Genetic Toxicology Technical Committee (GTTC)

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.

Working Groups

  • Education and Science Outreach Committee

    Launched in 2022, the Education and Science Outreach Working Group aims to promote genetic toxicology as a career path and equip the next generation of scientists with foundational skills and experiences. By creating opportunities for networking, skill-building, and mentorship, the group supports early-career researchers in advancing their expertise and connecting with leaders in the field.

    Since 2024, the GTTC has offered two professional development awards that help trainees share their research and grow professionally.

    • Professional Development Travel Award – This award supports attendance at scientific conferences and workshops, allowing trainees to engage with current research, expand their networks, and gain insights into cutting-edge topics in genetic toxicology.
    • Professional Development Training Award – This award supports travel for specialized training courses, cross-laboratory exchanges, and skill-building activities, this award is designed to strengthen core competencies and enhance the practical skills needed in research.

    All awardees are invited to the GTTC Annual Meeting to learn about emerging projects and science at HESI and to network with experts in the gene toxicology field.

    Leadership Team:
    Joel Bercu (Gilead)

    HESI Staff:
    Raechel Puglisi, MPH

  • Error-Corrected Sequencing

    This working group is focused on evaluating error corrected next generation sequencing (ECS) as an alternative method for assessing in vivo mutagenesis. It’s current focus is on investigating the suitability of ECS for regulatory mutagenicity testing. The working group is currently focused on:

    • Supporting efforts to develop a publicly available database to be housed at the Division of Translational Toxicology/ National Institute of Environmental Health Sciences (DTT/NIEHS);
    • Supporting and advancing the use of  ECS for in vivo mutagenicity testing to enable broader genomic model applications and improved quantitative risk assessment;
    • Advancing in vitro applications of ECS

    Leadership Team:
    Shaofei Zhang (Pfizer), Javier Revollo (US FDA/NCTR)

    HESI Staff:
    Connie Chen, PhD, MPH

  • Germ Cells

    This working group focuses on developing and refining protocols for assessing genotoxic effects on germ cells. Current efforts include:

    • Quantitative analyses of germ cell data
    • Genotoxic effects in oocytes
    • In vitro approaches for germ cell mutagenicity

    Leadership Team:
    Roger Godschalk (Maastricht University), Jan van Benthem, PhD (RIVM, Retired)

    HESI Staff:
    Connie Chen, PhD, MPH

  • In Vitro

    This working group aims to critically evaluate new approach methodologies (NAMs) for in vitro genotoxicity testing, aiming to expand current testing strategies and ultimately make recommendations for creating an “in vitro only” approach for genetox testing that meets the needs of various regulatory decision-makers. The group is currently focused on the first of its committee-defined goals, which involves a comprehensive critical evaluation of NAMS through four focus areas:

    • Identification of aneugens;
    • Metabolism;
    • Indirect genotoxicity;
    • IVIVE

    Leadership Team:
    Marc Beal (Merck & Co.), Giel Hendriks, PhD (Toxys B.V.)

    Subteam Leadership: IVIVE – Alexandra Long (Health Canada); Metabolism – Nikolai Chepelev (Health Canada), Xiaoqing Guo (US FDA/NCTR); Indirect GTX – Ashley Allemang (P&G), Inger Brandsma (Toxys); Aneugens – Xiaowen Sun (Pfizer)

    HESI Staff:
    Alexandra Taraboletti, PhD

  • In Vivo Follow-Up

    This working group is dedicated to offering detailed guidance and best practices for selecting and conducting in vivo tests following a positive genotoxicity result. A key focus is ensuring that follow-up testing aligns with regulatory requirements and scientific best practices. The current  focus is on cytotoxicity of in vivo comet assays (data collection for retrospective analysis and development of a novel in vivo study). The recent pilot study data are under analysis, and on the following:

    • Evaluating the sensitivity of in vivo methods to detect weak effects of known mutagens.
    • Investigating how tail intensity influences the ability to detect subtle genotoxic effects.
    • These efforts aim to refine in vivo follow-up testing strategies, enhancing their precision and reliability in genotoxicity assessments.

    Leadership Team:
    Carol Beevers (Corteva), Matt LeBaron (Dow Chemical Company), David Lovell (St. George’s University of London)

    HESI Staff:
    Connie Chen, PhD, MPH

  • Mechanism-based Genotoxicity Risk Assessment (MGRA)

    The MRGA working group integrates the efforts of the former MOA and Clean Sheet working groups to establish a new mechanism-based paradigm for genotoxicity risk assessment. The group is composed of two subgroups focusing on Nitrosamines, and Titanium Dioxide (TiO2).

