In vitro and in vivo screening of azole fungicides for antiandrogenic effects

Research output: Contribution to conferencePosterResearch

Abstract

In general, azole fungicides have a low acute toxicity, but we have only little knowledge about their potential health risks at low chronic exposures. Previously we have shown that prochloraz has multiple potential mechanisms of action in cell-based assays, and prochloraz possessed antiestrogenic and antiandrogenic effects both in vitro and in vivo. Two other 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 an AR reporter gene assay. The compounds were also analyzed for effects on steroidogenesis in H295R cells, a human adrenocorticocarcinoma cell line, used to detect effects on steroid production. In vitro tebuconazole and epoxiconazole proved to be antagonists of the AR, and in the H295R cell assay, they were able to inhibit testosterone and estradiol levels, and increase progesterone levels. In an in vivo study, designed to test for developmental effects on rat offspring after prenatal exposure, the effects on hormone levels in male fetuses and morphological signs of feminization of the male offspring were investigated. Tebuconazole caused an increase in testicular 17alfa-hydroxyprogesterone and progesterone levels, and a decrease in testosterone levels in male fetuses. Epoxiconazole had no effect on any of the mesured hormonelevels. Furthermore, tebuconazole increased the AGD in female pups and resulted in an increased number of nipples in male pups, a tendency that was also seen for epoxiconazole, though it was not statistically significant. In conclusion the results obtained in vitro are 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 dominating effect observed in vivo was a high frequency of stillbirths at the highest dose.
Original languageEnglish
Publication date2007
Publication statusPublished - 2007
Event4th Copenhagen Workshop on Endocrine Disrupters - Copenhagen University Hospital, Copenhagen, Denmark
Duration: 28 May 200731 May 2007
Conference number: 4
http://www.reproduction.dk/index-filer/Page304.htm

Workshop

Workshop4th Copenhagen Workshop on Endocrine Disrupters
Number4
LocationCopenhagen University Hospital
CountryDenmark
CityCopenhagen
Period28/05/200731/05/2007
Internet address

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