Price C J, Marr M C, Myers C B, Seely J C, Heindel J J, Schwetz B A
Chemistry and Life Sciences, Research Triangle Institute, Research Triangle Park, North Carolina, 27709-2194, USA.
Fundam Appl Toxicol. 1996 Dec;34(2):176-87. doi: 10.1006/faat.1996.0188.
Boric acid (BA), an ingredient of many pharmaceutical, cosmetic, and pesticide products, was previously shown to induce reproductive and developmental toxicity in laboratory rodents. In this study, BA (0, 62.5, 125, or 250 mg/kg/day, po) was administered on Gestational Days (GD) 6-19 to New Zealand White rabbits (18-23 pregnant/group). Maternal body weight, food consumption, and clinical condition were monitored at regular intervals throughout gestation. At termination (GD 30), the numbers of uterine implantations, resorptions, dead fetuses, and live fetuses were determined. Fetuses were weighed, and live fetuses examined for external, visceral, and skeletal defects. Maternal food intake decreased during treatment at 250 mg/kg/day and increased at >/=125 mg/kg/day after treatment. Maternal body weight (GD 9-30), weight gain during treatment, gravid uterine weight, and number of ovarian corpora lutea decreased at 250 mg/kg/day. In contrast, maternal corrected gestational weight gain increased at >/=125 mg/kg/day. Maternal liver weight was not affected. Relative (but not absolute) maternal kidney weight increased at 250 mg/kg/day, and microscopic evaluation revealed no treatment-related renal pathology. At 250 mg/kg/day, prenatal mortality was increased (90% resorptions/litter vs 6% for controls), the proportion of pregnant females with no live fetuses was increased (73% vs 0%), and live litter size was reduced (2.3 fetuses/litter vs 8.8). As a result, there were only 14 live fetuses (6 live litters) available for evaluation in the high-dose group, compared to 153-175 live fetuses (18-23 live litters) in the other groups. The percentage malformed fetuses/litter was increased at 250 mg/kg/day, primarily due to cardiovascular defects in 72% of high-dose fetuses vs 3% of controls. The most prevalent cardiovascular malformation (interventricular septal defect) was observed in 57% of high-dose fetuses compared to 0.6% among controls. At 250 mg/kg/day, average fetal body weight/litter was 92% of the average control weight (not statistically significant). In summary, no definitive maternal or developmental toxicity was observed at 62.5 or 125 mg/kg/day BA. Mild maternal effects and severe developmental toxicity were observed at 250 mg/kg/day.
硼酸（BA）是许多药品、化妆品和农药产品的一种成分，此前已证明它会在实验啮齿动物中诱发生殖和发育毒性。在本研究中，于妊娠第6至19天给新西兰白兔（每组18 - 23只怀孕兔）经口给予BA（0、62.5、125或250毫克/千克/天）。在整个妊娠期定期监测母兔体重、食物摄入量和临床状况。在妊娠末期（妊娠第30天），确定子宫着床数、吸收数、死胎数和活胎数。对胎儿进行称重，并对活胎检查其外部、内脏和骨骼缺陷。在250毫克/千克/天治疗期间母兔食物摄入量减少，治疗后摄入量在≥125毫克/千克/天增加。250毫克/千克/天组母兔体重（妊娠第9至30天）、治疗期间体重增加、妊娠子宫重量和卵巢黄体数减少。相比之下，≥125毫克/千克/天组母兔校正妊娠体重增加。母兔肝脏重量未受影响。250毫克/千克/天组母兔相对（而非绝对）肾脏重量增加，显微镜评估未发现与治疗相关的肾脏病理变化。在250毫克/千克/天剂量下，产前死亡率增加（每窝吸收90%，而对照组为6%），无活胎的怀孕母兔比例增加（73%对0%），每窝活胎数减少（每窝2.3只胎儿对8.8只）。结果，高剂量组仅有14只活胎（6窝活胎）可供评估，而其他组有153 - 175只活胎（18 - 23窝活胎）。在250毫克/千克/天剂量下，每窝畸形胎儿百分比增加，主要是因为高剂量组72%的胎儿有心血管缺陷，而对照组为3%。高剂量组57%的胎儿观察到最常见的心血管畸形（室间隔缺损）。对照组中这一比例为0.6%。在250毫克/千克/天剂量下，每窝胎儿平均体重为对照组平均体重的92%（无统计学意义）。总之，在62.5或125毫克/千克/天的BA剂量下未观察到明确的母体或发育毒性。在250毫克/千克/天剂量下观察到轻微的母体影响和严重的发育毒性。
