Abstract
Carbamazepine (CBZ) is an anticonvulsant medication with highly persistent properties in the aquatic environment, where it has the potential to affect nontarget biota. Because CBZ and many other pharmaceuticals are not readily removed in conventional sewage treatment plants (STP), additional STP effluent treatment technologies are being evaluated and implemented. Whole effluent ozonation is a prospective method to remove pharmaceuticals such as CBZ, yet knowledge on the toxicity of CBZ ozonation byproducts (OBPs) is lacking. This study presents, for the first time, in vivo individual and mixture toxicity of four putative OBPs, that is, carbamazepine 10,11-epoxide, 10,11-Dihydrocarbamazepine, 1-(2-benzaldehyde)-4-hydro-(1H,3H)-quinazoline-2-one (BQM), and 1-(2-benzaldehyde)-(1H,3H)-quinazoline-2,4-dione (BQD) in developing zebrafish (Danio rerio) embryos. BQM and BQD were isolated from the ozonated solution as they were not commercially available. The study confirmed that the OBP mixture caused embryotoxic responses comparable to that of ozonated CBZ. Individual compound embryotoxicity assessment further revealed that BQM and BQD were the drivers of embryotoxicity. OBP chemical stability in ozonated CBZ water solution during 2 week dark storage at 22 °C was also assessed. The OBP concentrations remained over time, except for BQD which decreased by 94%. Meanwhile, ozonated CBZ persistently induced embryotoxicity over 2 week storage, potentially illustrating environmental concern.
Highlights
Pharmaceutical residues in sewage treatment plant (STP) effluents are increasingly studied as they are suspected to have persistent and toxic properties in the aquatic environment.[1]Carbamazepine (CBZ) is an anticonvulsant pharmaceutical mainly prescribed to patients suffering from epilepsy and used to medicate symptoms of schizophrenia and bipolar disorder.[2]
The mode of action for CBZ is through sodium channel blocking by the therapeutically active carbamazepine 10,11epoxide (CBZ-EP) metabolite,[5,6] reducing synaptic activity in the central nervous system.[7]
Mass balance-based models have suggested that approximately 55 metric tons of CBZ has accumulated in the Baltic Sea since its introduction to the market because of its persistent properties.[9]
Summary
Pharmaceutical residues in sewage treatment plant (STP) effluents are increasingly studied as they are suspected to have persistent and toxic properties in the aquatic environment.[1]Carbamazepine (CBZ) is an anticonvulsant pharmaceutical mainly prescribed to patients suffering from epilepsy and used to medicate symptoms of schizophrenia and bipolar disorder.[2]. Pharmaceutical residues in sewage treatment plant (STP) effluents are increasingly studied as they are suspected to have persistent and toxic properties in the aquatic environment.[1]. CBZ is detected in surface water environments in the ng to μg L−1 concentration range.[10−12] CBZ is not prone to photodegradation.[13] Mass balance-based models have suggested that approximately 55 metric tons of CBZ has accumulated in the Baltic Sea since its introduction to the market because of its persistent properties.[9] Bioaccumulation of CBZ has been observed in, for example, bivalves[14] and fish.[15] Adverse effects resulting from CBZ exposure at concentrations proximal to environmental levels have been demonstrated in aquatic invertebrates.[16] Fish are considerably less sensitive to CBZ, with acute and chronic effect concentrations reported in the 10−100 mg L−1 range.[16−18] the constant release of CBZ and many other persistent and bioaccumulative pharmaceuticals warrants attention and could well be hazardous to fish because of mixture effects in polluted areas.[19]
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