James Thomas, Collins Samuel, Amlôt Richard, Marczylo Tim
Centre for Radiation, Chemicals and Environmental Hazards (CRCE), Public Health England, Chilton, United Kingdom.
Emergency Response Department Science & Technology, Public Health England, Porton Down, Salisbury, Wiltshire, United Kingdom.
Prehosp Disaster Med. 2020 Oct;35(5):482-487. doi: 10.1017/S1049023X20000825. Epub 2020 Jun 30.
To date, all human studies of mass-casualty decontamination for chemical incidents have relied on the collection and analysis of external samples, including skin and hair, to determine decontamination efficacy. The removal of a simulant contaminant from the surface of the body with the assumption that this translates to reduced systemic exposure and reduced risk of secondary contamination has been the main outcome measure of these studies. Some studies have investigated systemic exposure through urinary levels of simulant metabolites. The data obtained in these studies were confounded by high background concentrations from dietary sources. The unmetabolized simulants have never been analyzed in urine for the purposes of decontamination efficacy assessment.
Urinary simulant analysis could obviate the need to collect skin or hair samples during decontamination trials and provide a better estimate of both decontamination efficacy and systemic exposure. The study objective therefore was to determine whether gross skin contamination as part of a decontamination study would yield urine levels of simulants sufficient to evaluate systemic availability free from dietary confounders.
In this study, a gas chromatography-tandem mass spectrometry method was developed for the analysis of two chemical simulants, methyl salicylate (MeS) and benzyl salicylate (BeS), in urine. An extraction and sample clean-up method was validated, enabling quantitation of these simulants in urine. The method was then applied to urine collected over a 24-hour period following simulant application to the skin of volunteers.
Both MeS and BeS were present in all urine samples and were significantly increased in all post-application samples. The MeS levels peaked one hour after skin application. The remaining urinary levels were variable, possibly due to additional MeS exposures such as inhalation. In contrast, the urinary excretion pattern for BeS was more typical for urinary excretion curves, increasing clearly above baseline from four hours post-dose and peaking between 12.5 and 21 hours, a pattern consistent with dermal absorption and rapid excretion.
The authors propose BeS is a useful simulant for use in decontamination studies and that its measurement in urine can be used to model systemic exposures following skin application and therefore likely health consequences.
迄今为止，所有关于化学事故大规模伤亡去污的人体研究都依赖于收集和分析外部样本，包括皮肤和头发，以确定去污效果。从身体表面去除模拟污染物，并假设这意味着全身暴露减少和二次污染风险降低，一直是这些研究的主要结果衡量标准。一些研究通过模拟代谢物的尿液水平来调查全身暴露情况。这些研究中获得的数据受到饮食来源高背景浓度的干扰。为了评估去污效果，从未对尿液中的未代谢模拟物进行过分析。
尿液模拟物分析可以避免在去污试验期间收集皮肤或头发样本的需要，并能更好地估计去污效果和全身暴露情况。因此，该研究的目的是确定作为去污研究一部分的皮肤总体污染是否会产生足以评估不受饮食干扰的全身可用性的模拟物尿液水平。
在本研究中，开发了一种气相色谱 - 串联质谱法，用于分析尿液中的两种化学模拟物，水杨酸甲酯（MeS）和水杨酸苄酯（BeS）。验证了一种提取和样品净化方法，能够对尿液中的这些模拟物进行定量。然后将该方法应用于志愿者皮肤涂抹模拟物后24小时内收集的尿液。
所有尿液样本中均存在MeS和BeS，且所有涂抹后样本中的含量均显著增加。MeS水平在皮肤涂抹后1小时达到峰值。其余尿液水平存在差异，可能是由于吸入等额外的MeS暴露。相比之下，BeS的尿液排泄模式更符合典型的尿液排泄曲线，给药后4小时明显高于基线水平，并在12.5至21小时之间达到峰值，这一模式与皮肤吸收和快速排泄一致。
作者提出BeS是用于去污研究的有用模拟物，其尿液测量可用于模拟皮肤涂抹后的全身暴露情况，进而可能推断健康后果。
