Title
A comprehensive view on mechanistic approaches for cancer risk assessment of non-genotoxic agrochemicals
Author
Sewell, F.
Strupp, C.
van der Laan, J.W.
Wolf, D.C.
Wolterink, G.
Woutersen, R.
Zvonar, Z.
Heusinkveld, H.
Braakhuis, H.
Publication year
2020
Abstract
Currently the only methods for non-genotoxic carcinogenic hazard assessment accepted by most regulatory authorities are lifetime carcinogenicity studies. However, these involve the use of large numbers of animals and the relevance of their predictive power and results has been scientifically challenged. With increased availability of innovative test methods and enhanced understanding of carcinogenic processes, it is believed that tumour formation can now be better predicted using mechanistic information. A workshop organised by the European Partnership on Alternative Approaches to Animal Testing brought together experts to discuss an alternative, mechanism-based approach for cancer risk assessment of agrochemicals. Data from a toolbox of test methods for detecting modes of action (MOAs) underlying non-genotoxic carcinogenicity are combined with information from subchronic toxicity studies in a weight-of-evidence approach to identify carcinogenic potential of a test substance. The workshop included interactive sessions to discuss the approach using case studies. These showed that fine-tuning is needed, to build confidence in the proposed approach, to ensure scientific correctness, and to address different regulatory needs. This novel approach was considered realistic, and its regulatory acceptance and implementation can be facilitated in the coming years through continued dialogue between all stakeholders and building confidence in alternative approaches. © 2020 The Authors
Subject
3Rs
Alternative approaches to animal testing
Carcinogenicity
Human health risk assessment
Mode of action
NAMs
New approach methodologies
Non-genotoxic carcinogens
agricultural chemical
carcinogen
drug
cancer risk
carcinogenicity
case study
disease risk assessment
drug industry
evidence based medicine
exposure
feasibility study
government regulation
human
malignant neoplasm
measurement
non genotoxic carcinogenic hazard assessment
nonhuman
prediction
priority journal
Review
subchronic toxicity study
toxicity testing
toxicokinetics
uncertainty
weight of evidence approach
workshop
To reference this document use:
http://resolver.tudelft.nl/uuid:ffe14021-162d-43fb-bfb5-72a481767a45
DOI
https://doi.org/10.1016/j.yrtph.2020.104789
TNO identifier
955228
ISSN
0273-2300
Source
Regulatory Toxicology and Pharmacology, 118 (118)
Document type
article