Enhanced one-generation reproductive toxicity study in rats for
detecting endocrine-disrupting effects of chemicals
H. Aoyama and K. Suzuki
Laboratory of Reproductive Toxicology, Institute of
Environmental Toxicology, Japan;
Department of Veterinary Physiology, Nippon Veterinary and Animal
Science University, Japan
Abstract: An enhanced one-generation reproductive toxicity study
in rats without adjusting a litter size during the lactation period
is proposed as a rapid and reliable bioassay for providing the data
concerning adverse and/or low-dose effects of suspected endocrine disruptors.
In this study, pregnant females are treated with the test substance
from gestation day 0 through lactation day 21, in principle. F1 offspring
from one-half of the litters in each dose group are killed and necropsied
at weaning, while those from the remaining litters are examined for
sexual maturation, estrous cyclicity, and/or sperm production. A series
of pilot studies with ethynylestradiol as a reference chemical have
suggested that the exposure of estrogenic chemicals during the early
gestation period is critical for detecting effects on fertilization
and/or implantation of eggs and survival of implants, and that expression
of some genes including AR in the prostate and IGF-1 in the uterus of
F1 offspring may be sensitive markers for monitoring potential estrogenic
effects of the test compound.
*Report from a SCOPE/IUPAC project: Implication of
Endocrine Active Substances for Human and Wildlife (J. Miyamoto and
J.Burger, editors). Other reports are published in this issue,
pp. 1617-2615.
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