کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5857090 1131991 2014 18 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A human life-stage physiologically based pharmacokinetic and pharmacodynamic model for chlorpyrifos: Development and validation
ترجمه فارسی عنوان
یک مدل فارماکوکینتیک و فارماکودینامیک مبتنی بر فیزیولوژیک مبتنی بر انسان برای کلروفیفیف: توسعه و اعتبار سنجی
کلمات کلیدی
فارماکوکینتیک، آفت کش ها، حساسیت مرحله زندگی،
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی


- A life-stage PBPK/PD model for chlorpyrifos was developed.
- Simulations predict adults will have higher chlorpyrifos levels in blood.
- At doses ⩾0.6 mg/kg, infants will have higher chlorpyrifos-oxon levels in blood.
- At doses <0.6 mg/kg, adults will have higher chlorpyrifos-oxon levels in blood.
- Increased chlorpyrifos-oxon result in increased cholinesterase inhibition.

Sensitivity to some chemicals in animals and humans are known to vary with age. Age-related changes in sensitivity to chlorpyrifos have been reported in animal models. A life-stage physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed to predict disposition of chlorpyrifos and its metabolites, chlorpyrifos-oxon (the ultimate toxicant) and 3,5,6-trichloro-2-pyridinol (TCPy), as well as B-esterase inhibition by chlorpyrifos-oxon in humans. In this model, previously measured age-dependent metabolism of chlorpyrifos and chlorpyrifos-oxon were integrated into age-related descriptions of human anatomy and physiology. The life-stage PBPK/PD model was calibrated and tested against controlled adult human exposure studies. Simulations suggest age-dependent pharmacokinetics and response may exist. At oral doses ⩾0.6 mg/kg of chlorpyrifos (100- to 1000-fold higher than environmental exposure levels), 6 months old children are predicted to have higher levels of chlorpyrifos-oxon in blood and higher levels of red blood cell cholinesterase inhibition compared to adults from equivalent doses. At lower doses more relevant to environmental exposures, simulations predict that adults will have slightly higher levels of chlorpyrifos-oxon in blood and greater cholinesterase inhibition. This model provides a computational framework for age-comparative simulations that can be utilized to predict chlorpyrifos disposition and biological response over various postnatal life stages.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Regulatory Toxicology and Pharmacology - Volume 69, Issue 3, August 2014, Pages 580-597
نویسندگان
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