Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
Thalidomide (THA) is considered a representative teratogenic substance. However, THA does not induce morphological abnormalities in all rabbit fetuses, even though rabbits are sensitive to THA teratogenesis. To evaluate the risk of teratogenesis in female rabbits via male rabbit semen, a developmental toxicity test system for intravaginal exposures via semen should be newly considered. A new test system will be useful to determine whether and for how long male contraceptives should be used, when taking medications. We performed liquid chromatography-mass spectrometry to detect THA, its 5‑hydroxylated metabolite (major metabolite pathway in humans), and its 5’-hydroxylated metabolite (major metabolite pathway in rodents) in seminal and blood plasma after oral teratogenic doses of THA (250 and 500 mg/kg) in male rabbits. Based on this toxicokinetic information, we administered an intravaginal dose of THA to female rabbits. The results obtained showed an intravaginal THA treatment did not induce any teratogenic effects in rabbit fetuses.
In this symposium, we will compare the teratogenicity induced by oral treatment and intravaginal treatment in rabbits. Based on the pharmacokinetic results, we will discuss why THA does not induce morphological abnormalities in all rabbit fetuses.
