PMID- 11099646
OWN - NLM
STAT- MEDLINE
DCOM- 20010104
LR  - 20220330
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 58
IP  - 2
DP  - 2000 Dec
TI  - The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal 
      testosterone synthesis during sexual differentiation in the male rat.
PG  - 339-49
AB  - Phthalate esters (PE) such as DEHP are high production volume plasticizers used 
      in vinyl floors, food wraps, cosmetics, medical products, and toys. In spite of 
      their widespread and long-term use, most PE have not been adequately tested for 
      transgenerational reproductive toxicity. This is cause for concern, because 
      several recent investigations have shown that DEHP, BBP, DBP, and DINP disrupt 
      reproductive tract development of the male rat in an antiandrogenic manner. The 
      present study explored whether the antiandrogenic action of DEHP occurs by (1) 
      inhibiting testosterone (T) production, or by (2) inhibiting androgen action by 
      binding to the androgen receptor (AR). Maternal DEHP treatment at 750 mg/kg/day 
      from gestational day (GD) 14 to postnatal day (PND) 3 caused a reduction in T 
      production, and reduced testicular and whole-body T levels in fetal and neonatal 
      male rats from GD 17 to PND 2. As a consequence, anogenital distance (AGD) on PND 
      2 was reduced by 36% in exposed male, but not female, offspring. By GD 20, DEHP 
      treatment also reduced testis weight. Histopathological evaluations revealed that 
      testes in the DEHP treatment group displayed enhanced 3ss-HSD staining and 
      increased numbers of multifocal areas of Leydig cell hyperplasia as well as 
      multinucleated gonocytes as compared to controls at GD 20 and PND 3. In contrast 
      to the effects of DEHP on T levels in vivo, neither DEHP nor its metabolite MEHP 
      displayed affinity for the human androgen receptor at concentrations up to 10 
      microM in vitro. These data indicate that DEHP disrupts male rat sexual 
      differentiation by reducing T to female levels in the fetal male rat during a 
      critical stage of reproductive tract differentiation.
FAU - Parks, L G
AU  - Parks LG
AD  - Endocrinology Branch, MD-72, U.S. Environmental Protection Agency, National 
      Health and Environmental Effects Research Laboratory, Reproductive Toxicology 
      Division, Research Triangle Park, North Carolina 27711, USA. gray.earl@epa.gov
FAU - Ostby, J S
AU  - Ostby JS
FAU - Lambright, C R
AU  - Lambright CR
FAU - Abbott, B D
AU  - Abbott BD
FAU - Klinefelter, G R
AU  - Klinefelter GR
FAU - Barlow, N J
AU  - Barlow NJ
FAU - Gray, L E Jr
AU  - Gray LE Jr
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Plasticizers)
RN  - 3XMK78S47O (Testosterone)
RN  - C42K0PH13C (Diethylhexyl Phthalate)
SB  - IM
MH  - Abnormalities, Drug-Induced/*etiology
MH  - Animals
MH  - Body Weight/drug effects
MH  - Diethylhexyl Phthalate/*toxicity
MH  - Female
MH  - Genitalia, Male/*abnormalities
MH  - Leydig Cells/drug effects
MH  - Male
MH  - Plasticizers/*toxicity
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sex Differentiation/*drug effects
MH  - Testis/drug effects/metabolism/pathology
MH  - Testosterone/*biosynthesis
EDAT- 2000/12/02 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/12/02 11:00
PHST- 2000/12/02 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/12/02 11:00 [entrez]
AID - 10.1093/toxsci/58.2.339 [doi]
PST - ppublish
SO  - Toxicol Sci. 2000 Dec;58(2):339-49. doi: 10.1093/toxsci/58.2.339.