Effects of sub-chronic exposure to terbuthylazine on DNA damage, oxidative stress and parent compound/metabolite levels in adult male rats

- Male rats were orally exposed to terbuthylazine at doses 0.004, 0.4 and 2.29 mg/kg b.w./day for 28 days.
- Terbuthylazine was detected only in urine while its metabolite deethylterbuthylazine was detected in urine and plasma.
- Disturbance in oxidant/antioxidant status reflects in change of total antioxidant capacity and antioxidant enzymes activity.
- Applied pesticide doses result with low-level DNA instability, which was confirmed by the use of two genotoxicity endpoints.

Terbuthylazine is a selective pre- and post-emergency chloro-triazine herbicide used for a broad spectrum of weed control. We evaluated the potential of low doses of terbuthylazine to induce oxidative stress and cytogenetic damage in peripheral blood samples of adult male Wistar rats. Following 28-day repeated oral exposure at 0.004 mg/kg b.w./day, 0.4 mg/kg b.w./day and 2.29 mg/kg b.w./day, parameters of lipid peroxidation, total antioxidant capacity, and activities of antioxidant enzymes were measured in blood samples. Alkaline comet assay on leukocytes and erythrocyte micronucleus assay were used to measure DNA damage. In addition, the concentration of terbuthylazine and its metabolite in urine and plasma were determined using high performance liquid chromatography with UV diode-array detector (HPLC-UV-DAD). The fraction of terbuthylazine excreted in urine was negligible and was not found in plasma. Deethylterbuthylazine was only compound detected in plasma samples. Exposure to terbuthylazine did not induce significant lipid peroxidation products. The significant changes in antioxidant enzyme activities and the elevated total antioxidant capacity indicated that terbuthylazine at experimental conditions applied has potential to disturb oxidative/antioxidant balance. Results regarding the alkaline comet assay as well as micronucleated reticulocyte frequency indicated that treatment led to low-level DNA instability. Our results call for further research using other sensitive biomarkers of effect, along with different exposure scenarios.

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