SSRI's in WWTP effluents and their disposition and effects in salmonids and marine flatfish

We surveyed eight WWTP effluents for six different SSRIs and found total levels varied between 77 and 1,673 ng/L. The most abundant SSRIs (>90% of ∑SSRI) detected were citalopram >>> fluoxetine > sertraline. We subsequently performed a series of in vivo and in vitro exposures to assess the uptake, metabolism and effects of these SSRIs both as a mixture (at ratios observed in effluents) and as individual chemicals in salmonids and English sole. Static water exposures to an SSRI mixture in rainbow trout revealed sertraline was the most rapidly absorbed SSRI with an uptake clearance of approximately 35 ml/hr/g, nearly 10x more rapid than fluoxetine. Citalopram was the least absorbed SSRI. Subsequent continuous exposures of trout and English sole to a similar SSRI mixture indicated the kidney>> liver > brain were the tissues that accumulated the highest concentrations of SSRIs. Substantial formation of the sertraline metabolite norsertraline was observed in both trout and sole. Concentrations of norsertraline were similar or higher than sertraline in some tissues such as the liver and brain. High levels of sertraline and norsertraline were found in bile, which increased three fold after enzymatic deconjugation. In vitro studies using hepatocytes or liver homogenates confirmed sertraline is the most rapidly metabolized SSRI. Additional in vitro studies using primary pituitary cells and isolated ovarian follicles found the most sensitive effect of SSRI exposure was antagonism of the estrogen induced expression of the beta subunit for luteinizing hormone. These results suggest sertraline is the SSRI most likely to bioaccumulate and become biotransformed by fishes and achieve tissue levels near the threshold for biological effect. Supported by EPA-STAR grant R835167, WA Dept. of Ecology G1400206.