Leavens T L, Bond J A
University of North Carolina, Chapel Hill 27599-7270, USA.
Toxicology. 1996 Oct 28;113(1-3):310-3. doi: 10.1016/0300-483x(96)03463-4.
Coexposure to 1,3-butadiene (BD) and styrene occurs in the workplace of many polymer industries. The reactive epoxide metabolites of both compounds are responsible for their genotoxicity. A physiologically based pharmacokinetic (PBPK) model was developed to describe the simultaneous disposition of BD and styrene in mice coexposed by inhalation. A model with one oxidative pathway and competition between BD and styrene was compared with a model with two oxidation pathways for both BD and styrene. The different PBPK models were used to simulate the observed rate of BD metabolism and blood concentration of styrene from 8-h inhalation exposures of mice to mixtures of BD and styrene. The model with two oxidative pathways more accurately simulated the observed inhibition of BD uptake in coexposed mice.
在许多聚合物行业的工作场所中，会同时接触到1,3 - 丁二烯（BD）和苯乙烯。这两种化合物的活性环氧化代谢产物是其遗传毒性的原因。构建了一个基于生理的药代动力学（PBPK）模型，以描述通过吸入同时接触BD和苯乙烯的小鼠体内这两种物质的处置情况。将具有一条氧化途径且BD和苯乙烯之间存在竞争的模型与具有两条BD和苯乙烯氧化途径的模型进行了比较。不同的PBPK模型用于模拟从小鼠吸入BD和苯乙烯混合物8小时的暴露实验中观察到的BD代谢速率和苯乙烯血药浓度。具有两条氧化途径的模型更准确地模拟了在同时接触的小鼠中观察到的BD摄取抑制情况。
