کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8552988 | 1562280 | 2017 | 41 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The margin of internal exposure (MOIE) concept for dermal risk assessment based on oral toxicity data - A case study with caffeine
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کلمات کلیدی
systemic exposure dosePBKCmaxBMDLPODNOAELRisk Characterisation RatioMOSRCRAUC - AUCRisk assessment - ارزیابی ریسکRoute-to-route extrapolation - استخراج مسیر به مسیرMargin of safety - حاشیه ایمنیmaximum concentration - حداکثر غلظتphysiologically based kinetic - فیزیولوژیکی مبتنی بر جنبشی استPhysiologically based pharmacokinetic (PBPK) model - مدل فیزیولوژیکی مبتنی بر فارماکوکینتیک (PBPK)area under the curve - منطقه تحت منحنیPoint of departure - نقطه عزیمتNo observed adverse effect level - هیچ عوارض جانبی مشاهده نشدهsed - وMOE - وزارت صنایعCaffeine - کافئین
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Route-to-route extrapolation is a common part of human risk assessment. Data from oral animal toxicity studies are commonly used to assess the safety of various but specific human dermal exposure scenarios. Using theoretical examples of various user scenarios, it was concluded that delineation of a generally applicable human dermal limit value is not a practicable approach, due to the wide variety of possible human exposure scenarios, including its consequences for internal exposure. This paper uses physiologically based kinetic (PBK) modelling approaches to predict animal as well as human internal exposure dose metrics and for the first time, introduces the concept of Margin of Internal Exposure (MOIE) based on these internal dose metrics. Caffeine was chosen to illustrate this approach. It is a substance that is often found in cosmetics and for which oral repeated dose toxicity data were available. A rat PBK model was constructed in order to convert the oral NOAEL to rat internal exposure dose metrics, i.e. the area under the curve (AUC) and the maximum concentration (Cmax), both in plasma. A human oral PBK model was constructed and calibrated using human volunteer data and adapted to accommodate dermal absorption following human dermal exposure. Use of the MOIE approach based on internal dose metrics predictions provides excellent opportunities to investigate the consequences of variations in human dermal exposure scenarios. It can accommodate within-day variation in plasma concentrations and is scientifically more robust than assuming just an exposure in mg/kg bw/day.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 392, 1 December 2017, Pages 119-129
Journal: Toxicology - Volume 392, 1 December 2017, Pages 119-129
نویسندگان
Jos G.M. Bessems, Alicia Paini, Monika Gajewska, Andrew Worth,