TY - JOUR

T1 - Modernizing persistence–bioaccumulation–toxicity (PBT) assessment with high throughput animal-free methods

AU - Escher, Beate I.

AU - Altenburger, Rolf

AU - Blüher, Matthias

AU - Colbourne, John K.

AU - Ebinghaus, Ralf

AU - Fantke, Peter

AU - Hein, Michaela

AU - Köck, Wolfgang

AU - Kümmerer, Klaus

AU - Leipold, Sina

AU - Li, Xiaojing

AU - Scheringer, Martin

AU - Scholz, Stefan

AU - Schloter, Michael

AU - Schweizer, Pia Johanna

AU - Tal, Tamara

AU - Tetko, Igor

AU - Traidl-Hoffmann, Claudia

AU - Wick, Lukas Y.

AU - Fenner, Kathrin

N1 - 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).

PY - 2023/5/1

Y1 - 2023/5/1

N2 - 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.

AB - 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.

KW - Biodegradation

KW - Hazard assessment

KW - In vitro bioassay

KW - Mobility

KW - New approach methodologies (NAMs)

KW - Persistence

KW - Toxicity

UR - http://www.scopus.com/inward/record.url?scp=85150653906&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/79288e1c-36a2-3b85-9075-77a0cd1bc696/

U2 - 10.1007/s00204-023-03485-5

DO - 10.1007/s00204-023-03485-5

M3 - Journal articles

C2 - 36952002

AN - SCOPUS:85150653906

VL - 97

SP - 1267

EP - 1283

JO - Archives of Toxicology

JF - Archives of Toxicology

SN - 0340-5761

IS - 5

ER -