Institute of Biodiversity Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Crit Rev Toxicol. 2022 Mar;52(3):221-238. doi: 10.1080/10408444.2022.2091423. Epub 2022 Jul 27.
Anthropogenic chemicals are ubiquitous throughout the environment. Consequentially, humans are exposed to hundreds of anthropogenic chemicals daily. Current chemical risk assessments are primarily based on testing individual chemicals in rodents at doses that are orders of magnitude higher than that of human exposure. The potential risk from exposure to mixtures of chemicals is calculated using mathematical models of mixture toxicity based on these analyses. These calculations, however, do not account for synergistic or antagonistic interactions between co-exposed chemicals. While proven examples of chemical synergy in mixtures at low doses are rare, there is increasing evidence that, through non-conformance to current mixture toxicity models, suggests synergy. This review examined the published studies that have investigated exposure to mixtures of chemicals at low doses in mammalian systems. Only seven identified studies were sufficient in design to directly examine the appropriateness of current mixture toxicity models, of which three showed responses significantly greater than additivity model predictions. While the remaining identified studies were unable to provide evidence of synergistic toxicity, it became apparent that many results of such studies were not always explicable by current mixture toxicity models. Additionally, two data gaps were identified. Firstly, there is a lack of studies where individual chemical components of a complex mixture (>10 components) are tested in parallel to the chemical mixture. Secondly, there is a lack of dose-response data for mixtures of chemicals at low doses. Such data is essential to address the appropriateness and validity of future chemical mixture toxicity models.
人为化学物质在环境中无处不在。因此，人类每天都会接触到数百种人为化学物质。目前的化学风险评估主要基于在啮齿动物中测试单个化学物质，剂量比人类暴露的剂量高出几个数量级。通过基于这些分析的混合物毒性数学模型来计算接触混合物的潜在风险。然而，这些计算并未考虑到共同暴露的化学物质之间的协同或拮抗相互作用。虽然在低剂量下混合物中化学协同作用的实例很少得到证实，但越来越多的证据表明，通过不符合当前混合物毒性模型，存在协同作用。本综述检查了已发表的研究，这些研究调查了哺乳动物系统中低剂量接触化学混合物的情况。只有七项设计充分的研究能够直接检验当前混合物毒性模型的适宜性，其中三项研究显示的反应明显大于加和模型预测。虽然其余确定的研究未能提供协同毒性的证据，但显然，此类研究的许多结果并不总是可以用当前的混合物毒性模型来解释。此外，还确定了两个数据空白。首先，缺乏对复杂混合物（>10 个成分）中单个化学物质成分进行平行测试的研究。其次，缺乏低剂量化学混合物的剂量反应数据。此类数据对于解决未来化学混合物毒性模型的适宜性和有效性至关重要。
