Several Human Pharmaceutical Residues in Aquatic Environment may Result in Endocrine Disruption in Japanese Medaka(Oryzias latipes)

This study was conducted to determine the endorcrine disruption effects of the several major pharmaceutical residues in water using adult Japanese medaka (Oryzias latipes). Four frequently used pharmaceuticals including caffeine, ketoconazole, acetaminophen, and diltiazem were investigated for the vitellogenin(Vtg) induction in the medaka using Western blotting and ELISA. $17\beta$,-estradiol was used as a positive control. Vtg was qualified and quantified through Western blot and ELISA. Following SDS gel electrophoresis, the dominant protein band was identified to molecular weight approximately 205 kDa in whole body samples of vitellogenic female. With female medaka exposed to $17\beta,-estradiol$, no significant difference in total protein induction was noted. In contrast, three to five day exposure of male fish to $17\beta,-estradiol$ resulted in $63.07\%o$, increase of total protein comparing to that of control males (p<0.01). Vtg induction in male fish was observed with all the test pharmaceuticals: At concentrations greater than 1ppm of diltiazem, 2 ppm of caffeine, 4 ppm of acetaminophen, and 10 ppm of ketoconazole, Vtg induction was monotonously increased in a dose dependent manner. This study is one of the first reports suggesting potential endocrine disruption mechanism of common human pharmaceutical products in aquatic ecosystem. Although the effect concentrations obtained from this investigation are environmentally unrealistically high, endocrine disruption should be considered as one of the important consequences of pharmaceutical pollution in aquatic environment, and warrants due attention in future researches.