In general, azole fungicides have a low acute toxicity but little is known about their potential health risks at low chronic exposures. We have recently shown that prochloraz has multiple potential mechanisms of action, including interaction with the estrogen and androgen receptors, in cell-based assays. In vitro prochloraz proved to be an activator of the aryl hydrocarbon receptor (AhR), to inhibit aromatase activity and to possess antiestrogenic and antiandrogenic effects both in vitro and in vivo. Another two azole fungicides, tebuconazole and epoxiconazole, have now been investigated for antiandrogenic effects in vitro and in vivo as well. The fungicides were screened in two well-established cell assays, including testing for agonistic and antagonistic effects on AR in transfected CHO cells, using the AR reporter gene assay. Secondly the compounds were analyzed for effects on steroidogenesis in H295R cells, a cell line, which produces a wide range of steroid hormones in measurable quantities, including testosterone, progesterone and estradiol, a property that makes it suitable as a screening assay to detect effects on steroidogenesis. In the in vitro tebuconazole and epoxiconazole showed antiandrogenic effects, and in the H295R cell assay, tebuconazole and epoxiconazole were like prochloraz able to inhibit testosterone and estradiol levels and increase progesterone levels. For the in vivo testing, a study was conducted testing the developmental effects on offspring after prenatal exposure, by looking at endpoints like hormone levels in male fetuses and sign of feminazation of the male offspring. In vivo tebuconazole had an increasing effect on the testicular level of 17alpha-hydroxyprogesterone and progesterone, a decreasing effect on the level of testosterone, but no effect on testicular testosterone and progesterone production. Epoxiconazole showed now effect. Furthermore tebuconazole increased the AGD in female pups and resulted in an increased number of nipples in male pups at PND 13, a tendency that was also seen for epoxiconazole, though it was not significant. In conclusion the results obtained in vitro is in good agreement with the effects observed in vivo. Tebuconazole showed antiandrogenic effects both in vitro and in vivo. Antiandrogenic effects were also seen for epoxiconazole in vitro, however the observed effects in vivo was not quite what might be predicted from the in vitro experiments, which can be due to the fact, that in vitro generally is more sensitive than in vivo.
|Publication status||Published - 2006|
|Event||"Reaching the young scientist” eSI-Workshop (ecopa) - Alicante, Spain|
Duration: 29 Sep 2006 → 30 Sep 2006
|Conference||"Reaching the young scientist” eSI-Workshop (ecopa)|
|Period||29/09/2006 → 30/09/2006|