Timchalk Charles, Poet Torka S, Kousba Ahmed A, Campbell James A, Lin Yuehe
Pacific Northwest National Laboratory, MSIN: P7-59, 902 Battelle Blvd., PO Box 999, Richland, WA 99352, USA.
J Toxicol Environ Health A. 2004;67(8-10):635-50. doi: 10.1080/15287390490428035.
There is a need to develop approaches for assessing risk associated with acute exposures to a broad range of metals and chemical agents and to rapidly determine the potential implications to human health. Noninvasive biomonitoring approaches are being developed using reliable portable analytical systems to quantitate dosimetry utilizing readily obtainable body fluids, such as saliva. Saliva has been used to evaluate a broad range of biomarkers, drugs, and environmental contaminants, including heavy metals and pesticides. To advance the application of noninvasive biomonitoring a microfluidic/electrochemical device has also been developed for the analysis of lead (Pb), using square-wave anodic stripping voltametry. The system demonstrates a linear response over a broad concentration range (1-2000 ppb) and is capable of quantitating saliva Pb in rats orally administered acute doses of Pb acetate. Appropriate pharmacokinetic analyses have been used to quantitate systemic dosimetry based on determination of saliva Pb concentrations. In addition, saliva has recently been used to quantitate dosimetry following exposure to the organophosphate insecticide chlorpyrifos in a rodent model system by measuring the major metabolite, trichloropyridinol, and saliva cholinesterase inhibition following acute exposures. These results suggest that technology developed for noninvasive biomonitoring can provide a sensitive and portable analytical tool capable of assessing exposure and risk in real-time. By coupling these noninvasive technologies with pharmacokinetic modeling it is feasible to rapidly quantitate acute exposure to a broad range of chemical agents. In summary, it is envisioned that once fully developed, these monitoring and modeling approaches will be useful for evaluating acute exposure and health risk.
需要开发评估与广泛金属和化学制剂急性暴露相关风险的方法,并快速确定对人类健康的潜在影响。正在利用可靠的便携式分析系统开发非侵入性生物监测方法,以利用易于获取的体液(如唾液)对剂量测定进行定量。唾液已被用于评估广泛的生物标志物、药物和环境污染物,包括重金属和农药。为了推进非侵入性生物监测的应用,还开发了一种微流控/电化学装置,用于使用方波阳极溶出伏安法分析铅(Pb)。该系统在宽浓度范围(1-2000 ppb)内显示出线性响应,并且能够对口服急性剂量醋酸铅的大鼠唾液中的铅进行定量。基于唾液铅浓度的测定,已使用适当的药代动力学分析来定量全身剂量测定。此外,最近在啮齿动物模型系统中,通过测量主要代谢物三氯吡啶醇以及急性暴露后唾液胆碱酯酶抑制作用,唾液已被用于定量暴露于有机磷杀虫剂毒死蜱后的剂量测定。这些结果表明,为非侵入性生物监测开发的技术可以提供一种灵敏且便携式的分析工具,能够实时评估暴露和风险。通过将这些非侵入性技术与药代动力学模型相结合,快速定量广泛化学制剂的急性暴露是可行的。总之,可以设想,一旦充分开发,这些监测和建模方法将有助于评估急性暴露和健康风险。