Presented in this chapter are data on the principal hydrolysis products of Russian VX (VR) with excess and equimolar quantities of water. A highly selective gas chromatography technique was developed in order to monitor compliance with hygienic regulations in the Russian Federation. This consisted of a conversion of VR to fluorohydride on a tablet impregnated with silver fluoride, followed by thermal desorption of fluorohydride into a gas chromatograph from a sorption tube. A unified method of direct determination of VR and its conversion products in various matrices with HPLC-MS/MS technique is described. Data on environmental monitoring of VR are presented, as well as data on effects developed under chronic exposure of rats to VR, including kinetic parameters of blood platelet aggregation and electrophysiology of the nervus tibialis.

This chapter reviews the current understanding of chemical and biochemical mechanisms of metabolism of warfare nerve agents describing the role of the enzymes involved in this process. Among enzymes participating in metabolism of nerve agents, the roles of A-esterases, serum cholinesterase, carboxylesterase, prolidase, and lipase are discussed. This chapter also discusses other aspects of metabolism of the agents, such as protein binding and the role of tissue depots for these compounds.

Several genera of cyanobacteria are capable of producing toxins that may be accessible for use as chemical warfare agents. The manner in which cyanotoxins produce their toxic effects can vary among different groups. The principal toxins include those that primarily affect the liver, such as microcystins, nodularins, and cylindrospermopsin. The other most notable toxins that primarily affect the nervous system include anatoxin-a, anatoxin-a(s), and saxitoxins. These cyanotoxins vary in their toxicity, availability from natural or biological sources, and availability from synthetic sources. Among cyanotoxins, only saxitoxins are listed as Schedule 1 agents in the Chemical Weapons Convention.

Organophosphorus compounds (OPs) have been used as pesticides and developed as warfare nerve agents such as tabun, soman, sarin, VX, and others. Exposure to even small amounts of an organophosphorus compound can be fatal and death is usually caused by respiratory failure resulting from paralysis of the diaphragm and intercostal muscles, depression of the brain respiratory center, bronchospasm, and excessive bronchial secretions. The mechanism of OP poisoning involves phosphorylation of the serine hydroxyl group in the active site of acetylcholinesterase (AChE) leading to inactivation of this essential enzyme which has an important role in neurotransmission. AChE inhibition results in the accumulation of acetylcholine at cholinergic receptor sites, producing continuous stimulation of cholinergic fibers throughout the central and peripheral nervous systems. Presently, a combination of an antimuscarinic agent, for example, atropine, AChE reactivator, such as one of the recommended pyridinium oximes (PAM-2, TMB-4, HI-6, LüH-6), and diazepam are used for the treatment of organophosphate poisoning in humans. In this chapter we review the mechanisms of action of OP and the role of pyridinium oximes used as AChE reactivators in the treatment of OP poisonings.

Medical decontamination of skin should be suitable for a variety of biological surface detoxification and decontamination schemes for both chemical weapons and pesticides, such as those directed against cholinesterases (and known as organophosphates). With the constant threat of chemical warfare, terrorist acts, or spills of pesticides, the development of improved means of protecting and decontaminating individuals from exposure to these agents is critical. An understanding of skin, the primary barrier to chemical warfare agents, is required to develop novel treatments postexposure. The skin is therefore defined and explored below.

Chemical weapons are part of the “weapons of mass destruction” concept because they can cause a large number of casualties. After the September 11, 2001, terrorist attacks in the United States, there is a high-risk perception of possible terrorist attacks with chemical weapons. This chapter analyzes information from open sources about the possible use of chemical weapons by terrorist groups, especially by those affiliated or associated with the jihadist terrorist network.

