Dr George Johnson (pictured below) of Swansea University Medical School is the lead author of a research paper which has been selected as the “Editor’s Choice” to appear on the cover of this month’s edition of the Environmental Mutagenesis and Genomics Society's Journal, Environmental and Molecular Mutagenesis (EMM).
This important paper is entitled “Derivation of Point of Departure (PoD) Estimates in Genetic Toxicology Studies and Their Potential Applications in Risk Assessment”. It reports the outcome of a large collaborative international study led by Dr Johnson, Associate Professor in Genetics and member of the College’s DNA Damage Research Group, aimed at strengthening regulatory decision making, by establishing how genetic toxicology data can be used to set regulatory limits on chemical exposures.
Swansea University is globally renowned for Genetic Toxicology, or the ability of substances or physical agents to damage the DNA of cells which can lead to mutations that increase the likelihood of diseases such as cancer.
This honour from the Environmental Mutagenesis and Genomics Society recognises Dr Johnson as a world expert in this area and it highlights Swansea’s DNA Damage Group and Institute of Life Science as global leaders in this field within pre-clinical safety testing of drugs and other substances to which the human population are exposed.
Dr Johnson said: “It has been a privilege to lead this group of international experts from government regulatory bodies, industry and academia, to produce this paper that is already being used to improve human health risk assessments of potential carcinogenic substances.”
Professor Keith Lloyd, Head of Swansea University’s Medical School said: "Genetic toxicology is a fast emerging research strength in the College of Medicine. This paper by George and colleagues exemplifies our approach in Swansea of using basic research to benefit human health and well-being."
Identifying a Point-of-Departure (PoD) within a chemical dose response is standard practice in assessing the risk associated with toxic chemicals.
The PoD is used to extrapolate from the measured response in a test system to the lower levels typical of human exposures, which is a necessary step in setting the level of a chemical that poses an acceptable risk to human populations. Traditionally, this approach has not been applied to chemicals that damage DNA.
Typically, assays that measure DNA damage or mutation are used to determine whether a chemical is genotoxic, a classification that triggers a conservative extrapolation approach for estimating risk.
More recently, experimental evidence and biological understanding suggest that this default extrapolation approach is not always justified. But, compelling data regarding the performance of alternative approaches are needed to justify changing this long-standing and protective practice.
Under the auspices of the Quantitative Analysis Workgroup of the Genetic Toxicology Technical Committee (HESI/ISLI), this group of authors sought to systematically evaluate different statistical approaches for identifying a PoD from genetic toxicology data.
Dr Johnson and his co-authors collected and analysed 45 data sets from studies that analysed the induction of gene mutation or DNA damage (micronucleus formation) caused by two model mutagens (1-ethyl-1-nitrosourea or 1-methyl-1-nitrosourea).
They evaluated the performance of four different statistical approaches for calculating a PoD and concluded that the benchmark dose approach is the most useful for analysing continuous genetic toxicology data.
In addition, their analysis identified aspects of genetic toxicology study design that are necessary for accurate PoD determination.
The article includes a number of other important recommendations and insights for investigators in the field. Finally, the article describes how the methodology the Quantitative Analysis Workgroup recommends could be used to set regulatory limits for genotoxic chemicals in the future.
A copy of “Derivation of Point of Departure (PoD) Estimates in Genetic Toxicology Studies and Their Potential Applications in Risk Assessment” by George E. Johnson, Lya G. Soeteman-Hernandez, B. Bhaskar Gollapudi, Owen G. Bodger, Kerry L. Dearfield, Robert H. Heflich, J. Gregory Hixon, David Pl. Lovell, James T. MacGregor, Lynn H. Pottenger, Chad M. Thompson, Liz Abraham, Veronique Thybaud, Jennifer Y. Tanir, Errol Zeiger, Jan van Benthem, and Paul A. White can be accessed here http://onlinelibrary.wiley.com/doi/10.1002/em.21870/pdf.
- Friday 24 October 2014 10.30 GMT
- Thursday 19 January 2017 15.44 GMT
- Emma Turner