PMID- 17785682
OWN - NLM
STAT- MEDLINE
DCOM- 20071220
LR  - 20171116
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 100
IP  - 2
DP  - 2007 Dec
TI  - Endocrine-disrupting activities in vivo of the fungicides tebuconazole and 
      epoxiconazole.
PG  - 464-73
AB  - The triazole fungicides tebuconazole and epoxiconazole were investigated for 
      reproductive toxic effects after exposure during gestation and lactation. Rats 
      were dosed with epoxiconazole (15 or 50 mg/kg bw/day) or tebuconazole (50 or 100 
      mg/kg bw/day) during pregnancy from gestational day (GD) 7 and continued during 
      lactation until postnatal day (PND) 16. Some dams were randomly chosen for 
      cesarean section at GD 21 to evaluate effects on sexual differentiation in the 
      fetuses. Other dams delivered normally, and the pups were examined (e.g., 
      anogenital distance [AGD] and hormone levels) at birth, at PND 13 or PND 16, and 
      semen quality was assessed in adults. Both tebuconazole and epoxiconazole 
      affected reproductive development in the offspring after exposure in utero. Both 
      compounds virilized the female offspring as shown by an increased AGD PND 0. 
      Furthermore, tebuconazole had a feminizing effect on male offspring as shown by 
      increased nipple retention. This effect was likely caused by the reduced 
      testosterone levels seen in male fetuses. Tebuconazole increased the testicular 
      concentrations of progesterone and 17alpha-hydroxyprogesterone in male fetuses, 
      indicating a direct impact on the steroid synthesis pathway in the Leydig cells. 
      The high dose of epoxiconazole had marked fetotoxic effects, while the lower dose 
      caused increased birth weights. The increased birth weights may be explained by a 
      marked increase in testosterone levels in dams during gestation. Common features 
      for azole fungicides are that they increase gestational length, virilize female 
      pups, and affect steroid hormone levels in fetuses and/or dams. These effects 
      strongly indicate that one major underlying mechanism for the 
      endocrine-disrupting effects of azole fungicides is disturbance of key enzymes 
      like CYP17 involved in the synthesis of steroid hormones.
FAU - Taxvig, Camilla
AU  - Taxvig C
AD  - Department of Toxicology and Risk Assessment, National Food Institute, Technical 
      University of Denmark, Morkhoj Bygade 19, DK-2860, Soborg, Denmark.
FAU - Hass, Ulla
AU  - Hass U
FAU - Axelstad, Marta
AU  - Axelstad M
FAU - Dalgaard, Majken
AU  - Dalgaard M
FAU - Boberg, Julie
AU  - Boberg J
FAU - Andeasen, Helle Raun
AU  - Andeasen HR
FAU - Vinggaard, Anne Marie
AU  - Vinggaard AM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070904
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Endocrine Disruptors)
RN  - 0 (Epoxy Compounds)
RN  - 0 (Fungicides, Industrial)
RN  - 0 (Triazoles)
RN  - 3XMK78S47O (Testosterone)
RN  - 401ATW8TRW (tebuconazole)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 68-96-2 (17-alpha-Hydroxyprogesterone)
RN  - U80T84L776 (epoxiconazole)
SB  - IM
MH  - 17-alpha-Hydroxyprogesterone
MH  - Abnormalities, Drug-Induced/*etiology
MH  - Animals
MH  - Birth Weight/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Endocrine Disruptors/*toxicity
MH  - Epoxy Compounds/*toxicity
MH  - Female
MH  - Fungicides, Industrial/*toxicity
MH  - Genitalia, Female/abnormalities/drug effects
MH  - Lactation/drug effects
MH  - Male
MH  - Maternal Exposure
MH  - Nipples/drug effects/embryology/growth & development
MH  - Organ Size/drug effects
MH  - Pregnancy
MH  - Progesterone
MH  - Rats
MH  - Rats, Wistar
MH  - Reproduction/*drug effects
MH  - Sperm Count
MH  - Sperm Motility/drug effects
MH  - Spermatozoa/drug effects/physiology
MH  - Testis/drug effects/metabolism/pathology
MH  - Testosterone
MH  - Triazoles/*toxicity
EDAT- 2007/09/06 09:00
MHDA- 2007/12/21 09:00
CRDT- 2007/09/06 09:00
PHST- 2007/09/06 09:00 [pubmed]
PHST- 2007/12/21 09:00 [medline]
PHST- 2007/09/06 09:00 [entrez]
AID - kfm227 [pii]
AID - 10.1093/toxsci/kfm227 [doi]
PST - ppublish
SO  - Toxicol Sci. 2007 Dec;100(2):464-73. doi: 10.1093/toxsci/kfm227. Epub 2007 Sep 4.