The anticancer drug metabolites endoxifen and 4-hydroxy-tamoxifen induce toxic effects on Daphnia pulex in a two-generation study.

Details

Ressource 1Request a copy Sous embargo indéterminé.
State: Public
Version: Final published version
Serval ID
serval:BIB_67C40EF00BE6
Type
Article: article from journal or magazin.
Collection
Publications
Title
The anticancer drug metabolites endoxifen and 4-hydroxy-tamoxifen induce toxic effects on Daphnia pulex in a two-generation study.
Journal
Science of the Total Environment
Author(s)
Borgatta M., Decosterd L.A., Waridel P., Buclin T., Chèvre N.
ISSN
1879-1026 (Electronic)
ISSN-L
0048-9697
Publication state
Published
Issued date
2015
Volume
520
Pages
232-240
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Although pharmaceutical metabolites are found in the aquatic environment, their toxicity on living organisms is poorly studied in general. Endoxifen and 4-hydroxy-tamoxifen (4OHTam) are two metabolites of the widely used anticancer drug tamoxifen for the prevention and treatment of breast cancers. Both metabolites have a high pharmacological potency in vertebrates, attributing prodrug characteristics to tamoxifen. Tamoxifen and its metabolites are body-excreted by patients, and the parent compound is found in sewage treatment plan effluents and natural waters. The toxicity of these potent metabolites on non-target aquatic species is unknown, which forces environmental risk assessors to predict their toxicity on aquatic species using knowledge on the parent compounds. Therefore, the aim of this study was to assess the sensitivity of two generations of the freshwater microcrustacean Daphnia pulex towards 4OHTam and endoxifen. Two chronic tests of 4OHTam and endoxifen were run in parallel and several endpoints were assessed. The results show that the metabolites 4OHTam and endoxifen induced reproductive and survival effects. For both metabolites, the sensitivity of D. pulex increased in the second generation. The intrinsic rate of natural increase (r) decreased with increasing 4OHTam and endoxifen concentrations. The No-Observed Effect Concentrations (NOECs) calculated for the reproduction of the second generation exposed to 4OHTam and endoxifen were <1.8 and 4.3μg/L, respectively, whereas the NOECs that were calculated for the intrinsic rate of natural increase were <1.8 and 0.4μg/L, respectively. Our study raises questions about prodrug and active metabolites in environmental toxicology assessments of pharmaceuticals. Our findings also emphasize the importance of performing long-term experiments and considering multi-endpoints instead of the standard reproduction outcome.
Keywords
Tamoxifen metabolite, Prodrug, Two-generational study, Chronic effect, Measured concentration, Ecotoxicology
Pubmed
Web of science
Create date
18/05/2015 9:53
Last modification date
20/08/2019 15:23
Usage data