Teratogenicity of a single oral dose of retinyl palmitate in the rat, and the role of dietary vitamin A status.
Vitamin A, known for its teratogenic properties, may be present in high concentrations in consumption liver. It is as yet unclear whether congenital malformations can result from a single liver meal. In our first experiment, the teratogenicity of a single dose of retinyl palmitate was tested in the rat. Pregnant rats were treated at day 10 of gestation by gavage with 100, 300 or 1000 mg/kg body weight retinyl palmitate on a dietary background level of 5 mg/kg feed. At gestation day 11 the number of embryos with an open cranial neural tube had increased with the dose. At gestation day 21, the high dose group showed an increase in late resorptions, whereas both the high and the medium dose groups had a high incidence of foetuses with malformations typical of retinoid embryopathy. The data suggest that delayed neural tube closure had occurred in a large proportion of the embryos. In a second experiment, the high oral dose was applied on gestation day 10 in pregnant rats receiving retinyl palmitate at 1.5, 5, 15, or 50 mg/kg feed for 6 weeks. Delayed neural tube closure, post-implantation loss and the nature and incidence of malformations were similar between diet groups, as well as being reminiscent of the high dose group in the first experiment. Thus the dietary status of the animals did not seem to influence the teratogenic potential of a single high dose of retinyl palmitate.
Piersma
A H
AH
Unit Teratology, Endocrinology and Perinatal Screening, National Institute of Public Health, Bilthoven, The Netherlands.
Bode
W
W
Verhoef
A
A
Olling
M
M
D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000633:toxicity*; D004032:Diet; D004224:Diterpenes; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005865:Gestational Age; D011247:Pregnancy; D051381:Rats; D000084562:Retinyl Esters; D013723:Teratogens / Q000633:toxicity*; D014801:Vitamin A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism* / Q000633:toxicity
D016588:Anticarcinogenic Agents; D004224:Diterpenes; D000084562:Retinyl Esters; D013723:Teratogens; D014801:Vitamin A; C014794:retinol palmitate