weeks to months before testing of study subjects. (The next section describes the rationale for this criterion.)
As the committee reviewed the body of evidence, it was apparent that some studies of multiple outcomes could provide strong evidence for one of the outcomes and only weak evidence for another. For example, a study that was well-designed for assessing a neurobehavioral effect might not have been as well-designed for assessing peripheral neuropathy.
The committee evaluated long-term effects because they are most relevant to veterans whose exposures occurred during the Gulf War but whose symptoms persisted for months or years after cessation of exposure (Appendix A). Long-term effects of a given exposure can be distinct from short-term effects. For example, OP-insecticide exposure produces a well-defined short-term effect, the acute cholinergic syndrome (Chapter 3); this life-threatening syndrome is quite different in characteristics and severity from the long-term effects considered in this chapter.
Occupational studies of neurologic effects often do not permit the distinction between long-term effects (months or years) and short-term effects (hours to weeks), because many studies examine workers with both past and current (ongoing) exposure. Consequently, if a study finds a neurologic effect, it is difficult to determine whether the observed effect will persist or disappear on cessation of the exposure unless an exposure-free interval of weeks or months has passed before the effect is measured. Many of the studies reviewed by the committee were not designed to determine whether an effect was a long-term or short-term one.
The challenge of distinguishing long-term and short-term effects is greater for examining neurobehavioral effects than neurologic diseases, for reasons related to onset, reversibility, and availability of objective testing. Neurobehavioral effects (such as symptoms of memory loss and fatigue) can be short-term effects, long-term effects, or both; they can appear within hours of exposure or later; and they can persist or disappear after cessation of exposure. Neurobehavioral effects cannot usually be verified with pathologic or biochemical tests. Conversely, neurologic diseases are generally believed to be irreversible after a confirmed diagnosis and are associated with abnormal results of pathologic or biochemical tests. Thus, in evaluating the body of evidence specifically on long-term neurobehavioral effects, the committee required that an exposure-free interval of weeks to months elapse before testing. The committee also held sensory effects to that standard because sensory effects can also be reversible. For studies of peripheral neuropathy and neurologic diseases, the committee did not require an exposure-free interval, because these neurologic effects are almost always long-term effects (although some degree of recovery or lack of progression is possible).
The most immediate short-term effect of high OP exposure is known as the acute cholinergic syndrome. Its signs and symptoms are recognizable within minutes to hours and include pinpoint pupils, salivation, severe nausea, vomiting, and diarrhea. The acute cholinergic syndrome, which is highly dose-dependent, requires emergency care to prevent