Towards modelling of the environmental fate of pharmaceuticals using the QSPR-MM scheme

Pharmaceuticals are considered as a new, important group of pollutants. These compounds can enter the environment via several routes and can disturb the natural balance of ecosystems. Factors affecting the environmental fate of medical substances can be determined with computational modelling. The routine application of the modelling methodology in the environmental risk assessment for newly designed pharmaceuticals would enable prediction of their important physical/chemical properties and forecasting their long-range transport and fate. In this contribution, we present the existing state-of-the-art and review the currently available modelling tools of two groups: Quantitative Structure-Property Relationship techniques and Multimedia Mass-balance models. We discuss the current research needs in the context of extending the applicability of the existing tools onto pharmaceuticals, being a more structurally diversified group of contaminants than persistence organic pollutants, for which the majority of the existing models have been originally developed. Multimedia fate models applied for pharmaceuticals are reviewed.QSPR approach to predict physical/chemical properties of pharmaceuticals is reviewed.QSPR-MM combined model is suggested to predict Pov and LRTP of chemical pollutants.

[1]  Katarzyna Odziomek,et al.  A new metric for long-range transport potential of chemicals. , 2014, Environmental science & technology.

[2]  D. Mackay,et al.  Application of the QWASI (Quantitative Water Air Sediment Interaction) fugacity model to the dynamics of organic and inorganic chemicals in lakes , 1989 .

[3]  John C. Dearden,et al.  QSPR Correlation of Melting Point for Drug Compounds Based on Different Sources of Molecular Descriptors , 2006, J. Chem. Inf. Model..

[4]  D. Mackay,et al.  Finding fugacity feasible , 1979 .

[5]  K. Carroll,et al.  Exposure to 17 alpha-ethinylestradiol and bisphenol A--effects on larval moulting and mouthpart structure of Chironomus riparius. , 2003, Ecotoxicology and environmental safety.

[6]  J. Dearden,et al.  Linear QSAR regression models for the prediction of bioconcentration factors by physicochemical properties and structural theoretical molecular descriptors. , 2007, Chemosphere.

[7]  Paola Gramatica,et al.  Principles of QSAR models validation: internal and external , 2007 .

[8]  Tomasz Puzyn,et al.  Global versus local QSPR models for persistent organic pollutants: balancing between predictivity and economy , 2011 .

[9]  Lyn Denison,et al.  Stockholm Convention on Persistent Organic Pollutants , 2013 .

[10]  Beate I Escher,et al.  A screening level fate model of organic contaminants from advanced water treatment in a potable water supply reservoir. , 2011, Water research.

[11]  D Mackay,et al.  The evolution of mass balance models of persistent organic pollutant fate in the environment. , 1999, Environmental pollution.

[12]  Søren Brunak,et al.  Prediction of pH-Dependent Aqueous Solubility of Druglike Molecules , 2006, J. Chem. Inf. Model..

[13]  T. Ternes,et al.  Pharmaceuticals and personal care products in the environment: agents of subtle change? , 1999, Environmental health perspectives.

[14]  John Struger,et al.  Aquivalence revisited--new model formulation and application to assess environmental fate of ionic pharmaceuticals in Hamilton Harbour, Lake Ontario. , 2011, Environment international.

[15]  Peter Shanahan,et al.  Screening analysis of human pharmaceutical compounds in U.S. surface waters. , 2004, Environmental science & technology.

[16]  Tomasz Puzyn,et al.  Predicting logarithmic values of the subcooled liquid vapor pressure of halogenated persistent organic pollutants with QSPR: How different are chlorinated and brominated congeners? , 2010 .

[17]  McKone.  CalTOX: A multimedia total-exposure model for hazardous-wastes sites. Part 3, The multiple-pathway exposure model , 1992 .

[18]  Jerzy Leszczynski,et al.  Direct QSPR: the most efficient way of predicting organic carbon/water partition coefficient (log KOC) for polyhalogenated POPs , 2014, Structural Chemistry.

[19]  Kunal Roy,et al.  Predictive toxicology using QSAR: A perspective , 2010 .

[20]  Simon Webb,et al.  Exposure simulation for pharmaceuticals in European surface waters with GREAT-ER. , 2002, Toxicology letters.

[21]  Annemarie P van Wezel,et al.  Comparison of two screening level risk assessment approaches for six disinfectants and pharmaceuticals. , 2002, Chemosphere.

[22]  Kd Tripathi.  Pharmacological Classification of Drugs with Doses and Preparations , 2008 .

[23]  Christian G Daughton,et al.  Green pharmacy and pharmEcovigilance: prescribing and the planet , 2011, Expert review of clinical pharmacology.

[24]  P Lebrun,et al.  Inhibition of transglutaminase by hypoglycaemic sulphonylureas in pancreatic islets and its possible relevance to insulin release. , 1984, Research communications in chemical pathology and pharmacology.

[25]  Samuel H Yalkowsky,et al.  Prediction of aqueous solubility from SCRATCH. , 2010, International journal of pharmaceutics.

[26]  Jörg Huwyler,et al.  Computational aqueous solubility prediction for drug-like compounds in congeneric series. , 2008, European journal of medicinal chemistry.

[27]  Ulf Norinder,et al.  Global and Local Computational Models for Aqueous Solubility Prediction of Drug‐Like Molecules. , 2004 .

[28]  Sean Ekins,et al.  Troubleshooting computational methods in drug discovery. , 2010, Journal of pharmacological and toxicological methods.

[29]  Tomasz Puzyn,et al.  QSPR-based estimation of the atmospheric persistence for chloronaphthalene congeners , 2008 .

