Test No. 470: Mammalian Erythrocyte Pig-a Gene Mutation Assay

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doi:10.1787/4faea90e-en

Cited by 9 publications

(1 citation statement)

References 38 publications

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“…The test system for assessing the genotoxicity of environmental factors based on the detection of mutations of the Pig-a gene deserves special attention. Despite the fact that in vivo Pig-A assay demonstrated its prospects for assessing the end point of DNA damage in the form of mutations, back in 1999 [214], the OECD recommendation was received by the methodology only in mid-2022 [215]. The Pig-a gene encodes the catalytic subunit of Nacetylglucosamine transferase involved in the early synthesis of glycosylphosphatidylinositol [216,217], which binds protein markers on the surface of homopoietic cells of humans and laboratory mammals (for example, the product of the CD59 gene) [218].…”

Section: Modern Methods For Assessing the Genotoxicity Of Environment...mentioning

confidence: 99%

Systems for Genetic Assessment of the Impact of Environmental Factors

Kislyak,

Dugan,

Yalovenko

2024

Innov Biosyst Bioeng

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One of the most important components of environmental protection is the development of hygiene standards aimed at shielding the human population from the adverse effects of environmental pollution. The European and American Chemical Societies have reported approximately 800,000 chemicals, with no available information on potential risks to human genetic health and negative environmental impact. Given the exponential increase in chemical compounds generated by humanity in various industries, the issue of effectivly identifying and accounting for various genetic and carcinogenic hazards is particularle relevant. The assessment of potential genotoxicity of environmental factors is an integral part of genetic safety assessment for both prokaryotic and eukaryotic organisms, including humans. The evaluation of the genetic activity of chemical compounds is a fundamentsl requirement for their comprehensive toxicological assessment. From the perspective of genetic and epigenetic mechanisms of influence, our review considers standard methods for detecting and assessing the potential genetic hazard associated with environmental factors. These methods are part of a standard, generally accepted test system battery. Additionally, the review covers some modern experimental methods that are not widely accepted today. A detailed analysis of approaches to the assessment of potential genetic mutagenic activity was carried out, presenting their main advantages and disadvantages. Taking into account the recommendations issued by the Organisation for Economic Co-operation and Development on testing hazardous chemical compounds that may affect human health, an attempt was made to find optimal approaches to solving the task of predicting genetic effects and their consequences for humans.

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Section: Modern Methods For Assessing the Genotoxicity Of Environment...mentioning

confidence: 99%

Systems for Genetic Assessment of the Impact of Environmental Factors

Kislyak,

Dugan,

Yalovenko

2024

Innov Biosyst Bioeng

View full text Add to dashboard Cite

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Occupational Toxicology in the Pharmaceutical Industry

Dolan

Bercu

Graham³

et al. 2023

Patty's Toxicology

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Much of the activity in the pharmaceutical industry has its origins in the fine chemicals industry of the late nineteenth century. At that time, advances in chemistry and medicine led to the manufacture of pharmacologically active small molecules to produce desirable biological effects to treat diseases and illnesses at relatively low doses. Advances in biology and chemistry in the past quarter century have led to an increase in innovation resulting in a variety of novel modalities, especially recombinant proteins, antibody‐drug conjugates, cell and gene therapies, peptides and polypeptides, oligonucleotides, and vaccines. The roles and responsibilities of occupational toxicologists in the pharmaceutical industry have expanded dramatically in the twenty‐first century, commensurate with the changing regulatory requirements and treatment modalities. The occupational toxicologists' roles have become increasingly multidisciplinary and the scope of their involvement has expanded to encompass diverse aspects of worker safety as well as patient safety, and to include involvement throughout a molecule's development, from early development through postcommercialization.

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Severity of effect considerations regarding the use of mutation as a toxicological endpoint for risk assessment: A report from the 8th International Workshop on Genotoxicity Testing (IWGT)

Parsons,

Beal,

Dearfield

et al. 2024

Environ and Mol Mutagen

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Exposure levels without appreciable human health risk may be determined by dividing a point of departure on a dose–response curve (e.g., benchmark dose) by a composite adjustment factor (AF). An “effect severity” AF (ESAF) is employed in some regulatory contexts. An ESAF of 10 may be incorporated in the derivation of a health‐based guidance value (HBGV) when a “severe” toxicological endpoint, such as teratogenicity, irreversible reproductive effects, neurotoxicity, or cancer was observed in the reference study. Although mutation data have been used historically for hazard identification, this endpoint is suitable for quantitative dose–response modeling and risk assessment. As part of the 8th International Workshops on Genotoxicity Testing, a sub‐group of the Quantitative Analysis Work Group (WG) explored how the concept of effect severity could be applied to mutation. To approach this question, the WG reviewed the prevailing regulatory guidance on how an ESAF is incorporated into risk assessments, evaluated current knowledge of associations between germline or somatic mutation and severe disease risk, and mined available data on the fraction of human germline mutations expected to cause severe disease. Based on this review and given that mutations are irreversible and some cause severe human disease, in regulatory settings where an ESAF is used, a majority of the WG recommends applying an ESAF value between 2 and 10 when deriving a HBGV from mutation data. This recommendation may need to be revisited in the future if direct measurement of disease‐causing mutations by error‐corrected next generation sequencing clarifies selection of ESAF values.

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Test No. 470: Mammalian Erythrocyte Pig-a Gene Mutation Assay

Cited by 9 publications

References 38 publications

Systems for Genetic Assessment of the Impact of Environmental Factors

Systems for Genetic Assessment of the Impact of Environmental Factors

Occupational Toxicology in the Pharmaceutical Industry

Severity of effect considerations regarding the use of mutation as a toxicological endpoint for risk assessment: A report from the 8th International Workshop on Genotoxicity Testing (IWGT)

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