    Nitrosamines Working Group
    The primary objective of this subteam is to advance the scientific understanding and risk assessment of nitrosamines’ genotoxic potential through innovative mechanism-based testing approaches. (Leadership Team: Tetyana Cheairs (NY Medical College), Joel Bercu (Gilead))

    This subteam has four working groups:

    1. Ames Optimization – Goal: Develop an optimized Ames protocol that is predictive of the carcinogenic potential of nitrosamines (Leadership Team: Anthony Lynch (GSK), Joel Bercu (Gilead); HESI Staff: Raechel Puglisi, MPH)
    2. In Vitro Approaches – Goal: Identification and verification of in vitro assays to assist in nitrosamine risk identification (Leadership Team: Xiaowen Sun (Pfizer) and Xiaoqing (Carol) Guo (US FDA/NCTR); HESI Staff: Raechel Puglisi, MPH)
    3. In Vivo Folow-up – Goal: Develop an in vivo strategy to verify Ames data within the frame of ICH M7 (Leadership: Joel Bercu (Gilead), Robert Jolly (Eli Lilly), Sheroy Minocherhomji (Eli Lilly), Timothy McGovern (US FDA); HESI Staff: Raechel Puglisi, MPH)
    4. (Q)SAR/QM – Goal: Refine and extend the CPCA using (Q)SAR and QM for improved predictive performance. (Leadership: David Ponting (Lhasa), Jakub Kostal (George Washington University), Clarence Wybon (Independent); HESI Staff: Alex Taraboletti, PhD

    For more information about this subgroup – https://hesiglobal.org/gttc-nitrosamines/

    o-NNO Working Group
    This working group is focused on developing a science-based framework for evaluating the genotoxic and carcinogenic potential of n-nitroso compounds that are not nitrosamines (o-NNOs). The group will assess the current scientific data regarding genotoxicity and carcinogenicity of o-NNOs, identify data gaps, and generate experimental evidence and develop predictive models to inform quantitative risk assessment and safety limit setting

    Leadership Team:
    Michelle Kenyon (Pfizer)

    HESI Staff:
    Connie Chen, PhD, MPH

  • Mode of Action (MOA)

    This working group is completing several OECD AOP wikis. The first AOP “Oxidative DNA damage leading to mutations and chromosomal damage” was published on the AOPWiki in April 2023. The tubulin binding and topoisomerase II inhibition AOPs will be completed in early 2024, after which this work group will merge into the new MGRA work group.

    Leadership for Tubulin binding AOP:
    Yasmin Dietz (Sanofi)

    Leadership for Topoisomerase II AOP:
    Xiaowen Sun (Pfizer), Ryan Wheeldon (J&J)

    HESI Staff:
    Connie Chen, PhD, MPH

  • Quantitative Analysis (QA)

    This working group is driving advancements in genetic toxicology by evaluating chemical data and enhancing dose-response modeling tools. Key projects include:

    • Conducting a comprehensive genotoxicity dose-response study involving 48 mutagenic carcinogens.
    • Establishing critical effect size parameters to guide risk assessments.
      Providing data-driven insights to inform exposure limits for nitrosamines.
    • Collaborating with industry partners to expand the functionality of the GeneToxPi visualization tool.

    Research highlights involve optimizing in vivo study designs for precise Benchmark Dose (BMD) calculations and assessing inter-individual DNA repair variability. These efforts aim to promote broader adoption of dose-response modeling in regulatory decision-making.

    Leadership Team:
    George Johnson (GTox Ltd.), Andreas Zeller (Roche), Paul White (Health Canada)

    HESI Staff:
    Alexandra Taraboletti, PhD

HESI GTTC Professional Development Awardees 2026

The HESI Global Genetic Toxicology Technical Committee (GTTC) Education and Science Outreach Committee is pleased to announce the recipients of the 2026 Professional Development Travel Awards.

These awards will provide opportunities for new investigators to attend scientific conferences, workshops, or courses, etc., to build core competencies and transferable skills, and/or share their research.

Two award categories:

• Professional Development Travel Award: Provides $1,500 USD for travel to attend scientific conferences or workshops.
• Professional Development Training Award: Provides $4,000 USD for travel specific to training courses, cross-lab trainings, etc., to build core competencies and transferrable skills.

  • Past Award Winners

    2025 Travel Awardees: Alina Göpfert (BASF SE, Ludwigshafen / Free University Berlin), Caitlin Maggs (Swansea University), Deniz Akin (Swansea University), Gloria Melzi (University of Milan), Josie Jabbour (University of Ottawa), Sofija Stojanovic (University of Groningen, The Netherlands), Vanitha Thurairsu (National University of Malaysia)

    2025 Training Awardees: Alina Göpfert (BASF SE, Ludwigshafen / Free University Berlin), Alper James Alcaraz (University of Ottawa)

    2024 Travel Awardees: Elena Esina (University of Ottawa), Rim Nassar (University of Montpellier – France and Lebanese University), Madeleine Oman (University of Toronto), Lily Thompson (Thomas Jefferson University), Xinwen Zhang (NIEHS)

    2024 Training Awardee: Caitlin Maggs (Swansea University)

    2023 Awardees: Tony Okeke (Drexel University), Ammer Khawam (McGill University), Natalia Bertolez (University of Coruna), Sarah Park (Oak Ridge, US EPA), Victoria Bastos (Maastricht University), Alper Alcarez (NIEHS), Idoia Meaza Izusi (University of Louisville)

    2022 Spring Awardees: Jonathan Axellson (UOttawa), Julie Sanders (Sciensano), Anouk Thienpont (VUB), Sam Vielee (U Louisville), David Schuster (UOttawa), Danila Cuomo (Texas A&M).

    2022 Fall Awardees: Zhenming Yang (Rutgers), Lee Pribyl (MIT), Natalie Laspata (Pittsburg), Daniela Muoio (Pittsburg), Elizabeth Irvin (NC State), Rebekah Petroff (Michigan).

