Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Hakozaki 6-10-1, Higashi-ku, Fukuoka 812-8581, Japan.
Clinical Research Center, School of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Sci Total Environ. 2017 Dec 31;607-608:367-374. doi: 10.1016/j.scitotenv.2017.07.034. Epub 2017 Jul 27.
Organisms in natural environments are often exposed to a broad variety of chemicals, and the multi-chemical mixtures exposure may produce significant toxic effects, even though the individual chemicals are present at concentrations below their no-observed-effect concentrations. This study represents the first attempt that uses the accelerated failure time (AFT) model to quantify the interaction and toxicity of multi-chemical mixtures in environmental toxicology. We firstly conducted the acute immobilization tests with Daphnia magna exposed to mixtures of diazinon (DZN), fenitrothion (MEP); and thiobencarb (TB) in single, binary, and ternary formulations, and then fitted the results to the AFT model. The 48-h EC (concentration required to immobilize 50% of the daphnids at 48h) values for each pesticide obtained from the AFT model are within a factor of 2 of the corresponding values calculated from the single pesticide exposure tests, indicating the methodology is able to provide credible toxicity values. The AFT model revealed either significant synergistic (DZN and MEP; DZN and TB) or antagonistic (MEP and TB) interactions in binary mixtures, while the interaction pattern of ternary mixture depended on both the concentration levels and concentration ratios of pesticides. With a factor of 2, the AFT model accurately estimated the toxicities for 78% of binary mixture formulations that exhibited significant synergistic effects, and the toxicities for all the ternary formulations. Our results showed that the AFT model can provide a simple and efficient way to quantify the interactions between pesticides and to assess the toxicity of their mixtures. This ability may greatly facilitate the ecotoxicological risk assessment of exposure to multi-chemical mixtures.
在自然环境中,生物通常会接触到各种各样的化学物质,而多种化学物质的混合物暴露可能会产生显著的毒性效应,即使个别化学物质的浓度低于其无观察到效应浓度。本研究首次尝试使用加速失效时间(AFT)模型来量化环境毒理学中多化学混合物的相互作用和毒性。我们首先进行了急性固定试验,用大型溞暴露于二嗪农(DZN)、杀螟硫磷(MEP)和涕灭威(TB)的单一、二元和三元混合物中,然后将结果拟合到 AFT 模型中。从 AFT 模型获得的每种农药的 48 小时 EC(使 48 小时内 50%的溞类固定所需的浓度)值与从单一农药暴露试验计算出的相应值相差 2 倍以内,表明该方法能够提供可靠的毒性值。AFT 模型揭示了二元混合物中存在显著的协同作用(DZN 和 MEP;DZN 和 TB)或拮抗作用(MEP 和 TB),而三元混合物的相互作用模式取决于农药的浓度水平和浓度比。AFT 模型以 2 倍的因子准确估计了 78%表现出显著协同作用的二元混合物配方的毒性,以及所有三元配方的毒性。我们的结果表明,AFT 模型可以提供一种简单有效的方法来量化农药之间的相互作用,并评估其混合物的毒性。这种能力可能极大地促进对多种化学物质混合物暴露的生态毒理学风险评估。