PMID- 24798384
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20211021
IS  - 1096-0929 (Electronic)
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 140
IP  - 2
DP  - 2014 Aug 1
TI  - A short-term in vivo screen using fetal testosterone production, a key event in 
      the phthalate adverse outcome pathway, to predict disruption of sexual 
      differentiation.
PG  - 403-24
LID - 10.1093/toxsci/kfu081 [doi]
AB  - This study was designed to develop and validate a short-term in vivo protocol 
      termed the Fetal Phthalate Screen (FPS) to detect phthalate esters (PEs) and 
      other chemicals that disrupt fetal testosterone synthesis and testis gene 
      expression in rats. We propose that the FPS can be used to screen chemicals that 
      produce adverse developmental outcomes via disruption of the androgen synthesis 
      pathway more rapidly and efficiently, and with fewer animals than a postnatal 
      one-generation study. Pregnant rats were dosed from gestational day (GD) 14 to 18 
      at one dose level with one of 27 chemicals including PEs, PE alternatives, 
      pesticides known to inhibit steroidogenesis, an estrogen and a potent PPARalpha 
      agonist and ex vivo testis testosterone production (T Prod) was measured on GD 
      18. We also included some chemicals with "unknown" activity including DMEP, DHeP, 
      DHEH, DPHCH, DAP, TOTM, tetrabromo-diethyl hexyl phthalate (BrDEHP), and a 
      relatively potent environmental estrogen BPAF. Dose-response studies also were 
      conducted with this protocol with 11 of the above chemicals to determine their 
      relative potencies. CD-1 mice also were exposed to varying dose levels of DPeP 
      from GD 13 to 17 to determine if DPeP reduced T Prod in this species since there 
      is a discrepancy among the results of in utero studies of PEs in mice. Compared 
      to the known male reproductive effects of the PEs in rats the FPS correctly 
      identified all known "positives" and "negatives" tested. Seven of eight 
      "unknowns" tested were "negatives", they did not reduce T Prod, whereas DAP 
      produced an "equivocal" response. Finally, a dose-response study with DPeP in 
      CD-1 mice revealed that fetal T Prod can be inhibited by exposure to a PE in 
      utero in this species, but at a higher dose level than required in rats.Key 
      words. Phthalate Syndrome, Fetal endocrine biomarkers, Phthalate adverse outcome 
      pathway, testosterone production, fetal rat testis.
CI  - Published by Oxford University Press on behalf of Toxicological Sciences 2014. 
      This work is written by (a) US Government employee(s) and is in the public domain 
      in the US.
FAU - Furr, Johnathan R
AU  - Furr JR
AD  - Reproductive Toxicology Branch, TAD, NHEERL, ORD, USEPA, Research Triangle Park, 
      NC, 27711 gray.ear@epa.gov.
FAU - Lambright, Christy S
AU  - Lambright CS
AD  - Reproductive Toxicology Branch, TAD, NHEERL, ORD, USEPA, Research Triangle Park, 
      NC, 27711 gray.ear@epa.gov.
FAU - Wilson, Vickie S
AU  - Wilson VS
AD  - Reproductive Toxicology Branch, TAD, NHEERL, ORD, USEPA, Research Triangle Park, 
      NC, 27711.
FAU - Foster, Paul M
AU  - Foster PM
AD  - National Toxicology Program, NIEHS, NIH, DHHS, Research Triangle Park, North 
      Carolina 27709.
FAU - Gray, Leon E Jr
AU  - Gray LE Jr
AD  - Reproductive Toxicology Branch, TAD, NHEERL, ORD, USEPA, Research Triangle Park, 
      NC, 27711 gray.ear@epa.gov.
LA  - eng
GR  - RW7592285501-1/PHS HHS/United States
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20140505
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Phthalic Acids)
RN  - 3XMK78S47O (Testosterone)
SB  - IM
MH  - Animals
MH  - Female
MH  - Fetus/*metabolism
MH  - Phthalic Acids/*adverse effects
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Sex Differentiation
MH  - Testosterone/*biosynthesis
PMC - PMC4471440
OTO - NOTNLM
OT  - Fetal endocrine biomarkers
OT  - Phthalate Syndrome
OT  - Phthalate adverse outcome pathway
OT  - fetal rat testis
OT  - testosterone production
EDAT- 2014/05/07 06:00
MHDA- 2015/03/31 06:00
PMCR- 2015/08/01
CRDT- 2014/05/07 06:00
PHST- 2014/05/07 06:00 [entrez]
PHST- 2014/05/07 06:00 [pubmed]
PHST- 2015/03/31 06:00 [medline]
PHST- 2015/08/01 00:00 [pmc-release]
AID - kfu081 [pii]
AID - 10.1093/toxsci/kfu081 [doi]
PST - ppublish
SO  - Toxicol Sci. 2014 Aug 1;140(2):403-24. doi: 10.1093/toxsci/kfu081. Epub 2014 May 
      5.