HESI Staff

Leadership Team

  • Carol Beevers, PhD

    Corteva Agriscience

  • Francesco Marchetti, PhD

    Health Canada

Committee Events

Filter

Applied Genetic Toxicity for Regulatory Decision Making: The Road Ahead

March 22, 2018 – March 23, 2018

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 ...

Read more

WP_Query Object
(
    [query] => Array
        (
            [post_type] => event
            [posts_per_page] => 6
            [type] => 
            [area] => 
            [before] => 2050-01-01
            [after] => 
            [tags] => GTTC
            [showtitle] => false
            [meta_query] => Array
                (
                    [relation] => AND
                    [0] => Array
                        (
                            [key] => _ilsi_date
                            [value] => 2050-01-01
                            [compare] => <=
                        )

                    [1] => Array
                        (
                            [key] => _ilsi_end_date
                            [value] => 2050-01-01
                            [compare] => <=
                        )

                    [2] => Array
                        (
                            [key] => _ilsi_date
                            [value] => Array
                                (
                                    [0] => 2018-01-01
                                    [1] => 2018-12-31
                                )

                            [compare] => BETWEEN
                        )

                    [3] => Array
                        (
                            [key] => _ilsi_date
                            [value] => 2018-12-31
                            [compare] => <
                        )

                )

            [paged] => 1
            [tax_query] => Array
                (
                    [0] => Array
                        (
                            [taxonomy] => post_tag
                            [field] => name
                            [terms] => GTTC
                        )

                )

            [meta_key] => _ilsi_date
            [orderby] => meta_value
            [order] => DESC
        )

    [query_vars] => Array
        (
            [post_type] => event
            [posts_per_page] => 6
            [type] => 
            [area] => 
            [before] => 2050-01-01
            [after] => 
            [tags] => GTTC
            [showtitle] => false
            [meta_query] => Array
                (
                    [relation] => AND
                    [0] => Array
                        (
                            [key] => _ilsi_date
                            [value] => 2050-01-01
                            [compare] => <=
                        )

                    [1] => Array
                        (
                            [key] => _ilsi_end_date
                            [value] => 2050-01-01
                            [compare] => <=
                        )

                    [2] => Array
                        (
                            [key] => _ilsi_date
                            [value] => Array
                                (
                                    [0] => 2018-01-01
                                    [1] => 2018-12-31
                                )

                            [compare] => BETWEEN
                        )

                    [3] => Array
                        (
                            [key] => _ilsi_date
                            [value] => 2018-12-31
                            [compare] => <
                        )

                )

            [paged] => 1
            [tax_query] => Array
                (
                    [0] => Array
                        (
                            [taxonomy] => post_tag
                            [field] => name
                            [terms] => GTTC
                        )

                )

            [meta_key] => _ilsi_date
            [orderby] => meta_value
            [order] => DESC
            [error] => 
            [m] => 
            [p] => 0
            [post_parent] => 
            [subpost] => 
            [subpost_id] => 
            [attachment] => 
            [attachment_id] => 0
            [name] => 
            [pagename] => 
            [page_id] => 0
            [second] => 
            [minute] => 
            [hour] => 
            [day] => 0
            [monthnum] => 0
            [year] => 0
            [w] => 0
            [category_name] => 
            [tag] => 
            [cat] => 
            [tag_id] => 802
            [author] => 
            [author_name] => 
            [feed] => 
            [tb] => 
            [meta_value] => 
            [preview] => 
            [s] => 
            [sentence] => 
            [title] => 
            [fields] => all
            [menu_order] => 
            [embed] => 
            [category__in] => Array
                (
                )

            [category__not_in] => Array
                (
                )

            [category__and] => Array
                (
                )

            [post__in] => Array
                (
                )

            [post__not_in] => Array
                (
                )

            [post_name__in] => Array
                (
                )

            [tag__in] => Array
                (
                )

            [tag__not_in] => Array
                (
                )

            [tag__and] => Array
                (
                )

            [tag_slug__in] => Array
                (
                )

            [tag_slug__and] => Array
                (
                )

            [post_parent__in] => Array
                (
                )

            [post_parent__not_in] => Array
                (
                )

            [author__in] => Array
                (
                )

            [author__not_in] => Array
                (
                )

            [search_columns] => Array
                (
                )

            [ignore_sticky_posts] => 
            [suppress_filters] => 
            [cache_results] => 1
            [update_post_term_cache] => 1
            [update_menu_item_cache] => 
            [lazy_load_term_meta] => 1
            [update_post_meta_cache] => 1
            [nopaging] => 
            [comments_per_page] => 50
            [no_found_rows] => 
        )

    [tax_query] => WP_Tax_Query Object
        (
            [queries] => Array
                (
                    [0] => Array
                        (
                            [taxonomy] => post_tag
                            [terms] => Array
                                (
                                    [0] => GTTC
                                )

                            [field] => name
                            [operator] => IN
                            [include_children] => 1
                        )

                )

            [relation] => AND
            [table_aliases:protected] => Array
                (
                    [0] => wp_term_relationships
                )

            [queried_terms] => Array
                (
                    [post_tag] => Array
                        (
                            [terms] => Array
                                (
                                    [0] => GTTC
                                )

