The impacts of pH on the toxicity of mixtures of antidepressants to Daphnia magna

Selective Serotonin Reuptake Inhibitors (SSRI) including Citalopram (CTP), Fluoxetine (FLX) and Sertraline (SRT), Selective Norepinephrine Reuptake Inhibitor (SNRI) including Duloxetine (DUL), and Tricyclic Antidepressant (TCA) including Dosulepin (DOS) have been widely prescribed in antidepressants. While these pharmaceuticals have been frequently detected in surface waters, sediments and biota, extremely limited information is available on their in vivo toxicity, particularly in invertebrates. In the present study the individual and mixture neurotoxicity of antidepressants and its underlying mechanisms were investigated acutely and chronically at different pH levels (5.5, 6.0, 7.0, 7.5, 8.0, and 9.0) using Daphnia magna. A model was designed to calculate the expected EC50. The total amount (mg) of each antidepressant dispensed from 2009 to 2018 was calculated using dataset provided from National Health Service (NHS). It was grouped in three, A (2009-2011), B (2012-2014), and C (2015-2018), based on the change (%) of prescription. Concentration Addition (CA) model was used to test the mixture toxicity. Daphnia neonates were exposed to various expected concentrations of mixture A, B or C to determine the acute and chronic toxicity in various pH. The toxicity of antidepressants was increased acutely and chronically with increasing pH conditions. SSRIs commonly resulted reproduction enhancement and decrease in growth effects while reproduction inhibition and no effect on growth were determined with SNRI or TCA exposure on D. magna. Moreover, the dry mass of the daphnids was decreased as the size decreases. Our observation clearly indicates that survival, reproduction, growth, and dry mass performance in aquatic invertebrate could be affected by trace level exposure to studied antidepressants and the toxicity increases as pH increases. Our mixture results also clearly reflected the change of the antidepressant concentration in last decade in the UK. Hence, consequences of greater diverse class of antidepressants exposure on aquatic invertebrate warrant further investigation.