Prophylaxis against intoxication with organophosphate (OP) nerve agents is based on various approaches. Protection of acetylcholinesterase (AChE), the target enzyme for toxic action of OP nerve agents, is a basic requirement for effective prophylaxis. This can be achieved by using reversible AChE inhibitors, preferably carbamates (CMs). AChE inhibited by CMs is resistant to the action of an OP nerve agent for a transient period. After spontaneous recovery of the activity, normal AChE serves as a source of the active enzyme. Detoxification is carried out by the administration of enzymes hydrolyzing the OPs or evaluating specific enzymes (cholinesterases). The OP nerve agent is bound to the exogenously administered enzyme, and thus the OP level in the organism is decreased (“scavenger” effect). The administration of enzymes, such as AChE and butyrylcholinesterase, as scavengers seems to be very promising, as the enzyme acts at the very beginning of the toxic action, and without interaction with target tissues and without side effects. The antidotes currently used for the treatment of OP poisoning can be tested as prophylactics. This principle can be considered as a treatment in advance. Standard antidotes were studied in this respect; that is, anticholinergics, enzyme reactivators, anticonvulsants, and others. The problem with their use is the timing, duration, and achievement of sufficient levels of these antidotes after administration.

The use of chemicals in warfare dates back centuries, with modern chemical warfare beginning in World War I. More recent use of organophosphorus nerve agents in the Syrian civil war has highlighted the continuing worldwide concern for the misuse of chemical warfare agents (CWAs). A number of different types of CWAs can have deleterious effects on the nervous system. We briefly describe cellular function within the nervous system, factors that make the nervous system particularly sensitive to CWAs and other toxicants, and the different basic types of responses to neurotoxicants. Emphasis is placed on the acute and chronic neurological consequences of exposure to organophosphorus anticholinesterases, and both cholinergic and noncholinergic mechanisms in the expression of their toxicity and its modulation. A brief overview of the role of anticholinesterases in Gulf War illnesses is included. Additional information is provided with three other classes of CWAs, cyanides, sulfur mustard, and quinuclidinyl benzilate.

Organophosphate nerve agents (OPNAs) are highly toxic organophosphorus compounds (OPs) characterized according to their mechanism of action as substances influencing cholinergic nerve transmission via inhibition of acetylcholinesterase (AChE; EC 3.1.1.7). The manifestation of intoxication comprises nicotinic, muscarinic, and central symptoms. Some OPs are capable of causing a delayed neurotoxicity. Cholinesterases (AChE and butyrylcholinesterase, EC 3.1.1.8., BChE) could be characterized as the main enzymes involved in the toxic effect of these compounds including their different molecular forms. The activity of both AChE and BChE (in different molecular forms) is influenced mainly by inhibitors and other factors such as physiological and pathological states. Nevertheless, the determination of cholinesterase activity is a key diagnostic tool for diagnosis of poisoning with cholinesterase inhibitors (OPs and carbamates). There are different approaches for the determination of cholinesterase activity. The most frequently used method is based on the hydrolysis of thiocholine esters and subsequent colorimetric detection of the free thiol (-SH; sulfhydryl) group of the released thiocholine. The diagnosis of OP/NA poisoning is based on anamnesis, the clinical status of the intoxicated person/organism, and on cholinesterase activity determination in the blood. In the case of intoxication with NAs, red blood cell AChE is more diagnostically relevant than BChE activity in the plasma. This enzyme is a good diagnostic marker for intoxication with OP pesticides. Some other biochemical examinations are recommended, especially arterial blood gas, blood pH, minerals, and some other specialized parameters usually not always available in all clinical laboratories. For example: (1) determination of free OPNA or its metabolites (either in the blood or urine), (2) fluoride reactivation test, or (3) reactivation/adducts analysis after enzymatic digestion. These specialized analyses are important for prognosis of the intoxication, selection of effective treatment, and for retrospective analysis of the toxic agent of exposure.

The omnipresent colorless and odorless carbon monoxide (CO), generated by combustion, is the leading cause of unintentional death worldwide. CO binds to hemoglobin with affinity more than 200 times greater than oxygen and forms carboxyhemoglobin (COHb). The toxicity of CO is primarily attributable to formation of COHb and resultant hypoxia, which in turn leads to rebound hyperperfusion and generation of oxidant radicals; these oxidants can produce their own toxicity and add to that of CO. The toxicity of CO ranges from mild headache at COHb less than 10% to death at COHb more than 70%. CO is more toxic in subjects with cardiovascular diseases than in healthy individuals, and it increases maternal and fetal morbidity and mortality. Nonfatal exposure to CO can result in delayed neurological, myocardial, and other toxicities. At the same time, there is some adaptation to effects of CO on low-level chronic exposure. Hyperbaric oxygen remains the main therapy against CO poisoning.