An integrative test strategy for cancer hazard identification
article
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.
Topics
Carcinogenicitychromosome aberrationgenotoxic carcinogensgenotoxicitymutagenicitynon-genotoxic carcinogensregulatory implementationmutagenic agentbioassaycarcinogen testingcarcinogenicitygenotoxicitygenotoxicity assayhazard assessmentin vitro studyin vivo studymalignant neoplastic diseasenonhumanpharmacokineticsquantitative structure activity relationReviewtransgenic mouseproceduresstandardsAnimalsBiological AssayCarcinogenicity TestsCarcinogensDNA DamageHumansMutagenicity TestsMutagensNeoplasmsRisk Assessment
TNO Identifier
954721
ISSN
10408444
Source
Critical Reviews in Toxicology, 46(7), pp. 615-639.
Pages
615-639
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