PMID- 22659317
OWN - NLM
STAT- MEDLINE
DCOM- 20120921
LR  - 20211021
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 300
IP  - 1-2
DP  - 2012 Oct 9
TI  - Developmental triclosan exposure decreases maternal, fetal, and early neonatal 
      thyroxine: a dynamic and kinetic evaluation of a putative mode-of-action.
PG  - 31-45
LID - 10.1016/j.tox.2012.05.023 [doi]
AB  - This work tests the mode-of-action (MOA) hypothesis that maternal and 
      developmental triclosan (TCS) exposure decreases circulating thyroxine (T4) 
      concentrations via up-regulation of hepatic catabolism and elimination of T4. 
      Time-pregnant Long-Evans rats received TCS po (0-300mg/kg/day) from gestational 
      day (GD) 6 through postnatal day (PND) 21. Serum and liver were collected from 
      dams (GD20, PND22) and offspring (GD20, PND4, PND14, PND21). Serum T4, 
      triiodothyronine (T3), and thyroid-stimulating hormone (TSH) concentrations were 
      measured by radioimmunoassay. Ethoxy-O-deethylase (EROD), 
      pentoxyresorufin-O-depentylase (PROD) and uridine diphosphate 
      glucuronyltransferase (UGT) enzyme activities were measured in liver microsomes. 
      Custom Taqman((R)) qPCR arrays were employed to measure hepatic mRNA expression of 
      select cytochrome P450s, UGTs, sulfotransferases, transporters, and thyroid 
      hormone-responsive genes. TCS was quantified by LC/MS/MS in serum and liver. 
      Serum T4 decreased approximately 30% in GD20 dams and fetuses, PND4 pups and 
      PND22 dams (300mg/kg/day). Hepatic PROD activity increased 2-3 fold in PND4 pups 
      and PND22 dams, and UGT activity was 1.5 fold higher in PND22 dams only 
      (300mg/kg/day). Minor up-regulation of Cyp2b and Cyp3a expression in dams was 
      consistent with hypothesized activation of the constitutive androstane and/or 
      pregnane X receptor. T4 reductions of 30% for dams and GD20 and PND4 offspring 
      with concomitant increases in PROD (PND4 neonates and PND22 dams) and UGT 
      activity (PND22 dams) suggest that up-regulated hepatic catabolism may contribute 
      to TCS-induced hypothyroxinemia during development. Serum and liver TCS 
      concentrations demonstrated greater fetal than postnatal internal exposure, 
      consistent with the lack of T4 changes in PND14 and PND21 offspring. These data 
      support the MOA hypothesis that TCS exposure leads to hypothyroxinemia via 
      increased hepatic catabolism; however, the minor effects on thyroid hormone 
      metabolism may reflect the low efficacy of TCS as thyroid hormone disruptor or 
      highlight the possibility that other MOAs may also contribute to the observed 
      maternal and early neonatal hypothyroxinemia.
CI  - Published by Elsevier Ireland Ltd.
FAU - Paul, Katie B
AU  - Paul KB
AD  - University of North Carolina at Chapel Hill, Curriculum in Toxicology, CB 7270, 
      Chapel Hill, NC 27599, USA.
FAU - Hedge, Joan M
AU  - Hedge JM
FAU - Bansal, Ruby
AU  - Bansal R
FAU - Zoeller, R Thomas
AU  - Zoeller RT
FAU - Peter, Robert
AU  - Peter R
FAU - DeVito, Michael J
AU  - DeVito MJ
FAU - Crofton, Kevin M
AU  - Crofton KM
LA  - eng
GR  - R01 ES010026/ES/NIEHS NIH HHS/United States
GR  - T32 ES007126/ES/NIEHS NIH HHS/United States
GR  - T32-ES07126/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20120601
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 06LU7C9H1V (Triiodothyronine)
RN  - 4NM5039Y5X (Triclosan)
RN  - 9002-71-5 (Thyrotropin)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2B1)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
RN  - Q51BO43MG4 (Thyroxine)
SB  - IM
MH  - Animals
MH  - Animals, Newborn/blood/metabolism
MH  - Cytochrome P-450 CYP1A1/drug effects/metabolism
MH  - Cytochrome P-450 CYP2B1/drug effects/metabolism
MH  - Female
MH  - Fetus/chemistry/drug effects
MH  - Glucuronosyltransferase/drug effects/metabolism
MH  - Liver/drug effects/enzymology
MH  - Pregnancy
MH  - Radioimmunoassay
MH  - Rats
MH  - Rats, Long-Evans
MH  - Thyrotropin/blood
MH  - Thyroxine/*antagonists & inhibitors/blood
MH  - Triclosan/*adverse effects/analysis/blood
MH  - Triiodothyronine/blood
PMC - PMC3400151
MID - NIHMS390045
COIS- 9. Conflict of Interest The authors declare that there are no conflicts of 
      interest.
EDAT- 2012/06/05 06:00
MHDA- 2012/09/22 06:00
PMCR- 2013/10/09
CRDT- 2012/06/05 06:00
PHST- 2012/01/12 00:00 [received]
PHST- 2012/05/11 00:00 [revised]
PHST- 2012/05/22 00:00 [accepted]
PHST- 2012/06/05 06:00 [entrez]
PHST- 2012/06/05 06:00 [pubmed]
PHST- 2012/09/22 06:00 [medline]
PHST- 2013/10/09 00:00 [pmc-release]
AID - S0300-483X(12)00179-5 [pii]
AID - 10.1016/j.tox.2012.05.023 [doi]
PST - ppublish
SO  - Toxicology. 2012 Oct 9;300(1-2):31-45. doi: 10.1016/j.tox.2012.05.023. Epub 2012 
      Jun 1.