Far Eastern Federal University, Vladivostok, Russian Federation; Pacific Geographical Institute FEB RAS, Vladivostok, Russian Federation.
Far Eastern Federal University, Vladivostok, Russian Federation.
Sci Total Environ. 2020 Jul 20;727:138491. doi: 10.1016/j.scitotenv.2020.138491. Epub 2020 Apr 15.
Pesticides can potentially contribute to the development of numerous neurodegenerative diseases. This study evaluates the effects of a six-pesticide mixture at doses around the no-observed-adverse-effectlevels (0 × NOAEL, control) and 0.25, 1 and 5 × NOAEL on behavior of Wistar rats. After 3, 6 and 12 months, rats were observed for neurobehavioral changes using the techniques of elevated plus maze and universal problemchamber, and the experiment was conducted thrice. The 3-month exposure revealed a decrease in the cognitive ability at the dose of 5 × NOAEL, and a dose-dependent research activity and anxiety. The 6-month exposurerevealed non-monotonic effects on the cognitive ability, with a decrease by 0.25 and 5 × NOAEL, as well as non-monotonic effects on anxiety, withan increase by 0.25 and 1 × NOAEL. A decrease was also observed in research activity at 5 × NOAEL. However, the 12-month exposure resulted to an increase in cognitive ability by 0.25 × NOAEL and in anxiety by 1 × NOAEL, as well as to a dose-dependent research activity. Repeating the trial showed that the cognitive ability increased from one trial to another, while the researching activity decreased and the anxiety increased by 0× NOAEL. In the groups exposed to pesticides mixture, the trends were different, showing that the exposure to pesticides combined with repeated trials, also influence the response of the animals. The resultsdemonstrate the occurrence of several dose-dependent behavioral responses, with negative effects occurring at doses that are considered safe. This study provides novel insights about time-dependent mixtures biology, and an important perspective to consider when conducting risk assessments.
农药有可能导致多种神经退行性疾病的发生。本研究评估了六种农药混合物在接近无观察到不良效应水平（0×NOAEL，对照）和 0.25、1 和 5×NOAEL 剂量下对 Wistar 大鼠行为的影响。在 3、6 和 12 个月后，使用高架十字迷宫和通用问题箱技术观察大鼠的神经行为变化，实验进行了三次。3 个月的暴露显示，5×NOAEL 剂量下认知能力下降，且存在剂量依赖性的研究活动和焦虑。6 个月的暴露显示认知能力呈非单调变化，0.25 和 5×NOAEL 剂量下下降，焦虑呈非单调变化，0.25 和 1×NOAEL 剂量下增加。5×NOAEL 剂量下的研究活动也减少了。然而，12 个月的暴露导致 0.25×NOAEL 剂量下认知能力增加，1×NOAEL 剂量下焦虑增加，且研究活动呈剂量依赖性。重复试验表明，认知能力从一次试验增加到另一次试验，而研究活动减少，0×NOAEL 剂量下焦虑增加。在暴露于农药混合物的组中，趋势不同，表明暴露于农药与重复试验相结合也会影响动物的反应。结果表明，存在几种剂量依赖性的行为反应，在被认为安全的剂量下出现了负面效应。本研究提供了关于时间依赖性混合物生物学的新见解，在进行风险评估时是一个重要的考虑因素。
