title: Acute, mutagenicity, teratogenicity and subchronic oral toxicity studies of diaveridine in rodents.
abstract: Diaveridine (DVD) is a member of the 2,4-pyrimidinediamine class of dihydrofolate reductase inhibitors. It is used in combination with sulfaquinoxaline as an antiprotozoal agent in animals for the prophylaxis and treatment of coccidiosis and leucocytozoonosis. Herein, we report a complete toxicological safety assessment of DVD for clinical use. The study of toxicity, genetic toxicity (mammalian erythrocyte micronucleus assay, mice sperm abnormality test and in vivo chromosome aberration test of mammalian bone marrow), 90-day sub-chronic toxicity and teratogenicity test were performed. In the acute oral toxicity tests, median lethal dose, LD50, was more than 2378mg/kg body weight in Sprague Dawley rats (1025mg/kg body weight in ICR mice). The testing results for three terms of mutagenicity toxicity (mouse chromosome aberration, erythrocyte micronucleus and sperm abnormality) were all negative at 128-512mg/kg body weight. For 90-day feeding of DVD at the dosage of 10mg/kg body weight in both male and female SD rats, no signs of toxicological effects were detected. Meanwhile, for teratogenicity test in female SD rats at the dosage of 37mg/kg body weight, there were no toxicological signs observed. Thus, our results suggested that the DVD is safe when administered orally in rats at 10mg/kg body weight per day.
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China; Laboratory of Quality & Safety Risk Assessment for Animal Products on Chemical Hazards (Beijing), Ministry of Agriculture, Beijing 100193, People's Republic of China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China; Laboratory of Quality & Safety Risk Assessment for Animal Products on Chemical Hazards (Beijing), Ministry of Agriculture, Beijing 100193, People's Republic of China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Sun
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China; Laboratory of Quality & Safety Risk Assessment for Animal Products on Chemical Hazards (Beijing), Ministry of Agriculture, Beijing 100193, People's Republic of China.
authors.forename: Shusheng
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China; Laboratory of Quality & Safety Risk Assessment for Animal Products on Chemical Hazards (Beijing), Ministry of Agriculture, Beijing 100193, People's Republic of China.
authors.forename: Suxia
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China; Laboratory of Quality & Safety Risk Assessment for Animal Products on Chemical Hazards (Beijing), Ministry of Agriculture, Beijing 100193, People's Republic of China. Electronic address: cxy@cau.edu.cn.
authors.forename: Xingyuan
authors.initials: X
authors.lastname: Cao
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000473:pathology; D000284:Administration, Oral; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001835:Body Weight / Q000187:drug effects*; D002869:Chromosome Aberrations; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009152:Mutagenicity Tests; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013094:Spermatozoa / Q000187:drug effects; D023382:Toxicity Tests, Acute; D059550:Toxicity Tests, Subchronic
chemical_list: D000981:Antiprotozoal Agents; D011743:Pyrimidines; C033222:diaveridine
keywords: Diaveridine; Food safety; Safety evaluation; Toxicity studies