Evaluation of oxidative stress responses and primary DNA damage in blood and brain of rats exposed to low levels of tembotrione Blanka Tariba Lovakovi  c a, * , Vilena Ka  suba b , Anja Kati  c a , Nevenka Kopjar b , Ana Marija Marjanovi  c  Cermak c , Vedran Micek d , Mirta Mili  c b , Ivan Pavi  ci  c c , Alica Pizent a , Suzana  Zunec e , Davor  Zelje  zi  c b a Analytical Toxicology and Mineral Metabolism Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10 000, Zagreb, Croatia b Mutagenesis Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10 000, Zagreb, Croatia c Radiation Dosimetry and Radiobiology Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10 000, Zagreb, Croatia d Animal Breeding Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10 000, Zagreb, Croatia e Toxicology Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10 000, Zagreb, Croatia highlights graphical abstract  Male rats were orally exposed to low doses of tembotrione for 28 days.  Biochemical and enzyme activity- based endpoints were slightly changed by the treatment.  Tembotrione had the potency to inflict DNA damage in leukocytes and in brain cells.  Brain cells had higher level of pri- mary DNA damage than leukocytes. article info Article history: Received 24 January 2020 Received in revised form 24 March 2020 Accepted 27 March 2020 Available online 2 April 2020 Handling Editor: A. Gies Keywords: Tembotrione Comet assay Antioxidant enzymes Lipid peroxidation abstract Tembotrione is a rather novel pesticide, usually used for post-emergence weed control. Even though its use is rapidly growing, it is not followed by an adequate flow of scientific evidence regarding its toxicity towards non-target organisms. We evaluated the potential of low doses of tembotrione to induce oxidative stress and cytogenetic damage in blood and brain cells of adult male Wistar rats. Parameters of lipid peroxidation, glutathione levels, activities of antioxidant enzymes and primary DNA damage were assessed following 28-day repeated oral exposure to doses comparable with the currently proposed health-based reference values. The results of the alkaline comet assay showed that such low doses of tembotrione have the potency to inflict primary DNA damage in both peripheral blood leukocytes and brain of treated rats, even with only slight changes in the oxidative biomarker levels. The DNA damage in blood and brain cells of Wistar rats significantly increased at all applied doses, suggesting that tembo- trione genotoxicity is mainly a result of direct interaction with DNA while the induction of oxidative stress responses contributes to DNA instability in a lesser extent. The findings of the present study call for further research using other sensitive biomarkers of effect and different exposure scenarios. © 2020 Elsevier Ltd. All rights reserved. * Corresponding author. Analytical Toxicology and Mineral Metabolism Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, HR- 10001, Zagreb, Croatia. E-mail address: btariba@imi.hr (B. Tariba Lovakovi c). Contents lists available at ScienceDirect Chemosphere journal homepage: www.elsevier.com/locate/chemosphere https://doi.org/10.1016/j.chemosphere.2020.126643 0045-6535/© 2020 Elsevier Ltd. All rights reserved. Chemosphere 253 (2020) 126643