Two-generation reproduction and teratology studies of feeding aditoprim in Wistar rats

摘要

Aditoprim, a new bacteriostatic agent that belongs to diaminopyrimidines, has a broad antimicrobial spectrum, good antibacterial activity and excellent pharmacokinetics. To evaluate the reproductive toxicity and teratogenic potential of aditoprim, different concentrations of aditoprim were administered to Wistar rats by feeding diets containing 0, 20, 100 and 1000 mg kg(-1), respectively. Each group consisting of 18 males and 25 females (F-0) was treated with different concentrations of aditoprim through a 13-week period before mating and during mating, gestation, parturition and lactation. At weaning, 20 males and 25 females of the F-1 generation weanlings per group were selected randomly as parents for the F-2 generation. Selected F-1 weanlings were exposed to the same diet and treatment as their parents. At 1000 mg kg(-1) dose group, body weights in F-0 and F-1 rats, fetal body weight on day 21 (0, 4 and 21) after birth and number of viable fetuses in the F-0 and F-1 generation significantly decreased. Teratogenicity study was performed in combination with the F-1 generation of a two-generation reproduction study. F-1 parents of the reproduction study were mated after weaning of the F-2a pups. Pregnant female rats were subjected to cesarean section on gestational day 20 for teratogenic examination. At 1000 mg kg(-1) group, body weights, fetal body lengths, tail lengths, litter weights and number of viable fetuses were significantly decreased. No obvious external, skeletal or visceral malformations in fetuses were noted in any groups in the teratogenic test. The no-observed-adverse-effect level for reproduction/development toxicity of aditoprim was 100 mg kg(-1) diet (about 7.89-9.25 mg kg(-1) body weight day(-1)). Copyright (c) 2015 John Wiley & Sons, Ltd.