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In vitro and in vivo endocrine disrupting effects of the azole fungicides triticonazole and flusilazole.

Authors
  • Draskau, Monica Kam1
  • Boberg, Julie1
  • Taxvig, Camilla1
  • Pedersen, Mikael2
  • Frandsen, Henrik Lauritz2
  • Christiansen, Sofie1
  • Svingen, Terje3
  • 1 Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, Kemitorvet Building 202, Kongens Lyngby, DK-2800, Denmark. , (Denmark)
  • 2 Research Group for Analytical Food Chemistry, National Food Institute, Technical University of Denmark, Kemitorvet Building 202, Kongens Lyngby, DK-2800, Denmark. , (Denmark)
  • 3 Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, Kemitorvet Building 202, Kongens Lyngby, DK-2800, Denmark. Electronic address: [email protected] , (Denmark)
Type
Published Article
Journal
Environmental pollution (Barking, Essex : 1987)
Publication Date
Oct 03, 2019
Volume
255
Issue
Pt 2
Pages
113309–113309
Identifiers
DOI: 10.1016/j.envpol.2019.113309
PMID: 31610510
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Azoles are effective antifungal agents used in both medicine and agriculture. They typically work by inhibiting cytochrome P450 enzymes, primarily CYP51 of the ergosterol biosynthesis pathway, thus damaging the fungal cell membrane. However, apart from their desired antifungal properties, several azoles also exhibit endocrine disrupting properties in mammals, both in vitro and in vivo. Here, we have tested two currently used agricultural azole fungicides, triticonazole and flusilazole, for their in vitro anti-androgenic activity and potential effects on reproductive parameters. Both fungicides showed strong androgen receptor (AR) antagonism and disruption of steroid biosynthesis in vitro. Following gestational exposure to flusilazole (15 or 45 mg/kg bw/day) or triticonazole (150 or 450 mg/kg bw/day) in time-mated Sprague Dawley rats, triticonazole induced shorter male anogenital distance (AGD). Flusilazole exposure did not affect the AGD, but altered fetal male blood hormone profile, with increased androstenedione and decreased estrone levels. Flusilazole and triticonazole have dissimilar effects on reproductive parameters in vivo, but both show endocrine disrupting activities. Copyright © 2019 Elsevier Ltd. All rights reserved.

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