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Citation
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HERO ID
1249821
Reference Type
Journal Article
Title
Antiandrogenic activity of phthalate mixtures: validity of concentration addition
Author(s)
Christen, V; Crettaz, P; Oberli-Schrämmli, A; Fent, K
Year
2012
Is Peer Reviewed?
1
Journal
Toxicology and Applied Pharmacology
ISSN:
0041-008X
EISSN:
1096-0333
Volume
259
Issue
2
Page Numbers
169-176
Language
English
PMID
22245847
DOI
10.1016/j.taap.2011.12.021
Web of Science Id
WOS:000301329800004
URL
http://www.sciencedirect.com/science/article/pii/S0041008X11004856
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Abstract
Phthalates and bisphenol A have very widespread use leading to significant exposure of humans. They are suspected to interfere with the endocrine system, including the androgen, estrogen and the thyroid hormone system. Here we analyzed the antiandrogenic activity of six binary, and one ternary mixture of phthalates exhibiting complete antiandrogenic dose-response curves, and binary mixtures of phthalates and bisphenol A at equi-effective concentrations of EC(10), EC(25) and EC(50) in MDA-kb2 cells. Mixture activity followed the concentration addition (CA) model with a tendency to synergism at high and antagonism at low concentrations. Isoboles and the toxic unit approach (TUA) confirmed the additive to synergistic activity of the binary mixtures BBP+DBP, DBP+DEP and DEP+BPA at high concentrations. Both methods indicate a tendency to antagonism for the EC(10) mixtures BBP+DBP, BBP+DEP and DBP+DEP, and the EC(25) mixture of DBP+BPA. A ternary mixture revealed synergism at the EC(50), and weak antagonistic activity at the EC(25) level by the TUA. A mixture of five phthalates representing a human urine composition and reflecting exposure to corresponding parent compounds showed no antiandrogenic activity. Our study demonstrates that CA is an appropriate concept to account for mixture effects of antiandrogenic phthalates and bisphenol A. The interaction indicates a departure from additivity to antagonism at low concentrations, probably due to interaction with the androgen receptor and/or cofactors. This study emphasizes that a risk assessment of phthalates should account for mixture effects by applying the CA concept.
Keywords
Phthalates; Benzylbutylphthalate (BBP); Dibutyl phthalate (DBP); Diethylphthalate (DEP); Dimethyl phthalate (DMP); Di-2-ethylhexyl phthalate (DEHP); Bisphenol A; Mixture activity; Antiandrogenicity; Concentration addition; Toxic unit approach; Isobole method
Tags
IRIS
•
BBP (Butyl benzyl phthalate)
Literature Search
LitSearch Dec 2012
PubMed
WOS
TSCATS
Excluded: No Primary Data on Health Effects
Mixtures only
•
Dibutyl Phthalate (DBP)
Database Searches
Pubmed
Web of Science
LitSearch Nov 2012
PubMed
WOS
Merged reference set
LitSearch Dec 2012 - June 2013
Web of Science
Excluded: No Primary Data on Health Effects
Mixtures only
•
Diethyl phthalate (DEP)
Database searches
Initial Litsearch
Web of Science
Merged reference set
Aug 2013 update
Web of Science
Jan 2020 update
PubMed
Web of Science
Excluded: No Primary Data on Health Effects
Mixtures only
•
Phthalates – Targeted Search for Epidemiological Studies
Source – all searches
Pubmed
WOS
Toxnet
Excluded
Source – no date limit through June 2013 (Private)
Pubmed
WOS
ToxNet
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