[30]  P Gramatica,et al.  Modelling physico-chemical properties of (benzo)triazoles, and screening for environmental partitioning. , 2011, Water research.

[31]  Eduardo A. Castro,et al.  QSPR Studies on Aqueous Solubilities of Drug-Like Compounds , 2009, International journal of molecular sciences.

[32]  Andrew G. Garrow,et al.  The value of in silico chemistry in the safety assessment of chemicals in the consumer goods and pharmaceutical industries. , 2012, Drug discovery today.

[33]  Peter A. Vanrolleghem,et al.  A geo-referenced aquatic exposure prediction methodology for ‘down-the-drain’ chemicals , 1997 .

[34]  J Devillers,et al.  European Union System for the Evaluation of Substances (EUSES). Principles and structure. , 1997, Chemosphere.

[35]  Glen Huntly,et al.  Environmental footprint of pharmaceuticals : the significance of factors beyond direct excretion to sewers , 2010 .

[36]  Kevin C Jones,et al.  Modelling the fate of persistent organic pollutants in Europe: parameterisation of a gridded distribution model. , 2004, Environmental pollution.

[37]  Paola Gramatica,et al.  On the development and validation of QSAR models. , 2013, Methods in molecular biology.

[38]  S. Jørgensen,et al.  Occurrence, fate and effects of pharmaceutical substances in the environment--a review. , 1998, Chemosphere.

[39]  Dong-Sheng Cao,et al.  Prediction of aqueous solubility of druglike organic compounds using partial least squares, back‐propagation network and support vector machine , 2010 .

[40]  Anna-Karin Johansson,et al.  Are pharmaceuticals potent environmental pollutants? Part I: environmental risk assessments of selected active pharmaceutical ingredients. , 2006, The Science of the total environment.

[41]  Jahan B. Ghasemi,et al.  QSPR prediction of aqueous solubility of drug-like organic compounds. , 2007, Chemical & pharmaceutical bulletin.

[42]  Miriam Diamond,et al.  Models of multi-media partitioning of multi-species chemicals: The fugacity/aquivalence approach , 1992 .

[43]  Tomasz Puzyn,et al.  On the replacement of empirical parameters in multimedia mass balance models with QSPR data. , 2011, Journal of hazardous materials.

[44]  M Matthies,et al.  GREAT-ER: a new tool for management and risk assessment of chemicals in river basins. Contribution to GREAT-ER #10. , 2001, Water science and technology : a journal of the International Association on Water Pollution Research.

[45]  Charles R. Tyler,et al.  Long-Term Exposure to Environmental Concentrations of the Pharmaceutical Ethynylestradiol Causes Reproductive Failure in Fish , 2004, Environmental health perspectives.

[46]  Frank Wania,et al.  Evaluating the environmental fate of pharmaceuticals using a level III model based on poly-parameter linear free energy relationships. , 2006, The Science of the total environment.

[47]  Yuichi Moriguchi,et al.  Geo-referenced multimedia environmental fate model (G-CIEMS): model formulation and comparison to the generic model and monitoring approaches. , 2004, Environmental science & technology.

[48]  D Mackay,et al.  BETR North America: A regionally segmented multimedia contaminant fate model for North America , 2001, Environmental science and pollution research international.

[49]  Carina Carlsson,et al.  Are pharmaceuticals potent environmental pollutants? Part II: environmental risk assessments of selected pharmaceutical excipients. , 2006, The Science of the total environment.

[50]  E. Thurman,et al.  Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999-2000: a national reconnaissance. , 2002, Environmental science & technology.

[51]  D. Epel,et al.  Nitromusk and Polycyclic Musk Compounds as Long-Term Inhibitors of Cellular Xenobiotic Defense Systems Mediated by Multidrug Transporters , 2004, Environmental health perspectives.

[52]  D Mackay,et al.  A model for p-aminobenzoic acid ester narcosis in goldfish. , 1985, Journal of pharmaceutical sciences.

[53]  Tomasz Puzyn,et al.  Predicting enthalpy of vaporization for Persistent Organic Pollutants with Quantitative Structure–Property Relationship (QSPR) incorporating the influence of temperature on volatility , 2014 .

[54]  B. Ansell,et al.  Acetazolamide in Treatment of Epilepsy , 1956, British medical journal.

[55]  Tomasz Puzyn,et al.  How do the partitioning properties of polyhalogenated POPs change when chlorine is replaced with bromine? , 2008, Environmental science & technology.

[56]  Yi Li,et al.  Prediction of aqueous solubility of organic compounds using a quantitative structure-property relationship. , 2002, Journal of pharmaceutical sciences.

[57]  D. Grandjean,et al.  Occurrence of several acidic drugs in sewage treatment plants in Switzerland and risk assessment. , 2005, Water research.

[58]  Z R Li,et al.  Quantitative structure-pharmacokinetic relationships for drug clearance by using statistical learning methods. , 2006, Journal of molecular graphics & modelling.

[59]  K. Fent,et al.  Ecotoxicology of human pharmaceuticals. , 2006, Aquatic toxicology.

[60]  E. Cooper,et al.  Preliminary risk assessment database and risk ranking of pharmaceuticals in the environment. , 2008, The Science of the total environment.

[61]  J. Rominger,et al.  Modeling the fate of down-the-drain chemicals in rivers: An improved software for GREAT-ER , 2006, Environ. Model. Softw..

[62]  M. G. West,et al.  Inhibition of Salmonella Cultures by Streptomycin.∗ , 1945, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[63]  Emilio Benfenati,et al.  In silico methods to predict drug toxicity. , 2013, Current opinion in pharmacology.