Exposure, Epidemiology, and Risk Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.
Environ Health Perspect. 2010 Jan;118(1):125-30. doi: 10.1289/ehp.0901144.
A physiologically based pharmacokinetic (PBPK) model would make it possible to simulate the dynamics of chemical absorption, distribution, metabolism, and elimination (ADME) from different routes of exposures and, in theory, could be used to evaluate associations between exposures and biomarker measurements in blood or urine.
We used a PBPK model to predict urinary excretion of 3,5,6-trichloro-2-pyridinol (TCPY), the specific metabolite of chlorpyrifos (CPF), in young children.
We developed a child-specific PBPK model for CPF using PBPK models previously developed for rats and adult humans. Data used in the model simulation were collected from 13 children 36 years of age who participated in a cross-sectional pesticide exposure assessment study with repeated environmental and biological sampling.
The model-predicted urinary TCPY excretion estimates were consistent with measured levels for 2 children with two 24-hr duplicate food samples that contained 350 and 12 ng/g of CPF, respectively. However, we found that the majority of model outputs underpredicted the measured urinary TCPY excretion.
We concluded that the potential measurement errors associated with the aggregate exposure measurements will probably limit the applicability of PBPK model estimates for interpreting urinary TCPY excretion and absorbed CPF dose from multiple sources of exposure. However, recent changes in organophosphorus (OP) use have shifted exposures from multipathways to dietary ingestion only. Thus, we concluded that the PBPK model is still a valuable tool for converting dietary pesticide exposures to absorbed dose estimates when the model input data are accurate estimates of dietary pesticide exposures.
生理药代动力学（PBPK）模型可模拟不同暴露途径下的化学吸收、分布、代谢和消除（ADME）动力学，并且理论上可用于评估暴露与血液或尿液中生物标志物测量值之间的关联。
我们使用 PBPK 模型预测儿童体内 3,5,6-三氯-2-吡啶醇（TCPY）的尿排泄量，TCPY 是氯吡硫磷（CPF）的特异性代谢物。
我们利用先前为大鼠和成年人类开发的 PBPK 模型，为 CPF 开发了一个儿童特异性 PBPK 模型。模型模拟中使用的数据来自 13 名 3-6 岁的儿童，这些儿童参与了一项具有重复环境和生物采样的跨季节农药暴露评估研究。
模型预测的尿 TCPY 排泄量与 2 名儿童的 24 小时重复食物样本中的测量值相符，这两份样本中 CPF 的含量分别为 350 和 12ng/g。然而，我们发现大多数模型输出值都低估了测量的尿 TCPY 排泄量。
我们得出结论，与总暴露测量相关的潜在测量误差可能会限制 PBPK 模型估算值用于解释从多种暴露源摄入 TCPY 排泄量和 CPF 吸收剂量的适用性。然而，最近有机磷（OP）农药的使用变化已将暴露途径从多途径转变为仅通过饮食摄入。因此，我们得出结论，当模型输入数据是准确的饮食农药暴露估计值时，PBPK 模型仍然是将饮食农药暴露转化为吸收剂量估算值的有价值工具。
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