Analysis of Chemical Simulants in Urine: A Useful Tool for Assessing Emergency Decontamination Efficacy in Human Volunteer Studies

Abstract

Introduction: 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. Study Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

A controlled cross-over study to evaluate the efficacy of improvised dry and wet emergency decontamination protocols for chemical incidents

“…Another possibility is that MeS skin absorption is rapid and the 15-minute delay before commencing intervention is insufficient to influence systemic levels significantly. When MeS was examined in urine in a feasibility study using 100uL applied simulant [ 10 ] peak urine levels at 1h were significantly higher than baseline but other time points did not reach significance. Further examination of suitable MeS application dose and how to avoid MeS exposure from dietary and other sources is required.…”

“…Further examination of suitable MeS application dose and how to avoid MeS exposure from dietary and other sources is required. In addition, alternative simulant contaminants should be explored which may be more suitable for assessing systemic exposure in urine [ 10 ].…”

“…Skin sample analysis was conducted by gas chromatography tandem mass spectrometry (GC-MSMS) as outlined by James et al . [ 9 ] and MeS was extracted from urine samples by supported liquid extraction prior to GC-MSMS as outlined by James et al [ 10 ].…”

Human volunteer study of the decontamination of chemically contaminated hair and the consequences for systemic exposure

“…foodstuffs. A subsequent study by James et al 32 measuring parent MeS in urine also suggested that exogenous sources of MeS can confound data interpretation. Whilst the MeS data in this study should be interpreted within this context both MeS and BeS concentrations in this study were much higher in control and www.nature.com/scientificreports/ intervention samples than in baseline samples indicating that a systemic effect due to dermal penetration was being observed.…”

“…MeS and BeS in hair samples and swabs were measured by gas chromatography triple quadruple mass spectrometry (GC-MS/MS) according to the method described by James et al 34,35 . MeS and BeS in 24-urine samples were measured by GC-MS/MS according to James et al 32 .…”