title: Effects of melamine and cyanuric acid on embryo-fetal development in rats.
abstract: After the outbreak of acute renal failure associated with melamine-contaminated pet food, melamine and melamine-related compounds have become of great interest from a toxicologic perspective. We investigated the potential effects of melamine in combination with cyanuric acid (M + CA, 1:1) on pregnant dams and embryo-fetal development in rats. M + CA was orally administered to pregnant rats from gestational days 6 through 19 at doses of 0, 3, 10, and 30 mg/kg/day of both melamine and cyanuric acid. Maternal toxicity of rats administered 30 mg/kg/day M + CA was manifested as increased incidences of clinical signs and death; gross pathologic findings; higher blood urea nitrogen and creatinine levels; lower body weight gain and food intake; decreased thymus weight; and increased heart, lung, and kidney weights. Histopathological examinations revealed an increase in the incidence of congestion, tubular necrosis/degeneration, crystals, casts, mineralization, inflammatory cells in tubules, tubular dilation, and atrophy of glomeruli in maternal kidneys, whereas fetal kidneys did not show any histopathological changes. Developmental toxicity included a decrease in fetal (28%) and placental weights and a delay in fetal ossification (n = 7). Increased incidence of gross and histopathological changes in the maternal kidney was also found in the middle dose group (n = 12). No treatment-related maternal or developmental effects were observed in the low dose group (n = 12). Under these experimental conditions, M + CA is embryotoxic at an overt maternotoxic dose in rats and the no-observed-adverse-effect level of M + CA is considered to be 3 mg/kg/day for pregnant dams and 10 mg/kg/day for embryo-fetal development.
authors: College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea.
authors: Sung-Hwan
authors: SH
authors: Kim
authors: In-Chul
authors: IC
authors: Lee
authors: Hyung-Seon
authors: HS
authors: Baek
authors: Kyeong-Woo
authors: KW
authors: No
authors: Dong-Ho
authors: DH
authors: Shin
authors: Changjong
authors: C
authors: Moon
authors: Sung-Ho
authors: SH
authors: Kim
authors: Seung-Chun
authors: SC
authors: Park
authors: Jong-Choon
authors: JC
authors: Kim
mesh_terms: D000014:Abnormalities, Drug-Induced; D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D008297:Male; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014227:Triazines / Q000633:toxicity*
chemical_list: D014227:Triazines; C004632:cyanuric acid; C011907:melamine
keywords: Melamine; cyanuric acid; developmental toxicity; kidney; maternal toxicity