GenoITS: Implementation of an Integrated Testing Strategy workflow for genotoxicity using QSAR-based tools

Area of Science:

• Computational toxicology
• Regulatory science
• Chemical safety assessment

Background:

• EU REACH regulation mandates extensive chemical testing, posing economic and ethical challenges.
• Standard Information Requirements include genotoxicity assays, often involving animal testing.
• Minimizing animal use (3Rs) is a key regulatory objective.

Purpose of the Study:

• To develop an exclusively computational Integrated Testing Strategy for chemical genotoxicity assessment.
• To create an automated workflow, GenoITS, to streamline regulatory testing.
• To reduce the economic burden and ethical concerns associated with traditional genotoxicity testing.

Main Methods:

• Integration of diverse genotoxicity assays (gene mutation, cytogenotoxicity) into an automated workflow.
• Utilization of in-house Quantitative Structure-Activity Relationship (QSAR) models to fill data gaps.
• Development of GenoITS as part of the ProtoPRED prediction suite, following REACH genotoxicity assessment schema.

Main Results:

• GenoITS provides an automated workflow for genotoxicity testing.
• The system combines assay data and QSAR predictions for a binary classification (genotoxic/not genotoxic).
• The workflow is designed to meet regulatory requirements for chemical safety assessment.

Conclusions:

• The GenoITS workflow offers a viable computational alternative for genotoxicity testing.
• This approach supports regulatory compliance while adhering to the 3Rs principles.
• The web-based platform benefits the scientific community navigating REACH and other chemical regulations.