Immediate dry decontamination using efficient absorbent materials is beneficial following skin exposure to low-volatile toxic chemicals.

In a chemical mass casualty incident requiring skin decontamination, dry removal using absorbent materials may be beneficial to enable immediate decontamination. The efficacy of absorbent materials has therefore been evaluated, alone or procedures including both dry and wet decontamination, following skin exposure to two low volatile toxic chemicals using an in vitro human skin penetration model. Additionally, removal using active carbon wipes was evaluated with or without the Dahlgren Decon solution. All dry decontamination procedures resulted in a significantly decreased skin penetration rate of the industrial chemical 2-butoxyethanol compared to the control without decontamination. Wet decontamination following dry absorption significantly improved the efficacy compared to dry removal alone. Dry decontamination post-exposure to the chemical warfare nerve agent VX showed no decontamination efficacy. However, dry and wet decontamination resulted in a decreased agent skin penetration rate during the last hour of the experiment. At -15°C, significantly reduced VX skin penetration rates were demonstrated for both dry decontamination alone and the dry and wet decontamination procedure. The Dahlgren Decon solution significantly reduced the amount of VX penetrating the skin, but the active carbon wipe alone did not impact the skin penetration rate. In conclusion, absorbent materials are beneficial for the removal of low-volatile chemicals from the skin, but the degree of efficacy varies between chemicals. Despite the variability, immediate dry decontamination using available absorbent materials prior to wet decontamination is recommended as a general procedure for skin decontamination. The procedure should also be prioritized in cold-weather conditions to prevent patient hypothermia.

Efficient agent degradation within skin is important for decontamination of percutaneously exposed VX.

AIM OF THE STUDY: Following percutaneous exposure to the nerve agent VX, the remaining intact agent within the skin after decontamination is of great concern. Consequently, this leads to prolonged agent release to the blood circulation resulting in sustained intoxication, which may complicate the medical management. The decontamination procedure used should therefore possess the ability for agent removal both on and within the skin. The efficacy of three decontamination procedures was evaluated by measuring VX and the primary degradation product ethyl methyl phosphonic acid (EMPA) penetrated through human skin and the amount remaining within the skin. MATERIALS AND METHODS: Decontamination was initiated 5 min post-exposure to VX on human dermatomed skin. Experiments were conducted using an in vitro skin penetration model and the amount remaining within the skin was determined by combining the tape-stripping technique and acetylcholinesterase activity measurements. RESULTS: In control experiments without decontamination, higher amounts of VX were recovered in the deeper layers of skin compared to EMPA, which was primarily located in the stratum corneum. Both Reactive Skin Decontamination Lotion (RSDL) and the RSDL training kit (TRSDL) significantly reduced the amount of VX within the skin and decreased the penetration through the skin. However, the degradation ability of RSDL was demonstrated to be beneficial by the reduction of intact agents remaining in the skin compared to TRSDL without agent degradation capability. Soapy water decontamination caused a "wash-in" effect of VX with decreased agent amounts within stratum corneum but increased the amount VX penetrated through the skin. CONCLUSION: Efficient skin decontamination of VX requires skin decontaminants reaching deeper layers of the skin, and that both absorption and degradation properties are important. In addition, the "wash-in" effect by using soapy water may enhance VX release to the blood circulation.

OnPLS integration of transcriptomic, proteomic and metabolomic data shows multi-level oxidative stress responses in the cambium of transgenic hipI- superoxide dismutase Populus plants.

BACKGROUND: Reactive oxygen species (ROS) are involved in the regulation of diverse physiological processes in plants, including various biotic and abiotic stress responses. Thus, oxidative stress tolerance mechanisms in plants are complex, and diverse responses at multiple levels need to be characterized in order to understand them. Here we present system responses to oxidative stress in Populus by integrating data from analyses of the cambial region of wild-type controls and plants expressing high-isoelectric-point superoxide dismutase (hipI-SOD) transcripts in antisense orientation showing a higher production of superoxide. The cambium, a thin cell layer, generates cells that differentiate to form either phloem or xylem and is hypothesized to be a major reason for phenotypic perturbations in the transgenic plants. Data from multiple platforms including transcriptomics (microarray analysis), proteomics (UPLC/QTOF-MS), and metabolomics (GC-TOF/MS, UPLC/MS, and UHPLC-LTQ/MS) were integrated using the most recent development of orthogonal projections to latent structures called OnPLS. OnPLS is a symmetrical multi-block method that does not depend on the order of analysis when more than two blocks are analysed. Significantly affected genes, proteins and metabolites were then visualized in painted pathway diagrams. RESULTS: The main categories that appear to be significantly influenced in the transgenic plants were pathways related to redox regulation, carbon metabolism and protein degradation, e.g. the glycolysis and pentose phosphate pathways (PPP). The results provide system-level information on ROS metabolism and responses to oxidative stress, and indicate that some initial responses to oxidative stress may share common pathways. CONCLUSION: The proposed data evaluation strategy shows an efficient way of compiling complex, multi-platform datasets to obtain significant biological information.

Comparison of skin decontamination strategies in the initial operational response following chemical exposures.

