Chemical structure--teratogenicity relationships, toxicokinetics and metabolism in risk assessment of retinoids.

Abstract:

:Retinoic acid, an oxidative metabolite of vitamin A, is involved in the control of many biological processes including embryonic development and excess as well as deficiency of retinoids has been found to be teratogenic. The effects of retinoids in normal as well as abnormal development may be mediated by two members of retinoid receptors, the RARs and RXRs, which exhibit specific temporal and spatial expression during development. Evidence accumulates that any alteration of this complex retinoid system may be related to teratogenic effects. Here we investigate the influence of toxicokinetic parameters, including aspects of metabolism and placental transfer, on the teratogenic potency of retinoids. It is demonstrated that activation (oxidation of retinoic acids; hydrolysis of glycoconjugates) and deactivation reactions (isomerization from trans- into cis-configuration; beta-glucuronidation) relate to teratogenesis. The beta-glucuronides of retinoic acids show poor placental transfer and prolonged presence in the maternal organism. Non-retinoid compounds such as antiepileptic agents may exert some of their teratogenicity via alteration of endogenous retinoid levels.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Nau H

doi

10.1016/0378-4274(95)03624-5

subject

Has Abstract

pub_date

1995-12-01 00:00:00

pages

975-9

eissn

0378-4274

issn

1879-3169

pii

0378-4274(95)03624-5

journal_volume

82-83

pub_type

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