Four sulfur mustard exposure cases: Overall analysis of four types of biomarkers in clinical samples provides positive implication for early diagnosis and treatment monitoring

Abstract

In one event, Chinese male individuals accidentally exposed to unknown chemicals and emerged erythema or blisters on contacted organism derma, then hospitalized. To identify the causative agents, blood, urine and exudate samples were collected from the patients during the therapeutic course. Five established liquid chromatography–mass spectrometry (LC–MS) and gas chromatography (GC)–MS methods were employed to analyze the samples. Here, an overall analysis of four types of sulfur mustard biomarkers, including the hydrolysis/oxidation products, β-lyase metabolites, DNA adducts and hemoglobin adducts, was conducted toward the samples from exposed individuals. The results of all the four types of biomarkers in different biomedical matrices showed high relevance, and verified that this exposure is indeed originated from sulfur mustard. The concentrations of the biomarkers in specimens revealed a good correlation with the severity of the patient's symptom. The concentration-time profile demonstrated that most of the biomarkers quickly achieved maximum at the beginning of the course, and then decreased and kept a detectable level until the 7th day after exposure. The DNA adducts in urine samples still appeared on the 30th day, and the N-terminal valine adducts in hemoglobin could be monitored for over 90 days, which was meaningful for the concurrent study of clinical samples. To the best of our knowledge, this work provides the total analysis and profile of four categories of biomarkers in human specimens for the first time, and the good accordance between concentration and level of burns, between time course and biomarkers will be of great importance for early diagnosis and medical treatment monitoring of sulfur mustard exposure.

Accumulation of intact sulfur mustard in adipose tissue and toxicokinetics by chemical conversion and isotope-dilution liquid chromatography–tandem mass spectrometry

“…Work on destroying these abandoned chemical weapons is still in progress. The main hazards induced by the abandoned SM include environmental pollution (Bizzigotti et al 2008;Sanderson et al 2010) and potential threat to civilians (Xu et al 2014). As a highly reactive alkylating agent, SM can attack nearly all cell constituents and cause severe damage to the skin, eyes and respiratory system.…”

“…The excretion or toxicokinetic profiles of these metabolites and adducts were studied to get an insight into the mechanism of toxicity and metabolism of SM. Xu et al (2014) reported the overall analysis of four types of biomarkers in an accident with four sulfur mustard exposure cases. Urinary excretion profiles were measured for hydrolysis products thiodiglycol (TDG) and thiodiglycol sulfoxide (TDGO), β-lyase metabolites derived from glutathione conjugates and DNA adducts of SM after cutaneous application in rats (Black et al 1992a;Li et al 2013;Yue et al 2014;Zhang et al 2014) and rabbits Nie et al 2014).…”

Sulfur Mustard: Persisting Threat

“…Uvedené metabolity mohou být stanoveny až dva týdny po expozici. V moči neexponovaných osob se zmíněné látky nevyskytují, a proto jsou považovány za perspektivní biomarkery expozice sirnému yperitu (29,30).…”

An improved method for retrospective quantification of sulfur mustard exposure by detection of its albumin adduct using ultra-high pressure liquid chromatography-tandem mass spectrometry

“…It was again used as CWAs by Iraq during the Iran-Iraq conflict [4]. Together with the recent occurrence of some accidental human exposure during demilitarization of HD munitions or containers [5], HD will continue to be of great concern to public health risks in spite of the Chemical Weapons Convention (CWC) prohibiting its production, stockpiling, and use. Furthermore, potential threat to public safety will also be aggravated if abused by terrorists because of its ease of preparation.…”

“…Based on these metabolites in vivo, HD exposure to humans is diagnosed and assessed [4,5]. The hydrolytic metabolite thiodiglycol and its oxidation product thiodiglycol sulfoxide, a series of β-lyase metabolite products, and HD-DNA adducts at N 7 , O 6 positions of guanine, N 3 position of adenine had been diagnosed as biomarkers for clinical samples of HD exposure in many cases, and provided credible information for medical treatment [5][6][7]. However, one common disadvantage of these biomarkers is that they predominantly occur within 2 wk after an exposure.…”