Critical period and minimum single oral dose of ochratoxin A for inducing developmental toxicity in pregnant Wistar rats.
Ochratoxin A (OTA), a potent in vivo teratogen, has been tested in various laboratory animal species. Present investigation was conducted to determine critical dose and critical time for the developmental toxicity of OTA in pregnant Wistar rats after single oral dose administration. OTA at different graded dose levels (2-4 mg/kg body weight) and at different gestation days (6-15), caused variable developmental defects in developing fetuses. OTA at 2.75 mg/kg body weight, dissolved in 0.1 M sodium bicarbonate (vehicle) and administered by oral intubation as a single dose on one of the gestational days 6-15, caused significant maternal toxicity in the dams and various gross, visceral and skeletal anomalies in the fetuses. The major gross malformations were external hydrocephaly, incomplete closure of skull and omphalocele. Internal hydrocephaly, microphthalmia, enlarged renal pelvis and renal hypoplasia were the main internal soft tissue anomalies. Major skeletal defects were developmental defects in skull bones, sternebrae, vertebrae and ribs. The gestational days 6 and 7 were found to be the most critical for the induction of teratogenicity in rats. Single oral dose of 2.75 mg/kg body weight OTA was found to be the minimum effective teratogenic dose in pregnant Wistar rats.
Patil
Rajendra D
RD
Division of Pathology, Indian Veterinary Research Institute, Izatnagar 243 122, Uttar Pradesh, India. rdpatil02@rediffmail.com
Dwivedi
Prabhaker
P
Sharma
Anil K
AK
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000015:Abnormalities, Multiple / Q000139:chemically induced; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D047109:Fetal Development / Q000187:drug effects*; D005315:Fetal Diseases / Q000139:chemically induced; D005865:Gestational Age; D006849:Hydrocephalus / Q000139:chemically induced; D006869:Hydronephrosis / Q000139:chemically induced; D008297:Male; D008431:Maternal-Fetal Exchange / Q000187:drug effects*; D008850:Microphthalmos / Q000139:chemically induced; D009793:Ochratoxins / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013723:Teratogens / Q000737:chemistry / Q000633:toxicity; D013997:Time Factors
D002273:Carcinogens; D009793:Ochratoxins; D013723:Teratogens; C025589:ochratoxin A