Genetic risk extrapolation from animal data to human disease

Favor, Jack; Layton, David; Sega, Gary A.; Wassom, John S.; Burkhart, Jim; Douglas, G. Manuel; Dearfield, Kerry L.; Brusick, David

doi:10.1016/0027-5107(93)e0261-n

Cited by 13 publications

(2 citation statements)

References 23 publications

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“…Frameworks have been proposed and used for the risk assessment of mutagens [Favor et al, 1993;EPA, 1986;Dearfield et al, 2002;Sanner and Dybing, 2005;EC, 2008;Soeteman-Hernandez et al, 2016]. In particular, a recent risk assessment by the Scientific Committee on Consumer Products [SCCP, 2005] for glyoxal used an approach presented by Sanner and Dybing [2005].…”

Section: Implications Of Hazard Characterization and Classification Amentioning

confidence: 99%

Use of genetic toxicity data in GHS mutagenicity classification and labeling of substances

Ball¹,

Hollnagel²

2017

Environ and Mol Mutagen

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One of the key outcomes of testing the potential genotoxicity or mutagenicity of a substance is the conclusion on whether the substance should be classified as a germ cell mutagen and the significance of this for other endpoints such as carcinogenicity. The basis for this conclusion are the criteria presented in classification and labelling systems such as the Globally Harmonized System for classification and labeling (GHS). This article reviews the classification criteria for germ cell mutagenicity and carcinogenicity and how they are applied to substances with evidence of mutagenicity. The implications and suitability of such a classification for hazard communication, risk assessment, and risk management are discussed. It is proposed that genotoxicity assessments should not focus on specifically identifying germ cell mutagens, particularly given the challenges associated with communicating this information in a meaningful way. Rather the focus should be on deriving data to characterize the mode of action and for use in the risk assessment of mutagens, which could then feed into a more robust, risk based management of mutagenic substances versus the current more hazard based approaches. Environ. Mol. Mutagen. 58:354-360, 2017. © 2017 Wiley Periodicals, Inc.

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Section: Implications Of Hazard Characterization and Classification Amentioning

confidence: 99%

Use of genetic toxicity data in GHS mutagenicity classification and labeling of substances

Ball¹,

Hollnagel²

2017

Environ and Mol Mutagen

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“…Also, many commentators have identified the importance of using mechanistic data in risk assessments (18,35,37,42), and genetic data are part of the mechanistic information that can be used. Genetic information has also been useful in extrapolating from animals to humans (15,30,53).…”

Section: The Use Of Genetic Information In Quantitative Risk Assessmentmentioning

confidence: 99%

Genetic Susceptibility and the Setting of Occupational Health Standards

Schulte

Howard

2011

Annu. Rev. Public Health

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As more is learned about genetic susceptibility to occupational and environmental hazards, there will be increasing pressure to use genetic susceptibility information in setting occupational health standards. Historically, this has not been done, but a growing body of research assesses inherited genetic factors as modifiers of the effects of hazardous exposures. Additionally, acquired genetic and epigenetic characteristics could also be used in standard setting. However, for both inherited and acquired genetic characteristics, many scientific, ethical, legal, and social issues could arise. Investigators need to examine the potential role and implications of using genetic information in standard setting. In this review, we focus primarily on inherited genetic factors and their role in occupational health standard setting.

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Germ cell mutagens: Risk assessment challenges in the 21st century

Singer

Yauk

2010

Environ and Mol Mutagen

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Heritable mutations may result in a wide variety of detrimental outcomes, from embryonic lethality to genetic disease in the offspring. Despite this, today's commonly used test batteries do not include assays for germ cell mutation. Current challenges include a lack of practical assays and concrete evidence for human germline mutagens, and large data gaps that often impede risk assessment. Moreover, most regulatory assessments are based on the assumption that somatic cell mutation assays also protect the germline by default, which has not been adequately confirmed. The field is also faced with new challenges aimed at dramatically reducing animal testing, and attempts to rapidly classify thousands of chemicals using high throughput in vitro assays. These approaches may not adequately capture effects that may be particular to gametes, since many aspects of the germline are unique. In light of these challenges, an urgent need exists to develop new approaches to evaluate the potential of toxicants to cause germline mutation. The application of new technologies will greatly enhance our understanding of mutation in humans exposed to environmental mutagens. However, we must be poised to collect and interpret these data, and facilitate risk translation to regulators and the public. Genetic toxicologists must also become actively involved in the development of high-throughput tools to study germline mutation. Appropriate attention to these areas will result in the development of policies that prioritize the protection of the germline and future generations from DNA sequence mutations.

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Genetic risk extrapolation from animal data to human disease

Cited by 13 publications

References 23 publications

Use of genetic toxicity data in GHS mutagenicity classification and labeling of substances

Use of genetic toxicity data in GHS mutagenicity classification and labeling of substances

Genetic Susceptibility and the Setting of Occupational Health Standards

Germ cell mutagens: Risk assessment challenges in the 21st century

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