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ESTROGENIC ACTIVITY OF DICOFOL WITH THE HUMAN ESTROGEN RECEPTOR: ISOMER- AND ENANTIOMER-SPECIFIC IMPLICATIONS
HOEKSTRA, P. F., B. K. BURNISON, A. W. GARRISON, T. NEHELI, AND D. C. MUIR. ESTROGENIC ACTIVITY OF DICOFOL WITH THE HUMAN ESTROGEN RECEPTOR: ISOMER- AND ENANTIOMER-SPECIFIC IMPLICATIONS. CHEMOSPHERE. Elsevier Science Ltd, New York, NY, 64(1):174-177, (2006).
Dicofol is a non-systemic acaricide/miticide currently registered in the U.S. and Canada for use on a wide variety of crops. This agrochemical has been identified as a potential candidate substance for the United Nations Economic Commission for Europe (UN-ECE) Persistent Organic Pollutant (POP) Protocol and implicated as a potential endocrine disrupting compound. The technical product is usually synthesized from technical DDT and consists of approximately 80 percent and 20 percent of p,p´- and o,p´-dicofol isomers. The o,p´-substituted isomer of dicofol is chiral and may have enantiomer-specific activity; however, the stereospecific activity of o,p´-dicofol has not been reported. In this study, we examined the isomer- and enantiomer-specific endocrine disruption potential of dicofol using yeast-based steroid hormone receptor gene transcription assay designed with the human estrogen receptor (hER). Estrogenic activity of (plus)-17-beta estradiol (positive control), p,p´-dicofol, racemic o,p´-dicofol [(plus minus)-o,p´-dicofol] and the individual o,p´-dicofol enantiomers was measured via quantification of beta-galactosidase. The (plus minus)-o,p´- and p,p´-dicofol were weak estrogen mimics (EC50: 4.2 × 10(-6) M and 1.6 × 10(-6) M, respectively) relative to estradiol (3.7 × 10(-10) M). For o,p´-dicofol, the beta-galactosidase induction by (-)-o,p´-dicofol (EC50: 5.1 × 10(-7) M) was greater than the racemic mixture. However, the (+)-o,p´-dicofol enantiomer was found to have negligible estrogenic activity. These data indicate that dicofol is a weak hER agonist due to activity of the achiral p,p´-isomer and (-)-o,p´-substituted enantiomer and emphasizes the influence of chemical structure and configuration on biological responses to exposure from chiral compounds.
To determine the environmental occurrences, fate, and effects of the enantiomers of selected chiral pesticides and other chiral pollutants.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL EXPOSURE RESEARCH LAB
ECOSYSTEMS RESEARCH DIVISION
PROCESSES & MODELING BRANCH