First report on interspecies quantitative correlation of ecotoxicity of pharmaceuticals Supratik Kar, Kunal Roy * Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, India article info Article history: Received 25 May 2010 Received in revised form 8 July 2010 Accepted 12 July 2010 Available online 9 August 2010 Keywords: QSAR Ecotoxicity Pharmaceuticals Interspecies correlation abstract Pharmaceuticals being extensively and progressively used in human and veterinary medicine are emerg- ing as significant environmental contaminants. Pharmaceuticals are designed to have a specific mode of action and many of them are persistent in the body. These features among others make pharmaceuticals to be evaluated for potential effects on aquatic flora and fauna. Low levels of pharmaceuticals have been detected in many countries in sewage treatment plant effluents, surface waters, groundwater and drink- ing waters. In contrast, there is a general scarcity of publicly available ecotoxicological data concerning pharmaceuticals. Interspecies toxicity correlations provide a tool for estimating contaminant sensitivity with known levels of uncertainty for a diversity of wildlife species. In this context, we have developed interspecies toxicity correlation between Daphnia magna (zooplankton) and fish (species according to OECD guidelines) assessing the ecotoxicological hazard potential of diverse 77 pharmaceuticals. The developed models are validated and consensus models are presented to predict toxicity of the individual compounds for any one species when the data for the other species are available. Informative illustrations of the contributing structural fragments which are responsible for the greater toxicity of the diverse phar- maceuticals are identified by the developed models. Developed models are also used to predict fish tox- icities of 59 pharmaceuticals (for which Daphnia toxicities are present) and Daphnia toxicities of 30 pharmaceuticals (for which fish toxicities are present). This study will allow a better and comprehensive risk assessment of pharmaceuticals for which toxicity data is missing for a particular endpoint. Ó 2010 Elsevier Ltd. All rights reserved. 1. Introduction Residues of pharmaceuticals in surface and drinking waters have increased in recent time immeasurably (Ternes et al., 2001). Major pharmaceuticals are frequently detected in rivers, streams, sewage effluents, surface water, and groundwater and even in drinking water (Ternes, 1998; Daughton and Jones-Lepp, 2001). This is creating a big dilemma as drinking water treatment dimin- ishes residues, but it is not able to remove those substances en- tirely (Heberer et al., 1997). In a 2002 nationwide study of ‘‘emerging pollutants” in waters, the US Geological Survey (USGS) tested for pharmaceuticals and personal care products (PPCPs) in several US locations in 139 rivers in 30 states detecting a wide range of biologically active compounds (Kolpin et al., 2002). Some majorly found drugs in rivers were beta blockers (e.g. Metoprolol up to 1.54 lgL 1 ) and beta-sympathomimetics (Sedlak and Pinkston, 2001), analgesic and anti-inflammatory drugs (e.g. Diclofenac up to 1.2 lgL 1 )(Ternes, 1998; Buser et al., 1999), estrogens (e.g. 17b-estradiol up to 0.013 lgL 1 )(Adler et al., 2001; Huang and Sedlak, 2001) and also antibiotics (e.g. Erythro- mycin up to 1.7 lgL 1 )(Adler et al., 2001; Lindsey et al., 2001) as well as lipid lowering agents (e.g. Clofibrinic acid up to 0.2 lgL 1 ) (Ahrer et al., 2001) and anti-epileptic drugs (e.g. Carbamazepine up to 2.1 lgL 1 )(Ternes, 1998; Seiler et al., 1999). Even in tap water, pharmaceuticals like Clofibric acid could be detected in concentrations up to 270 ng L 1 (Heberer et al., 1997; Ternes et al., 2001). A number of reservoirs tapped for drinking water were monitored along the Lergue River in Southern France where pharmaceuticals such as paracetamol, Diclofenac, and Carbamazepine were found (Rabiet et al., 2006). Clofibric acid and diazepam were detected in treated drinking water in Milan, Italy (Zuccato et al., 2000). Heberer and colleagues (Heberer et al., 2001; Heberer, 2002) have reported the presence of Clofibric acid, propylphenazone, and Diclofenac in the drinking water of Berlin in the concentration range of several hundreds of nano- grams per liter. Frick detected three widely used nonprescription drugs, caffeine, cotinine, and acetaminophenone, in samples of potable water collected near Atlanta, Georgia (Frick et al., 2001). Stackelberg and colleagues identified 17 organic contaminants including Carbamazepine (0.258 lgL 1 ) in the finished water of 0045-6535/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.chemosphere.2010.07.019 E-mail address: kunalroy_in@yahoo.com (K. Roy). URL: http://sites.google.com/site/kunalroyindia/ (K. Roy). Chemosphere 81 (2010) 738–747 Contents lists available at ScienceDirect Chemosphere journal homepage: www.elsevier.com/locate/chemosphere