                            [field] => name
                        )

                )

            [primary_table] => wp_posts
            [primary_id_column] => ID
        )

    [meta_query] => WP_Meta_Query Object
        (
            [queries] => Array
                (
                    [0] => Array
                        (
                            [key] => _ilsi_date
                        )

                    [1] => Array
                        (
                            [0] => Array
                                (
                                    [key] => _ilsi_date
                                    [value] => 2050-01-01
                                    [compare] => <=
                                )

                            [1] => Array
                                (
                                    [key] => _ilsi_end_date
                                    [value] => 2050-01-01
                                    [compare] => <=
                                )

                            [2] => Array
                                (
                                    [key] => _ilsi_date
                                    [value] => Array
                                        (
                                            [0] => 2018-01-01
                                            [1] => 2018-12-31
                                        )

                                    [compare] => BETWEEN
                                )

                            [3] => Array
                                (
                                    [key] => _ilsi_date
                                    [value] => 2018-12-31
                                    [compare] => <
                                )

                            [relation] => AND
                        )

                    [relation] => AND
                )

            [relation] => AND
            [meta_table] => wp_postmeta
            [meta_id_column] => post_id
            [primary_table] => wp_posts
            [primary_id_column] => ID
            [table_aliases:protected] => Array
                (
                    [0] => wp_postmeta
                    [1] => mt1
                    [2] => mt2
                    [3] => mt3
                    [4] => mt4
                )

            [clauses:protected] => Array
                (
                    [wp_postmeta] => Array
                        (
                            [key] => _ilsi_date
                            [compare] => =
                            [compare_key] => =
                            [alias] => wp_postmeta
                            [cast] => CHAR
                        )

                    [mt1] => Array
                        (
                            [key] => _ilsi_date
                            [value] => 2050-01-01
                            [compare] => <=
                            [compare_key] => =
                            [alias] => mt1
                            [cast] => CHAR
                        )

                    [mt2] => Array
                        (
                            [key] => _ilsi_end_date
                            [value] => 2050-01-01
                            [compare] => <=
                            [compare_key] => =
                            [alias] => mt2
                            [cast] => CHAR
                        )

                    [mt3] => Array
                        (
                            [key] => _ilsi_date
                            [value] => Array
                                (
                                    [0] => 2018-01-01
                                    [1] => 2018-12-31
                                )

                            [compare] => BETWEEN
                            [compare_key] => =
                            [alias] => mt3
                            [cast] => CHAR
                        )

                    [mt4] => Array
                        (
                            [key] => _ilsi_date
                            [value] => 2018-12-31
                            [compare] => <
                            [compare_key] => =
                            [alias] => mt4
                            [cast] => CHAR
                        )

                )

            [has_or_relation:protected] => 
        )

    [date_query] => 
    [request] => SELECT SQL_CALC_FOUND_ROWS  wp_posts.ID
					 FROM wp_posts  LEFT JOIN wp_term_relationships ON (wp_posts.ID = wp_term_relationships.object_id) INNER JOIN wp_postmeta ON ( wp_posts.ID = wp_postmeta.post_id )  INNER JOIN wp_postmeta AS mt1 ON ( wp_posts.ID = mt1.post_id )  INNER JOIN wp_postmeta AS mt2 ON ( wp_posts.ID = mt2.post_id )  INNER JOIN wp_postmeta AS mt3 ON ( wp_posts.ID = mt3.post_id )  INNER JOIN wp_postmeta AS mt4 ON ( wp_posts.ID = mt4.post_id )
					 WHERE 1=1  AND ( 
  wp_term_relationships.term_taxonomy_id IN (802)
) AND ( 
  wp_postmeta.meta_key = '_ilsi_date' 
  AND 
  ( 
    ( mt1.meta_key = '_ilsi_date' AND mt1.meta_value <= '2050-01-01' ) 
    AND 
    ( mt2.meta_key = '_ilsi_end_date' AND mt2.meta_value <= '2050-01-01' ) 
    AND 
    ( mt3.meta_key = '_ilsi_date' AND mt3.meta_value BETWEEN '2018-01-01' AND '2018-12-31' ) 
    AND 
    ( mt4.meta_key = '_ilsi_date' AND mt4.meta_value < '2018-12-31' )
  )
) AND ((wp_posts.post_type = 'event' AND (wp_posts.post_status = 'publish' OR wp_posts.post_status = 'acf-disabled')))
					 GROUP BY wp_posts.ID
					 ORDER BY wp_postmeta.meta_value DESC
					 LIMIT 0, 6
    [posts] => Array
        (
            [0] => WP_Post Object
                (
                    [ID] => 6968
                    [post_author] => 12
                    [post_date] => 2018-05-18 09:10:09
                    [post_date_gmt] => 2018-05-18 14:10:09
                    [post_content] => 
		
	
						
			
	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.


