Belz Regina G, Piepho Hans-Peter
University of Hohenheim, Agroecology Unit, Hans-Ruthenberg Institute, 70593, Stuttgart, Germany.
University of Hohenheim, Biostatistics Unit, Institute of Crop Science, 70593, Stuttgart, Germany.
Chemosphere. 2017 Jul;178:88-98. doi: 10.1016/j.chemosphere.2017.03.047. Epub 2017 Mar 13.
Predicting hormesis in mixtures is challenging, but essential considering that chemical exposures often occur in mixtures and at low doses. This study investigated mixture effects with two herbicides prone to induce hormesis and to interact, namely pelargonic acid versus glyphosate. Five independent mixture experiments were conducted in vitro to assess effects on root growth of lettuce. Mixture effects on the dose were analyzed using classical joint-action models in terms of deviation from the reference model of concentration addition. For effects on the hormetic magnitude (y), a linear reference model was utilized. Hormesis was inconsistent across rays, so that effects on inhibitory doses and y could be evaluated, but not effects on hormetic doses. Mixture effects on the dose were additive at lower doses changing to strong high-dose synergism. Mixture effects on y followed a linear change with mixture ratio or significantly deviated from linearity with a one-sided trend across rays in two experiments. The trend was antipodal between experiments, but well described by a curved y model based on single dose-response relationships. Atypical y deviations were associated with strong synergism at ED, suggesting that the linearity model applies for chemicals showing no/minor interaction at ED, while for strongly interacting chemicals y predictions seem more critical. The study unambiguously proved synergism on the dose for pelargonic acid versus glyphosate and indicated an impact of these joint effects on y. The study confirms the predictability of hormesis in mixtures and provides a further methodological step towards an incorporation of hormesis into mixture-toxicity evaluations.
预测混合物中的兴奋效应具有挑战性，但鉴于化学物质暴露通常以混合物形式且在低剂量下发生，这又是必不可少的。本研究调查了两种易于诱导兴奋效应并相互作用的除草剂（壬酸与草甘膦）的混合物效应。在体外进行了五项独立的混合物实验，以评估对生菜根系生长的影响。使用经典的联合作用模型，根据与浓度相加参考模型的偏差，分析混合物对剂量的效应。对于对兴奋效应强度（y）的影响，使用了线性参考模型。不同实验中的兴奋效应并不一致，因此可以评估对抑制剂量和y的影响，但无法评估对兴奋剂量的影响。混合物对剂量的效应在较低剂量下呈相加性，在高剂量下则变为强烈的协同作用。混合物对y的影响随混合比例呈线性变化，或者在两项实验中显著偏离线性，且在不同实验中有单边趋势。不同实验中的趋势相反，但基于单剂量反应关系的曲线y模型能很好地描述这种情况。非典型的y偏差与有效剂量（ED）下的强烈协同作用相关，这表明线性模型适用于在有效剂量下无相互作用/相互作用较小的化学物质，而对于相互作用强烈的化学物质，y的预测似乎更为关键。该研究明确证明了壬酸与草甘膦在剂量上的协同作用，并表明这些联合效应会对y产生影响。该研究证实了混合物中兴奋效应的可预测性，并为将兴奋效应纳入混合物毒性评估提供了进一步的方法步骤。
