Toxalim, Université de Toulouse, INRAE, INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul Sabatier, Toulouse, France.
Models for Ecotoxicology and Toxicology Unit (DRC/VIVA/METO), Institut National de l'Environnement Industriel et des Risques (INERIS), Verneuil en Halatte, France.
Toxicol Lett. 2020 Jun 15;326:99-105. doi: 10.1016/j.toxlet.2020.03.007. Epub 2020 Mar 14.
Polycyclic Aromatic Hydrocarbons (PAHs) form a family of compounds that are generally found in complex mixtures. PAHs can lead to the development of carcinogenesis. The Toxicity Equivalent Factor (TEF) approach has been suggested for estimating the toxicity of PAHs, however, due to the relative weakness of available data, TEF have not been applied for the risk characterization of PAHs as food contaminants in Europe. The determination of new TEFs for a large number of PAHs could overcome some limitations of the current method and improve cancer risk assessment. The present investigation aimed at deriving new TEFs for PAHs, based on their genotoxic effect measured in vitro and analyzed with mathematical models. For this purpose, we used a genotoxicity assay (γH2AX) with three human cell lines to analyze the genotoxic properties of 27 selected PAHs after 24 h treatment. For 11 compounds, we did not detect any genotoxic potential. For the remaining 16 PAHs, the concentration-response for genotoxic effect was modelled with the Hill equation; equivalency between PAHs at low dose was assessed by applying constraints to the model parameters. We developed for each compound, in each cell line, Genotoxic Equivalent Factor (GEF). Calculated GEF for the tested PAHs were similar in all cell lines and generally higher than the TEF usually used. These new equivalent factors for PAHs should improve cancer risk assessment.
多环芳烃（PAHs）是一组通常存在于复杂混合物中的化合物。PAHs 可导致致癌作用的发展。毒性等效因子（TEF）方法已被提议用于估计 PAHs 的毒性，但由于现有数据相对较弱，TEF 尚未应用于欧洲作为食品污染物的 PAHs 的风险特征描述。确定大量 PAHs 的新 TEF 可以克服当前方法的一些局限性，并改善癌症风险评估。本研究旨在基于体外测量的遗传毒性效应并通过数学模型进行分析，为 PAHs 推导新的 TEF。为此，我们使用了一种遗传毒性测定法（γH2AX），用三种人类细胞系分析了 27 种选定的 PAHs 在 24 小时处理后的遗传毒性特性。对于 11 种化合物，我们没有检测到任何遗传毒性潜力。对于其余的 16 种 PAHs，用 Hill 方程对遗传毒性效应的浓度反应进行了建模；通过对模型参数施加约束，评估了低剂量 PAHs 之间的等效性。我们为每个化合物在每个细胞系中开发了遗传毒性等效因子（GEF）。在所有细胞系中，测试的 PAHs 的计算出的 GEF 相似，并且通常高于通常使用的 TEF。这些新的 PAHs 等效因子应能改善癌症风险评估。
