CHART: a novel system for detector evaluation against toxic chemical aerosols.

Concern over the possibility of deliberate dispersion of chemical warfare agents and highly toxic pharmaceutical based agents as persistent aerosols has raised the need for experimental assessment of current and future defensive capabilities of armed forces and law enforcement agencies. Therefor we herewith present the design, realization and validation of the Chemical Hot Aerosol Research Tool (CHART) as a validated and safe experimental set-up for performance evaluation of chemical detection and identification equipment against chemical warfare agents and other highly toxic compounds. In the CHART liquid and solid compounds in solution or suspension are being dispersed as aerosols in a nebulization chamber. A broad dynamic particle size range can be generated, including particles known to be able to reach the lower respiratory tract. The aerosol generated is presented to the detection system-under-test while being monitored and characterized in real-time, using an optical particle counter and a time-of-flight aerosol analyzer, respectively. Additionally, the chemical composition of the aerosol is ex situ measured by analytical chemical methods. Evidently, in the design of the CHART significant emphasis was placed on laboratory safety and containment of toxic chemicals. The CHART presented in this paper has proven to be an indispensable experimental tool to study detectors and fieldable identification equipment against toxic chemical aerosols.

Real-time characterization of chemical threat agent aerosols for improvement of inhalation studies.

OBJECTIVES: Deliberate or accidental release of chemical treat agents in the aerosol form can cause an inhalation hazard. Since the relationship between aerosol properties and health hazards is poorly understood, research into the toxicological consequences of exposure to aerosols is needed. The aim of the present study was to improve the characterization of particles for inhalation studies. METHODS: Several aerosol measurement technologies were compared for their potential to physically and chemically characterize particles in the inhalation size range in real-time. For that purpose, we compared the performance of an aerodynamic particle sizer (APS), a scanning mobility particle sizer (SMPS) and an electrical low-pressure impactor (ELPI) in an experimental set-up in which particles were generated by a Collison nebulizer and subsequently delivered into a nose-only inhalation exposure system. RESULTS: We found that more than 95% of the number of particles, equating to more than 83% of the mass generated by the 6-jet Collison nebulizer, were below 0.5 µm. To characterize the entire size range, the APS as single detector has only limited value, therefore the addition of supplementary instrumentation such as the SMPS or the ELPI is required. After real-time measurements in the size range of 30 nm to 10 µm, ex-situ chromatographic chemical analysis is essential for quantification of the delivered mass concentration. CONCLUSIONS: In summary, the present work demonstrates the utility of the ELPI technology, in combination with off-line analysis, for characterizing aerosols with various size, shape, charge, and composition. This makes the aerosol generation and analysis suite described a promising tool for quantitative inhalation exposure studies.

Multiple analysis techniques were applied for real-time aerosol characterizationAerosol size distributions are characterized for inhalation exposure studies.Analytical analysis following ELPI measurements is essential for mass quantification.

Application of the Ugi Multicomponent Reaction in the Synthesis of Reactivators of Nerve Agent Inhibited Acetylcholinesterase.

Recently, a new class of reactivators of chemical warfare agent inhibited acetylcholinesterase (AChE) with promising in vitro potential was developed by the covalent linkage of an oxime nucleophile and a peripheral site ligand. However, the complexity of these molecular structures thwarts their accessibility. We report the compatibility of various oxime-based compounds with the use of the Ugi multicomponent reaction in which four readily accessible building blocks are mixed together to form a product that links a reactivating unit and a potential peripheral site ligand. A small library of imidazole and imidazolium reactivators was successfully synthesized using this method. Some of these compounds showed a promising ability to reactivate AChE inhibited by various types of CWA in vitro. Molecular modeling was used to understand differences in reactivation potential between these compounds. Four compounds were evaluated in vivo using sarin-exposed rats. One of the reactivators showed improved in vivo efficacy compared to the current antidote pralidoxime (2-PAM).