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 (F 0 ) 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 F 1 generation weanlings per group were selected randomly as parents for the F 2 generation. The selected F 1 weanlings were exposed to the same diet and treatment as their parents. In the F 0 and F 1 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 noobserved-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).

Metabolism and Tissue Elimination of Diaveridine in Swine, Chickens, and Rats Using Radioactive Tracing Coupled with LC–ESI–IT–TOF/MS

“…The kidneys and liver showed the highest concentrations of radioactivity during the sample collection time, implying that these are the key organs for toxicology concerns. Significant toxic effects on the kidneys and liver were confirmed by observing fibroblasts in the kidneys and inflammation in the liver in toxicological studies . The rapid elimination of DVD-related metabolites in swine compared to that in chickens and rats may be related to its extensive metabolism to form polar compounds which promote drug clearance.…”

“…Significant toxic effects on the kidneys and liver were confirmed by observing fibroblasts in the kidneys and inflammation in the liver in toxicological studies. 12 The rapid elimination of DVD-related metabolites in swine compared to that in chickens and rats may be related to its extensive metabolism to form polar compounds which promote drug clearance. Our research showed that the DVD-related residues in the kidneys were eliminated more slowly than those in the liver and other tissues/organs.…”

“…DVD has potential reproductive toxicity, developmental toxicity, and genotoxicity. − As shown by the in vivo comet test, kidney, liver, spleen, and lung cells all exhibit substantial increases in migration values after receiving a single oral dosage of DVD, and this effect is dose-dependent . Both the TA100 and TA98 test strains are resistant to DVD mutagenic effects either in the presence or absence of rat S9 mix; following metabolic activation by hamster S9 mix, DVD becomes mutagenic for the TA100 strain .…”