                    [post_title] => Applied Genetic Toxicity for Regulatory Decision Making: The Road Ahead
                    [post_excerpt] => 
                    [post_status] => publish
                    [comment_status] => closed
                    [ping_status] => closed
                    [post_password] => 
                    [post_name] => applied-genetic-toxicity-for-regulatory-decision-making-the-road-ahead
                    [to_ping] => 
                    [pinged] => 
                    [post_modified] => 2020-10-28 14:43:24
                    [post_modified_gmt] => 2020-10-28 14:43:24
                    [post_content_filtered] => 
                    [post_parent] => 0
                    [guid] => https://hesiglobal.org/?post_type=event&p=6968
                    [menu_order] => 0
                    [post_type] => event
                    [post_mime_type] => 
                    [comment_count] => 0
                    [filter] => raw
                )

        )

    [post_count] => 1
    [current_post] => -1
    [before_loop] => 
    [in_the_loop] => 
    [post] => WP_Post Object
        (
            [ID] => 6968
            [post_author] => 12
            [post_date] => 2018-05-18 09:10:09
            [post_date_gmt] => 2018-05-18 14:10:09
            [post_content] => 
		
	
						
			
	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.


            [post_title] => Applied Genetic Toxicity for Regulatory Decision Making: The Road Ahead
            [post_excerpt] => 
            [post_status] => publish
            [comment_status] => closed
            [ping_status] => closed
            [post_password] => 
            [post_name] => applied-genetic-toxicity-for-regulatory-decision-making-the-road-ahead
            [to_ping] => 
            [pinged] => 
            [post_modified] => 2020-10-28 14:43:24
            [post_modified_gmt] => 2020-10-28 14:43:24
            [post_content_filtered] => 
            [post_parent] => 0
            [guid] => https://hesiglobal.org/?post_type=event&p=6968
            [menu_order] => 0
            [post_type] => event
            [post_mime_type] => 
            [comment_count] => 0
            [filter] => raw
        )

    [comment_count] => 0
    [current_comment] => -1
    [found_posts] => 1
    [max_num_pages] => 1
    [max_num_comment_pages] => 0
    [is_single] => 
    [is_preview] => 
    [is_page] => 
    [is_archive] => 1
    [is_date] => 
    [is_year] => 
    [is_month] => 
    [is_day] => 
    [is_time] => 
    [is_author] => 
    [is_category] => 
    [is_tag] => 1
    [is_tax] => 
    [is_search] => 
    [is_feed] => 
    [is_comment_feed] => 
    [is_trackback] => 
    [is_home] => 
    [is_privacy_policy] => 
    [is_404] => 
    [is_embed] => 
    [is_paged] => 
    [is_admin] => 
    [is_attachment] => 
    [is_singular] => 
    [is_robots] => 
    [is_favicon] => 
    [is_posts_page] => 
    [is_post_type_archive] => 
    [query_vars_hash:WP_Query:private] => fa576065994d6aab0ad64ffacccfc5ab
    [query_vars_changed:WP_Query:private] => 
    [thumbnails_cached] => 
    [allow_query_attachment_by_filename:protected] => 
    [stopwords:WP_Query:private] => 
    [compat_fields:WP_Query:private] => Array
        (
            [0] => query_vars_hash
            [1] => query_vars_changed
        )

    [compat_methods:WP_Query:private] => Array
        (
            [0] => init_query_flags
            [1] => parse_tax_query
        )

    [query_cache_key:WP_Query:private] => wp_query:5e5fb3b0cb00ed3ec15690bdab10138a
)

Committee Publications

Filter

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

Mutation Research / Genetic Toxicology and Environmental Mutagenesis, 2018

Marchetti F, Aardema MJ, Beevers C, van Benthem J, Godschalk R, ...

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 ...

Read more

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

Mutation Research / Genetic Toxicology and Environmental Mutagenesis, 2019

Kirkland D, Levy DD, LeBaron MJ, Aardema MJ, Beevers C, Bhalli J, ...

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 ...

Read more

Recommendations for Conducting the Rodent Erythrocyte Pig‐a Assay: A Report from the HESI GTTC Pig‐a Workgroup

Environmental and Molecular Mutagenesis, 2021

Dertinger SD, Bhalli JA, Roberts DJ, Stankowski LF, Gollapudi BB, ...

The rodent Pig‐a assay is a flow cytometric, phenotype‐based method used to measure in vivo somatic cell mutation. An Organization for Economic Co‐operation and Development (OECD) test guideline is currently being developed to support routine use of the assay for regulatory purposes (OECD project number ...

Read more

Permitted Daily Exposure Limits for Noteworthy N-Nitrosamines

Environmental and Molecular Mutagenesis, 2021

Johnson GE, Dobo K, Gollapudi B, Harvey J, Kenny J, Kenyon M, ...

A genotoxic carcinogen, N-nitrosodimethylamine (NDMA), was detected as a synthesis impurity in some valsartan drugs in 2018, and other N-nitrosamines, such as N-nitrosodiethylamine (NDEA), were later detected in other sartan products. N-nitrosamines are pro-mutagens that can react with DNA following metabolism to produce ...

Read more

Utility of a next-generation framework for assessment of genomic damage: A case study using the pharmaceutical drug candidate etoposide

Environmental and Molecular Mutagenesis, 2021

Nicolette J, Luijten M, Sasaki JC, Custer L, Embry M, Froetschl R, ...

The HESI Genetic Toxicology Technical Committee (GTTC) applies their systematic and flexible approach for assessing the risk of genetic damage due to exposure to chemical substances to etoposide, a drug used in certain types of cancer treatments, as a representative pharmaceutical case study.

