This study assessed the potential adverse health effects of long-term low-dose exposure to chemical mixtures simulating complex real-life human exposures. Four groups of Sprague Dawley rats were administered mixtures containing carbaryl, dimethoate, glyphosate, methomyl, methyl parathion, triadimefon, aspartame, sodium benzoate, calcium disodium ethylene diamine tetra-acetate, ethylparaben, butylparaben, bisphenol A, and acacia gum at doses of 0, 0.25, 1 or 5 times the respective Toxicological Reference Values (TRV): acceptable daily intake (ADI) or tolerable daily intake (TDI) in a 24 weeks toxicity study. Body weight gain, feed and water consumption were evaluated weekly. At 24 weeks blood was collected and biochemistry parameters and redox status markers were assessed. Adverse effects were observed on body weight gain and in hepatotoxic parameters such as the total bilirubin, alanine aminotransferase (ALT) and alkaline phosphatase (ALP), especially in low dose and affecting mainly male rats. The low dose group showed increased catalase activity both in females and males, whereas the high dose group exhibited decreased protein carbonyl and total antioxidant capacity (TAC) levels in both sex groups. Non-monotonic effects and adaptive responses on liver function tests and redox status, leading to non-linear dose-responses curves, are probably produced by modulation of different mechanisms.

这项研究评估了长期低剂量暴露于模拟复杂的现实生活中人类暴露的化学混合物对健康的潜在不利影响。四组Sprague Dawley大鼠以0的剂量服用了含有甲萘威，乐果，草甘膦，灭多威，甲基对硫磷，三唑酮，阿斯巴甜，苯甲酸钠，乙二胺二乙酸二钠钙，对羟基苯甲酸乙酯，对羟基苯甲酸丁酯，双酚A和阿拉伯胶的混合物分别是毒理学参考值（TRV）的0.25、1或5倍：在24周的毒性研究中可接受的每日摄入量（ADI）或耐受的每日摄入量（TDI）。每周评估体重增加，饲料和水消耗。在第24周时，收集血液并评估生化参数和氧化还原状态标记。在体重增加和肝毒性参数（如总胆红素，丙氨酸氨基转移酶（ALT）和碱性磷酸酶（ALP））中观察到不利影响，特别是在低剂量时，主要影响雄性大鼠。低剂量组在雌性和雄性中均显示过氧化氢酶活性增加，而高剂量组在两个性别组中均显示出蛋白羰基和总抗氧化能力（TAC）水平降低。肝功能测试和氧化还原状态的非单调效应和适应性反应，可能导致非线性剂量反应曲线，可能是通过调节不同的机制产生的。而高剂量组在两个性别组中均显示出蛋白质羰基和总抗氧化能力（TAC）水平降低。肝功能测试和氧化还原状态的非单调效应和适应性反应，可能导致非线性剂量反应曲线，可能是通过调节不同的机制产生的。而高剂量组在两个性别组中均显示出蛋白质羰基和总抗氧化能力（TAC）水平降低。肝功能测试和氧化还原状态的非单调效应和适应性反应，可能导致非线性剂量反应曲线，可能是通过调节不同的机制产生的。