Effect of subchronic exposure to mesotrione on histomorphological structure of the thyroid gland, kidney and liver in rats

  • Authors: N.M. Nedopytanska, N.V. Tereschenko, E.S. Zalinyan, L.V. Tkachenko
  • UDC: 632.954:631.453.777.5/.6
  • DOI: 10.33273/2663-4570-2022-92-1-54-67
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LI Medved’s Research Centre of Preventive Toxicology, Food and Chemical Safety, Ministry of Health, Ukraine (State Enterprise), Kyiv, Ukraine


Abstract. The use of poor-quality pesticides can lead to the development of pest resistance, increased levels of residues in finished products with corresponding risks to human health and the environment. In Ukraine, on the basis of mesotrione, a widely used systemic herbicide, more than 20 compounds, mainly generics, have been registered. To date, due to the lack of relevant data, the risks to humans associated with the consumption of food and drinking water with residues of mesotrione and/or its metabolites have not been definitively established.

Aim. To study histomorphological changes caused by mesotrione in a sub chronic experiment on male Wistar Hannover rats.

Materials and Methods. Male Wistar Hannover rats (n = 180) were orally administered one of three technical mesotrione samples (A, B, C) for 90 days at doses 0; 0.1; 0.4 and 4 mg/kg of body weight. At the end of the experiment, histological examinations of the main target organs exposed to the toxic effects of mesotrione: liver, kidney and thyroid gland were performed.

Results. Changes in the stroma and parenchyma of the liver under the exposure to mesotrione were not observed. Mild thyrotoxic effect at 4 mg/mg mesotrione exposure for samples A and B, as well as mild nephrotoxic effect at 4 mg/mg mesotrione exposure at sample C were detected. The most common changes detected in kidney were the intratubular micro petrifications, eosinophilic content in cortical tubules, the desquamation of the epithelium of the cortical tubules and hydropic degeneration, in the thyroid gland - degenerativedesquamative disorder, focal fibrosis and epithelioid cysts.

Conclusions. In a sub chronic experiment in Wistar Hannover male rats, two samples of mesotrione demonstrated a mild thyrotoxic effect at a dose of 4 mg/kg and one sample had a mild nephrotoxic effect at a dose of 4 mg/kg. According to the indicator of nonspecific dystrophic changes in the thyroid gland (samples A and B) and in the renal cortex (sample C), the dose of 0.4 mg/kg can be considered as NOAEL.

Key Words: mesotrione, rats, sub chronic experiment, histomorphological changes.



1. Population 2030. Demographic challenges and opportunities for sustainable development planning. https://www.un.org/en/development/desa/population/publications/pdf/trends/Population2030.pdf

2. Food and Agriculture Organization of the United Nations. Path to Zero Hunger by 2030 http://www.fao.org/resources/infographics/infographics-details/en/c/1003923/.

3. Quality Control of Pesticide Products. Prepared by the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture. https://www-pub.iaea.org/MTCD/publications/PDF/te_1612_web.pdf

4. Sarkar S, Dias Bernardes J, Keeley J. The use of pesticides in developing countries and their impact on health and the right to food. European Parliament's online database. 2021. https://www.europarl.europa.eu/RegData/etudes/STUD/2021/653622/EXPO_STU(2021)653622_EN.pdf

5. Tkachenko IV, Antonenko AM, Bardov VG. Hygienic Assessment of Changes in the Assortment and Ranges of Application of Pesticides in the Agriculture of Ukraine from 2015 to 2019. Medical Science of Ukraine (MSU). 2019;15(3–4):64–8.

6. Tsatsakis A, Petrakis D, Nikolouzakis TK. COVID-19, an opportunity to reevaluate the correlation between long-term effects of anthropogenic pollutants on viral epidemic/pandemic events and prevalence. Food Chem Toxicol. 2020;141:111418.

7. European Food Safety Authority (EFSA). Peer review of the pesticide risk assessment of the active substance mesotrione. EFSA Journal. 2016;14(3):4419.

