In Vivo Assessment of Cardiotoxicity Induced by Difenoconazole and Prothioconazole in a Rodent Model

The application of triazole fungicides in agriculture has raised concerns regarding their potential deleterious effects on human health. Thus, the present study aimed to evaluate the in vivo cardiotoxicity of fungicides difenoconazole (DFZ) and prothioconazole (PRZ), in Wistar rats subjected to daily administration of 1 mg/kg/day, corresponding to the non-observed adverse effect level (NOAEL), by gavage over a period of 28 consecutive days. No significant alterations were observed in the weights of the heart, right atrium, left atrium, spleen, liver, and lungs of the animals. Histopathological analyses of the myocardium revealed no evidence of cardiac hypertrophy. Electrocardiographic assessments did not indicate significant changes in P wave duration, PR and QT intervals, QRS complex, or RR interval. Furthermore, during the cardiac stress tests induced by caffeine and dobutamine, DFZ and PRZ did not increase the likelihood of developing cardiac arrhythmias, nor did they augment the infarct area as measured by TTC/Evans Blue staining. Also, serum levels of the cardiac biomarkers CK-MB and LDH were comparable to those of the control group. Collectively, these results suggest that DFZ and PRZ, at the administered dose and time frame, do not induce structural or electrical alterations in the hearts of rats.