Read more

WP_Query Object
(
    [query] => Array
        (
            [post_type] => publication
            [posts_per_page] => 6
            [type] => 
            [area] => 
            [committee] => GTTC
            [authors] => true
            [showtitle] => false
            [meta_query] => Array
                (
                    [relation] => AND
                )

            [tax_query] => Array
                (
                    [0] => Array
                        (
                            [taxonomy] => ilsi_committee
                            [field] => name
                            [terms] => GTTC
                        )

                )

            [paged] => 4
            [meta_key] => _ilsi_date
            [orderby] => meta_value
            [order] => ASC
        )

    [query_vars] => Array
        (
            [post_type] => publication
            [posts_per_page] => 6
            [type] => 
            [area] => 
            [committee] => GTTC
            [authors] => true
            [showtitle] => false
            [meta_query] => Array
                (
                    [relation] => AND
                )

            [tax_query] => Array
                (
                    [0] => Array
                        (
                            [taxonomy] => ilsi_committee
                            [field] => name
                            [terms] => GTTC
                        )

                )

            [paged] => 4
            [meta_key] => _ilsi_date
            [orderby] => meta_value
            [order] => ASC
            [error] => 
            [m] => 
            [p] => 0
            [post_parent] => 
            [subpost] => 
            [subpost_id] => 
            [attachment] => 
            [attachment_id] => 0
            [name] => 
            [pagename] => 
            [page_id] => 0
            [second] => 
            [minute] => 
            [hour] => 
            [day] => 0
            [monthnum] => 0
            [year] => 0
            [w] => 0
            [category_name] => 
            [tag] => 
            [cat] => 
            [tag_id] => 
            [author] => 
            [author_name] => 
            [feed] => 
            [tb] => 
            [meta_value] => 
            [preview] => 
            [s] => 
            [sentence] => 
            [title] => 
            [fields] => all
            [menu_order] => 
            [embed] => 
            [category__in] => Array
                (
                )

            [category__not_in] => Array
                (
                )

            [category__and] => Array
                (
                )

            [post__in] => Array
                (
                )

            [post__not_in] => Array
                (
                )

            [post_name__in] => Array
                (
                )

            [tag__in] => Array
                (
                )

            [tag__not_in] => Array
                (
                )

            [tag__and] => Array
                (
                )

            [tag_slug__in] => Array
                (
                )

            [tag_slug__and] => Array
                (
                )

            [post_parent__in] => Array
                (
                )

            [post_parent__not_in] => Array
                (
                )

            [author__in] => Array
                (
                )

            [author__not_in] => Array
                (
                )

            [search_columns] => Array
                (
                )

            [ignore_sticky_posts] => 
            [suppress_filters] => 
            [cache_results] => 1
            [update_post_term_cache] => 1
            [update_menu_item_cache] => 
            [lazy_load_term_meta] => 1
            [update_post_meta_cache] => 1
            [nopaging] => 
            [comments_per_page] => 50
            [no_found_rows] => 
            [taxonomy] => ilsi_committee
            [term_id] => GTTC
        )

    [tax_query] => WP_Tax_Query Object
        (
            [queries] => Array
                (
                    [0] => Array
                        (
                            [taxonomy] => ilsi_committee
                            [terms] => Array
                                (
                                    [0] => GTTC
                                )

                            [field] => name
                            [operator] => IN
                            [include_children] => 1
                        )

                )

            [relation] => AND
            [table_aliases:protected] => Array
                (
                    [0] => wp_term_relationships
                )

            [queried_terms] => Array
                (
                    [ilsi_committee] => Array
                        (
                            [terms] => Array
                                (
                                    [0] => GTTC
                                )

                            [field] => name
                        )

                )

            [primary_table] => wp_posts
            [primary_id_column] => ID
        )

    [meta_query] => WP_Meta_Query Object
        (
            [queries] => Array
                (
                    [0] => Array
                        (
                            [key] => _ilsi_date
                        )

                    [relation] => OR
                )

            [relation] => AND
            [meta_table] => wp_postmeta
            [meta_id_column] => post_id
            [primary_table] => wp_posts
            [primary_id_column] => ID
            [table_aliases:protected] => Array
                (
                    [0] => wp_postmeta
                )

            [clauses:protected] => Array
                (
                    [wp_postmeta] => Array
                        (
                            [key] => _ilsi_date
                            [compare] => =
                            [compare_key] => =
                            [alias] => wp_postmeta
                            [cast] => CHAR
                        )

                )

            [has_or_relation:protected] => 
        )

