Business Unit Quality and Safety (Q&S), Department Research & Development, TNO, Zeist, The Netherlands.
Toxicol Lett. 2010 Oct 5;198(2):144-51. doi: 10.1016/j.toxlet.2010.06.008. Epub 2010 Jun 20.
Biological monitoring has become one of the methods to measure exposure, with the advantage that it gives information about the concentration of a substance that actually enters the body and reflects the inter-individual differences in uptake and metabolic variation. However, limited information is available on inter- and intra-individual variability of biomarkers. The aim of this study was to gather information about the biological component of inter-individual variation in biomarkers using results from volunteer studies. Open literature and other (internal) sources were searched to find human volunteer studies utilizing biological monitoring. Ultimately 41 studies were included in our analysis, with a total of 6747 observations for one or more biomarkers from 223 volunteers. The data from these studies were grouped on the basis of study, substance under investigation, exposure route, biological matrix, exposure duration, dose and number of exposure events to obtain 278 homogeneous groups (strata) for statistical analysis. Variability was assessed in two ways. Firstly, estimates of biomarker half-life were calculated for each individual, thereby allowing the estimation of inter-individual variability in half-lives within the homogeneous groups. Secondly, variation in biomarker concentrations at a given time point was estimated. For estimated half-lives the GSDs ranged from 1.0 to 6.8. The variability in estimated half-lives did not differ much for the different types of substances. For concentrations at a given time point the average GSDs within strata ranged from 1.0 to 5.6. Again, variability did not differ much for different groups (e.g., type of substance). The median variability component was 0.11 (range 0-3.0). In conclusion, volunteer studies enable the estimation of both variation in half-lives and variation in biomarker levels in the well-defined homogeneous groups. Comparison of our results with other studies indicates that variation due to biological differences within and between people is quite substantial in homogeneous exposure groups. The relative contribution of this biological component to the total variation will be smaller when variance components are estimated in less homogeneous groups, such as those in occupational and environmental settings.
生物监测已成为衡量暴露的方法之一，其优势在于它提供了实际进入人体的物质浓度信息，并反映了个体间吸收和代谢变化的差异。然而，关于生物标志物的个体内和个体间可变性的信息有限。本研究的目的是利用志愿者研究的结果收集关于生物标志物个体间变异的生物成分信息。开放文献和其他（内部）来源被搜索，以找到利用生物监测的人类志愿者研究。最终，有 41 项研究被纳入我们的分析，共有 223 名志愿者的一项或多项生物标志物的 6747 个观察值。根据研究、研究物质、暴露途径、生物基质、暴露持续时间、剂量和暴露事件次数对这些研究的数据进行分组，以获得 278 个同质组（层）进行统计分析。通过两种方式评估变异性。首先，为每个个体计算生物标志物半衰期的估计值，从而可以在同质组内估计半衰期的个体间变异性。其次，在给定时间点估计生物标志物浓度的变化。对于估计的半衰期，GSD 范围为 1.0 至 6.8。不同类型物质的半衰期估计值变异性差异不大。对于给定时间点的浓度，层内的平均 GSD 范围为 1.0 至 5.6。同样，不同组（例如，物质类型）之间的变异性差异不大。中位数变异性分量为 0.11（范围 0-3.0）。总之，志愿者研究能够估计半寿期和生物标志物水平在定义明确的同质组中的变化。将我们的结果与其他研究进行比较表明，在同质暴露组中，由于人与人之间的生物学差异导致的变异性相当大。当在异质组（如职业和环境环境中的组）中估计方差分量时，该生物学成分对总变异性的相对贡献将会更小。
