Maruyama Wakae, Yoshida Kikuo, Tanaka Takayuki, Nakanishi Junko
Graduate School of Environment and Information Sciences, Yokohama National University, Hodogaya, Kanagawa, Japan.
Chemosphere. 2002 Feb;46(7):975-85. doi: 10.1016/s0045-6535(01)00208-9.
The tissue-blood partition coefficients for a physiologically based pharmacokinetic (PBPK) model were determined, and the concentrations of 17 congeners of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) in tissues in Japanese people were estimated using the model. According to the PBPK model established by Lawrence and Gobas [Chemosphere 35 (1997) 427-452], we assumed a steady-state fugacity model for Japanese people in general, and set the route of PCDD/Fs exposure only from food intake. The required partition coefficients for liver, kidney, adipose, muscle, skin, bile, gut and viscera (richly perfused tissue) were calculated using available autopsy data from eight Japanese men and women who were not accidentally exposed to PCDD/Fs. For validation of the partition coefficients, estimated PCDD/F concentrations in liver, kidney, fat, blood and muscle using the model were compared to other two sets of measured concentration data in Japanese tissues. Good agreement was obtained between estimated data and measured data, and most of the measured data were within the simulated concentration range in liver, kidney, blood and muscle. From these results, our model and calculated partition coefficients seem applicable for the estimation of congener-specific concentrations in human tissues.
确定了基于生理的药代动力学（PBPK）模型的组织-血液分配系数，并使用该模型估算了日本人组织中17种多氯二苯并对二恶英和多氯二苯并呋喃（PCDD/Fs）同系物的浓度。根据劳伦斯和戈巴斯建立的PBPK模型[《环境化学》35（1997）427-452]，我们假定了一个适用于一般日本人的稳态逸度模型，并设定PCDD/Fs仅通过食物摄入的暴露途径。利用8名未意外接触PCDD/Fs的日本男女的尸检数据，计算了肝脏、肾脏、脂肪、肌肉、皮肤、胆汁、肠道和内脏（高灌注组织）所需的分配系数。为了验证分配系数，将使用该模型估算的肝脏、肾脏、脂肪、血液和肌肉中的PCDD/F浓度与另外两组日本人组织中的实测浓度数据进行了比较。估算数据与实测数据之间取得了良好的一致性，大多数实测数据都在肝脏、肾脏、血液和肌肉的模拟浓度范围内。从这些结果来看，我们的模型和计算出的分配系数似乎适用于估算人体组织中同系物特异性浓度。
