Your browser doesn't support javascript.
loading
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, Barbara L; Beal, Marc A; Dearfield, Kerry L; Douglas, George R; Gi, Min; Gollapudi, B Bhaskar; Heflich, Robert H; Horibata, Katsuyoshi; Kenyon, Michelle; Long, Alexandra S; Lovell, David P; Lynch, Anthony M; Myers, Meagan B; Pfuhler, Stefan; Vespa, Alisa; Zeller, Andreas; Johnson, George E; White, Paul A.
Afiliación
  • Parsons BL; Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas, USA.
  • Beal MA; Bureau of Chemical Safety, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.
  • Dearfield KL; U.S. Environmental Protection Agency and U.S. Department of Agriculture, Washington, DC, USA.
  • Douglas GR; Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.
  • Gi M; Department of Environmental Risk Assessment, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
  • Gollapudi BB; Toxicology Consultant, Midland, Michigan, USA.
  • Heflich RH; Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas, USA.
  • Horibata K; National Institute of Health Sciences, Kawasaki, Japan.
  • Kenyon M; Portfolio and Regulatory Strategy, Drug Safety Research and Development, Pfizer, Groton, Connecticut, USA.
  • Long AS; Existing Substances Risk Assessment Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.
  • Lovell DP; Population Health Research Institute, St George's Medical School, University of London, London, UK.
  • Lynch AM; GSK, Genetic Toxicology, Ware, UK.
  • Myers MB; Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas, USA.
  • Pfuhler S; The Procter & Gamble Company, Mason, Ohio, USA.
  • Vespa A; Pharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.
  • Zeller A; Pharmaceutical Sciences, pRED Innovation Center Basel, Hoffmann-La Roche Ltd, Basel, Switzerland.
  • Johnson GE; Swansea University Medical School, Swansea University, Swansea, Wales, UK.
  • White PA; Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.
Environ Mol Mutagen ; 2024 Jun 03.
Article en En | MEDLINE | ID: mdl-38828778
ABSTRACT
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.
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Environ Mol Mutagen Asunto de la revista: BIOLOGIA MOLECULAR / SAUDE AMBIENTAL Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Environ Mol Mutagen Asunto de la revista: BIOLOGIA MOLECULAR / SAUDE AMBIENTAL Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos