High levels of inorganic arsenic (iAs) exposure are associated with severe health effects. Less clear are effects of lower exposure levels on neurodevelopment. Relative to maternal intake, there is limited lactational transfer of arsenic in humans or rodents, yet there are few rodent studies which directly exposed preweaning animals. To more clearly determine iAs developmental neurotoxicity, 28 pregnant Sprague-Dawley rats were exposed to arsenate (AsV) via drinking water (0, 23.6, 47.7, 71.0 ppm) (n = 5-7/group) from gestational day (GD) 6 through GD 22 with targeted doses of 0, 2.33, 4.67, 7.00 mg/kg/day, respectively. Offspring were dosed by gavage daily with the same mg/kg AsV dose as intended for their dam from postnatal day (PND) 1 to 21. Gestational water intake was reduced at all AsV doses, but returned to control levels on lactational day (LD) 1 when control water was returned. Gestational body weight was reduced only at the highest dose on GD 22 and lactational body weight was unaffected. Food intake was unaffected. iAs exposure did not alter offspring body weight (PNDs 1-21) or age at fur development and bilateral ear opening. Incisor eruption, however, was significantly delayed in offspring of the 4.67 and 7.00 mg/kg groups. Further, all iAs groups were significantly delayed in bilateral eye opening. Righting reflex (PNDs 3-6) was unaffected, while slant board performance (PNDs 8-11) was significantly poorer at the highest dose. Brains of culled pups (PND 1) showed dose-dependent increases of iAs. There were no significant AsV-related effects on PND 21 brain regional concentrations of dopamine, DOPAC, HVA, 5-HT or 5-HIAA. These hazard identification results will guide the study designs of developmental iAs exposure at human-relevant levels essential for risk-assessment.

中文翻译：

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Sprague-Dawley大鼠中无机砷暴露的发育神经毒性。

大量摄入无机砷（iAs）与严重的健康影响有关。较低的暴露水平对神经发育的影响尚不清楚。相对于母体摄入，人或啮齿动物中砷的乳酸转移受限制，但是很少有啮齿动物研究直接暴露断奶前的动物。为了更清楚地确定iAs的发育神经毒性，从妊娠日（GD）起，通过饮用水（0、23.6、47.7、71.0 ppm）将28只怀孕的Sprague-Dawley大鼠暴露于砷酸（AsV）中（n = 5-7 /组）6通过GD 22给药，目标剂量分别为0、2.33、4.67、7.00 mg / kg / day。从出生后第1天到21天，每天通过管饲法给后代给予与母鼠相同的mg / kg AsV剂量。在所有AsV剂量下，减少了妊娠期摄水，但在哺乳期第1天（LD），则在返回对照水时恢复到对照水平。妊娠体重仅在GD 22上以最高剂量降低，而泌乳期体重不受影响。食物摄入不受影响。iAs暴露不会改变后代体重（PNDs 1-21）或毛皮发育和双侧耳朵张开时的年龄。然而，在4.67和7.00 mg / kg组的后代中，门牙喷发明显延迟。此外，所有iAs组的双眼张开都明显延迟。扶正反射（PND 3-6）不受影响，而最大剂量下的斜板性能（PND 8-11）明显较差。被淘汰的幼犬（PND 1）的大脑显示iAs呈剂量依赖性增加。对多巴胺，多巴胺，DOPAC，HVA，5-HT或5-HIAA的PND 21脑区域浓度无明显的AsV相关影响。