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Development of Baseline Quantitative Structure-Activity Relationships (QSARs) for the Effects of Active Pharmaceutical Ingredients (APIs) to Aquatic Species

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Book cover Ecotoxicological QSARs

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

The aim of this work was to develop predictive approaches for acute and chronic toxicity in fish, Daphnia, and algae utilizing baseline toxicity models. Currently available public active pharmaceutical ingredient (API) ecotoxicity data were compared to published baseline toxicity QSARs and classification schemes for industrial chemicals. The results showed that methods of assessing ecotoxicity for industrial chemicals are not adequate for the assessment of APIs. To develop equivalent prediction methods for APIs, acute baseline toxicity QSARs for APIs based on hydrophobicity (as log P) were constructed, and the lower limits of toxicity for the public API data were compared with published industrial baseline toxicity QSARs for fish, Daphnia, and algae. These baseline toxicity QSARs were subsequently compared to the available acute toxicity data from the iPiE database. Since 75% of APIs are ionizable, baseline toxicity QSARs were also constructed using log D at pH 7.0. For chronic toxicity baselines, uncensored NOEC and LOEC data from the iPiE database were plotted using either log P or log D at pH 7.0. An alternative methodology was used to develop chronic baseline toxicity QSARs which consisted of iteratively refining the line of best fit until approximately 90% of the values were above the baseline toxicity QSARs. These chronic baseline toxicity QSARs could subsequently be used to identify groups which exhibit toxicity in excess of the baseline (i.e., greater than 10× the hydrophobicity-predicted toxicity).

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Acknowledgments

The financial contribution of the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in-kind contribution through the European Union Innovative Medicines Initiative (IMI) iPiE Project (Grant Agreement no. 115735) is gratefully acknowledged.

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Authors and Affiliations

  1. School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK

    David J. Ebbrell, Mark T. D. Cronin, Claire M. Ellison, James W. Firman & Judith C. Madden

Authors
  1. David J. Ebbrell
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  2. Mark T. D. Cronin
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  3. Claire M. Ellison
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  4. James W. Firman
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  5. Judith C. Madden
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Corresponding author

Correspondence to Judith C. Madden .

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Editors and Affiliations

  1. Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India

    Kunal Roy

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Ebbrell, D.J., Cronin, M.T.D., Ellison, C.M., Firman, J.W., Madden, J.C. (2020). Development of Baseline Quantitative Structure-Activity Relationships (QSARs) for the Effects of Active Pharmaceutical Ingredients (APIs) to Aquatic Species. In: Roy, K. (eds) Ecotoxicological QSARs. Methods in Pharmacology and Toxicology. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0150-1_15

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  • DOI: https://doi.org/10.1007/978-1-0716-0150-1_15

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0149-5

  • Online ISBN: 978-1-0716-0150-1

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