PMID- 19463926
OWN - NLM
STAT- MEDLINE
DCOM- 20090714
LR  - 20131121
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 189
IP  - 1
DP  - 2009 Aug 25
TI  - Effects of plasticizers and their mixtures on estrogen receptor and thyroid 
      hormone functions.
PG  - 67-77
LID - 10.1016/j.toxlet.2009.05.004 [doi]
AB  - Plasticizers are additives used to increase the flexibility or plasticity of the 
      material to which they are added, normally rigid plastic and as additives in 
      paint and adhesives. They are suspected to interfere with the endocrine system, 
      including the estrogen and the thyroid hormone (TH) systems. We investigated in 
      vitro the thyroid hormone-like and estrogenic activities of a range of widely 
      used plasticizers and phenols including benzyl butyl phthalate (BBP), dibutyl 
      phthalate (DBP), dioctyl phthalate (DOP), diisodecyl phthalate (DIDP), diisononyl 
      phthalate (DINP), di(2-ethylhexyl) phthalate (DEHP), bis(2-ethylhexyl) adipate 
      (DEHA), 4-tert-octylphenol (tOP), 4-chloro-3-methylphenol (CMP), 
      2,4-dichlorophenol (2,4-DCP), 2-phenylphenol (2-PP) and resorcinol. The TH 
      disrupting potential was determined by the effect on the TH-dependent rat 
      pituitary GH3 cell proliferation (T-screen). The estrogenic activities of the 
      compounds were assessed in MVLN cells, stably transfected with an estrogen 
      receptor (ER) luciferase reporter vector. Furthermore, the combined effect of a 
      multi-components mixture of six plasticizers was evaluated for its estrogenic and 
      TH-like activities. All the tested compounds, but 2-PP, significantly affected 
      the GH3 cell proliferation. tOP, BBP and DBP activated ER transactivity, whereas 
      DEHP antagonized the 17beta-estradiol induced ER function. The mixture 
      significantly induced ER transactivity in an additive manner, whereas in the 
      T-screen, the observed mixture effect was lower than predicted, suggesting a 
      potential antagonizing effect of the mixture. In conclusion, the tested 
      plasticizers and phenols elicited endocrine-disrupting potential that can be 
      mediated via interference with the estrogen and TH systems. Moreover, the 
      observed mixture effect stresses the importance of considering the combined 
      effect of the compounds for risk assessment of human health.
FAU - Ghisari, Mandana
AU  - Ghisari M
AD  - Unit of Cellular and Molecular Toxicology, Center of Arctic Medicine, Department 
      of Environmental and Occupational Medicine, Institute of Public Health, 
      University of Aarhus, Bartholins alle 2, Build. 1260, Aarhus C DK-8000, Denmark.
FAU - Bonefeld-Jorgensen, Eva Cecilie
AU  - Bonefeld-Jorgensen EC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090520
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Complex Mixtures)
RN  - 0 (Endocrine Disruptors)
RN  - 0 (Plasticizers)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 06LU7C9H1V (Triiodothyronine)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Complex Mixtures/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Endocrine Disruptors/chemistry/*toxicity
MH  - Estradiol/pharmacology
MH  - Humans
MH  - Molecular Structure
MH  - Plasticizers/chemistry/*toxicity
MH  - Rats
MH  - Receptors, Estrogen/biosynthesis/genetics/*physiology
MH  - Receptors, Thyroid Hormone/biosynthesis/*physiology
MH  - Structure-Activity Relationship
MH  - Transcriptional Activation/drug effects
MH  - Triiodothyronine/pharmacology
EDAT- 2009/05/26 09:00
MHDA- 2009/07/15 09:00
CRDT- 2009/05/26 09:00
PHST- 2009/03/05 00:00 [received]
PHST- 2009/05/06 00:00 [revised]
PHST- 2009/05/08 00:00 [accepted]
PHST- 2009/05/26 09:00 [entrez]
PHST- 2009/05/26 09:00 [pubmed]
PHST- 2009/07/15 09:00 [medline]
AID - S0378-4274(09)00253-7 [pii]
AID - 10.1016/j.toxlet.2009.05.004 [doi]
PST - ppublish
SO  - Toxicol Lett. 2009 Aug 25;189(1):67-77. doi: 10.1016/j.toxlet.2009.05.004. Epub 
      2009 May 20.