Review of triazine antiprotozoal drugs used in veterinary medicine

et al. 2020

Birth Defects Research

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

Section: Introductionmentioning

confidence: 99%

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

Zhao

et al. 2020

Birth Defects Research

“…However, the widely use of triazine coccidiostats for their clinical effects have generated resistance to the genus Eimeria in recent years [5,6]. Fortunately, no crossresistance was observed in triazine coccidiostats [5].…”

Section: Introductionmentioning

confidence: 99%

“…Ethanamizuril (Figure 1), a novel triazine coccidiostat, namely (N-(4-(4-(3,5-dioxo-4,5-dihydro-1,2,4-triazin-2-(3H)-yl)-2-methylphenoxy) phenyl)acetamide, has been independently established by the Shanghai Veterinary Research Institute of the Chinese Academy of Agricultural Sciences in recent years and exert wide application prospective in future [5,7]. In China and Japan Patents, the chemical synthesis of ethanamizuril and the chemical structure have been published [8].…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Wei

et al. 2020

Preprint

Background: Triazine coccidiostats are widely used in chickens and turkeys for coccidiosis control. Ethanamizuril is a novel triazine compound that exhibits anticoccidial activity in poultry. This study evaluated the subchronic toxicity of ethanamuzuril in beagle dogs administered ethanamizuril by diet at doses of 12, 60 or 300 mg/kg/day for 90 days.Results: Ethanamizuril was well tolerated at low and middle dosages and in these dose groups there were no ethanamizuril related effects on survival, clinical observations, clinical pathology parameters, organs weight, macroscopic or microscopic evaluations. The ethanamizuril related changes were limited to effects on food consumption and histologic changes of kidneys in the 300 mg/kg/day group in both sexes. However, renal lesions resolved in dogs given ethanamizuril at 300 mg/kg/day when evaluated four weeks after the end of exposure.Conclusions: Therefore, the no-observed-adverse-effect level (NOAEL) was considered to be 60 mg/kg/day, the middle dosage level tested. These results add to the safety database for ethanamizuril with potential for use as a novel coccidiostat.

“…Consequently, the resulting letdown of treatment promotes a constant demand for innovative products with safe and e cient. Triazines are benzene-aceto-nitrile compounds including diclazuril, toltrazuril, ponazuril and clazuril, which have been used globally in the interception and therapy of protozoal diseases, most commonly in coccidiosis of veterinary interest since 1980s [5]. However, the widely use of triazine coccidiostats for their clinical effects have generated resistance to the genus Eimeria in recent years [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…However, the widely use of triazine coccidiostats for their clinical effects have generated resistance to the genus Eimeria in recent years [5,6]. Fortunately, no cross-resistance was observed in triazine coccidiostats [5].…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Wei

et al. 2020

Preprint

Background: Triazine coccidiostats are widely used in chickens and turkeys for coccidiosis control. Ethanamizuril is a novel triazine compound that exhibits anticoccidial activity in poultry. To support the safety assessment of the new potent anticoccidial agent, the subchronic toxicity of ethanamizuril was studied in beagle dogs administered ethanamizuril by diet at doses of 12, 60 or 300 mg/kg/day for 90 days.Results: Ethanamizuril was well tolerated at low and middle dosages and there were no ethanamizuril related effects on survival, clinical observations, clinical pathology parameters, organs weight, macroscopic or microscopic evaluations. The ethanamizuril related changes were limited to effects on food consumption and histologic changes of kidneys in the 300 mg/kg/day group in both sexes. However, the characteristic toxicities of ethanamizuril in kidneys are recoverable in convalescence dogs of 300 mg/kg/day group. Conclusions: Therefore, the no-observed-adverse-effect level (NOAEL) was considered to be 60 mg/kg/day, the middle dosage level tested. These results add to the safety database for ethanamizuril with potential for use as a novel coccidiostat.