Journal article
Mixture effects of endocrine disrupting compounds in vitro
Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark1
National Food Institute, Technical University of Denmark2
Environmental Chemistry, Department of Environmental Engineering, Technical University of Denmark3
Department of Environmental Engineering, Technical University of Denmark4
P>Four different equi-molar mixtures were investigated for additive endocrine disrupting effects in vitro using the concentration addition model. It was found that additive effects on the same molecular target (the androgen receptor; AR) can be predicted for both mixtures of compounds with effect on the AR (flutamide, procymidone and vinclozolin) and of compounds with and without effects on the AR [finasteride, mono-(2-ethylhexyl) phthalate, prochloraz and vinclozolin].
For a paraben mixture (methyl paraben, ethyl paraben, propyl paraben, butyl paraben and iso-butyl paraben) antagonistic effect on AR could not be predicted under assumption of additivity in our model system. For a mixture containing three azole fungicides (epoxiconazole, propiconazole and tebuconazole), the observed AR antagonistic effects were close to the predicted effect assuming additivity.
Azole fungicides are known inhibitors of androgen biosynthesis and in the steroid synthesis assay using H295R cells, the inhibition of testosterone production was close to additive, whereas the inhibition of oestradiol production was over-estimated for the mixture of azole fungicides, when compared with the effect predicted when assuming additivity.
Overall these and other studies show that weak endocrine disrupting compounds, like parabens and azole fungicides, give rise to combination effects when they occur in mixtures. These combination effects should be taken into account in regulatory risk assessment not to under-estimate the risks for adverse effects associated with exposure to disrupting chemicals.
Language: | English |
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Year: | 2010 |
Pages: | 425-433 |
ISSN: | 13652605 , 01056263 and 01061607 |
Types: | Journal article |
DOI: | 10.1111/j.1365-2605.2009.01034.x |
ORCIDs: | Taxvig, Camilla and Nellemann, Christine Lydia |
Androgen Antagonists Animals Bridged Bicyclo Compounds CHO Cells Cell Line, Tumor Cricetinae Cricetulus Drug Combinations Endocrine Disruptors Estradiol Flutamide Fungicides, Industrial Genes, Reporter Humans Oxazoles Parabens Receptors, Androgen Testosterone Triazoles procymidone propiconazole tebuconazole vinclozolin