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RELATIVE BINDING AFFINITY OF ALKYLPHENOLS TO RAINBOW TROUT ESTROGEN RECEPTOR
Citation:
Henry, T R., J. S. Denny, AND P K. Schmieder. RELATIVE BINDING AFFINITY OF ALKYLPHENOLS TO RAINBOW TROUT ESTROGEN RECEPTOR. Presented at SOT, San Francisco, CA, March 25-29, 2001.
Description:
RELATIVE BINDING AFFINITY OF ALKYLPHENOLS TO RAINBOW TROUT ESTROGEN RECEPTOR. T R Henry1, J S Denny2 and P K Schmieder2. USEPA, ORD, NHEERL, 1Experimental Toxicology Division and 2Mid-Continent Ecology Division, Duluth, MN, USA.
The USEPA has been mandated to screen industrial chemicals and pesticides for potential endocrine activity. Current assays for measuring endocrine activity are primarily mammalian-based. The appropriateness of extrapolating mammalian results to non-mammalian species is uncertain; primarily due to the lack of non-mammalian data from which to make such an assessment. The primary objective of the study was to establish the relative binding affinity of a number of alkylphenols in a widely used non-mammalian toxicity model, the rainbow trout. Binding affinity to the rainbow trout estrogen receptor (rtER) was measured by radioligand competition assay. Trout liver cytosol (320 l) was incubated (20 hr at 4oC) with a saturating concentration (5 nM) of 3H-estradiol (3H-E2) and a range of alkylphenol concentrations. Bound alkylphenol was determined as the amount of 3H-E2 displaced from the rtER. The relative binding affinity (RBA) for each alkylphenol was calculated by dividing the IC50 of E2 by the IC50 of the alkylphenol and expressed as a percent (E2=100). A variety of alkylphenols were tested and found to have relative binding affinities several orders of magnitude lower than that of E2. The rank order RBAs for alkylphenols tested was 4-tert-octylphenol (RBA = 0.01) > 4-n-pentylphenol (RBA = 0.007) > 4-tert-pentylphenol (RBA = 0.004) 4-n-butylphenol (RBA = 0.003) > 4-sec-butylphenol (RBA = 0.002) = 4-tert-butylphenol (RBA = 0.002). The alkylphenol RBAs determined for rtER are approximately an order of magnitude greater than those reported for human ER and rat ER, indicating greater binding potential of alkylphenols in rainbow trout than in mammals. However, the structure-activity relationships relating alkyl group size to estrogenic activity observed for the rtER appear to be similar to those reported for human ER and rat ER. This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.