Title
An integrative test strategy for cancer hazard identification
Author
Luijten, M.
Olthof, E.D.
Hakkert, B.C.
Rorije, E.
van der Laan, J.-W.
Woutersen, R.A.
van Benthem, J.
Publication year
2016
Abstract
Assessment of genotoxic and carcinogenic potential is considered one of the basic requirements when evaluating possible human health risks associated with exposure to chemicals. Test strategies currently in place focus primarily on identifying genotoxic potential due to the strong association between the accumulation of genetic damage and cancer. Using genotoxicity assays to predict carcinogenic potential has the significant drawback that risks from non-genotoxic carcinogens remain largely undetected unless carcinogenicity studies are performed. Furthermore, test systems already developed to reduce animal use are not easily accepted and implemented by either industries or regulators. This manuscript reviews the test methods for cancer hazard identification that have been adopted by the regulatory authorities, and discusses the most promising alternative methods that have been developed to date. Based on these findings, a generally applicable tiered test strategy is proposed that can be considered capable of detecting both genotoxic as well as non-genotoxic carcinogens and will improve understanding of the underlying mode of action. Finally, strengths and weaknesses of this new integrative test strategy for cancer hazard identification are presented. Chemicals / CAS Carcinogens; Mutagens.
Subject
Carcinogenicity
chromosome aberration
genotoxic carcinogens
genotoxicity
mutagenicity
non-genotoxic carcinogens
regulatory implementation
mutagenic agent
bioassay
carcinogen testing
carcinogenicity
genotoxicity
genotoxicity assay
hazard assessment
in vitro study
in vivo study
malignant neoplastic disease
nonhuman
pharmacokinetics
quantitative structure activity relation
Review
transgenic mouse
procedures
standards
Animals
Biological Assay
Carcinogenicity Tests
Carcinogens
DNA Damage
Humans
Mutagenicity Tests
Mutagens
Neoplasms
Risk Assessment
Life
RAPID - Risk Analysis for Products in Development
To reference this document use:
http://resolver.tudelft.nl/uuid:c12875e3-0071-4a39-b53f-b4bcd3d24b56
DOI
https://doi.org/10.3109/10408444.2016.1171294
TNO identifier
954721
ISSN
1040-8444
Source
Critical Reviews in Toxicology, 46 (46), 615-639
Document type
article