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A framework and case studies for evaluation of enzyme ontogeny in children's health risk evaluation.
Ginsberg, Gary; Vulimiri, Suryanarayana V; Lin, Yu-Sheng; Kancherla, Jayaram; Foos, Brenda; Sonawane, Babasaheb.
Afiliación
  • Ginsberg G; a Partnership in Pediatric and Environmental Health , Hartford , CT , USA.
  • Vulimiri SV; b National Center for Environmental Assessment, Office of Research and Development , U.S. Environmental Protection Agency , Washington , DC , USA.
  • Lin YS; b National Center for Environmental Assessment, Office of Research and Development , U.S. Environmental Protection Agency , Washington , DC , USA.
  • Kancherla J; c Center for Bioinformatics and Computational Biology , University of Maryland , College Park , MD , USA.
  • Foos B; d Office of Children's Health Protection , U.S. Environmental Protection Agency , Washington , DC , USA.
  • Sonawane B; b National Center for Environmental Assessment, Office of Research and Development , U.S. Environmental Protection Agency , Washington , DC , USA.
J Toxicol Environ Health A ; 80(10-12): 569-593, 2017.
Article en En | MEDLINE | ID: mdl-28891786
Knowledge of the ontogeny of Phase I and Phase II metabolizing enzymes may be used to inform children's vulnerability based upon likely differences in internal dose from xenobiotic exposure. This might provide a qualitative assessment of toxicokinetic (TK) variability and uncertainty pertinent to early lifestages and help scope a more quantitative physiologically based toxicokinetic (PBTK) assessment. Although much is known regarding the ontogeny of metabolizing systems, this is not commonly utilized in scoping and problem formulation stage of human health risk evaluation. A framework is proposed for introducing this information into problem formulation which combines data on enzyme ontogeny and chemical-specific TK to explore potential child/adult differences in internal dose and whether such metabolic differences may be important factors in risk evaluation. The framework is illustrated with five case study chemicals, including some which are data rich and provide proof of concept, while others are data poor. Case studies for toluene and chlorpyrifos indicate potentially important child/adult TK differences while scoping for acetaminophen suggests enzyme ontogeny is unlikely to increase early-life risks. Scoping for trichloroethylene and aromatic amines indicates numerous ways that enzyme ontogeny may affect internal dose which necessitates further evaluation. PBTK modeling is a critical and feasible next step to further evaluate child-adult differences in internal dose for a number of these chemicals.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Salud Infantil / Enzimas / Modelos Teóricos Tipo de estudio: Etiology_studies / Prognostic_studies / Qualitative_research / Risk_factors_studies Límite: Child / Humans Idioma: En Revista: J Toxicol Environ Health A Asunto de la revista: SAUDE AMBIENTAL / TOXICOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Salud Infantil / Enzimas / Modelos Teóricos Tipo de estudio: Etiology_studies / Prognostic_studies / Qualitative_research / Risk_factors_studies Límite: Child / Humans Idioma: En Revista: J Toxicol Environ Health A Asunto de la revista: SAUDE AMBIENTAL / TOXICOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido