Evaluation of the impact of the exposure route on the human kinetic adjustment factor.
Regul Toxicol Pharmacol
; 59(2): 258-69, 2011 Mar.
Article
en En
| MEDLINE
| ID: mdl-20969910
The objective of this study was to assess the impact of the exposure route on the human kinetic adjustment factor (HKAF), for which a default value of 3.16 is used in non-cancer risk assessment. A multi-route PBPK model was modified from the literature and used for computing the internal dose metrics in adults, neonates, children, elderly and pregnant women following three route-specific scenarios to chloroform, bromoform, tri- or per-chloroethylene (TCE or PERC). These include 24-h inhalation exposure, body-weight adjusted oral exposure and 30 min dermal exposure to contaminated drinking water. Distributions for body weight (BW), height (BH) and hepatic cytochrome P450 2E1 (CYP2E1) content were obtained from the literature, whereas model parameters (flows, volumes) were calculated from BW and BH. Monte Carlo simulations were performed and the HKAF was calculated as the ratio of the 95th percentile value of internal dose metrics in subpopulation to the 50th percentile value in adults. On the basis of the area under the parent compound's arterial blood concentration vs time curve (AUC(pc)), highest HKAFs were obtained in neonates for every scenario considered, and were the highest for bromoform (range: 3.6-7.4). Exceedance of the default value based on AUC(PC) was also observed for an oral exposure to chloroform in neonates (4.9). In all other cases, HKAFs remained below the default value. Overall, this study has pointed out the dependency of the HKAF on the exposure route, dose metrics and subpopulation considered, as well as characteristics of the chemicals investigated.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Contaminantes Químicos del Agua
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Farmacocinética
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Modelos Biológicos
Tipo de estudio:
Etiology_studies
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Evaluation_studies
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Prognostic_studies
Límite:
Adult
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Aged
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Aged80
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Child
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Child, preschool
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Female
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Humans
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Infant
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Middle aged
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Newborn
Idioma:
En
Revista:
Regul Toxicol Pharmacol
Año:
2011
Tipo del documento:
Article
País de afiliación:
Canadá
Pais de publicación:
Países Bajos