    [date_query] => 
    [request] => SELECT SQL_CALC_FOUND_ROWS  wp_posts.ID
					 FROM wp_posts  LEFT JOIN wp_term_relationships ON (wp_posts.ID = wp_term_relationships.object_id) INNER JOIN wp_postmeta ON ( wp_posts.ID = wp_postmeta.post_id )
					 WHERE 1=1  AND ( 
  wp_term_relationships.term_taxonomy_id IN (77)
) AND ( 
  wp_postmeta.meta_key = '_ilsi_date'
) AND ((wp_posts.post_type = 'publication' AND (wp_posts.post_status = 'publish' OR wp_posts.post_status = 'acf-disabled')))
					 GROUP BY wp_posts.ID
					 ORDER BY wp_postmeta.meta_value ASC
					 LIMIT 18, 6
    [posts] => Array
        (
            [0] => WP_Post Object
                (
                    [ID] => 21726
                    [post_author] => 2
                    [post_date] => 2019-09-06 12:55:31
                    [post_date_gmt] => 2019-09-06 17:55:31
                    [post_content] => 
                    [post_title] => Identifying Germ Cell Mutagens Using OECD Test Guideline 488 (Transgenic Rodent Somatic and Germ Cell Gene Mutation Assays) and Integration with Somatic Cell Testing
                    [post_excerpt] => 
                    [post_status] => publish
                    [comment_status] => closed
                    [ping_status] => closed
                    [post_password] => 
                    [post_name] => identifying-germ-cell-mutagens-using-oecd-test-guideline-488-transgenic-rodent-somatic-and-germ-cell-gene-mutation-assays-and-integration-with-somatic-cell-testing
                    [to_ping] => 
                    [pinged] => 
                    [post_modified] => 2020-10-28 14:50:40
                    [post_modified_gmt] => 2020-10-28 14:50:40
                    [post_content_filtered] => 
                    [post_parent] => 0
                    [guid] => https://hesiglobal.org/?post_type=publication&p=21726
                    [menu_order] => 0
                    [post_type] => publication
                    [post_mime_type] => 
                    [comment_count] => 0
                    [filter] => raw
                )

            [1] => WP_Post Object
                (
                    [ID] => 21724
                    [post_author] => 2
                    [post_date] => 2019-09-06 12:43:14
                    [post_date_gmt] => 2019-09-06 17:43:14
                    [post_content] => 
                    [post_title] => Analysis of Historical Negative Control Group Data from the In Vitro Micronucleus Assay Using Human Lymphocytes
                    [post_excerpt] => 
                    [post_status] => publish
                    [comment_status] => closed
                    [ping_status] => closed
                    [post_password] => 
                    [post_name] => analysis-of-historical-negative-control-group-data-from-the-in-vitro-micronucleus-assay-using-human-lymphocytes
                    [to_ping] => 
                    [pinged] => 
                    [post_modified] => 2020-10-28 14:49:49
                    [post_modified_gmt] => 2020-10-28 14:49:49
                    [post_content_filtered] => 
                    [post_parent] => 0
                    [guid] => https://hesiglobal.org/?post_type=publication&p=21724
                    [menu_order] => 0
                    [post_type] => publication
                    [post_mime_type] => 
                    [comment_count] => 0
                    [filter] => raw
                )

            [2] => WP_Post Object
                (
                    [ID] => 21725
                    [post_author] => 2
                    [post_date] => 2019-09-06 12:50:25
                    [post_date_gmt] => 2019-09-06 17:50:25
                    [post_content] => 
                    [post_title] => A Comparison of Transgenic Rodent Mutation and In Vivo Comet Assay Responses for 91 Chemicals
                    [post_excerpt] => 
                    [post_status] => publish
                    [comment_status] => closed
                    [ping_status] => closed
                    [post_password] => 
                    [post_name] => a-comparison-of-transgenic-rodent-mutation-and-in-vivo-comet-assay-responses-for-91-chemicals
                    [to_ping] => 
                    [pinged] => 
                    [post_modified] => 2020-10-28 14:48:16
                    [post_modified_gmt] => 2020-10-28 14:48:16
                    [post_content_filtered] => 
                    [post_parent] => 0
                    [guid] => https://hesiglobal.org/?post_type=publication&p=21725
                    [menu_order] => 0
                    [post_type] => publication
                    [post_mime_type] => 
                    [comment_count] => 0
                    [filter] => raw
                )

            [3] => WP_Post Object
                (
                    [ID] => 23901
                    [post_author] => 2
                    [post_date] => 2021-03-05 15:24:51
                    [post_date_gmt] => 2021-03-05 15:24:51
                    [post_content] => 
                    [post_title] => Recommendations for Conducting the Rodent Erythrocyte Pig‐a Assay: A Report from the HESI GTTC Pig‐a Workgroup
                    [post_excerpt] => 
                    [post_status] => publish
                    [comment_status] => closed
                    [ping_status] => closed
                    [post_password] => 
                    [post_name] => recommendations-for-conducting-the-rodent-erythrocyte-pig%e2%80%90a-assay-a-report-from-the-hesi-gttc-pig%e2%80%90a-workgroup
                    [to_ping] => 
                    [pinged] => 
                    [post_modified] => 2021-03-05 18:12:50
                    [post_modified_gmt] => 2021-03-05 18:12:50
                    [post_content_filtered] => 
                    [post_parent] => 0
                    [guid] => https://hesiglobal.org/?post_type=publication&p=23901
                    [menu_order] => 0
                    [post_type] => publication
                    [post_mime_type] => 
                    [comment_count] => 0
                    [filter] => raw
                )

