Abstract：
We are facing a rapidly growing geriatric population (65+) that will live for multiple decades and are challenged with environmental pollution far exceeding that of previous generations. Consequently, we currently have a poor understanding of how environmental pollution will impact geriatric health distinctly from younger populations. Few toxicology studies have considered age differences with geriatric individuals. Critically, all top ten most prevalent age-related diseases are linked to metal exposures. Hexavalent chromium [Cr(VI)] is a metal of major environmental health concern that can induce aging phenotypes and neurotoxicity. However, there are many knowledge gaps for Cr(VI) neurotoxicity, including how Cr(VI) impacts behavior. To address this, we exposed male rats across three ages (3-, 7-, and 18-months old) to Cr(VI) in drinking water (0, 0.05, 0.1 mg/L) for 90 days. These levels reflect the maximum contaminant levels determined by the World Health Organization (WHO) and the U.S. Environmental Protection Agency (US EPA). Here, we report how these Cr(VI) drinking water levels impacted rat behaviors using a battery of behavior tests, including grip strength, open field assay, elevated plus maze, Y-maze, and 3-chamber assay. We observed adult rats were the most affected age group and memory assays (spatial and social) exhibited the most significant effects. Critically, the significant effects were surprising as rats should be particularly resistant to these Cr(VI) drinking water levels due to the adjustments applied in risk assessment from rodent studies to human safety, and because rats endogenously synthesize vitamin C in their livers (vitamin C is a primary reducer of Cr[VI] to Cr[III]). Our results emphasize the need to broaden the scope of toxicology research to consider multiple life stages and suggest the current regulations for Cr(VI) in drinking water need to be revisited.
摘要：
我们正面临着快速增长的老年人口（65岁以上），他们将生活数十年，并且面临着远远超过前几代人的环境污染的挑战。因此,目前，我们对环境污染将如何影响年轻人群的老年健康知之甚少。很少有毒理学研究考虑了老年人的年龄差异。严重的,所有与年龄相关的十大最常见疾病都与金属接触有关。六价铬[Cr（VI）]是一种主要的环境健康关注的金属，可以诱导衰老表型和神经毒性。然而,关于Cr(VI)神经毒性有很多知识空白，包括Cr(VI)如何影响行为。为了解决这个问题，我们暴露了三个年龄的雄性大鼠(3-，7-,和18个月大）至饮用水中的Cr（VI）（0、0.05、0.1mg/L）90天。这些水平反映了世界卫生组织（WHO）和美国环境保护局（USEPA）确定的最大污染物水平。这里,我们使用一系列行为测试报告了这些Cr（VI）饮用水水平如何影响大鼠行为，包括握力，开放场测定，高架加上迷宫，Y-迷宫,和3室测定。我们观察到成年大鼠是受影响最大的年龄组，记忆测定（空间和社交）表现出最显著的影响。严重的,显著的影响是令人惊讶的，因为大鼠应该特别抵抗这些Cr（VI）饮用水水平，由于在风险评估中应用从啮齿动物研究到人类安全的调整，并且因为大鼠在肝脏中内源性合成维生素C（维生素C是Cr[VI]至Cr[III]的主要还原剂）。我们的结果强调需要扩大毒理学研究的范围，以考虑多个生命阶段，并建议需要重新审视饮用水中Cr（VI）的现行法规。
