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 - 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

KW - Chemistry

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

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 -