Relationship between the results of in vitro receptor binding assay to human estrogen receptor alpha and in vivo uterotrophic assay: Comparative study with 65 selected chemicals

Akahori, Y; Nakai, M; Yamasaki, K; Takatsuki, M; Shimohigashi, Y; Ohtaki, M

HERO ID

679721

Reference Type

Journal Article

Year

2008

Language

English

PMID

17904329

HERO ID 679721
In Press No
Year 2008
Title Relationship between the results of in vitro receptor binding assay to human estrogen receptor alpha and in vivo uterotrophic assay: Comparative study with 65 selected chemicals
Authors Akahori, Y; Nakai, M; Yamasaki, K; Takatsuki, M; Shimohigashi, Y; Ohtaki, M
Journal Toxicology In Vitro
Volume 22
Issue 1
Page Numbers 225-231
Abstract For screening chemicals possessing endocrine disrupting potencies, the uterotrophic assay has been placed in a higher level in the OECD testing framework than the ER binding assay to detect ER-mediated activities. However, there are no studies that can demonstrate a clear relationship between these assays. In order to clarify the relationship between the in vitro ER binding and in vivo uterotrophic assays and to determine meaningful binding potency from the ER binding assay, we compared the results from these assays for 65 chemicals spanning a variety of chemicals classes. Under the quantitative comparison between logRBAs (relative binding affinities) and logLEDs (lowest effective doses), the log RBA was well correlated with both logLEDs of estrogenic and anti-estrogenic compounds at r(2)=0.67 (n=28) and 0.79 (n=23), respectively. The RBA of 0.00233% was found to be the lowest ER binding potency to elicit estrogenic or anti-estrogenic activities in the uterotrophic assay, accordingly this value is considered as the detection limit of estrogenic or anti-estrogenic activities in the uterotrophic assay. The usage of this value as cutoff provided the best concordance rate (82%). These findings are useful in a tiered approach for identifying chemicals that have potential to induce ER-mediated effects in vivo.
Doi 10.1016/j.tiv.2007.08.004
Pmid 17904329
Wosid WOS:000252907100026
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English
Keyword Binding assay; Uterotrophic assay; Concordance
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