guidelines. For CWAs, an adverse effect is considered an operationally relevant performance decrement or an adverse health effect.

Throughout the DOD report, low-level exposures to CWAs that may cause miosis have been emphasized (pupillary constriction); that effect occurs earlier and more reliably than other adverse effects. Although miosis typically has been considered the critical effect and most frequently used indicator of toxicity, questions about other adverse effects at low-level exposures remain. As noted in Chapter 3, Hartgraves and Murphy (1992) and Wolfe et al. (1992) observed decrements in equilibrium performance in primates at soman (GD) doses that generally do not produce classic signs of cholinergic toxicity, and Chilcott et al. (2003) found that mastication consistently preceded miosis and salivation in minipigs treated with high percutaneous doses of VX. Therefore, DOD should conduct research to determine whether there are more sensitive toxicity end points than miosis from low-level exposures to CWAs.

QUESTION 2. HOW MUCH OF A DECREMENT IN THE CRITICAL RESPONSE IS ADVERSE?

In the military operational risk management (ORM) context, this means identifying the degree of decrement that is operationally relevant, including the potential for the decrement to result in a field unit to become ineffective for combat or other mission-related activities. This information is currently not available. As noted above, if miosis is selected as the critical response, studies must determine what level of pupillary constriction from miosis is operationally relevant. For example, determining that a specific exposure or dose will cause a 10% decrement in pupil size is not sufficient without knowing whether that decrement is operationally relevant and determining what other operational factors must be considered. For example, a degree of pupillary constriction that represents no decrement in performance for daylight operations may represent a significant impairment for evening or night operations. Under daylight conditions with adequate lighting, a moderate degree of miosis may not be operationally relevant. It is normal for human pupil diameters to decrease by 50% when moving from dim to bright light conditions, such as when one moves from a dark room to outside when the sun is shining brightly. This suggests that different CWA exposure limits may be appropriate for use under different lighting conditions. Furthermore, miosis has been reported to improve visual acuity of presbyopic



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