Abstract
A key step in deriving an Environmental Quality Standard (EQS) is assessing the reliability and relevance of the underpinning ecotoxicity data. While the assessment of data reliability is relatively well established, the detailed evaluation of data relevancy is a more recent development. We applied broadly accepted relevancy criteria to a series of non-standard ecotoxicity studies on diclofenac, focusing on some aspects that should be accounted for in studies used in EQS derivation. Specific relevancy issues include potential experimental bias, claimed ‘significant effects’ that are indistinguishable from controls, or within the range of normal, and lack of environmental applicability. We highlight that rigorous, comprehensive and, where necessary, specialist assessment of data relevancy for studies potentially applicable for EQS setting is critical if studies are to be appropriately used regulatory decision-making. We provide recommendations for researchers and environmental practitioners to ensure robust accounting of relevancy in non-standard studies is undertaken.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
ANZG (2018) Australian and New Zealand Guidelines for Fresh and Marine Water Quality. Australian and New Zealand Governments and Australian state and territory governments, Canberra ACT, Australia. Available at www.waterquality.gov.au/anz-guidelines
Bickley LB, van Aerle R, Brown AR, Hargreaves A, Huby R, Cammack V, Jackson R, Santos EM, Tyler CR (2017) Bioavailability and Kidney Responses to Diclofenac in the Fathead Minnow (Pimephales promelas). Environmental Science Technology 51:1764–1774
Birzle C (2015) Etablierung und Validierung quantitativ-morphologischer Parameter bei Regenbogenforellen im Rahmen ökotoxikologischer Fragestellungen. PhD-Thesis Ludiwig-Maximilians-Universität Munich. ISBN: 978-3-8439-2059-9. Pp292
Carvalho RN, Marinov D, Loos R, Napierska D, Chirico N, Lettieri T (2016) Monitoring-based Exercise: Second Review of the Priority Substances List under the Water Framework Directive. Monitoring-based exercise. Joint Research Centre, Institute for Environment and Sustainability, Water Resources Unit TP 121, Ispra, Italy. Pp301
Crissman JW, Goodman DG, Hildebrandt PK, Maronpot RR, Prater DA, Riley JH, Seaman WJ, Thake DC (2004) Best practices guideline: toxicologic histopathology. Toxicol Pathol 32:126–131
Donnachie RL, Johnson AC, Sumpter JP (2016) A rational approach to selecting and ranking some pharmaceuticals of concern for the aquatic environment and their relative importance compared with other chemicals. Environ Toxicol Chem 35:1021–1027
EC (European Commission) (2018) Common Implementation Strategy for the Water Framework Directive (2000/60/EC) Guidance Document No. 27 Technical Guidance For Deriving Environmental Quality Standards. European Communities. Revised Edition
ECHA (2011) Guidance on information requirements and chemical safety assessment Chapter R.4: Evaluation of available information. Version 1.1. European Chemicals Agency. Accessed September 2011: https://echa.europa.eu/documents/10162/13643/information_requirements_r4_en.pdf/d6395ad2-1596-4708-ba86-0136686d205e
Efosa NJ, Kleiner W, Kloas W, Hoffmann F (2017) Diclofenac can exhibit estrogenic modes of action in male Xenopus laevis and affects the hypothalamus-pituitary-gonad axis and mating vocalizations. Chemosphere 173:69–77
Fagerland JA, Wall HG, Pandher K, LeRoy BE, Gagne GD (2012) Ultrastructural analysis in preclinical safety evaluation. Toxicol Pathol 40:391–402
Groner F, Hohne C, Kleiner W, Kloas W (2017) Chronic diclofenac exposure affects gill integrity and pituitary gene expression and displays estrogenic activity in nile tilapia (Oreochromis niloticus). Chemosphere 166:473–481
