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Screening of selected pesticides for oestrogen receptor activation in vitro.

Twenty pesticides were tested for their ability to activate the oestrogen receptor in vitro using an MCF7 cell proliferation assay and a Yeast Oestrogen Screen. The fungicides fenarimol, triadimefon, and triadimenol were identified as weak oestrogen receptor agonists, which at 10 microM induces a 2.0, 2.4, and 1.9-fold increase in proliferation of human MCF7 breast cancer cells (E3 clone). The relative proliferation efficiency (RPE) was 43-69%, indicating partial agonism at the oestrogen receptor. Several pesticides did not have any effect on the proliferation response after 6 days of exposure, including: chlorpyrifos, diuron, iprodion, linuron, pentachlorphenol, prochloraz, propioconazol, propyzamine, quintozen, tetrachorvinphos and tetradifon. Some pesticides resulted in a negligible proliferation response, which was not statistically significant under the present experimental conditions. These were: bromopropylate, chlorfenvinphos, chlorobenzilate, dicofol, heptachlor, and imazalil. Fenarimol and dicofol also gave rise to a positive oestrogenic response in yeast cells transfected with the oestrogen receptor alpha, whereas the remaining compounds resulted in a negative response due either to biological inactivity or cytotoxocity to the yeast cells. The EC50 for fenarimol was estimated to be 13 microM in the yeast cells, compared with an EC50 of 3 microM in the MCF7 cells, indicating higher sensitivity of the latter assay. No in vivo data for fenarimol, triadimefon or triadimenol have previously been published that support oestrogenic activity in the intact animal. Thus, from the present results we suggest that oestrogen receptor activation may not be an important mode of action for these compounds. The need to include at least two bioassays in a screening procedure and for combining in vitro and in vivo data is emphasized.