Environmental Health Science and Research Bureau, Health Canada, K1A 0K9, Ottawa, ON, Canada; Scitovation, Research Triangle Park, NC, 27709, USA.
Environmental Health Science and Research Bureau, Health Canada, K1A 0K9, Ottawa, ON, Canada.
Food Chem Toxicol. 2019 Nov;133:110785. doi: 10.1016/j.fct.2019.110785. Epub 2019 Aug 23.
Hexabromocyclododecane (HBCD) is a flame retardant largely found in textiles, electrical equipment and building materials. The potential exposure associated with adverse effects described in animals make HBCD a substance of interest. To better characterize the risk in humans, it is important to understand the dose-response relationship using available data concerning the exposure and toxicity of environmental contaminants such as HBCD. For this reason, a physiologically-based pharmacokinetic (PBPK) model was developed to describe the disposition of α-HBCD after a single oral administration. The results showed that the model can appropriately predict blood and tissue concentration in rodents. The model described that lipoproteins play a key role in the distribution of α-HBCD in the body even though its lipophilic nature would suggest preferential storage in adipose tissue. The model was also adapted to humans to predict plasma exposure to α-HBCD and showed reasonable estimates when compared against estimated diet levels and biomonitoring measures. As part of a larger study on integrating new toxicity data for human health risk assessment, the present PBPK model will serve as a supporting tool to help extrapolate and interpret in vitro and in vivo kinetics of flame retardants such as HBCD.
六溴环十二烷（HBCD）是一种广泛存在于纺织品、电器设备和建筑材料中的阻燃剂。由于其在动物体内具有潜在的有害影响，因此 HBCD 是一种受到关注的物质。为了更好地描述人类面临的风险，了解 HBCD 等环境污染物的暴露和毒性的可用数据对于建立剂量-反应关系非常重要。出于这个原因，开发了一个基于生理学的药代动力学（PBPK）模型，以描述单次口服α-HBCD 后的分布情况。结果表明，该模型可以适当地预测啮齿动物的血液和组织浓度。该模型描述了脂蛋白在α-HBCD 在体内的分布中起着关键作用，尽管其亲脂性可能表明其优先储存在脂肪组织中。该模型还被改编用于预测人体对α-HBCD 的血浆暴露，并与估计的饮食水平和生物监测措施进行了比较，显示出合理的估计。作为将新的毒性数据整合到人类健康风险评估中的更大研究的一部分，本 PBPK 模型将作为一种支持工具，有助于推断和解释阻燃剂（如 HBCD）的体外和体内动力学。