8. US EPA Memorandum. Mesotrione. Human Health Risk Assessment for Amended Uses on Corn, 2015. https://www3.epa.gov/pesticides/chem_search/hhbp/D427385.pdf

9. Державний реєстр пестицидів і агрохімікатів, дозволених до використання в Україні. https://mepr.gov.ua/files/docs/pesticide/2021/pesticides2008_2019+2020-2021.xlsx

10. OECD Guideline for the Testing of Chemicals: № 408 Repeated Dose 90 day Oral Toxicity Study in Rodent. https://www.oecd.org/chemicalsafety/testing/RevisionOECD-TG408-repeated-dose-90-day-oral-toxicity-study-inrodents.pdf

11. Mann PC, Vahle J, Keenan CM. International harmonization of toxicologic pathology nomenclature: an overview and review of basic principles. Toxicol Pathol. 2012;40(4):7–13.

12. Mesotrione. EPA Pesticides Fact Sheet. https://www3.epa.gov/pesticides/chem_search/reg_actions/registration/fs_PC-122990_04-Jun-01.pdf

13. Felisbino K, Santos-Filho R, Piancini LDS. Mesotrione herbicide does not cause genotoxicity, but modulates the genotoxic effects of Atrazine when assessed in mixture using a plant test system (Allium cepa). Pestic Biochem Physiol. 2018;150:83–8.

14. Waxman DJ. P450 gene induction by structurally diverse xenochemicals: Central role of nuclear receptors CAR, PXR, and PPAR. Archives of biochemistry and biophysics. 1999;369(1):11-23.

15. Identification of Cumulative Assessment Groups of Pesticides, Question NoQ-2009-1092. EFSA, 2012. https://efsa.onlinelibrary.wiley.com/doi/pdfdirect/10.2903/sp.efsa.2012.EN-269

16. Li S, Zhu L, Du Z. Mesotrione-induced oxidative stress and DNA damage in earthworms (Eisenia fetida). Ecological Indicators. 2018;95(1):436–43.

17. Zhang F, Yao X, Sun S. Effects of mesotrione on oxidative stress, subcellular structure, and membrane integrity in Chlorella vulgaris. Chemosphere. 2020;247:125668.

18. Could a pesticide harm our defense against COVID-19? https://local12.com/news/coronavirus/could-a-pesticideharm-our-defense-against-covid-19.

19. Liguori I, Russo G, Curcio F. Oxidative stress, aging, and diseases. Clin Interv Aging. 2018;13:757–72.

20. Centers for Disease Control and Prevention. COVID-19: People of Increased Risk. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/index.html

21. Schönrich G, Raftery MJ, Samstag Y. Devilishly radical NETwork in COVID-19: Oxidative stress, neutrophil extracellular traps (NETs), and T cell suppression. Adv Biol Regul. 2020;77:100741.

22. Sarkesh A, Sorkhabi AD, Sheykhsaran E. Extrapulmonary Clinical Manifestations in COVID-19 Patients. Am J Trop Med Hyg. 2020;103(5):1783–96.

23. Xing H, Li S, Wang Z. Oxidative stress response and histopathological changes due to atrazine and chlorpyrifos exposure in common carp. Pesticide Biochemistry and Physiology. 2012;103(1):74–80.

24. Li X, Zhang W, Cao Q. Mitochondrial dysfunction in fibrotic diseases. Cell Death Discov. 2020;6:80.

25. Committee for Risk Assessment. Opinion proposing harmonised classification and labelling at EU level of mesotrione. Adopted 14 September 2018. https://echa.europa.eu/documents/10162/5cc45ca7-fb5b-0fe8-198a-d3efa8c0d815

26. Mesotrione (Ref: ZA 1296). Pesticide Properties DataBase. https://sitem.herts.ac.uk/aeru/ppdb/en/Reports/442.htm

27. Nielsen E, Nоrhede P, Boberg J. EXTERNAL SCIENTIFIC REPORT submitted to EFSA. Identification of Cumulative Assessment Groups of Pesticides. April 2012.