Heindel J J, Price C J, Field E A, Marr M C, Myers C B, Morrissey R E, Schwetz B A
Developmental and Reproductive Toxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Fundam Appl Toxicol. 1992 Feb;18(2):266-77. doi: 10.1016/0272-0590(92)90055-m.
Boric acid (BORA), an ingredient of many cosmetics, pharmaceuticals, and pesticides, was tested for developmental toxicity in timed-pregnant Swiss mice and Sprague-Dawley rats (n = 26-28/group). BORA (0, 0.1, 0.2, or 0.4% in feed) was provided throughout gestation to attain steady-state exposure as early as possible during prenatal development. Average doses (mg/kg/day) were 248, 452, or 1003 in mice, and 78, 163, or 330 in rats. To limit prenatal mortality, BORA (0.8% or 539 mg/kg/day) was provided to an additional group of rats on Gestational Days (GD) 6 to 15 only. On GD 17 (mice) or 20 (rats), fetuses were weighed and examined for malformations (external, visceral, skeletal). Mouse dams exhibited mild renal lesions (greater than or equal to 0.1%), increased water intake and relative kidney weight (0.4%), and decreased weight gain (0.4%) during treatment. There was a reduction of fetal body weight (greater than or equal to 0.2%) and an increased incidence of resorptions and malformed fetuses per litter (0.4%). Morphological changes included an increased incidence of short rib XIII (a malformation) and a decreased incidence of rudimentary or full rib(s) at lumbar I (an anatomical variation). Maternal rats exhibited increased liver and kidney weights at greater than or equal to 0.2%, altered water and/or food intake at greater than 0.2%, and decreased weight gain at greater than 0.4%. Average fetal body weight/litter was reduced at all doses. Prenatal mortality was increased only at 0.8%. The incidence of fetal malformations was significantly increased at greater than or equal to 0.2%. The most frequently observed malformations were enlarged lateral ventricles of the brain and agenesis or shortening of rib XIII. In rats, the no-observable-adverse-effect level (NOAEL) for maternal toxicity was 78 mg/kg (0.1%), while in mice the low dose of 248 mg/kg (0.1%) approached the maternal NOAEL with mild renal lesions in only 2 of 10 females. Embryo/fetal toxicity occurred in all groups of rats at greater than or equal to 78 mg/kg (greater than or equal to 0.1%) while the NOAEL for developmental toxicity in mice was 248 mg/kg (0.1%). Thus developmental toxicity occurred below maternally toxic levels in rats as well as in the presence of maternal toxicity in mice and rats.
硼酸（BORA）是许多化妆品、药品和杀虫剂的成分，在定时怀孕的瑞士小鼠和斯普拉格-道利大鼠（每组n = 26 - 28只）中进行了发育毒性测试。在整个妊娠期提供BORA（饲料中含量为0、0.1、0.2或0.4%），以便在产前发育尽可能早地达到稳态暴露。小鼠的平均剂量（mg/kg/天）为248、452或1003，大鼠为78、163或330。为了限制产前死亡率，仅在妊娠第6至15天给另一组大鼠提供BORA（0.8%或539 mg/kg/天）。在妊娠第17天（小鼠）或第20天（大鼠），对胎儿称重并检查是否有畸形（外部、内脏、骨骼）。小鼠母鼠在治疗期间出现轻度肾脏病变（大于或等于0.1%）、饮水量增加和相对肾脏重量增加（0.4%）以及体重增加减少（0.4%）。胎儿体重有所减轻（大于或等于0.2%），每窝吸收胎和畸形胎儿的发生率增加（0.4%）。形态学变化包括第XIII对短肋（一种畸形）的发生率增加以及第I腰椎处未发育或完整肋骨（一种解剖变异）的发生率降低。母鼠肝脏和肾脏重量增加大于或等于0.2%、水和/或食物摄入量改变大于0.2%以及体重增加减少大于0.4%。所有剂量下每窝胎儿平均体重均降低。仅在0.8%剂量时产前死亡率增加。胎儿畸形发生率在大于或等于0.2%时显著增加。最常观察到的畸形是脑侧脑室扩大以及第XIII对肋骨发育不全或缩短。在大鼠中，母体毒性的无观察到有害作用水平（NOAEL）为78 mg/kg（0.1%），而在小鼠中，低剂量248 mg/kg（0.1%）接近母体NOAEL，仅10只雌性中有2只出现轻度肾脏病变。在大于或等于78 mg/kg（大于或等于0.1%）的所有大鼠组中均出现胚胎/胎儿毒性，而小鼠发育毒性的NOAEL为248 mg/kg（0.1%）。因此，大鼠在低于母体毒性水平时发生发育毒性，而小鼠和大鼠在存在母体毒性时也发生发育毒性。
