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New perspectives for alternative approaches to carcinogenicity testing: a regulator viewpoint
1Preclinical Assessment Group of the Medicines Evaluation Board in The Netherlands, National Institute of Public Health and the Environment, BA.
Abstract:
Genotoxic compounds are thought more likely to be transspecies carcinogens inducing carcinomas in more than one species, implying a hazard to humans. Non-genotoxic compounds will have a certain threshold concentration below which they are definitely not carcinogenic. What are we looking for in the case of pharmaceuticals? New animal models would be helpful to enhance the quality of assessment of carcinogenic potential, based on 'weight of evidence', in order to reach the goal of replacing animal life span studies without compromising human safety. Such studies should supplement life span studies and provide additional information not readily available from the long-term assay. Short- or medium-term assays may be helpful in confirming the transspecies character of carcinogens.
Insights
Genotoxic compounds pose a higher cancer risk across species, including humans. New animal models and shorter tests can improve carcinogenicity assessments for pharmaceuticals, aiming to reduce animal testing while ensuring safety.
Area of Science:
- Toxicology
- Pharmacology
- Carcinogenesis
Background:
- Genotoxic compounds are more likely to be transspecies carcinogens, posing a risk to humans.
- Non-genotoxic compounds have a threshold concentration below which they are not carcinogenic.
- Assessing the carcinogenic potential of pharmaceuticals requires robust methodologies.
Purpose of the Study:
- To explore the utility of new animal models for carcinogenicity assessment.
- To evaluate the role of short- or medium-term assays in pharmaceutical safety evaluation.
- To support the goal of replacing animal lifespan studies without compromising human safety.
Main Methods:
- Review of existing knowledge on genotoxic and non-genotoxic carcinogens.
- Discussion on the 'weight of evidence' approach for carcinogenicity assessment.
- Consideration of novel animal models and alternative testing strategies.
Main Results:
- Genotoxic compounds are presumed to be transspecies carcinogens, indicating a potential human hazard.
- Non-genotoxic compounds exhibit a threshold effect, below which they are not carcinogenic.
- Short- or medium-term assays can aid in confirming the transspecies nature of carcinogens.
Conclusions:
- New animal models are needed to enhance the assessment of carcinogenic potential.
- Alternative assays can supplement long-term studies and provide crucial data.
- The development of such methods is key to reducing animal use in pharmaceutical safety testing.