats
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DOI：
10.1016/j.ntt.2004.09.007
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发表时间：
2005-01-01
影响因子：
2.9
通讯作者：
Hannigan, JH
中科院分区：
文献类型：
--
作者：
Bowen, SE;Batis, JC;Hannigan, JH
在美国，吸入滥用仅次于酒精、大麻和尼古丁滥用。胶水和清洁剂中含有的甲苯是最常被滥用的吸入剂之一。虽然已经研究了因职业接触有机溶剂（即相对长期接触较低浓度）导致的致畸性，但有机溶剂滥用（即短暂吸入接触非常高浓度）的致畸潜力尚未得到彻底检查。在胎儿溶剂暴露滥用模式的临床前模型中，从妊娠第 8 天 (GD8) 到 GD20，定时怀孕的大鼠暴露于百万分之 8000 (ppm) 或 12,000 ppm 的甲苯或空气 (0 ppm)，每次 15 分钟，每天两次。分娩后，幼崽从出生后第 4 天（PN4）到 PN21 在发育测试组中进行测试，包括生长测量（即体重）、成熟里程碑（即耳廓展开、门牙萌出和眼睛张开）和生物行为发育（例如负向地性、表面矫正和握力）。在 PN16 之前的所有年龄段，在子宫内暴露于 12,000 ppm 甲苯的幼崽的体重均明显低于对照幼崽。甲苯导致围产期不良结局指数显着增加（即畸形、“矮小”和新生儿死亡的组合）和负趋地性缺陷。在达到成熟里程碑方面没有明显的延迟。结果表明，产前短暂、反复接触高浓度甲苯会导致大鼠生长受限、畸形和生物行为发育受损。将目前的结果与之前的职业接触模式研究进行比较表明，对于给定的每日甲苯“剂量”，暴饮暴食的接触模式可能会给胎儿发育带来更大的风险。由于本实验中的暴露模式模拟了人类溶剂滥用中的暴饮暴食，因此结果表明，滥用吸入有机溶剂（例如甲苯）可能会导致人类出现类似的致畸结果。(C) 2004 Elsevier Inc. 保留所有权利。
Inhalant abuse in the United States trails only alcohol, marijuana and nicotine abuse. Toluene, found in glues and cleaners, is among the most commonly abused inhalants. While teratogenicity due to occupational exposure to organic solvents (i.e., relatively long-term exposure to lower concentrations) has been studied, the teratogenic potential of organic solvent abuse (i.e., brief inhalation exposures to very high concentrations) has not been thoroughly examined. In a preclinical model of abuse patterns of fetal solvent exposure, timed-pregnant rats were exposed to 8000 parts per million (ppm) or 12,000 ppm of toluene, or to air (0 ppm), for 15 min twice daily from gestation day 8 (GD8) through GD20. After parturition, pups were tested from postnatal day 4 (PN4) to PN21 in a developmental test battery including measures of growth (i.e., body weight), maturational milestones (i.e., pinnae unfolding, incisor eruption and eye opening) and biobehavioral development (e.g., negative geotaxis, surface righting and grip strength). Pups exposed in utero to 12,000 ppm toluene weighed significantly less than the control pups at all ages before PN16. There were significant toluene-induced increases in an index of poor perinatal outcome (i.e., a combination of malformations, "runting" and neonatal death) and deficits in negative geotaxis. There were no significant delays in reaching maturational milestones. The results demonstrate that brief, repeated, prenatal exposure to high concentrations of toluene can cause growth restriction, malformation and impairments of biobehavioral development in rats. A comparison of the present outcomes to previous studies of occupational exposure patterns suggests that for a given daily "dose" of toluene, a binge pattern of exposure may pose a greater risk for fetal development. Since the pattern of exposure in this experiment models binge exposure in human solvent abuse, the results imply that abuse of inhaled organic solvents, such as toluene, can cause similar teratogenic outcomes in humans.(C) 2004 Elsevier Inc. All rights reserved.