Tyl R W, Ballantyne B, Fisher L C, Fait D L, Savine T A, Dodd D E, Klonne D R, Pritts I M
Bushy Run Research Center, Export, Pennsylvania.
Fundam Appl Toxicol. 1995 Jan;24(1):57-75. doi: 10.1006/faat.1995.1008.
Ethylene glycol (EG) is a major industrial chemical, shown to be teratogenic at high doses by gavage in rodents. Since one route of industrial exposure is to the aerosol at high concentrations, timed-pregnant CD rats and CD-1 mice were exposed, whole-body, to a respirable aerosol of EG (mass median aerodynamic diameter, 2.3 microns) on Gestational Days (GD) 6 through 15 for 6 hr per day at target exposure concentrations of 0, 150, 1000, or 2500 mg/m3 (analytical concentrations of 0, 119 +/- 13, 888 +/- 149, and 2090 +/- 244 mg/m3, respectively), with 25 plug-positive animals per species per group. Clinical observations and maternal body weights were documented throughout gestation for both species. Maternal food and water consumption was measured in rats only throughout gestation. At scheduled necropsy (GD 21 for rats, GD 18 for mice), maternal animals were evaluated for body weight, liver weight, kidney weight, gravid uterine weight, number of ovarian corpora lutea, and status of implantation sites, i.e., resorptions, dead fetuses, live fetuses. Fetuses were dissected from the uterus, counted, weighed, sexed, and examined for external, visceral, and skeletal malformations and variations. All rat dams survived to scheduled termination. Minimal maternal toxicity was indicated by a significant increase in absolute and relative liver weight at 2500 mg/m3. Food and water consumption, maternal body weights and weight gain, and maternal organ weights (other than liver) were unaffected by exposure. Gestational parameters were unaffected by exposure, including pre- and post-implantation loss, live fetuses/litter, sex ratio, and fetal body weight/litter. There was no treatment-related increase in the incidence of any individual malformation, in the incidence of pooled external, visceral, or skeletal malformations, or in the incidence of total malformations by fetus or by litter. There were no increases in the incidence of external or visceral variations. Evidence of fetotoxicity, expressed as reduced ossification in the humerus, the zygomatic arch, and the metatarsals and proximal phalanges of the hind-limb, was observed at 1000 and 2500 mg/m3. All mouse dams survived to scheduled termination. One dam at 2500 mg/m3 was carrying a totally resorbed litter at termination. Maternal toxicity was observed at 1000 and 2500 mg/m3, expressed as reduced body weight and weight gain during and after the exposure period, and reduced gravid uterine weight. (Maternal effects may have been due, in part or whole, to effects on the conceptuses; see below.)(ABSTRACT TRUNCATED AT 400 WORDS)
乙二醇（EG）是一种主要的工业化学品，经口灌胃给予高剂量时，在啮齿动物中显示具有致畸性。由于工业接触的一种途径是高浓度气溶胶，因此在妊娠第6天至15天，将定时怀孕的CD大鼠和CD - 1小鼠全身暴露于可吸入的EG气溶胶（质量中位空气动力学直径为2.3微米）中，每天暴露6小时，目标暴露浓度分别为0、150、1000或2500毫克/立方米（分析浓度分别为0、119±13、888±149和2090±244毫克/立方米），每组每种动物有25只怀孕阳性动物。在整个妊娠期记录了两种动物的临床观察和母体体重。仅在整个妊娠期测量了大鼠的母体食物和水消耗量。在预定的尸检时（大鼠为妊娠第21天，小鼠为妊娠第18天），对母体动物进行体重、肝脏重量、肾脏重量、妊娠子宫重量、卵巢黄体数量以及着床部位状态（即吸收、死胎、活胎）的评估。从子宫中取出胎儿，计数、称重、确定性别，并检查外部、内脏和骨骼畸形及变异情况。所有大鼠母鼠均存活至预定的终止时间。在2500毫克/立方米时，绝对和相对肝脏重量显著增加，表明母体毒性最小。食物和水消耗量、母体体重及体重增加以及母体器官重量（肝脏除外）均不受暴露影响。妊娠参数不受暴露影响，包括着床前和着床后损失、每窝活胎数、性别比例以及每窝胎儿体重。任何个体畸形的发生率、合并的外部、内脏或骨骼畸形的发生率，或按胎儿或窝计算的总畸形发生率均未因治疗而增加。外部或内脏变异的发生率也未增加。在1000和2500毫克/立方米时，观察到胎儿毒性的证据，表现为肱骨、颧弓以及后肢跖骨和近端指骨的骨化减少。所有小鼠母鼠均存活至预定的终止时间。在2500毫克/立方米时，有一只母鼠在终止时怀有一窝完全吸收的胎儿。在1000和2500毫克/立方米时观察到母体毒性，表现为暴露期间及之后体重和体重增加减少，以及妊娠子宫重量减少。（母体效应可能部分或全部归因于对胚胎的影响；见下文。）（摘要截断于400字）
