Acute, mutagenicity, teratogenicity and subchronic oral toxicity studies of diaveridine in rodents

•We studied a complete toxicological safety assessment of diaveridine (DVD).•The safety assessment includes genetic toxicity, 90-day sub-chronic toxicity and teratogenicity.•The results indicate that there were no mutagenicity toxic effects.•The no-observed-adverse-effect-level (NOAEL) for the DVD was determined to be 10 mg/kg body weight for 90 days.•We have provided detailed toxicity with a wide spectrum of doses for DVD.

Diaveridine (DVD) is a member of the 2,4-pyrimidinediamine class of dihydrofolate reductase inhibitors. It is used in combination with sulfaquinoxaline as an antiprotozoal agent in animals for the prophylaxis and treatment of coccidiosis and leucocytozoonosis. Herein, we report a complete toxicological safety assessment of DVD for clinical use. The study of toxicity, genetic toxicity (mammalian erythrocyte micronucleus assay, mice sperm abnormality test and in vivo chromosome aberration test of mammalian bone marrow), 90-day sub-chronic toxicity and teratogenicity test were performed. In the acute oral toxicity tests, median lethal dose, LD50, was more than 2378 mg/kg body weight in Sprague Dawley rats (1025 mg/kg body weight in ICR mice). The testing results for three terms of mutagenicity toxicity (mouse chromosome aberration, erythrocyte micronucleus and sperm abnormality) were all negative at 128–512 mg/kg body weight. For 90-day feeding of DVD at the dosage of 10 mg/kg body weight in both male and female SD rats, no signs of toxicological effects were detected. Meanwhile, for teratogenicity test in female SD rats at the dosage of 37 mg/kg body weight, there were no toxicological signs observed. Thus, our results suggested that the DVD is safe when administered orally in rats at 10 mg/kg body weight per day.

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