TY - JOUR
KW - Chemical safety
KW - Human health protection
KW - new approach methodologies
KW - Next generation risk assessment
KW - Regulatory risk assessment
KW - Regulatory toxicology
AU - Sebastian Schmeisser
AU - Andrea Miccoli
AU - Martin von Bergen
AU - Elisabet Berggren
AU - Albert Braeuning
AU - Wibke Busch
AU - Christian Desaintes
AU - Anne Gourmelon
AU - Roland Grafström
AU - Joshua Harrill
AU - Thomas Hartung
AU - Matthias Herzler
AU - George E. N. Kass
AU - Nicole Kleinstreuer
AU - Marcel Leist
AU - Mirjam Luijten
AU - Philip Marx-Stoelting
AU - Oliver Poetz
AU - Bennard van Ravenzwaay
AU - Rob Roggeband
AU - Vera Rogiers
AU - Adrian Roth
AU - Pascal Sanders
AU - Russell S. Thomas
AU - Anne Marie Vinggaard
AU - Mathieu Vinken
AU - Bob van de Water
AU - Andreas Luch
AU - Tewes Tralau
AB - The predominantly animal-centric approach of chemical safety assessment has increasingly come under pressure. Society is questioning overall performance, sustainability, continued relevance for human health risk assessment and ethics of this system, demanding a change of paradigm. At the same time, the scientific toolbox used for risk assessment is continuously enriched by the development of “New Approach Methodologies” (NAMs). While this term does not define the age or the state of readiness of the innovation, it covers a wide range of methods, including quantitative structure–activity relationship (QSAR) predictions, high-throughput screening (HTS) bioassays, omics applications, cell cultures, organoids, microphysiological systems (MPS), machine learning models and artificial intelligence (AI). In addition to promising faster and more efficient toxicity testing, NAMs have the potential to fundamentally transform today’s regulatory work by allowing more human-relevant decision-making in terms of both hazard and exposure assessment. Yet, several obstacles hamper a broader application of NAMs in current regulatory risk assessment. Constraints in addressing repeated-dose toxicity, with particular reference to the chronic toxicity, and hesitance from relevant stakeholders, are major challenges for the implementation of NAMs in a broader context. Moreover, issues regarding predictivity, reproducibility and quantification need to be addressed and regulatory and legislative frameworks need to be adapted to NAMs. The conceptual perspective presented here has its focus on hazard assessment and is grounded on the main findings and conclusions from a symposium and workshop held in Berlin in November 2021. It intends to provide further insights into how NAMs can be gradually integrated into chemical risk assessment aimed at protection of human health, until eventually the current paradigm is replaced by an animal-free “Next Generation Risk Assessment” (NGRA).
BT - Environment International
DA - 2023-08-01
DO - 10.1016/j.envint.2023.108082
LA - en
N2 - The predominantly animal-centric approach of chemical safety assessment has increasingly come under pressure. Society is questioning overall performance, sustainability, continued relevance for human health risk assessment and ethics of this system, demanding a change of paradigm. At the same time, the scientific toolbox used for risk assessment is continuously enriched by the development of “New Approach Methodologies” (NAMs). While this term does not define the age or the state of readiness of the innovation, it covers a wide range of methods, including quantitative structure–activity relationship (QSAR) predictions, high-throughput screening (HTS) bioassays, omics applications, cell cultures, organoids, microphysiological systems (MPS), machine learning models and artificial intelligence (AI). In addition to promising faster and more efficient toxicity testing, NAMs have the potential to fundamentally transform today’s regulatory work by allowing more human-relevant decision-making in terms of both hazard and exposure assessment. Yet, several obstacles hamper a broader application of NAMs in current regulatory risk assessment. Constraints in addressing repeated-dose toxicity, with particular reference to the chronic toxicity, and hesitance from relevant stakeholders, are major challenges for the implementation of NAMs in a broader context. Moreover, issues regarding predictivity, reproducibility and quantification need to be addressed and regulatory and legislative frameworks need to be adapted to NAMs. The conceptual perspective presented here has its focus on hazard assessment and is grounded on the main findings and conclusions from a symposium and workshop held in Berlin in November 2021. It intends to provide further insights into how NAMs can be gradually integrated into chemical risk assessment aimed at protection of human health, until eventually the current paradigm is replaced by an animal-free “Next Generation Risk Assessment” (NGRA).
PY - 2023
EP - 108082
T2 - Environment International
TI - New approach methodologies in human regulatory toxicology – Not if, but how and when!
UR - https://www.sciencedirect.com/science/article/pii/S0160412023003550
VL - 178
Y2 - 2023-07-20
SN - 0160-4120
ER -