Vitamin A acetate: a behavioral teratology study in rats
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Published on: July 13, 2014
S A Kutz1, N J Troise, R E Cimprich
1ICI Pharmaceuticals Group, Wilmington, Delaware 19897-0001.
Insights
Maternal vitamin A acetate supplementation in rats, especially at high doses, negatively impacts pup development. High doses reduced live birth and survival rates, delayed physical development, and affected body weight gain in offspring.
Area of Science:
- Toxicology
- Developmental Biology
- Reproductive Science
Background:
- Vitamin A is essential for mammalian development.
- Excessive vitamin A can be teratogenic.
- Understanding dose-dependent effects of vitamin A supplementation during pregnancy is crucial.
Purpose of the Study:
- To investigate the effects of maternal vitamin A acetate administration on rat pup development and behavior.
- To determine dose-response relationships for adverse effects on offspring.
Main Methods:
- Pregnant rats received vitamin A acetate (25,000–100,000 IU/kg/day) via oral gavage during gestation days 6-19.
- Evaluated pup parameters including live birth index, survival, body weight gain, physical development milestones (pinna detachment, eye opening, incisor eruption), and behavioral tests.
- Compared outcomes across different dosage groups and with a control group.
Main Results:
- High-dose (100,000 IU/kg/day) maternal vitamin A acetate significantly reduced live birth and 24/48-hour survival indices.
- Significant reductions in pup body weight gain were observed at 100,000 IU/kg/day across multiple early life stages.
- Delayed pinna detachment and eye opening occurred in pups from dams receiving 50,000 and 100,000 IU/kg/day; delayed incisor eruption was noted at 25,000 and 50,000 IU/kg/day.
- No significant effects were found on dam weight change, gestation length, litter size, or several behavioral and developmental assessments.
Conclusions:
- Maternal vitamin A acetate administration during critical gestation periods can lead to significant adverse effects on rat pup viability and development.
- Developmental delays and reduced growth are dose-dependent, with higher doses causing more severe outcomes.
- While some developmental milestones and behaviors were unaffected, the observed reductions in birth index, survival, and growth warrant careful consideration of vitamin A supplementation levels during pregnancy.
Abstract:
We evaluated the effects of maternal administration of vitamin A acetate on pup development and behavior. Vitamin A acetate was administered by oral gavage to pregnant rats (N = 10/treatment) on gestation days 6-19 at doses of 25,000, 50,000 or 100,000 I.U./kg/day. Male and female pups from dams that received 100,000 I.U./kg/day showed a significantly reduced live birth index but few external abnormalities. Twenty-four and 48 hour survival indices were also significantly reduced. The mean pup body weight gain at 100,000 I.U./kg/day was significantly reduced at days 1-3, 3-7 and 21-42. Pinna detachment and eye opening were significantly delayed in all male pups and in female pups from the 50,000 and 100,000 I.U./kg/day groups. Incisor eruption was significantly delayed in male and female pups from the 25,000 and 50,000 I.U./kg/day groups. The following showed no treatment effects: dam mean weight change, length of gestation, total litter size, surface righting, cliff avoidance, negative geotaxis, swimming development, open field activity and discriminatory learning.
