This is an internal GTTC Committee Meeting. Contact HESI Staff for more info.
HESI GTTC Annual Meeting
May 15, 2022 – May 18, 2022
Washington, DC, USA
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.
The United Nations subcommittee on the Globally Harmonized System of Classification and Labelling of Chemicals is examining whether or not to revise it’s definition of a germ cell mutation. Changes to the definition could impact the classification and labeling for many chemicals. HESI’s Genetic Toxicology Technical Committee Germ Cell Working Group is working to support their evaluation by re-visiting existing data regarding a substance’s molecular interaction with germ cell DNA. The working group will provide their opinion on what positive endpoints in somatic tissues and/or level of exposure in gonads would allow classification and labelling as a germ cell mutagen.
The GTTC HCD Working Group is querying laboratories about their experiences with compiling, maintaining and using historical control data and distributions for genetic toxicology assay acceptance and evaluation. The compiled data will be used to determine where consensus approaches exist and, where possible, make recommendations on compiling, maintaining and monitoring historical control data and distributions.
Historical Control Distribution Working Group Survey
The GTTC HCD Working Group is querying laboratories about their experiences with compiling, maintaining and using historical control data and distributions for genetic toxicology assay acceptance and evaluation. The compiled data will be used to determine where consensus approaches exist and, where possible, make recommendations on compiling, maintaining and monitoring historical control data and distributions.
Completed surveys should be sent to Connie Chen (cchen@hesiglobal.org) by April 15, 2022.
Please download both the survey (excel-based survey) and the PDF instructions that you can use as a reference.
NOTE: If you have trouble editing the xls file survey please try two things: 1) Enable editing 2) Enable macros
Leadership Team:
Robert Smith (Labcorp)
Robert Heflich (US Food and Drug Administration)
HESI Staff:
Connie Chen, PhD, MPH
The work group has evaluated the current testing paradigm for genotoxicity assessment of nanomaterials and is publishing the findings and recommendations for modifying the tests as needed. They are currently considering publishing a series of protocols for genetic toxicity testing of products containing nanomaterials.
Leadership Team:
Rosalie Elespuru, PhD (US Food and Drug Administration)
Shareen Doak, PhD (Swansea University)
HESI Staff:
Connie Chen, PhD, MPH
This work group was formed in 2016. This working group focused on providing more detailed advice about which in vivo tests to choose to follow-up on in vitro positive results and how to conduct the tests. As a first step, the group compared data for 90 chemicals for the transgenic rodent assay, the in vivo comet assay, and cancer data. This work was published in Mutation Research/Genetic Toxicology and Environmental Mutagenesis in January 2019 in an article titled “A Comparison of Transgenic Rodent Mutation and In Vivo Comet Assay Responses for 91 Chemicals.” Two follow-up areas include (1) providing best practices on the in vivo comet assay and collecting data on substances that are positive (i.e., induce micronuclei [MN]) in vivo and (2) comparing the plasma concentrations at the lowest effective dose (LOED) with the lowest effective concentration (LOEC) for MN induction in vitro, which could shed some light as to whether there is any relationship between LOEC and LOED for MN-inducing compounds.
Leadership Team:
Dan Roberts, PhD (Charles River Laboratories)
David Lovell, PhD (St. George’s University of London)
Matt LeBaron, PhD (Dow Chemical Company)
HESI Staff:
E’Lissa Flores, PhD
The MOA Work Group established four subteams to develop tubulin binding, topoisomerase II inhibition, aurora kinase inhibition, and reactive oxygen species activation adverse outcome pathways (AOPs). These AOPs will be submitted to the OECD AOPWiki site, a public repository for approved AOPs. Once these four subteams complete their work, the goal will be to merge them with the Clean Sheet Work Group.
Leadership Team:
Mirjam Luitjen, PhD (National Institute for Public Health and the Environment, RIVM, The Netherlands)
Jan van Benthem, PhD (National Institute for Public Health and the Environment, RIVM, The Netherlands)
Stefan Pfuhler, PhD (Procter & Gamble Company)
HESI Staff:
Connie Chen, PhD, MPH
Work for this group is centered around establishing/enhancing protocols for conducting genotoxicity assessment of effects to germ cells. After a series of publications in 2019, the group is finalizing a review on the impact of analyzing mutations in fast proliferating tissues at 28+28. This group is also considering future projects and the course of action for 2020–2021.
The United Nations subcommittee on the Globally Harmonized System of Classification and Labelling of Chemicals is examining whether or not to revise it’s definition of a germ cell mutation. Changes to the definition could impact the classification and labeling for many chemicals. HESI’s Genetic Toxicology Technical Committee Germ Cell Working Group is working to support their evaluation by re-visiting existing data regarding a substance’s molecular interaction with germ cell DNA. The working group will provide their opinion on what positive endpoints in somatic tissues and/or level of exposure in gonads would allow classification and labelling as a germ cell mutagen. The terms of reference and work program information can be found here: UN-SCEGHS-ToR GCM IGW
Leadership Team:
Jan van Benthem, PhD (National Institute for Public Health and the Environment, RIVM, The Netherlands)
Francesco Marchetti, PhD (Health Canada)
HESI Staff:
Connie Chen, PhD, MPH
This work group had their Detailed Review Paper (DRP) and a Validation/Retrospective Performance Analysis document accepted by OECD. It is currently drafting a Test Guideline to be reviewed and accepted by OECD in the future.
