Vinggaard, Anne3; Breinholt, Vibeke4; Larsen, John Christian1
1 National Food Institute, Technical University of Denmark2 Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark3 Copenhagen Center for Health Technology, Center, Technical University of Denmark4 Technical University of Denmark
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 mu M 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 oil 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 nor 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 rite 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 nas estimated to be 13 mu M in the yeast cells, compared with an EC50 of 3 mu M 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 Mie 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.
Food Additives and Contaminants, 1999, Vol 16, Issue 12, p. 533-542