The need for epigenotoxicity testing.

Area of Science:

• Toxicology
• Genetics
• Environmental Health

Background:

• Cell phenotype is determined by genetics and external factors (exposome), involving gene x environment interaction (GxE).
• Epigenetics, including DNA methylation and histone modifications, influences gene accessibility and protein expression.
• Epigenetic changes can retain memory of exposures, impacting susceptibility to subsequent environmental factors.

Purpose of the Study:

• To provide an overview of epigenetics in toxicology.
• To advocate for systematic assessment of epigenetic changes in toxicity evaluations.
• To propose strategies for predicting individual risk using human-relevant models, biomarkers, and AI.

Main Methods:

• Review of epigenetic mechanisms (DNA methylation, histone modifications, non-coding RNAs, DNA packaging).
• Discussion of epigenetics' role in gene x environment interaction (GxE) and disease pathology.
• Proposal of tools and strategies including human-relevant models, biomarkers, and artificial intelligence (AI).

Main Results:

• Epigenetics provides a mechanism for understanding how environmental exposures influence health outcomes.
• Epigenetic memory of exposure can reveal insights into mixture toxicity and non-simultaneous exposures.
• Understanding epigenetics can inform the development of novel drugs for diseases like cancer and neurodegenerative disorders.

Conclusions:

• Integrating epigenetics into toxicology assessments is crucial for understanding disease and predicting risk.
• Systematic assessment of epigenetic changes can enhance toxicity evaluations and regulatory practices.
• Utilizing epigenetics can lead to safer products and improved protection for individuals and future generations.