Modernizing persistence–bioaccumulation–toxicity (PBT) assessment with high throughput animal-free methods

Research output: Journal contributionsJournal articlesResearchpeer-review


  • Beate I. Escher
  • Rolf Altenburger
  • Matthias Blüher
  • John K. Colbourne
  • Ralf Ebinghaus
  • Peter Fantke
  • Michaela Hein
  • Wolfgang Köck
  • Klaus Kümmerer
  • Sina Leipold
  • Xiaojing Li
  • Martin Scheringer
  • Stefan Scholz
  • Michael Schloter
  • Pia Johanna Schweizer
  • Tamara Tal
  • Igor Tetko
  • Claudia Traidl-Hoffmann
  • Lukas Y. Wick
  • Kathrin Fenner

The assessment of persistence (P), bioaccumulation (B), and toxicity (T) of a chemical is a crucial first step at ensuring chemical safety and is a cornerstone of the European Union’s chemicals regulation REACH (Registration, Evaluation, Authorization, and Restriction of Chemicals). Existing methods for PBT assessment are overly complex and cumbersome, have produced incorrect conclusions, and rely heavily on animal-intensive testing. We explore how new-approach methodologies (NAMs) can overcome the limitations of current PBT assessment. We propose two innovative hazard indicators, termed cumulative toxicity equivalents (CTE) and persistent toxicity equivalents (PTE). Together they are intended to replace existing PBT indicators and can also accommodate the emerging concept of PMT (where M stands for mobility). The proposed “toxicity equivalents” can be measured with high throughput in vitro bioassays. CTE refers to the toxic effects measured directly in any given sample, including single chemicals, substitution products, or mixtures. PTE is the equivalent measure of cumulative toxicity equivalents measured after simulated environmental degradation of the sample. With an appropriate panel of animal-free or alternative in vitro bioassays, CTE and PTE comprise key environmental and human health hazard indicators. CTE and PTE do not require analytical identification of transformation products and mixture components but instead prompt two key questions: is the chemical or mixture toxic, and is this toxicity persistent or can it be attenuated by environmental degradation? Taken together, the proposed hazard indicators CTE and PTE have the potential to integrate P, B/M and T assessment into one high-throughput experimental workflow that sidesteps the need for analytical measurements and will support the Chemicals Strategy for Sustainability of the European Union.

Original languageEnglish
JournalArchives of Toxicology
Issue number5
Pages (from-to)1267-1283
Number of pages17
Publication statusPublished - 01.05.2023

Bibliographical note

Funding Information:
We are grateful to a larger consortium of researchers affiliated with the Helmholtz Association that have met within the frame of the “Cooperation Across Research Fields” MACE (Mainstreaming Environmental Assessment for Complex Exposure) to discuss new pathways towards sustainable chemicals. In addition to the coauthors of this communication, we are grateful to Martin von Bergen, Monika Egerer, Jürgen Gandraß, Ivonne Nijenhuis, Nico Jehmlich, Deniz Tasdemir and Ralf Zimmermann for their contribution to the discussion.

Funding Information:
Open Access funding enabled and organized by Projekt DEAL. Some authors have received co-funding from the European Commission EU’s Horizon Europe research and innovation programme under Grant Agreement No 965406 (PrecisionTox) and 101057014 (PARC) and the German Ministry for Environment and Consumer protection. Main support was by the Helmholtz Association within the Helmholtz Research Field Earth and Environment POF IV Topic 9 “Healthy Planet- towards a non-toxic environment”. This output reflects only the authors’ views, and the European Union cannot be held responsible for any use that may be made of the information contained therein.

Publisher Copyright:
© 2023, The Author(s).

    Research areas

  • Biodegradation, Hazard assessment, In vitro bioassay, Mobility, New approach methodologies (NAMs), Persistence, Toxicity