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Improvements in Estimating Bioaccumulation Metrics in the Light of Toxicokinetic Models and Bayesian Inference


The surveillance of chemical substances in the scope of Environmental Risk Assessment (ERA) is classically performed through bio-assays from which data are collected and then analysed and/or modelled. Some analysis are based on the fitting of toxicokinetic (TK) models to assess the bioaccumulation capacity of chemical substances via the estimation of bioaccumulation metrics as required by regulatory documents. Given that bio-assays are particularly expensive and time consuming, it is of crucial importance to deeply benefit from all information contained in the data. By revisiting the calculation of bioaccumulation metrics under a Bayesian framework, this paper suggests changes in the way of characterising the bioaccumulation capacity of chemical substances. For this purpose, a meta-analysis of a data-rich TK database was performed, considering uncertainties around bioaccumulation metrics. Our results were statistically robust enough to suggest an additional criterion to the single median estimate of bioaccumulation metrics to assign a chemical substance to a given bioaccumulation capacity. Our proposal is to use the 75th percentile of the uncertainty interval of the bioaccumulation metrics, which revealed an appropriate complement for the classification of chemical substances (e.g. PBT (persistent, bioaccumulative and toxic) and vPvB (very persistent and very bioaccumulative) under the EU chemicals legislation). The 75% quantile proved its efficiency, similarly classifying 90% of the chemical substances as the conventional method.

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Data Availability

Supplementary information is available at All data used in this paper is downloadable from the MOSAICbioacc web tool, directly from the associated TK database freely accessible at


  • Adler D, Kelly ST (2020) vioplot: violin plot. R package version 0.3.7

  • Armitage JM, Toose L, Camenzuli L, Redman AD, Parkerton TF, Saunders D, Wheeler J, Martin A, Vaiopoulou E, Arnot JA (2021) A critical review and weight of evidence approach for assessing the bioaccumulation of phenanthrene in aquatic environments. Integr Environ Assess Manag 17:911–925.

    CAS  Article  Google Scholar 

  • Arnot JA, Gobas FA (2006) A review of bioconcentration factor (BCF) and bioaccumulation factor (BAF) assessments for organic chemicals in aquatic organisms. Environ Rev 14(4):257–297.

    CAS  Article  Google Scholar 

  • Baudrot V, Charles S (2019) Recommendations to address uncertainties in environmental risk assessment using toxicokinetics–toxicodynamics models. Nat Sci Rep 9:11432.

    CAS  Article  Google Scholar 

  • Charles S, Wu D, Ducrot V (2021) How to account for the uncertainty from standard toxicity tests in species sensitivity distributions: an example in non-target plants. PLOS ONE 16(1):e0245071.

    CAS  Article  Google Scholar 

  • Charles S, Ratier A, Baudrot V, Multari G, Siberchicot A, Wu D, Lopes C (2022) Taking full advantage of modelling to better assess environmental risk due to xenobiotics—the all-in-one facility MOSAIC. Environ Sci Pollut Res 29:29244–29257.

    Article  Google Scholar 

  • Chojnacka K, Mikulewicz M (2014) Bioaccumulation. In: Wexler P (ed) Encyclopedia of toxicology, 3rd edn. Academic Press, Oxford, pp 456–460. (ISBN 978-0-12-386455-0)

    Chapter  Google Scholar 

  • Cousins IT, Ng CA, Wang Z, Scheringer M (2019) Why is high persistence alone a major cause of concern? Environ Sci: Processes Impacts 21:781–792.

    CAS  Article  Google Scholar 

  • EFSA Scientific Committee (2018) Guidance on uncertainty analysis in scientific assessments. EFSA J 16(1):1–39.

    Article  Google Scholar 

  • European Commission (2006) COMMISSION REGULATION (EU) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and 2000/21/EC.

  • European Commission (2013) European Commission (EU) No 283/2013 of 1 March 2013 setting out the data requirements for active substances, in accordance with Regulation (EC) No 1107/2009 of the European Parliament and of the Council concerning the placing of plant protection product.

  • Gobas FA, Lee Y-S, Lo JC, Parkerton TF, Letinski DJ (2020) A toxicokinetic framework and analysis tool for interpreting organisation for economic co-operation and development guideline 305 dietary bioaccumulation tests. Environ Toxicol Chem 39(1):171–188.

    CAS  Article  Google Scholar 

  • Government of Canada (1999) Canadian Environmental Protection Act

  • Hartmann NB, Gottardo S, Sokull-Klüttgen B (2014) Review of available criteria for non-aquatic organisms within PBT/vPvB frameworks. Publications Office of the European Union.

  • Ockleford C, Adriaanse P, Berny P, Brock T, Duquesne S, Grilli S, Hernandez-Jerez AF, Bennekou SH, Klein M, Kuhl T, Laskowski R, Machera K, Pelkonen O, Pieper S, Smith RH, Stemmer M, Sundh I, Tiktak A, Topping CJ, Wolterink G, Cedergreen N, Charles S, Focks A, Reed M, Arena M, Ippolito A, Byers H, Teodorovic I (2018) Scientific Opinion on the state of the art of Toxicokinetic/Toxicodynamic (TKTD) effect models for regulatory risk assessment of pesticides for aquatic organisms. EFSA J 16(8):5377.

