Hood R D, Thacker G T, Patterson B L
Environ Health Perspect. 1977 Aug;19:219-22. doi: 10.1289/ehp.7719219.
Initial experiments involving mouse development employed single IP injections of 45 mg/kg sodium arsenate on one of days 6-12 of gestation and produced a spectrum of developmental defects. Embryotoxicity was indicated by high prenatal mortality and decreased fetal weights. A chelating agent, 2,3-dimercaptopropanol (BAL), was then employed in an attempt to alleviate the adverse effects of prenatal arsenate. BAL was administered 4 hr before, concurrently with, or 4 hr after arsenate. All BAL treatments diminished arsenate-induced gross malformations and growth retardation; the concurrent treatment alleviated skeletal malformation. Injection of rats IP with arsenate has also been reported to result in teratogenicity, including renal agenesis. Further reports indicated that 40 mg/kg arsenate administered to mice by gavage on days 9-11 increased prenatal mortality, reduced fetal weights, and was associated with minor malformations. According to our recent work, however, single oral doses of arsenate must be around 120 mg/kg to cause prenatal toxicity. Multiple doses of 60 mg/kg on 3 days had little effect. Sodium arsenite has also been found to be fetotoxic and teratogenic. Such effects were seen at IP doses of 10-12 mg/kg.
最初涉及小鼠发育的实验是在妊娠第6至12天中的一天单次腹腔注射45毫克/千克砷酸钠，结果产生了一系列发育缺陷。高出生前死亡率和胎儿体重减轻表明存在胚胎毒性。随后使用了一种螯合剂2,3-二巯基丙醇（BAL），试图减轻产前砷酸盐的不良影响。BAL在砷酸盐注射前4小时、同时或注射后4小时给药。所有BAL处理均减少了砷酸盐诱导的严重畸形和生长迟缓；同时给药减轻了骨骼畸形。据报道，给大鼠腹腔注射砷酸盐也会导致致畸性，包括肾缺如。进一步的报告表明，在第9至11天给小鼠灌胃40毫克/千克砷酸盐会增加出生前死亡率、降低胎儿体重，并伴有轻微畸形。然而，根据我们最近的研究，单次口服砷酸盐剂量必须达到约120毫克/千克才会导致产前毒性。连续3天每天多次给予60毫克/千克的剂量几乎没有影响。已发现亚砷酸钠也具有胚胎毒性和致畸性。在腹腔注射剂量为10至12毫克/千克时可观察到此类效应。
