In vitro endocrine disruption potential of organophosphate flame retardants via human nuclear receptors.
Various organophosphate flame retardants (OPFRs) are widely used in building materials, textiles and electric appliances, and have been reported to cause indoor environmental pollution in houses and office buildings. In this study, using cell-based transactivation assays, we characterized the agonistic and/or antagonistic activities of 11 OPFRs against human nuclear receptors; estrogen receptor α (ERα), ERβ, androgen receptor (AR), glucocorticoid receptor (GR), thyroid hormone receptor α1 (TRα1), TRβ1, retinoic acid receptor α (RARα), retinoid X receptor α (RXRα), pregnane X receptor (PXR), peroxisome proliferator-activated receptor α (PPARα), and PPARγ. Of the 11 OPFRs tested, triphenyl phosphate (TPhP) and tricrecyl phosphate (TCP) showed ERα and/or ERβ agonistic activity. In addition, tributyl phosphate (TBP), tris(1,3-dichloro-2-propyl) phosphate (TDCPP), TPhP and TCP showed AR antagonistic activity, and TBP, tris(2-ethylhexyl) phosphate (TEHP), TDCPP, TPhP and TCP showed GR antagonistic activity. Furthermore, we found that seven compounds, TBP, tris(2-chloro-1-methylethyl) phosphate (TCPP), TEHP, tris(2-butoxyethyl) phosphate (TBEP), TDCPP, TPhP, and TCP, display PXR agonistic activity. However, none of test compounds showed agonistic or antagonistic activity against TRα/β, or agonistic activity against RARα, RXRα or PPARα/γ. Taken together, these results suggest that several OPFRs may have potential endocrine disrupting effects via ERα, ERβ, AR, GR and PXR.
Hokkaido Institute of Public Health, Kita-19, Nishi-12, Kita-ku, Sapporo 060-0819, Japan. Electronic address: kojima@iph.pref.hokkaido.jp.
Hiroyuki
H
Kojima
Shinji
S
Takeuchi
Toshihiro
T
Itoh
Mitsuru
M
Iida
Satoshi
S
Kobayashi
Takahiko
T
Yoshida
D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors; D005411:Flame Retardants / Q000633:toxicity*; D017930:Genes, Reporter / Q000187:drug effects; D006801:Humans; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010957:Plasmids / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects; D001616:beta-Galactosidase / Q000378:metabolism
D052244:Endocrine Disruptors; D005411:Flame Retardants; D009943:Organophosphorus Compounds; D018160:Receptors, Cytoplasmic and Nuclear; D001616:beta-Galactosidase
Flame retardant; Human; Nuclear receptor; Organophosphate; Reporter gene assay