Nerve agents defined

Figure 1. Generic structures of nerve agents defined in Schedule 1 of the CWC...

Application of in vitro test methods have become advantageous in specific cases, such as structurally defined compounds and delayed neuropathy, since target cell data and biochemical processes associated in delayed neuropathy are known. Microscopic studies reveal that cases of OPIDN have degeneration of axons followed by demyelination of the nervous system.25,26 Epidemiologic studies have indicated mild impairment of the brainstem, spinal cord, and peripheral nerve functions in Gulf War veterans.27 Such studies are consistent with the spectrum of OPIDN syndrome. The main nerve agents have been shown to inhibit NTE in vitro as well as in vivo. Sarin has been shown to produce delayed neurotoxicity when administered at higher doses in protected hens.25-27... 

OPIDN is defined as a delayed onset central and peripheral distal sensorimotor polyneuropathy caused by exposure to nerve agents (Brown and Brix, 1998), typically within 1 to 2 weeks, and less than 4 weeks, after exposure (Johnson, 1980). Symptoms attributable to effects on sensory (numbness, tingling, pain) and motor (fatigue, weakness, and paralysis) targets are present and display a typical axonal length-associated pattern (e.g. predominantly lower extremities, with upper extremities affected at higher agent exposure). No treatment exists, and recovery is slow and rarely complete. 

Low dose is sometimes defined in terms of exposure to levels of nerve agent that are described as asymptomatic in that they do not induce overt acute signs or symptoms. While this chapter will focus primarily on the potential effects of such asymptomatic exposures, levels of nerve agent that induce miosis and those which result in transitory disruption of behaviour with minor clinical signs will also be considered. 

It is common practice for toxicologists to differentiate exposure to chemicals based on the dose and the duration of exposure. Lour timeframes have been used to define duration of exposures acute, subacute, subchronic, and chronic. It is useful in light of today s interest in long-term, low-levef exposures to clarify these terms. Acute exposure is defined as exposure to a chemical for less than 24 h. Subacute exposure refers to an exposure of 1 month or less, subchronic for 1 to 3 months, and chronic for more than 3 months. These exposures can be by any route for most chemicals it is the oral route with the chemical given in the diet. However, the limited animal studies using nerve agents have usually employed parenteral administration... 

The mode of biological activity of mustard is less well defined than that of the nerve agents. The initial event is felt to be a reaction of mustard and deoxyribonucleic acid (DNA) with subsequent damage to the DNA. A series of intracellular events then occur, leading to cellular damage accompanied by inflammation and cellular death. Cellular damage begins within 1 to 2 minutes of contact of mustard to skin or mucous membranes.6... 

Response time is defined as the minimum time required to obtain a positive, reproducible response at the Limit of Detection and at a very high concentration that is approximately equivalent to an Ect5o [1] for severe human effects by vapor inhalation of agents (10 to 50 mg-min/m for nerve agents and 100 mg-min/m for blister agents). 

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