            [4] => WP_Post Object
                (
                    [ID] => 24047
                    [post_author] => 2
                    [post_date] => 2021-06-08 14:22:29
                    [post_date_gmt] => 2021-06-08 14:22:29
                    [post_content] => 
                    [post_title] => Permitted Daily Exposure Limits for Noteworthy N-Nitrosamines
                    [post_excerpt] => 
                    [post_status] => publish
                    [comment_status] => closed
                    [ping_status] => closed
                    [post_password] => 
                    [post_name] => permitted-daily-exposure-limits-for-noteworthy-n-nitrosamines
                    [to_ping] => 
                    [pinged] => 
                    [post_modified] => 2021-06-08 14:22:29
                    [post_modified_gmt] => 2021-06-08 14:22:29
                    [post_content_filtered] => 
                    [post_parent] => 0
                    [guid] => https://hesiglobal.org/?post_type=publication&p=24047
                    [menu_order] => 0
                    [post_type] => publication
                    [post_mime_type] => 
                    [comment_count] => 0
                    [filter] => raw
                )

            [5] => WP_Post Object
                (
                    [ID] => 24298
                    [post_author] => 16
                    [post_date] => 2021-11-14 19:18:07
                    [post_date_gmt] => 2021-11-14 19:18:07
                    [post_content] => 
                    [post_title] => Utility of a next-generation framework for assessment of genomic damage: A case study using the pharmaceutical drug candidate etoposide
                    [post_excerpt] => 
                    [post_status] => publish
                    [comment_status] => closed
                    [ping_status] => closed
                    [post_password] => 
                    [post_name] => utility-of-a-next-generation-framework-for-assessment-of-genomic-damage-a-case-study-using-the-pharmaceutical-drug-candidate-etoposide
                    [to_ping] => 
                    [pinged] => 
                    [post_modified] => 2021-12-03 22:02:27
                    [post_modified_gmt] => 2021-12-03 22:02:27
                    [post_content_filtered] => 
                    [post_parent] => 0
                    [guid] => https://hesiglobal.org/?post_type=publication&p=24298
                    [menu_order] => 0
                    [post_type] => publication
                    [post_mime_type] => 
                    [comment_count] => 0
                    [filter] => raw
                )

        )

    [post_count] => 6
    [current_post] => -1
    [before_loop] => 
    [in_the_loop] => 
    [post] => WP_Post Object
        (
            [ID] => 21726
            [post_author] => 2
            [post_date] => 2019-09-06 12:55:31
            [post_date_gmt] => 2019-09-06 17:55:31
            [post_content] => 
            [post_title] => Identifying Germ Cell Mutagens Using OECD Test Guideline 488 (Transgenic Rodent Somatic and Germ Cell Gene Mutation Assays) and Integration with Somatic Cell Testing
            [post_excerpt] => 
            [post_status] => publish
            [comment_status] => closed
            [ping_status] => closed
            [post_password] => 
            [post_name] => identifying-germ-cell-mutagens-using-oecd-test-guideline-488-transgenic-rodent-somatic-and-germ-cell-gene-mutation-assays-and-integration-with-somatic-cell-testing
            [to_ping] => 
            [pinged] => 
            [post_modified] => 2020-10-28 14:50:40
            [post_modified_gmt] => 2020-10-28 14:50:40
            [post_content_filtered] => 
            [post_parent] => 0
            [guid] => https://hesiglobal.org/?post_type=publication&p=21726
            [menu_order] => 0
            [post_type] => publication
            [post_mime_type] => 
            [comment_count] => 0
            [filter] => raw
        )

    [comment_count] => 0
    [current_comment] => -1
    [found_posts] => 45
    [max_num_pages] => 8
    [max_num_comment_pages] => 0
    [is_single] => 
    [is_preview] => 
    [is_page] => 
    [is_archive] => 1
    [is_date] => 
    [is_year] => 
    [is_month] => 
    [is_day] => 
    [is_time] => 
    [is_author] => 
    [is_category] => 
    [is_tag] => 
    [is_tax] => 1
    [is_search] => 
    [is_feed] => 
    [is_comment_feed] => 
    [is_trackback] => 
    [is_home] => 
    [is_privacy_policy] => 
    [is_404] => 
    [is_embed] => 
    [is_paged] => 1
    [is_admin] => 
    [is_attachment] => 
    [is_singular] => 
    [is_robots] => 
    [is_favicon] => 
    [is_posts_page] => 
    [is_post_type_archive] => 
    [query_vars_hash:WP_Query:private] => 354d2e97f232cbca107944837167ac7d
    [query_vars_changed:WP_Query:private] => 
    [thumbnails_cached] => 
    [allow_query_attachment_by_filename:protected] => 
    [stopwords:WP_Query:private] => 
    [compat_fields:WP_Query:private] => Array
        (
            [0] => query_vars_hash
            [1] => query_vars_changed
        )

    [compat_methods:WP_Query:private] => Array
        (
            [0] => init_query_flags
            [1] => parse_tax_query
        )

    [query_cache_key:WP_Query:private] => wp_query:f6004aba86fa30d86302c59397d73f35
)

Center for Translational Sciences

The Genetic Toxicology Technical Committee (GTTC) is part of the Center for Translational Sciences. This HESI Center serves as a focal point for staff to share strategic approaches, scientific developments, management best practices and innovations with other related HESI committees.

Other Committees in the Center for Translational Sciences are:

For questions about the Center contact:

Contact Us

Health and Environmental Sciences Institute (HESI)

hesi@hesiglobal.org
Phone: +1-202-659-8404
Fax: +1-202-659-8403

740 15th Street NW, Suite 600
Washington, DC 20005

Stay Informed

Sign up for our monthly e-newsletter.