Replacing Regulatory Default Assumptions of Linear Extrapolation of Risk with Benchmark Dose for Next Generation Genotoxicity Risk Assessments

May 22, 2024

Elevating NAMs in genotoxicity to reduce reliance on animal testing is a focus of our research efforts at ScitoVation. In addition to launching a 21st Century Genotoxicity program, we want to ensure you receive highly relevant information on the latest development in genotoxicity research. As such, we are pleased to host George Johnson PhD, from Swansea University. Dr Johnson is an expert in dose-response assessment of genotoxicity to derive benchmark dose and point of departure for next generation genotoxicity risk assessments.

What you will learn:

  • Which statistical methods should be used to define which metric for use as a point of departure (PoD)
  • Use of genotoxicity data to calculate health-based guidance values (HBGV)
  • Case study showing that genotoxicity data based risk assessment to identity HBGV does not place the human population at an increased risk.

Watch the Recording

About our Speaker:

George is an Associate Professor at Swansea University, Wales UK. He is co-chair of the Health and Environmental Sciences Institute (HESI) Genetic Toxicology Technical Committee (GTTC) and co-chair of the quantitative workgroup, working on projects including nitrosamine impurities. He has recently been co-chair of the IWGT 2022 meeting on quantitative genetic toxicology, and is a working member of the Committee on Mutagenicity (COM). George works with industry, academia and regulatory bodies, and specializes in genetic toxicology, dose response modeling and risk assessment.


The Health and Environmental Science Institute (HESI) Genetic Toxicology Technical Committee (GTTC) and other expert groups including the International Workshop on Genetic Toxicology (IWGT), have assessed the use of genetic toxicity data for risk assessment purposes. Other toxicological endpoints are often used to calculate health-based guidance values (HBGV), and genetic toxicity data should also be used in a quantitative manner for risk assessment, either as an adverse outcome, or as a key event towards the cancer adverse outcome. Key concepts around this topic, are which statistical method should be used to define which metric for use as a point of departure (PoD), with the benchmark dose (BMD) approach in PROAST at a critical effect size (CES) of 50% being supported. To calculate a HBGV, the rodent derived BMD lower confidence interval (BMDL50) is converted to a human value by multiplication to human body weight, and division by a series of uncertainty factors (UF). Current data indicate that the default UF are reasonable i.e. 10 for interindividual and 10 for study duration with current effect severity UF at a recommendation for 2 to 10. There are some examples of environmental chemicals and pharmaceutical impurities where relative potency has been shown between in vivo genotoxicity and cancer bioassay data, which show that the human population is at no increased risk when using genetic toxicity data in risk assessment.

About ScitoVation:

ScitoVation helps clients assess chemical compound safety using innovative science, next-generation technology, and professional expertise. ScitoVation is known for partnership, flexibility, and proven success in its work to develop safer and more effective pharmaceuticals, food ingredients, agricultural chemicals, commodity chemicals and consumer products. A spin-off of the former The CIIT and The Hammer Institutes for Chemical & Drug Safety Sciences, ScitoVation is an industry leader of New Approach Methods (NAMS) for chemical/drug discovery & development in the rapidly evolving global regulatory landscape.