Arsenic is a ubiquitous contaminant, with typical human dietary intake below 1 μg/kg bw/d and extreme drinking water exposures up to ∼50 μg/kg bw/d. The formation and binding of trivalent metabolites are central to arsenic toxicity and strong human evidence suggests special concern for early life exposures in the etiology of adult diseases, especially cancer. This study measured the metabolism and disposition of arsenite in neonatal mice to understand the role of maturation in metabolic activation and detoxification of arsenic. Many age-related differences were observed after gavage administration of arsenite, with consistent evidence in blood and tissues for higher exposures to trivalent arsenic species in neonatal mice related to the immaturity of metabolic and/or excretory functions. The evidence for greater tissue binding of arsenic species in young mice is consistent with enhanced susceptibility to toxicity based on metabolic and toxicokinetic differences alone. Lactational transfer from arsenite-dosed dams to suckling mice was minimal, based on no dosing-related changes in the levels of arsenic species in pup blood or milk collected from the dams. Animal models evaluating whole-life exposure to inorganic arsenic must use direct dosing in early neonatal life to predict accurately potential toxicity from early life exposures in children.

砷是一种普遍存在的污染物，典型的人类饮食摄入量低于1μg/ kg bw / d，极端饮水量高达〜50μg/ kg bw / d。三价代谢物的形成和结合是砷毒性的关键，强有力的人类证据表明，在成年疾病（尤其是癌症）的病因中，应特别关注早期生命暴露。这项研究测量了新生小鼠中砷的代谢和处置，以了解成熟在砷的代谢活化和排毒中的作用。管饲亚砷酸盐后观察到许多与年龄有关的差异，并且在血液和组织中有一致的证据表明新生小鼠中三价砷物种的更高暴露与代谢和/或排泄功能的不成熟有关。幼鼠中砷种类具有更大的组织结合力的证据与仅基于代谢和毒代动力学差异而产生的对毒性的敏感性增强相一致。从无砷的母坝到哺乳小鼠的泌乳量极少，这是基于从母坝中收集的幼犬血液或牛奶中的砷种类水平没有与剂量相关的变化。评估终身暴露于无机砷的动物模型必须在新生儿早期使用直接给药，以准确预测儿童早期接触砷的潜在毒性。基于从大坝采集的幼犬血液或牛奶中砷种类水平的无剂量相关变化。评估终身暴露于无机砷的动物模型必须在新生儿早期使用直接剂量，以准确预测儿童早期接触砷的潜在毒性。基于从大坝采集的幼犬血液或牛奶中砷种类水平的无剂量相关变化。评估终身暴露于无机砷的动物模型必须在新生儿早期使用直接给药，以准确预测儿童早期接触砷的潜在毒性。