Title
Relative developmental toxicity potencies of retinoids in the embryonic stem cell test compared with their relative potencies in in vivo and two other in vitro assays for developmental toxicity
Author
Louisse, J.
Gönen, S.
Rietjens, I.M.C.M.
Verwei, M.
Publication year
2011
Abstract
The present study determines the relative developmental toxicity potencies of retinoids in the embryonic stem (ES)-D3 cell differentiation assay of the embryonic stem cell test, and compares the outcomes with their relative potencies in in vivo and two other in vitro assays for developmental toxicity. The results reveal that the potency ranking obtained in the ES-D3 cell differentiation assay is similar to the reported potency rankings in the two other in vitro assays for developmental toxicity. TTNPB ((E)-4[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid) was the most potent retinoid, whereas etretinate and retinol had the lowest potency. All- trans-retinoic acid, 13- cis-retinoic acid, 9- cis-retinoic acid and acitretin showed an intermediate potency. In vivo potency rankings of the developmental toxicity of retinoids appear to be dependent on the species and/or exposure regimens used. The obtained in vitro potency ranking does not completely correspond with the in vivo potency rankings, although TTNPB is correctly predicted to be the most potent and retinol the least potent congener. The lack of in vivo kinetic processes in the ES-D3 cell differentiation assay might explain the deviating potency predictions of some retinoids. Therefore, knowledge on the species-dependent in vivo kinetics is essential when using in vitro toxicity data for the estimation of in vivo developmental toxicity potencies within series of related compounds. © 2011 Elsevier Ireland Ltd.
Subject
Life
PHS - Pharmacokinetics & Human Studies
EELS - Earth, Environmental and Life Sciences
Pharmacology
Benchmark dose
Developmental toxicity
Embryonic stem cell test
Embryotoxicity
In vitro
Retinoids
To reference this document use:
http://resolver.tudelft.nl/uuid:143912e6-b146-4b1d-a0b7-798e4295fec6
DOI
https://doi.org/10.1016/j.toxlet.2011.02.01
TNO identifier
429279
ISSN
0378-4274
Source
Toxicology Letters, 203 (1), 1-8
Document type
article