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This thesis is presented in partial fulfilment of the requirements for the award of the degree Doctor of Philosophy (PhD), by prior publication of a coherent body of research work. The threads that link this body of work together are continued development of forensic chemistry practice and sustained commitment to research into forensic chemistry techniques applied to hazardous materials. The work explores the competencies, knowledge and skills required to perform the duties of a forensic chemist in operational environments that involve hazards as diverse and challenging as chemical warfare agents, illicit controlled substances and toxic industrial materials, during both the response and investigation phases of an incident. The peer-reviewed publications presented in this thesis focus on issues and incidents the author has encountered during his operational duties as a forensic chemist. The publications provide an assessment of those incidents in the context of underlying core competencies, knowledge and skills which support the effective performance of a forensic chemist in these operational environments. The compilation of publications covers the following core competency areas: • Illicit drugs specifically looking at amphetamine, methamphetamine and heroin production • Chemical Warfare Agents • Hazardous Materials and Repurposed Containers at Clandestine Laboratories • Mobile Laboratories The thesis also examines the complex issue of multiuse chemicals across a range of incidents. Multiuse chemicals pose several challenges for the forensic chemist based on their wide range of potential applications across all the core competency areas considered. These include the potential to be used in the preparation of illicit drugs, explosives and chemical warfare agents as well as their application and use in toxic industrial chemicals or chemical processes. For instance, the thesis and related publications examine the application of multiuse chemicals in the novel production of amphetamine using an unrestricted amino acid as the primary precursor. ii In the area of illicit drugs, the author identifies novel reaction markers associated with an emerging trend within the Afghan heroin trade, whilst also conclusively dispelling the widely-held notion that heroin might be produced from morphine by using acetic acid as an acetylating agent. The author has further researched and developed a comprehensive review of synthetic methods and routes for the manufacture of amphetamine and methamphetamine which is used as a forensic and investigative reference standard internationally. The subject matter area of chemical warfare agents includes a detailed review of the first 41 proficiency tests by the Organisation for the Prohibition of Chemical Weapons (OPCW), providing laboratories with information to help develop and establish analytical procedures. Such as those used by the ChemCentre in Western Australia as part of their emergency response capabilities (ChemCentre, 2018). The thesis also provides several examples where the core competencies described have been applied in an operational setting - first, a large-scale drug manufacture site in South East Asia where a novel modification in the process used for methamphetamine manufacture was identified; and second, repurposing of gas cylinders to produce and store toxic corrosive gases. This latter example has significant implications for clandestine laboratory and hazmat response, and also relates to their potential use as improvised chemical warfare agent containment and delivery systems. The need for rapid identification of chemicals from a range of incidents in an Australian domestic setting has necessitated the development and deployment of mobile laboratory facilities. The authors publications in this area are internationally accepted benchmark papers for the design, operation and deployment of mobile laboratories for CBRN response, based on those developed specifically for the Australian domestic setting. This original research has been used to develop and enhance similar capabilities globally such as that developed by the Brazilian Army (Cardozo et al., 2018) The thesis also addresses the communication skills required by the forensic chemist for effective scientific and technical communication in order to interact with multidisciplinary response teams and command structures. This includes the ability to operate in, and provide critical risk-based advice on, the personal protective iii equipment and decontamination systems available to, or required by responders at an incident or within a laboratory setting. In summary the thesis, and associated publications, make an original contribution to the academic understanding of the core competencies, knowledge and skills required by a responding forensic chemist, to identify and mitigate current and emerging threats encountered during emergency response and hazardous materials investigations and incidents

From 1997 until 2016, the Organisation for the Prohibition of Chemical Weapons (OPCW) has coordinated 40 proficiency tests for the analysis and identification of intact chemical warfare agents, precursor chemicals, degradation and reaction products. This chapter reviews the chemicals used to spike the proficiency test samples, identifying those that have been used multiple times and the distribution of chemicals based upon the schedules in the chemical warfare convention (CWC). The aim of this chapter is not to provide an easy route to pass the proficiency tests but rather to illustrate the range of chemicals that should be considered during method development and/or validation for laboratories participating in, or considering participating in the OPCW Proficiency Test regime.

ObjectivePharmacoresistance remains an unsolved therapeutic challenge in status epilepticus (SE) and in cholinergic SE induced by nerve agent intoxication. SE triggers a rapid internalization of synaptic γ-aminobutyric acid A (GABAA ) receptors and externalization of N-methyl-d-aspartate (NMDA) receptors that may explain the loss of potency of standard antiepileptic drugs (AEDs). We hypothesized that a drug combination aimed at correcting the consequences of receptor trafficking would reduce SE severity and its long-term consequences.MethodsA severe model of SE was induced in adult Sprague-Dawley rats with a high dose of lithium and pilocarpine. The GABAA receptor agonist midazolam, the NMDA receptor antagonist ketamine, and/or the AED valproate were injected 40 min after SE onset in combination or as monotherapy. Measures of SE severity were the primary outcome. Secondary outcomes were acute neuronal injury, spontaneous recurrent seizures (SRS), and Morris water maze (MWM) deficits.ResultsMidazolam-ketamine dual therapy was more efficient than double-dose midazolam or ketamine monotherapy or than valproate-midazolam or valproate-ketamine dual therapy in reducing several parameters of SE severity, suggesting a synergistic mechanism. In addition, midazolam-ketamine dual therapy reduced SE-induced acute neuronal injury, epileptogenesis, and MWM deficits.SignificanceThis study showed that a treatment aimed at correcting maladaptive GABAA receptor and NMDA receptor trafficking can stop SE and reduce its long-term consequences. Early midazolam-ketamine dual therapy may be superior to monotherapy in the treatment of benzodiazepine-refractory SE.