Center of Toxicology Science & Research, Medical School, University of Crete, Heraklion, Crete, Greece; Spin-Off Toxplus S.A., 71601, Heraklion, Greece.
Department of Toxicology, University of Medicine and Pharmacy, Faculty of Pharmacy, Craiova, 200349, Romania.
Toxicol Lett. 2019 Nov;316:154-170. doi: 10.1016/j.toxlet.2019.09.004. Epub 2019 Sep 12.
The present study investigates the genotoxic and cytotoxic effects of long term exposure to low doses of a mixture consisting of methomyl, triadimefon, dimethoate, glyphosate, carbaryl, methyl parathion, aspartame, sodium benzoate, EDTA, ethylparaben, buthylparaben, bisphenol A and acacia gum in rats. Four groups of ten Sprangue Dawley rats (5 males and 5 females per group) were exposed for 18 months to the mixture in doses of 0xNOAEL, 0.0025xNOAEL, 0.01xNOAEL and 0.05xNOAEL (mg/kg bw/day). After 18 months of exposure, the rats were sacrificed and their organs were harvested. Micronuclei frequency was evaluated in bone marrow erythrocytes whereas the organs were cytopathologically examined by the touch preparation technique. The exposure to the mixture caused a genotoxic effect identified only in females. Cytopathological examination showed specific alterations of tissue organization in a tissue-type dependent manner. The observed effects were dose-dependent and correlated to various tissue parameters. Specifically, testes samples revealed degenerative and cellularity disorders, liver hepatocytes exhibited decreased glycogen deposition whereas degenerative changes were present in gastric cells. Lung tissue presented increased inflammatory cells infiltration and alveolar macrophages with enhanced phagocytic activity, whereas brain tissue exhibited changes in glial and astrocyte cells' numbers. In conclusion, exposure to very low doses of the tested mixture for 18 months induces genotoxic effects as well as monotonic cytotoxic effects in a tissue-dependent manner.
本研究调查了长期接触由甲拌磷、三唑酮、乐果、草甘膦、西维因、甲基对硫磷、阿斯巴甜、苯甲酸钠、EDTA、乙基对羟基苯甲酸酯、丁基对羟基苯甲酸酯、双酚 A 和阿拉伯树胶组成的混合物低剂量对大鼠的遗传毒性和细胞毒性影响。四组 10 只斯普拉格道利大鼠（每组 5 只雄性和 5 只雌性）暴露于混合物中 18 个月，剂量分别为未观察到不良作用水平（NOAEL）的 0x、0.0025x、0.01x 和 0.05x（mg/kg bw/day）。暴露 18 个月后，处死大鼠并采集其器官。在骨髓红细胞中评估微核频率，而通过触片制备技术对器官进行细胞病理学检查。混合物暴露仅在雌性中引起遗传毒性作用。细胞病理学检查显示组织类型依赖性的特定组织组织改变。观察到的效应是剂量依赖性的，并与各种组织参数相关。具体而言，睾丸样本显示出退行性和细胞数量紊乱，肝肝细胞显示出糖原沉积减少，而胃细胞存在退行性变化。肺组织呈现出增加的炎症细胞浸润和肺泡巨噬细胞的吞噬活性增强，而脑组织显示出神经胶质细胞和星形胶质细胞数量的变化。总之，暴露于测试混合物的非常低剂量 18 个月会导致遗传毒性效应以及组织依赖性的单调细胞毒性效应。
