Short Communication Estrogenic activity of dicofol with the human estrogen receptor: Isomer- and enantiomer-specific implications

Dicofol is a non-systemic acaricide/miticide currently registered in the US 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% and 20% of p,p 0 - and o,p 0 -dicofol isomers. The o,p 0 -substituted isomer of dicofol is chiral and may have enantiomer-specific activity; however, the stereospecific activity of o,p 0 -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 (+)-17-b estradiol (positive control), p,p 0 -dicofol, racemic o,p 0 -dicofol [(±)-o,p 0 -dicofol] and the individual o,p 0 -dicofol enantiomers was measured via quantification of b-galactosidase. The (±)-o,p 0 - and p,p 0 -dicofol were weak estrogen mimics (EC50: 4.2 · 10 � 6 and 1.6 · 10 � 6 M, respectively) relative to estradiol (3.7 · 10 � 10 M). For o,p 0 -dicofol, the b-galactosidase induction by (� )-o,p 0 -dicofol (EC50: 5.1 · 10 � 7 M) was greater than the racemic mixture. However, the (+)-o,p 0 -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 0 -isomer and (� )-o,p 0 -substituted enan