    Article  Google Scholar 

  • OECD (2008) Test No. 315: bioaccumulation in sediment-dwelling benthic oligochaetes

  • OECD (2012) Test No. 305: bioaccumulation in fish: aqueous and dietary exposure

  • Popek E (2018) Chapter 2—environmental chemical pollutants. In: Sampling and analysis of environmental chemical pollutants, 2nd edn, pp 13–69. Elsevier. ISBN 978-0-12-803202-2.

  • Prescott MJ, Lidster K (2017) Improving quality of science through better animal welfare: the NC3Rs strategy. Lab Anim 46(4):152–156.

    Article  Google Scholar 

  • Ratier A, Charles S (2022) Accumulation-depuration data collection in support of toxicokinetic modelling. Nat Sci Data 9:130.

    CAS  Article  Google Scholar 

  • Ratier A, Baudrot V, Kaag M, Siberchicot A, Lopes C, Charles S (2022a) rbioacc: an R-package to analyse toxicokinetic data. Ecotoxicol Environ Saf 242:113875.

    CAS  Article  Google Scholar 

  • Ratier A, Lopes C, Multari G, Mazerolles V, Carpentier P, Charles S (2022b) New perspectives on the calculation of bioaccumulation metrics for active substances in living organisms. Integr Environ Assess Manag 18(1):10–18.

    CAS  Article  Google Scholar 

  • Rubach MN, Ashauer R, Maund SJ, Baird DJ, Van den Brink PJ (2010) Toxicokinetic variation in 15 freshwater arthropod species exposed to the insecticide chlorpyrifos. Environ Toxicol Chem 29(10):2225–2234.

    CAS  Article  Google Scholar 

  • Russell WMS, Burch RL (1959) The principles of humane experimental technique

  • Saito T, Otani T, Seike N, Okazaki M (2011) Final act of the conference of plenipotentiaries on the Stockholm convention on persistent organic pollutants: conference of plenipotentiaries on the Stockholm convention on persistent organic pollutants. Soil Sci Plant Nutr 57(1):157–166

    CAS  Article  Google Scholar 

  • Tennekes M. (2017) treemap: treemap visualization. R package version 2.4-2

  • Topuz E, van Gestel CAM (2015) Toxicokinetics and toxicodynamics of differently coated silver nanoparticles and silver nitrate in Enchytraeus crypticus upon aqueous exposure in an inert sand medium. Environ Toxicol Chem 34(12):2816–2823.

    CAS  Article  Google Scholar 

  • United States Environmental Protection Agency USEPA (1979) Toxic substances control act (TSCA) chemical substance inventory: User guide and indices to the initial inventory

  • Wang H, Xia X, Wang Z, Liu R, Muir DCG, Wang WX (2021) Contribution of dietary uptake to PAH bioaccumulation in a simplified pelagic food chain: modeling the influences of continuous vs intermittent feeding in zooplankton and fish. Environ Sci Technol 55(3):1930–1940.

    CAS  Article  Google Scholar 

  • Wassenaar PN, Verbruggen EM, Cieraad E, Peijnenburg WJ, Vijver MG (2020) Variability in fish bioconcentration factors: influences of study design and consequences for regulation. Chemosphere 239:124731.

    CAS  Article  Google Scholar 

  • Wilkinson MD, Dumontier M, Aalbersberg IJ, Appleton G, Axton M, Baak A, Blomberg N, Boiten JW, da Silva Santos LB, Bourne PE, Bouwman J, Brookes AJ, Clark T, Crosas M, Dillo I, Dumon O, Edmunds S, Evelo CT, Finkers R, Gonzalez-Beltran A, Gray AJ, Groth P, Goble C, Grethe JS, Heringa J, ’t Hoen PA, Hooft R, Kuhn T, Kok R, Kok J, Lusher SJ, Martone ME, Mons A, Packer AL, Persson B, Rocca-Serra P, Roos M, van Schaik R, Sansone SA, Schultes E, Sengstag T, Slater T, Strawn G, Swertz MA, Thompson M, van der Lei J, van Mulligen E, Velterop J, Waagmeester A, Wittenburg P, Wolstencroft K, Zhao J, Mons B (2016) The FAIR Guiding Principles for scientific data management and stewardship. Sci Data 3:1–9.

    Article  Google Scholar 

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This work was performed using the computing facilities of the CC LBBE/PRABI.


The authors are thankful to ANSES for providing the financial support for the development of the MOSAIC\(_\mathrm{bioacc}\) web tool (CNRS contract number 208483). This work is part of the ANR project APPROve (ANR-18-CE34-0013) for an integrated approach to propose proteomics for biomonitoring: accumulation, fate and multi-markers ( A large part of the work benefited from the French GDR “Aquatic Ecotoxicology” framework which aims at fostering stimulating scientific discussions and collaborations for more integrative approaches. At last, this work was made with the financial support of the Graduate School H2O’Lyon (ANR-17-EURE-0018) and “Université de Lyon” (UdL), as part of the program “Investissements d’ Avenir” run by “Agence Nationale de la Recherche” (ANR).

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All authors contributed to the investigation of the TK database. Raw data collection and first analyses were performed by Aude Ratier and Sandrine Charles. The first draft of the manuscript was written by Aude Ratier and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Sandrine Charles.

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Ratier, A., Lopes, C. & Charles, S. Improvements in Estimating Bioaccumulation Metrics in the Light of Toxicokinetic Models and Bayesian Inference. Arch Environ Contam Toxicol (2022).

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