Leadership Team:
Steven Dertinger, PhD (Litron Laboratories)
Bob Heflich, PhD (US Food and Drug Administration)
HESI Staff:
Connie Chen, PhD, MPH
The work group is evaluating chemical data and enhancing tools for genetic toxicology dose-response modeling. The group has a planned 2020 virtual EMGS workshop scheduled for December 2020. Additionally, the group is planning to present at the International Workshops on Genotoxicity Testing (IWGT) 2021 meeting and is working on publishing guidance for the standard use and regulatory acceptance of using the benchmark dose (BMD) approach with genetic toxicology data.
Leadership Team:
George Johnson, PhD (Swansea University)
Andreas Zeller, PhD (Roche)
HESI Staff:
E’Lissa Flores, PhD
The MGRA Working Group will develop a new mechanism-based risk assessment paradigm for genotoxicity, based on the Clean Sheet approach and using genotoxicity AOP’s including the ones developed by GTTC. Case studies will be used to demonstrate the usefulness of innovative, mechanism-based, testing approaches to the scientific and regulatory community in a real risk assessment context. A series of workshops will also be established to identify challenges and hurdles for acceptance of innovative methods, where successful examples will be discussed with relevant stakeholders.
Leadership Team:
Mirjam Luitjen, PhD (National Institute for Public Health and the Environment, RIVM, The Netherlands)
Jan van Benthem, PhD (National Institute for Public Health and the Environment, RIVM, The Netherlands)
Stefan Pfuhler, PhD (Procter & Gamble Company)
HESI Staff:
E’Lissa Flores, PhD
This group is evaluating error-corrected next-generation sequencing (NGS) as an alternative methodology for evaluating in vivo mutagenesis. Over the past year, the group worked to qualify this platform in a second species and other mouse strains and began to work out the details on a technology transfer. Currently, the group is discussing the different workstreams/subgroups that would need to be established to move this project to the next phase, along with collaborations with both the eSTAR and CT-TRACs committees.
Leadership Team:
Bob Young, MS (MilliporeSigma)
Francesco Marchetti, PhD (Health Canada)
Sheroy Minocherhomji, PhD (Amgen)
HESI Staff:
Connie Chen, PhD, MPH
This newly established work group started this year with the following goals: (1) critically evaluate NAMs for in vitro genotoxicity testing, (2) envision how NAMs could expand current in vitro genetic toxicology testing strategies (e.g., developing a weight-of-evidence approach), and (3) make recommendations for creating an “in vitro only” approach for genetic toxicology testing that would meet the needs of various regulatory decision-makers.
Leadership Team:
Giel Hendriks, PhD (Toxys B.V.)
Stepahnie Smith-Roe, PhD (National Institute of Environmental Health Sciences, National Toxicology Program)
HESI Staff:
Connie Chen, PhD, MPH
National Institute for Public Health and the Environment, RIVM, The Netherlands
Charles River Laboratories
May 15, 2022 – May 18, 2022
Washington, DC, USA
This is an internal GTTC Committee Meeting. Contact HESI Staff for more info.
May 23, 2022 – May 26, 2022
Maastricht, Netherlands
The Health and Environmental Sciences Institute (HESI) Genetic Toxicology Technical Committee (GTTC) is proud to be a sponsor of the upcoming International Comet Assay Workshop & Environmental Mutagenesis and Genomics Society meeting. If you will be attending the ICAW-EEMGS 2022 meeting, stop by the HESI booth and say hi to ...
Toxicological Sciences, 2018
Nanomaterials (NMs) present unique challenges in safety evaluation. An international working group, the Genetic Toxicology (GTTC) Committee of the Health and Environmental Sciences Institute, has addressed issues related to the genotoxicity assessment of NMs.
Environmental and Molecular Mutagenesis, 2011
Appropriate follow-up actions and decisions are needed when evaluating and interpreting clear positive results obtained in the in vitro assays used in the initial genotoxicity screening battery (i.e., the battery of tests generally required by regulatory authorities) to assist in overall risk-based decision making ...
Environmental and Molecular Mutagenesis, 2014
Genetic toxicology data have traditionally been employed for qualitative, rather than quantitative evaluations of hazard.
Environmental and Molecular Mutagenesis, 2022
HESI Genetic Toxicology Technical Committee's first adverse outcome pathway (AOP) describing modes of actions leading to potentially heritable genomic damage is now online! This AOP focused on oxidative DNA damage and resulting mutations and chromosomal aberrations. It is currently included in the OECD workplan and is ...
Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2017
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 ...
Mutation Research / Genetic Toxicology and Environmental Mutagenesis, 2019
The HESI Genetic Toxicology (GTTC) Committee Data Interpretation Workgroup initiated a project to collect and collate sets of data from established and experienced laboratories into a standardized database.
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