Endocrine effects after ozonation of tamoxifen

Ozonation is used as additional wastewater treatment option to remove recalcitrant micropollutants. It also removes the estrogenic activity found in wastewater but not always the anti-estrogenic activity. This can be explained by an incomplete removal of anti-estrogenic micropollutants or by formation of transformation products (TPs) which retain the activity. The present study investigates the degradation of the anti-estrogenic pharmaceutical tamoxifen in pure water, regarding TP formation and related anti-estrogenic effect using Arxula adeninivorans yeast estrogen screen (A-YES). In total, five transformation products were detected: three N-oxides and two further products (TP 270 and TP 388). For the transformation product TP 270 a correlation of the extent of formation with an increase of the anti-estrogenic activity was determined, demonstrating that transformation products from ozonation can be more active in a bioassay than the parent compounds. Our study shows also that the transformation of tamoxifen to N-oxides reduces the anti-estrogenic activity. The reactivity of amines towards ozone typically increases with pH, since only deprotonated amines react with ozone. Hence, removal of the endocrine activity by N-oxide formation may be disfavored at low pH.