Genotoxic, cytotoxic, and cytopathological effects in rats exposed for 18 months to a mixture of 13 chemicals in doses below NOAEL levels

• Published in: Toxicology letters Vol. 316; pp. 154 - 170
• Main Authors: Tsatsakis, Aristidis, Docea, Anca Oana, Constantin, Carolina, Calina, Daniela, Zlatian, Ovidiu, Nikolouzakis, Taxiarchis Konstantinos, Stivaktakis, Polychronis D., Kalogeraki, Alexandra, Liesivuori, Jyrki, Tzanakakis, George, Neagu, Monica
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.11.2019
• Subjects: Cytotoxicity; Food additives; Genotoxicity; Mixtures; Pesticides; Cytotoxicity; Mixtures; Food additives; Pesticides; Genotoxicity
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2019.09.004

•Long term exposure to very low doses of chemicals mixture lead to genotoxic and cytotoxic effects.•Monotonic genotoxic effect observed only in female’s rat.•Dose-dependent cytotoxic effects in testis in males.•Dose-dependent cytotoxic effects in liver, stomach, kidney, lung, brain- both sexes. 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.