Fluoride subacute testicular toxicity in Wistar rats: Benchmark dose analysis for the redox parameters, essential elements and DNA damage

Excessive fluoride (F−) levels in the environment could induce different pathological changes, including comorbidities in reproductive functions. Hence, the aim of the present in vivo study was to explore F− subacute toxicity mechanisms via Benchmark dose (BMD) methodology on rat's testicles. The experiment was conducted on thirty male Wistar rats for 28 days, divided into six groups (n = 5): 1) Control (tap water); 2) 10 mg/L F−; 3) 25 mg/L F−; 4) 50 mg/L F−; 5) 100 mg/L F−; 6) 150 mg/L F−. Testicles were dissected out and processed for the determination of F− tissue concentrations, redox status parameters, essential elements level, and DNA damage. PROASTweb 70.1 software was used for determination of external and internal dose-response relationship. The results confirmed a significant increase in superoxide anion (O2.-), total oxidative status (TOS), copper (Cu), zinc (Zn), iron (Fe), DNA damage levels, and decrease in superoxide dismutase activity (SOD1) and total thiol (SH) groups. The dose-dependent changes were confirmed for SOD1 activity and DNA damage. The most sensitive parameters were SOD1 activity and DNA damage with the lowest BMDLs 0.1 μg F−/kg b. w. Since human and animal populations are daily and frequently unconsciously exposed to F−, this dose-response study is valuable for further research regarding the F− health risk assessment