Subchronic Toxicity Study Of Cyadox In Beagle Dogs

Quinoxalines are synthetic antimicrobial agents with growth-promoting activity, and have been used extensively in food animals since 1970s. Cyadox was invented as a new quinoxaline antimicrobial promoter in animal husbandry in our lab. Cyadox is a growth-promoter used in a large scope and a long period, its toxicity must be studied systemically. To date, there are many previous toxicity study of cyadox in rodents, especially in rats, but there are little toxicity data in non-rodents, which was too limited to reveal the toxicity of cyadox sufficiently and convincingly. Therefore, the present study was to investigate the potential oral subchronic toxicity of cyadox in Beagle dogs with a wide range of doses, and thus to provide experimental evidence of the safety of cyadox for future clinical trials and approvement.To investigate the subchronic toxicity of cyadox in non-rodents, male and female Beagle dogs were randomly divided into four groups and two animals from the control and high-dose group were assigned for 2-weeks recovery groups. The dogs were fed with the diets containing cyadox (0,100,450 and 2500 mg/kg) for 13 weeks. During the treatment and recovery periods, the effects of cyadox on clinical signs, body weight, food consumption, hematology, serum biochemistry, urinalysis, electrocardiogram, temperature, necorpsy, organ weights and histopathology were carefully examined. During the study, the only adverse effect observed was that the serum K+ level increased significantly in the male high-dose group compared with control at week 13 (p<0.05). However, the effect was not noted in recovery periods. No other toxicity response due to the cyadox was observed. We demonstrated that the slight subchronic toxicity of cyadox for dogs and the no-observed-adverse-effect level (NOAEL) of cyadox in this study was considered to be 450 mg/kg diet, which approximately represents nine times than that of recommended dose for clinical applications and approximately equivalent to 16 mg/kg b.w.. There are no significant difference when compared the NOAEL obtained from beagle dogs with that obtained from wistar rats in subchronic toxicity study. On the basis of the NOAEL in dogs and rats, ADI was calculated to be 0.15 mg/kg b.w. according to method of FDA. Safe concentration of cyadox is 30,90,180 and 180μg/g for muscle, liver, kidney and fat respectively. The safe concentrations of all the above tissues were much larger than residues of cyadox or its metabolites detected in tissues of food animals given cyadox in diet. Therefore, cyadox shows good safety using in food-producing animals, and has little effect on food safety of humans. In a conclusion, the research shows that cyadox is safe for using in food-producing animals, and the research perfects the toxicity data of cyadox, which could guarantee the food safety of humans and promote the approvement and application of cyadox.