Domingo J L, Bosque M A, Corbella J
Laboratory of Toxicology and Biochemistry, School of Medicine, Reus, Spain.
Life Sci. 1990;47(19):1745-50. doi: 10.1016/0024-3205(90)90348-u.
The present study was conducted to evaluate the effects of meso-2,3-dimercaptosuccinic acid (DMSA) on late gestation and postnatal viability and growth in the mouse. DMSA was given po to four groups of pregnant Swiss mice at 0, 200, 400, and 800 mg/kg/day from day 14 of pregnancy until postnatal day 21. At birth, the following data were recorded: length of gestation, number of live, dead, and abnormal pups, sex, and individual pup weights. Each pup was weighed again on day 4, 14, and 21 of lactation. Pinna detachment, incisor eruption and eye opening were also monitored. No treatment-related signs of toxicity were noted in any of the dams during the study. No adverse effects on offspring survival or development were evident in the 200 or 400 mg DMSA/kg/day groups. However, on days 14 and 21 of lactation a significant decrease in pup body weight was observed in the 800 mg/kg/day group. Also, a significant increase in the relative weight of the brain was seen in this group. The "no observable effect level" (NOEL) for health hazards to the developing pup was greater than 400 mg/kg/day. This dose is higher than the amounts of DMSA usually given in the treatment of human heavy metal intoxications.
本研究旨在评估中-2,3-二巯基丁二酸(DMSA)对小鼠妊娠后期及出生后生存能力和生长的影响。从妊娠第14天至出生后第21天,对四组怀孕的瑞士小鼠经口给予DMSA,剂量分别为0、200、400和800mg/kg/天。出生时,记录以下数据:妊娠期长度、存活、死亡和异常幼崽数量、性别以及个体幼崽体重。在哺乳期第4、14和21天,再次对每只幼崽称重。还监测了耳廓分离、门齿萌出和睁眼情况。在研究期间,未在任何母鼠中观察到与治疗相关的毒性迹象。在200或400mg DMSA/kg/天组中,未发现对后代存活或发育有明显不良影响。然而,在800mg/kg/天组中,在哺乳期第14天和21天观察到幼崽体重显著下降。此外,该组幼崽大脑相对重量显著增加。对发育中的幼崽健康危害的“无可见效应水平”(NOEL)大于400mg/kg/天。该剂量高于通常用于治疗人类重金属中毒的DMSA剂量。