Two generation reproduction and teratogenicity studies of feeding diaveridine in Wistar rats

Abstract

Diaveridine (DVD), belonging to the class of compounds called diaminopyrimidines, has been widely used as a bacteriostatic agent. To evaluate the reproductive toxicity and teratogenic potential of DVD, different concentrations of DVD were administered to Wistar rats by feeding diets containing 0, 23, 230, 1150 and 2000 mg kg⁻¹ of DVD. Each group consisting of 18 males and 25 females (F₀) was treated with different concentrations of DVD through a 13-week period prior to mating, during mating, gestation, parturition and lactation. At weaning, 20 males and 25 females of F₁ generation weanlings per group were selected randomly as parents for the F₂ generation. The selected F₁ weanlings were exposed to the same diet and treatment as their parents. In the F₀ and F₁ generation of the 1150 and 2000 mg kg⁻¹ diet groups, the body weight, feed efficiency, weight gain of pregnant rats, litter and average number of live fetuses and fetus body weight significantly decreased. In the highest dose group, uterine wall contraction, narrow uterine cavity and uterine tumor were observed. Combined with the 2nd generation reproduction test to investigate the teratogenic toxicity of DVD in Wistar rats, the pregnant rats were subjected to caesarean section on the 20th gestational day for examination. For the 1150 and 2000 mg kg⁻¹ groups, the litter weights, body weights, body length, tail length of fetus and number of viable fetuses significantly decreased. There were no obvious external, skeletal and visceral effects in all the groups. The no-observed-adverse-effect level for reproduction/development toxicity of DVD was 23 mg kg⁻¹ diet (about 2.3–2.8 mg per kg b.w. per day).