Summit Toxicology, LLP, Falls Church, VA, USA.
Regul Toxicol Pharmacol. 2010 Oct;58(1):33-44. doi: 10.1016/j.yrtph.2010.05.011. Epub 2010 Jun 1.
The National Health and Nutrition Examination Survey (NHANES) generates population-representative biomonitoring data for many chemicals including volatile organic compounds (VOCs) in blood. However, no health or risk-based screening values are available to evaluate these data from a health safety perspective or to use in prioritizing among chemicals for possible risk management actions. We gathered existing risk assessment-based chronic exposure reference values such as reference doses (RfDs), reference concentrations (RfCs), tolerable daily intakes (TDIs), cancer slope factors, etc. and key pharmacokinetic model parameters for 47 VOCs. Using steady-state solutions to a generic physiologically-based pharmacokinetic (PBPK) model structure, we estimated chemical-specific steady-state venous blood concentrations across chemicals associated with unit oral and inhalation exposure rates and with chronic exposure at the identified exposure reference values. The geometric means of the slopes relating modeled steady-state blood concentrations to steady-state exposure to a unit oral dose or unit inhalation concentration among 38 compounds with available pharmacokinetic parameters were 12.0 microg/L per mg/kg-d (geometric standard deviation [GSD] of 3.2) and 3.2 microg/L per mg/m(3) (GSD=1.7), respectively. Chemical-specific blood concentration screening values based on non-cancer reference values for both oral and inhalation exposure range from 0.0005 to 100 microg/L; blood concentrations associated with cancer risk-specific doses at the 1E-05 risk level ranged from 5E-06 to 6E-02 microg/L. The distribution of modeled steady-state blood concentrations associated with unit exposure levels across VOCs may provide a basis for estimating blood concentration screening values for VOCs that lack chemical-specific pharmacokinetic data. The screening blood concentrations presented here provide a tool for risk assessment-based evaluation of population biomonitoring data for VOCs and are most appropriately applied to central tendency estimates for such datasets.
国家健康和营养检查调查（NHANES）为许多化学物质生成具有代表性的人群生物监测数据，包括血液中的挥发性有机化合物（VOCs）。然而，目前尚无健康或基于风险的筛选值可从健康安全角度评估这些数据，或用于优先考虑可能需要采取风险管理措施的化学物质。我们收集了现有的基于风险评估的慢性暴露参考值，如参考剂量（RfD）、参考浓度（RfC）、每日耐受摄入量（TDI）、癌症斜率因子等，以及 47 种 VOC 的关键药代动力学模型参数。使用通用生理药代动力学（PBPK）模型结构的稳态解，我们估计了与单位口服和吸入暴露率以及与所确定的暴露参考值的慢性暴露相关的特定化学物质的稳态静脉血液浓度。对于具有可用药代动力学参数的 38 种化合物，模型稳态血液浓度与单位口服剂量或单位吸入浓度稳态暴露相关的斜率的几何平均值分别为 12.0μg/L/（mg/kg-d）（几何标准差[GSD]为 3.2）和 3.2μg/L/（mg/m3）（GSD=1.7）。基于口服和吸入暴露的非癌症参考值的特定化学物质血液浓度筛选值范围为 0.0005 至 100μg/L；与癌症风险特定剂量（1E-05 风险水平）相关的血液浓度范围为 5E-06 至 6E-02μg/L。在 VOC 中，与单位暴露水平相关的模型稳态血液浓度的分布可为缺乏特定化学物质药代动力学数据的 VOC 估计血液浓度筛选值提供依据。这里提出的筛选血液浓度为基于风险评估的 VOC 人群生物监测数据评估提供了一种工具，最适合用于此类数据集的中心趋势估计。