In mass casualty incidents including hazardous chemical skin exposure, decontamination is the primary intervention to avoid systemic uptake of the toxic compound. The protocol needs to be both simple and efficient to enable a rapid response and avoid delay of patient management. In the present study, decontamination strategies included in the initial operational response were evaluated following human skin exposure in vitro to four different contaminants. Results demonstrated that the efficacy of selected decontamination procedures was highly dependent on the chemical contaminant used. Dry removal of the sulfur mustard simulant methyl salicylate prior to wet decontamination was found beneficial compared to wet decontamination alone. Rapidly initiated wet decontamination was more efficient compared to dry and wet removal of the industrial chemical 2-butoxyethanol and the nerve agent tabun. Following VX-exposure, all wet decontamination procedures resulted in increased agent penetration compared to the control. In conclusion, challenges in establishing simple and efficient decontamination procedures for a broad-spectrum of chemicals have been demonstrated. The impact of including a dry removal step during decontamination was evidently agent specific. Despite the variation in efficacy, immediately initiated dry removal may facilitate patient management until wet decontamination resources are available and to reduce the risk of secondary contamination.

In vitro human skin decontamination efficacy of MOF-808 in decontamination lotion following exposure to the nerve agent VX.

Metal-organic frameworks (MOFs) have shown promising properties for removal of chemical warfare agents, in particular for material decontamination and functionalized fabrics. The MOF-properties could also be beneficial for skin decontamination, especially when exposed to highly toxic and low volatile nerve agents. In such exposures, efficient decontamination is crucial for adequate medical management. In the present study, seven zirconium-based MOFs were evaluated for their ability to degrade VX and subsequently tested in vitro for decontamination of VX on human dermatomed skin. Of the MOFs evaluated, MOF-808 showed the greatest ability to degrade VX in an alkaline buffer with complete degradation of VX within 5 min. PCN-777, Zr-NDC and NU-1000 displayed degradation half-lives of approximately 10 min. When including MOF-808 in a skin friendly carrier with slightly acidic pH, a decreased agent degradation rate was observed, requiring over 24 h to reach complete degradation. In skin decontamination experiments, MOF-808 enhanced the efficacy compared to the carrier alone, essentially by improved agent absorption. Adding MOF-808 to Reactive Skin Decontamination Lotion (RSDL) did not improve the high effectiveness of RSDL alone. The present study showed that including MOF in skin decontamination lotions could be beneficial. Further studies should include optimizing the particulates and formulations.

Attribution of fentanyl analogue synthesis routes by multivariate data analysis of orthogonal mass spectral data.

Chemical attribution signatures (CAS) can be used to obtain useful forensic information and evidence from illicit drug seizures. A CAS is typically generated using hyphenated chemical analysis techniques and consists of a fingerprint of the by-products and additives present in a sample. Among other things, it can provide information on the sample's origin, its method of production, and the sources of its precursors. This work investigates the possibility of using multivariate CAS analysis to identify the synthetic methods used to prepare seized fentanyl analogues, independently of the analogues' acyl derivatization. Three chemists working in two labs synthesized three different fentanyl analogues, preparing each one in duplicate by six different routes. The final collection of analogues (96 samples) and two intermediates (16 + 32 samples) were analysed by GC-MS and UHPLC-HRMS, and the resulting analytical data were used for multivariate modelling. Independently of analogue structure, the tested fentanyls could be classified based on the method used in the first step of their synthesis. The multivariate model's ability to classify unknown samples was then evaluated by applying it to six new fentanyl analogues. Additionally, seized fentanyl samples was analysed and classified by the model.

Determination of methylmercury, ethylmercury, and inorganic mercury in mouse tissues, following administration of thimerosal, by species-specific isotope dilution GC-inductively coupled plasma-MS.

Isotopically enriched HgO standards were used to synthesize CH3(200)Hg+ and C2H5(199)Hg+ using Grignard reagents. These species were employed for isotope dilution GC-ICPMS to study uptake and biotransformation of ethylmercury in mice treated with thimerosal, (sodium ethylmercurithiosalicylate) 10 mg L(-1) in drinking water ad libitum for 1, 2.5, 6, or 14 days. Prior to analysis, samples were spiked with aqueous solutions of CH3(200)Hg+, C2H5(199)Hg+, and 201Hg2+ and then digested in 20% tetramethylammonium hydroxide and extracted at pH 9 with DDTC/toluene. Extracted mercury species were reacted with butylmagnesium chloride to form butylated derivatives. Absolute detection limits for CH3Hg+, C2H5Hg+, and Hg2+ were 0.4, 0.2, and 0.6 pg on the basis of 3sigma of five separate blanks. Up to 9% of the C2H5Hg+ was decomposed to Hg2+ during sample preparation, and it is therefore crucial to use a species-specific internal standard when determining ethylmercury. No demethylation, methylation, or ethylation during sample preparation was detected. The ethylmercury component of thimerosal was rapidly taken up in the organs of the mice (kidney, liver, and mesenterial lymph nodes), and concentrations of C2H5Hg+ as well as Hg2+ increased over the 14 days of thimerosal treatment. This shows that C2H5Hg+ in mice to a large degree is degraded to Hg2+. Increased concentrations of CH3Hg+ were also observed, which was found to be due to impurities in the thimerosal.