Predicting the carcinogenicity of chemicals with alternative approaches: recent advances

Area of Science:

• Toxicology
• Chemical Safety Assessment
• In Vitro Methods

Background:

• Rodent bioassays are traditional but limited for early chemical safety assessment.
• Need for alternative methods to identify problematic drugs, biocides, and environmental chemicals.
• Existing safety documentation is often inadequate for environmental chemicals.

Purpose of the Study:

• To review alternative approaches to rodent bioassays for chemical safety.
• To discuss methods for addressing false-positive and false-negative results in alternative testing.
• To propose a framework for reducing animal testing and enhancing human health protection.

Main Methods:

• Review of genotoxicity testing, integrative DNA-reactivity and tissue disorganization assays.
• Exploration of omics technologies (ToxCast/Tox21) and pragmatic approaches (read-across, category formation).
• Analysis of strengths and limitations of various alternative testing strategies.

Main Results:

• Differential approaches are needed to manage false negatives and false positives.
• Quantitative structure-activity relationships and in vitro tests can minimize false negatives.
• Mechanistically based follow-up studies can resolve false positives.

Conclusions:

• A framework combining various alternative methods can reduce reliance on animal testing.
• Accurate identification of chemical hazards improves human health protection.
• Alternative methods offer a viable path for comprehensive chemical safety assessment.