Genetic Toxicology (GTTC) Committee

Mission Statement

The mission of this committee is to improve the scientific basis of the interpretation of results from genetic toxicology tests for purposes of more accurate hazard identification and assessment of human risk; to develop follow-up strategies for determining the relevance of test results to human health; to provide a framework for integration of testing results into a risk-based assessment of the effects of chemical exposures on human health; to promote the integration and use of new techniques and scientific knowledge in the evaluation of genetic toxicology; and to monitor and promote the development of innovative tests and testing strategies.

HESI Staff

Leadership Team

  • Mirjam Luitjen, PhD

    National Institute for Public Health and the Environment, RIVM, The Netherlands

  • Leon Stankowski, PhD

    Charles River Laboratories

Committee Events

Quantitative Interpretation of Genetic Toxicity Dose Response Data for Risk Assessment and Regulatory Decision-Making: Current Status, Persistent Challenges, and Emerging Priorities

Virtual workshop, hosted by HESI and the Environmental Mutagenesis and Genomics Society (EMGS)

The workshop will (1) provide a brief overview of the state of the science regarding quantitative interpretation of genetic toxicity dose-response data, including a brief overview of the BMD combined covariate approach for potency ranking and MOA investigation, (2) a summary of recent genotoxicity risk assessment case ...

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Validation of New Approaches in Genetic Toxicology

Newark, Delaware, USA

Novel in vitro and in vivo assays have been developed to improve the reliability of tools employed for identification of genotoxic hazard. Several of the new assays can provide insight into mode-of-action (MoA). As emerging technologies generally used for evaluating human hazard and/or risk, these novel ...

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Applied Genetic Toxicity for Regulatory Decision Making: The Road Ahead

Potsdam, Germany

Applied genetic toxicology is undergoing a major paradigm shift towards changing the strategies employed for assessment of chemically-induced genomic damage, evaluation methods of the mechanisms by which that damage translates into adverse effects, and the quantitative methods used to interpret dose-response data. This ...

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Workshop Agenda

Workshop Objectives

Mirjam Luitjen, RIVM

Path Forward for Genetic Toxicity Assessment

Kerry Dearfield, Former USDA

The New Strategy in Practice: Case Study Examples

Veronique Thybaud, Sanofi & Nicholas Ball, DOW

Incorporating Mode of Action into Genetic Toxicity Assessment

Roland Frötschl, BfArM, Germany

Novel Approaches and Technologies to Assess Genotoxic Modes of Action

Stefan Pfuhler, Procter & Gamble

Genetic Toxicity Mini-Adverse Outcome Pathways (mini-AOPs)

Azeddine Elhajouji, Novartis

Approaches for Analyses and Interpretation of Genetic Toxicity Dose-Response

Paul White, Health Canada

Quantitative Dose-Response Analyses for Risk Assessment and Regulatory Decision Making: Issues, Applications, and Challenges

George Johnson, Swansea University

Background and Objectives
Applied genetic toxicology is undergoing a major paradigm shift towards changing the strategies employed for assessment of chemically-induced genomic damage, evaluation methods of the mechanisms by which that damage translates into adverse effects, and the quantitative methods used to interpret dose-response data. This shift entails a movement away from simple dichotomous evaluations of genotoxicity (i.e., yes/no), that only supports identification of potential carcinogens, and towards a greater understanding of the diversity of adverse outcomes related to genomic damage, of the multitude of mechanisms (or modes of action) underscoring genomic damage, and the ability to determine point of departure metrics for human health risk assessment and regulatory decision making. Moreover, advanced technologies to investigate genotoxic mechanisms and to analyze dose-response functions are being developed and incorporated into assessments of genomic damage.

 

This workshop was organized by the HESI Genetic Toxicology Technical Committee (GTTC). The HESI GTTC brings together an international cohort of genetic toxicologists from industry, academia, and government to address issues related to all aspects of genetic toxicity assessment. These aspects include the development and validation of assessment approaches, technologies and strategies for mode-of-action determination, and approaches for data interpretation. The GTTC is comprised of experts in the fields of genetic and general toxicology, risk assessment, and computational biology. The workshop will examine a new generation of testing strategy for assessment of genomic damage, new approaches and technologies for mode-of-action determination and interpretation, and recent developments in quantitative interpretation of genetic toxicity dose-response data.

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Committee Publications

Filter

A Comparison of Transgenic Rodent Mutation and In Vivo Comet Assay Responses for 91 Chemicals

Whilst the TGR and comet assays are available for measuring genotoxic effects in multiple rodent tissues, there has been no systematic comparison of their performance in detecting genotoxicity per se. A working group of the Genetic Toxicology Technical Committee (GTTC), part of the Health and Environmental Sciences Institute ...

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Identifying Germ Cell Mutagens Using OECD Test Guideline 488 (Transgenic Rodent Somatic and Germ Cell Gene Mutation Assays) and Integration with Somatic Cell Testing

The Organisation for Economic Co-operation and Development Test Guideline 488 (TG 488) provides recommendations for assessing germ cell and somatic cell mutagenicity using transgenic rodent (TGR) models. However, important data gaps exist for selecting an optimal approach for simultaneously evaluating mutagenicity in ...

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Simulation of Mouse and Rat Spermatogenesis to Inform Genotoxicity Testing Using OECD Test Guideline 488

The Germ Cell Workgroup of the Genetic Toxicology (GTTC) Committee of the Health and Environmental Sciences Institute modeled mouse and rat spermatogenesis to better define the exposure history of the cell population collected from seminiferous tubules.

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Analysis of Negative Historical Control Group Data from the In Vitro Micronucleus Assay Using TK6 Cells

The recent revisions of the Organisation for Economic Co-operation and Development (OECD) genetic toxicology test guidelines emphasize the importance of historical negative controls both for data quality and interpretation. The goal of a HESI Genetic Toxicology (GTTC) Committee workgroup was to collect data from ...

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