Hernández Antonio F, Tsatsakis Aristidis M
Department of Legal Medicine and Toxicology, University of Granada School of Medicine, Granada, Spain.
Center of Toxicology Science & Research, Medical School, University of Crete, Heraklion, Crete, Greece.
Food Chem Toxicol. 2017 May;103:188-193. doi: 10.1016/j.fct.2017.03.012. Epub 2017 Mar 7.
Little is known about the potential adverse effects from longterm exposure to complex mixtures at low doses, close to health-based reference values. Traditional chemical-specific risk assessment based on animal testing may be insufficient and the lack of toxicological studies on chemical mixtures remains a major regulatory challenge. Hence, new methodologies on cumulative risk assessment are being developed but still present major limitations. Evaluation of chemical mixture effects requires an integrated and systematic approach and close collaboration across different scientific fields, particularly toxicology, epidemiology, exposure science, risk assessment and statistics for a proper integration of data from all these disciplines. Well designed and conducted epidemiological studies can take advantage of this new paradigm and can provide insight to support the correlation between humans low-dose exposures and diseases, thus avoiding the uncertainty associated with extrapolation across species. In this regard, human epidemiology studies may play a significant role in the new vision of toxicity testing. However, this type of information has not been fully considered in risk assessment, mainly due to the inherent limitations of epidemiologic studies. An integrated approach of in vivo, in vitro and in silico data, together with systematic reviews or meta-analysis of high quality epidemiological studies will improve the robustness of risk assessment of chemical mixtures and will provide a stronger basis for regulatory decisions. The ultimate goal is that experimental and mechanistic data can lend support and biological plausibility to the human epidemiological observations.
对于长期低剂量接触接近基于健康的参考值的复杂混合物的潜在不良影响，人们了解甚少。基于动物试验的传统化学物质特异性风险评估可能并不充分，而且缺乏对化学混合物的毒理学研究仍然是一个重大的监管挑战。因此，正在开发累积风险评估的新方法，但这些方法仍存在重大局限性。评估化学混合物的影响需要一种综合、系统的方法，以及不同科学领域之间的密切合作，特别是毒理学、流行病学、暴露科学、风险评估和统计学，以便恰当地整合所有这些学科的数据。精心设计和实施的流行病学研究可以利用这一新范式，并能够提供见解以支持人类低剂量暴露与疾病之间的关联，从而避免与跨物种外推相关的不确定性。在这方面，人类流行病学研究可能在毒性测试的新视野中发挥重要作用。然而，这类信息在风险评估中尚未得到充分考虑，主要是由于流行病学研究的固有局限性。体内、体外和计算机模拟数据的综合方法，以及对高质量流行病学研究的系统评价或荟萃分析，将提高化学混合物风险评估的稳健性，并为监管决策提供更有力的依据。最终目标是实验和机制数据能够为人类流行病学观察提供支持和生物学合理性。
