PMID- 15788727
OWN - NLM
STAT- MEDLINE
DCOM- 20050818
LR  - 20121115
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 85
IP  - 2
DP  - 2005 Jun
TI  - Perinatal exposure to the fungicide prochloraz feminizes the male rat offspring.
PG  - 886-97
AB  - Prochloraz is a commonly used fungicide that has shown multiple mechanisms of 
      action in vitro. It antagonizes the androgen and the estrogen receptors, agonizes 
      the Ah receptor, and inhibits aromatase activity. In vivo prochloraz acts 
      antiandrogenically in the Hershberger assay by reducing weights of reproductive 
      organs, affecting androgen-regulated gene expressions, and increasing luteinizing 
      hormone (LH) levels. The purpose of this study was to investigate reproductive 
      toxic effects after exposure during gestation and lactation to prochloraz alone 
      and a mixture of five pesticides (deltamethrin, methiocarb, prochloraz, simazine, 
      and tribenuron-methyl). Prochloraz (30 mg/kg/day) or the mixture (20 mg/kg/day) 
      was dosed to pregnant Wistar dams from gestational day (GD) 7 until postnatal day 
      (PND) 16. Some dams were taken for cesarean section at GD 21, and others were 
      allowed to give birth. Results showed that prochloraz and the mixture 
      significantly reduced plasma and testicular testosterone levels in GD 21 male 
      fetuses, whereas testicular progesterone was increased. Gestational length was 
      increased by prochloraz. Chemical analysis of the rat breast milk showed that 
      prochloraz was transferred to the milk. In males a significant increase of nipple 
      retention was found, and the bulbourethral gland weight was decreased, whereas 
      other reproductive organs were unaffected. In addition cytochrome P450 (CYP)1A 
      activities in livers were induced by prochloraz, possibly as a result of Ah 
      receptor activation. Behavioral studies showed that the activity level and sweet 
      preference of adult males were significantly increased. Overall these results 
      strongly indicate that prochloraz feminizes the male offspring after perinatal 
      exposure, and that these effects are due, at least in part, to diminished fetal 
      steroidogenesis.
FAU - Vinggaard, Anne Marie
AU  - Vinggaard AM
AD  - Department of Toxicology and Risk Assessment, Danish Institute for Food and 
      Veterinary Research, DK-2860 Soborg, Denmark. amv@dfvf.dk
FAU - Christiansen, Sofie
AU  - Christiansen S
FAU - Laier, Peter
AU  - Laier P
FAU - Poulsen, Mette Erecius
AU  - Poulsen ME
FAU - Breinholt, Vibeke
AU  - Breinholt V
FAU - Jarfelt, Kirsten
AU  - Jarfelt K
FAU - Jacobsen, Helene
AU  - Jacobsen H
FAU - Dalgaard, Majken
AU  - Dalgaard M
FAU - Nellemann, Christine
AU  - Nellemann C
FAU - Hass, Ulla
AU  - Hass U
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050323
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Fungicides, Industrial)
RN  - 0 (Gonadal Steroid Hormones)
RN  - 0 (Imidazoles)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - 99SFL01YCL (prochloraz)
SB  - IM
MH  - Animals
MH  - Animals, Newborn/*physiology
MH  - Behavior, Animal/drug effects
MH  - Cesarean Section
MH  - Cytochrome P-450 Enzyme System/metabolism
MH  - Female
MH  - Feminization/*chemically induced
MH  - Food Preferences/drug effects
MH  - Fungicides, Industrial/*toxicity
MH  - Genitalia, Male/drug effects/growth & development
MH  - Gonadal Steroid Hormones/blood
MH  - Habituation, Psychophysiologic/drug effects
MH  - Imidazoles/*toxicity
MH  - Male
MH  - Maze Learning/drug effects
MH  - Milk/chemistry
MH  - Motor Activity/drug effects
MH  - Nipples/drug effects/growth & development
MH  - Organ Size/drug effects
MH  - Play and Playthings
MH  - Rats
MH  - Rats, Wistar
MH  - Semen/cytology/drug effects
MH  - Sexual Maturation/drug effects
MH  - Taste/drug effects
EDAT- 2005/03/25 09:00
MHDA- 2005/08/19 09:00
CRDT- 2005/03/25 09:00
PHST- 2005/03/25 09:00 [pubmed]
PHST- 2005/08/19 09:00 [medline]
PHST- 2005/03/25 09:00 [entrez]
AID - kfi150 [pii]
AID - 10.1093/toxsci/kfi150 [doi]
PST - ppublish
SO  - Toxicol Sci. 2005 Jun;85(2):886-97. doi: 10.1093/toxsci/kfi150. Epub 2005 Mar 23.