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

Abstract

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 (F0 ) 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 F1 generation weanlings per group were selected randomly as parents for the F2 generation. Selected F1 weanlings were exposed to the same diet and treatment as their parents. At 1000 mg kg(-1) dose group, body weights in F0 and F1 rats, fetal body weight on day 21 (0, 4 and 21) after birth and number of viable fetuses in the F0 and F1 generation significantly decreased. Teratogenicity study was performed in combination with the F1 generation of a two-generation reproduction study. F1 parents of the reproduction study were mated after weaning of the F2a 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) ).

• Authors: Xu Wang, Ziqiang Tan, Guyue Cheng, Ihsan Awais, Lingli Huang, Dongmei Chen, Yuanhu Pan, Zhenli Liu, Zonghui Yuan
• Journal: Journal of applied toxicology : JAT (J Appl Toxicol) Vol. 35 Issue 12 Pg. 1531-8 (Dec 2015) ISSN: 1099-1263 [Electronic] England
• PMID: 25663540 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 John Wiley & Sons, Ltd.

Chemical References

• Anti-Bacterial Agents
• aditoprim
• Trimethoprim

Topics

• Abnormalities, Drug-Induced (etiology)
• Administration, Oral
• Animals
• Anti-Bacterial Agents (chemistry, toxicity)
• Dose-Response Relationship, Drug
• Female
• Fetal Development (drug effects)
• Male
• Molecular Structure
• No-Observed-Adverse-Effect Level
• Pregnancy
• Prenatal Exposure Delayed Effects (chemically induced)
• Rats, Wistar
• Trimethoprim (analogs & derivatives, chemistry, toxicity)