Hoeger B, Kollner B, Dietrich DR, Hitzfeld B (2005) Water-borne diclofenac affects kidney and gill integrity and selected immune parameters in brown trout (Salmo trutta f. fario). Aquatic toxicology 75:53–64
Klimisch HJ, Andreae M, Tillmann U (1997) A systematic approach for evaluating the quality of experimental toxicological and ecotoxicological data. Regul Toxicol Pharmacol 25:1–5
Lewis RW, Billington R, Debryune E, Gamer A, Lang B, Carpanini F (2002) Recognition of adverse and nonadverse effects in toxicity studies. Toxicol Pathol 30:66–74
Mehinto AC, Hill EM, Tyler CR (2010) Uptake and biological effects of environmentally relevant concentrations of the nonsteroidal anti-inflammatory pharmaceutical diclofenac in rainbow trout (Oncorhynchus mykiss). Environ Sci Technol 44:2176–2182
Memmert U, Peither A, Burri R, Weber K, Schmidt T, Sumpter JP, Hartmann A (2013) Diclofenac: New data on chronic toxicity and bioconcentration in fish. Environ Toxicol Chem 32(2):442–452
Moermond CT, Kase R, Korkaric M, Ågerstrand M (2016) CRED: Criteria for the reporting and evaluating ecotoxicity data. Environ Toxicol Chem 35:1297–1309
Naslund J, Fick J, Asker N, Ekman E, Larsson DGJ, Norrgren L (2017) Diclofenac affects kidney histology in the three-spined stickleback (Gasterosteus aculeatus) at low µg/L concentrations. Aquatic Toxicology 189:87–96
Praskova E, Plhalova L, Chromcova L, Stepanova S, Bedanova I, Blahova J, Hostovsky M, Skoric M, Marsalek P, Volsarova E, Svobodova Z (2014) Effects of subchronic exposure of diclofenac on growth, histopathological changes, and oxidative stress in zebrafish (Danio rerio). Sci World J 2014:645737
Schwaiger J, Ferling H, Mallow U, Wintermayr H, Negele RD (2004) Toxic effects of the non- steroidal anti-inflammatory drug diclofenac: Part I: histopathological alterations and bioaccumulation in rainbow trout. Aquatic Tox 68:141–150
Schwarz S, Schmieg H, Scheurer M, Koehler HR, Triebskorn R (2017) Effects of NSAID diclofenac on the survival, health and behaviour of embryonic and juvenile brown trout Salmo trutta f. fario. Sci Total Environ 607–608:1026–1036
Triebskorn R, Casper H, Heyd A, Eikemper R, Köhler HR, Schwaiger J (2004) Toxic effects of the non-steroidal anti-inflammatory drug diclofenac: Part II. Cytological effects in liver, kidney, gills and intestine of rainbow trout (Oncorhynchus mykiss). Aquat Toxicol 68:151–166
Triebskorn R, Casper H, Scheil V, Schwaiger J (2007) Ultrastructural effects of pharmaceuticals (carbamazepine, clofibric acid, metoprolol, diclofenac) in rainbow trout (Oncorhynchus mykiss) and common carp (Cyprinus carpio). Anal Bioanal Chem 387:1405–1416
UBA (Umweltbundesamt) (2018) EQS DATASHEET, ENVIRONMENTAL QUALITY STANDARD DICLOFENAC. Dossier Diclofenac_Draft_JRC-2017_V4.1
Zanuri NBM, Bentley MG, Caldwell GS (2017) Assessing the impact of diclofenac, ibuprofen and sildenafil citrate (Viagra®) on the fertilisation biology of broadcast spawning marine invertebrates. Mar Environ Res 127:126–136
Acknowledgements
The Authors would like to thank Jeff Wolf of EPL for his technical support in reviewing the histopathology studies, to the anonymous reviewers for their valuable input to the manuscript, and to GSK for funding this assessment.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Merrington, G., Leverett, D., Peters, A. et al. Perspectives on Relevancy Assessment for Non-Standard Ecotoxicity Data in Environment Quality Standard derivation: Examples for Diclofenac. Bull Environ Contam Toxicol 105, 665–670 (2020). https://doi.org/10.1007/s00128-020-03025-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00128-020-03025-2