title: Effects of melamine on pregnant dams and embryo-fetal development in rats.
abstract: There are worldwide concerns regarding the potential adverse effect of melamine. This study investigated the potential effects of melamine on pregnant dams and embryo-fetal development in Sprague-Dawley rats following maternal exposure on gestational days (GD) 6-20. Melamine was administered to pregnant rats by gavage at doses of 0, 200, 400 and 800 mg kg⁻¹ per day (n = 8-10 for each group). All dams were subjected to a Caesarean section on GD 21 and their fetuses were examined for morphological abnormalities. With administration of melamine at 800 mg kg⁻¹ per day, maternal toxicity manifested as increased incidences of clinical signs and death, lower body weight gain and food intake, and increases in heart, adrenal gland and kidney weights. Histopathological examinations revealed an increase in incidences of congestion, tubular necrosis/degeneration, crystals, casts, inflammatory cells in tubules, tubular dilation and tubular hyaline droplets in the maternal kidneys, while fetal kidneys (one fetus/litter) did not show any histopathological changes. Developmental toxic effects included a decrease in fetal weight, an increase in the incidence of skeletal variations and a delay in fetal ossification. No treatment-related maternal or developmental effects were observed at doses ≤ 400 mg kg⁻¹ per day. These results show that 15-day repeated oral dosing of melamine is embryo-/fetotoxic at a maternotoxic dose, but not teratogenic in rats. The no-observed-adverse-effect level of melamine for pregnant dams and embryo-fetal development is considered to be 400 mg kg⁻¹ per day.
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju, 500-757, Korea.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Kim
authors.forename: In-Chul
authors.initials: IC
authors.lastname: Lee
authors.forename: Jeong-Hyeon
authors.initials: JH
authors.lastname: Lim
authors.forename: In-Sik
authors.initials: IS
authors.lastname: Shin
authors.forename: Changjong
authors.initials: C
authors.lastname: Moon
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Kim
authors.forename: Seung-Chun
authors.initials: SC
authors.lastname: Park
authors.forename: Hyoung-Chin
authors.initials: HC
authors.lastname: Kim
authors.forename: Jong-Choon
authors.initials: JC
authors.lastname: Kim
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D020567:Fetal Weight / Q000187:drug effects; D005333:Fetus / Q000187:drug effects* / Q000196:embryology*; D007668:Kidney / Q000187:drug effects / Q000196:embryology; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014227:Triazines / Q000633:toxicity*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D014227:Triazines; C011907:melamine