Your browser doesn't support javascript.
loading
Use of a probabilistic PBPK/PD model to calculate Data Derived Extrapolation Factors for chlorpyrifos.
Poet, Torka S; Timchalk, Charles; Bartels, Michael J; Smith, Jordan N; McDougal, Robin; Juberg, Daland R; Price, Paul S.
Afiliación
  • Poet TS; Summit Toxicology, Richland, WA, 99352, USA. Electronic address: tspoet99@gmail.com.
  • Timchalk C; Battelle, Pacific Northwest Division, Richland, WA, 99354, USA.
  • Bartels MJ; ToxMetrics.com LLC, Midland, MI, 48642, USA.
  • Smith JN; Battelle, Pacific Northwest Division, Richland, WA, 99354, USA.
  • McDougal R; Dug Safety and Metabolism, AstraZeneca, Gatehouse Park, Waltham, Boston, 02451, USA.
  • Juberg DR; Dow AgroSciences, Indianapolis, IA, 46268, USA.
  • Price PS; ToxMetrics.com LLC, Midland, MI, 48642, USA.
Regul Toxicol Pharmacol ; 86: 59-73, 2017 Jun.
Article en En | MEDLINE | ID: mdl-28238854
A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model combined with Monte Carlo analysis of inter-individual variation was used to assess the effects of the insecticide, chlorpyrifos and its active metabolite, chlorpyrifos oxon in humans. The PBPK/PD model has previously been validated and used to describe physiological changes in typical individuals as they grow from birth to adulthood. This model was updated to include physiological and metabolic changes that occur with pregnancy. The model was then used to assess the impact of inter-individual variability in physiology and biochemistry on predictions of internal dose metrics and quantitatively assess the impact of major sources of parameter uncertainty and biological diversity on the pharmacodynamics of red blood cell acetylcholinesterase inhibition. These metrics were determined in potentially sensitive populations of infants, adult women, pregnant women, and a combined population of adult men and women. The parameters primarily responsible for inter-individual variation in RBC acetylcholinesterase inhibition were related to metabolic clearance of CPF and CPF-oxon. Data Derived Extrapolation Factors that address intra-species physiology and biochemistry to replace uncertainty factors with quantitative differences in metrics were developed in these same populations. The DDEFs were less than 4 for all populations. These data and modeling approach will be useful in ongoing and future human health risk assessments for CPF and could be used for other chemicals with potential human exposure.
Asunto(s)
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 Asunto principal: Inhibidores de la Colinesterasa / Cloropirifos / Eritrocitos / Insecticidas / Modelos Biológicos Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male / Pregnancy Idioma: En Revista: Regul Toxicol Pharmacol Año: 2017 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores de la Colinesterasa / Cloropirifos / Eritrocitos / Insecticidas / Modelos Biológicos Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male / Pregnancy Idioma: En Revista: Regul Toxicol Pharmacol Año: 2017 Tipo del documento: Article Pais de publicación: Países Bajos