Two‐generation reproduction and limited teratology studies of ethanamizuril fed to rats

Abstract

Ethanamizuril, a new anticoccidial agent that belongs to triazine derivatives, has a broad and good anticoccidial activity. To evaluate the reproductive toxicity and teratogenic potential of ethanamizuril, different concentrations of ethanamizuril were administered to Sprague-Dawley rats by feeding diets containing 0, 2, 8, and 30 ppm, respectively. Each group consisting of 30 males and 30 females (F0) was treated with different concentrations of ethanamizuril through a 13-week period before mating and during mating, gestation, parturition and lactation. In the 30 ppm dose group, pup body weight on days 7 and 21 in F1 offspring and day 21 in the F2a offspring were significantly decreased.A limited teratogenicity study was performed in combination with the F1 generation of a two-generation reproduction study. F1 offspring of the reproduction study were mated after weaning of the F2a offspring. Pregnant female rats were subjected to cesarean section on gestational day 20 for teratogenic examination. No obvious body weights, fetal body lengths, tail lengths, litter weights, number of viable fetuses, external, skeletal, or visceral malformations in fetuses were noted in any groups in the teratogenic test, but ethanamizuril could be passed on to offspring through lactation. K E Y W O R D S ethanamizuril, feeding in diet, reproductive toxicity, Sprague-Dawley rats, teratogenicity

Beagle dog 90-day oral toxicity study of a novel coccidiostat – ethanamizuril

“…In addition, the high dose of toltrazuril caused the weight of the testes and weight of the prostate decreased [13]. However, no obvious body weights, fetal body lengths, tail lengths, litter weights, number of viable fetuse, sexternal, skeletal or visceral malformations in fetuses were noted in any groups in two-generation reproduction and teratogenic test with ethanamizuril, and no adverse effects on the central nervous system, cardiovascular system, and respiratory system were showed in safety pharmacology test either [15,17,18]. Furthermore, the studies of 30 and 90-day subchronic toxicity with feeding ethanamizuril fed to SD rats revealed that the high dose of ethanamizuril, above 60 mg/kg dietary level, could cause minor damage to the liver, kidneys, and other organs, and induce alopecia [11,12].…”

Beagle dog 90-day oral toxicity study of a novel coccidiostat – ethanamizuril

“…In addition, the high dose of toltrazuril caused the mean weight of the testes and weight of the prostate decreased [13]. However, no obvious body weights, fetal body lengths, tail lengths, litter weights, number of viable fetuse, sexternal, skeletal or visceral malformations in fetuses were noted in any groups in two-generation reproduction and teratogenic test with ethanamizuril, and no adverse effects on the central nervous system, cardiovascular system, and respiratory system were showed in safety pharmacology test too [15,17,18]. Furthermore, the studies of 30 and 90-day subchronic toxicity with feeding ethanamizuril fed to SD rats revealed that the high dose of ethanamizuril, above 60 mg/kg dietary level, could cause minor damage to the liver, kidneys, and other organs, and induce alopecia [11,12].…”

Beagle dog 90-day oral toxicity study of a novel coccidiostat – ethanamizuril

“…In addition, the high dose of toltrazuril caused the mean weight of the testes and weight of the prostate decreased [13]. However, no obvious body weights, fetal body lengths, tail lengths, litter weights, number of viable fetuse, sexternal, skeletal or visceral malformations in fetuses were noted in any groups in two-generation reproduction and teratogenic test with ethanamizuril, and no adverse effects on the central nervous system, cardiovascular system, and respiratory system were showed in safety pharmacology test too [15,16,17]. Furthermore, the studies of 30 and 90-day subchronic toxicity with feeding ethanamizuril fed to SD rats revealed that the high dose of ethanamizuril, above 60 mg/kg dietary level, could cause minor damage to the liver, kidneys, and other organs, and induce alopecia [11,12].…”

“…To the best of our knowledge, a series of toxicity evaluation of ethanamizuril has been carried out in rats and mice, and the NOAEL for the dietary administration of ethanamizuril in the 90-day oral toxicity study for rats was greater than 20 mg/kg. According to VICH's guidelines for repeated dose toxicity tests, the dog is the default non-rodent species which was required in repeat-dose toxicity testing, and the toxicity evaluation in beagle dogs has not been reported [11,12,15,16]. This is unfavourable for understanding the safety and clinical use of ethanamizuril.…”