Exposure to Hexavalent Chromium Resulted in Significantly Higher Tissue Chromium Burden Compared With Trivalent Chromium Following Similar Oral Doses to Male F344/N Rats and Female B6C3F1 Mice
Exposure to Hexavalent Chromium Resulted in Significantly Higher Tissue Chromium Burden Compared With Trivalent Chromium Following Similar Oral Doses to Male F344/N Rats and Female B6C3F1 Mice
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DOI：
10.1093/toxsci/kfq263
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发表时间：
2010-12-01
影响因子：
3.8
通讯作者：
Hooth, Michelle J.
中科院分区：
文献类型：
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作者：
Collins, Bradley J.;Stout, Matthew D.;Hooth, Michelle J.
在国家毒理学计划的2年研究中，在饮用水中给予六价铬[Cr（VI）]在雄性和雌性大鼠和小鼠中具有明显的致癌性，导致小鼠小肠上皮肿瘤，剂量相当于或在人体剂量的数量级内，这可能是由于饮用铬污染的饮用水造成的，假设剂量按体重（3/4）（体重的3/4次方）缩放。相比之下，暴露于浓度高得多的三价铬[Cr（III）]可能对雄性大鼠具有致癌性，但对小鼠或雌性大鼠没有致癌性。作为这些研究的一部分，测量了其他雄性大鼠和雌性小鼠组的组织和排泄物中的总铬。这些数据用于推断Cr（VI）的摄取和分布，因为Cr（VI）在体内被还原为Cr（III），并且没有方法可用于组织铬的形态。与Cr（III）相比，暴露于Cr（VI）后，相当的外部剂量导致组织铬浓度高得多，表明部分Cr（VI）逃脱了胃还原并全身分布。暴露于Cr（VI）后，观察到组织中总铬的线性或超线性剂量反应，表明这些暴露并未饱和胃还原能力。当Cr（VI）暴露标准化为摄入剂量时，小鼠肝脏和腺胃中的铬浓度较高，而大鼠肾脏中的铬浓度较高。体外研究表明，Cr（VI），而不是Cr（III），是钠/硫酸盐协同转运蛋白的底物，为Cr（VI）的更大吸收提供了部分解释。
In National Toxicology Program 2-year studies, hexavalent chromium [Cr(VI)] administered in drinking water was clearly carcinogenic in male and female rats and mice, resulting in small intestine epithelial neoplasms in mice at a dose equivalent to or within an order of magnitude of human doses that could result from consumption of chromium-contaminated drinking water, assuming that dose scales by body weight(3/4) (body weight raised to the 3/4 power). In contrast, exposure to trivalent chromium [Cr(III)] at much higher concentrations may have been carcinogenic in male rats but was not carcinogenic in mice or female rats. As part of these studies, total chromium was measured in tissues and excreta of additional groups of male rats and female mice. These data were used to infer the uptake and distribution of Cr(VI) because Cr(VI) is reduced to Cr(III) in vivo, and no methods are available to speciate tissue chromium. Comparable external doses resulted in much higher tissue chromium concentrations following exposure to Cr(VI) compared with Cr(III), indicating that a portion of the Cr(VI) escaped gastric reduction and was distributed systemically. Linear or supralinear dose responses of total chromium in tissues were observed following exposure to Cr(VI), indicating that these exposures did not saturate gastric reduction capacity. When Cr(VI) exposure was normalized to ingested dose, chromium concentrations in the liver and glandular stomach were higher in mice, whereas kidney concentrations were higher in rats. In vitro studies demonstrated that Cr(VI), but not Cr(III), is a substrate of the sodium/sulfate cotransporter, providing a partial explanation for the greater absorption of Cr(VI).