with documented acute exposure to sarin (Duffy et al., 1979); and victims of the sarin terrorist attacks in Matsumoto City in 1994 and Tokyo in 1995 (Morita et al., 1995; Okumura et al., 1996). Other studies on military volunteers have been summarized (Marrs et al., 1996) but have not been published; thus, the latter studies were not considered by the committee in reaching its conclusions.

Given the extreme dose dependence of sarin’s acute health effects—which are literally a matter of life and death—a key question is, Do nonlethal doses of sarin have long-term health effects and, if so, are they too dose dependent? The possibility of low-level sarin exposure of U.S. troops during the Gulf War has generated much interest in whether sarin has long-term effects after a relatively short exposure at levels that are insufficient to produce an acute cholinergic syndrome.

A major limitation of most human studies of either long- or short-term health effects is the inability to document actual exposure levels. Most studies of sarin were undertaken in the aftermath of occupational accidents or terrorist attacks. In such cases, the exposure levels were inferred from clinical effects. As explained earlier, high-level exposure is inferred from the acute cholinergic syndrome (see Table 5.2) with outcomes including miosis, rhinorrhea, apnea, convulsions, and possibly death. High-level exposure requires hospitalization or emergency treatment. Intermediate-level exposure is inferred from minimal or threshold cholinergic effects such as miosis or rhinorrhea and limited decline in cholinesterase activity measured in the blood (<20 percent). Low-level exposure can be inferred from proximity to a documented exposure with no clinically detectable cholinergic signs or symptoms or detectable change in blood cholinesterase activity (Brown and Brix, 1998).6

As seen in the following review, there have been relatively few human studies of sarin’s long-term health effects. There are more human studies of OP insecticides, whose mechanism of action is similar to sarin. Although the committee was charged with evaluating the literature on sarin, it also examined relevant studies on OP insecticides to contribute to its understanding of sarin. The committee’s evaluation of the long-term effects of OP insecticides is contained in Appendix E. The studies described there do find a higher prevalence of neurological and/or psychiatric symptoms, as measured through either self-reports or standardized questionnaires, at all levels of acute OP exposure. With intermediate- or high-level acute exposures, higher symptom reporting is supported by poorer performance on standardized neuropsychological tests several years later. With low-level acute exposures (insufficient to produce cholinergic signs and symptoms), the higher symptom reporting is not consistently supported by poor performance on standardized neuropsychological tests.


The U.S. federal guidelines for general population exposure to military OP nerve agents are based on values for minimum clinical cholinergic effects (i.e., the intermediate level) reduced by a hundredfold safety factor (Brown and Brix, 1998).

The National Academies of Sciences, Engineering, and Medicine
500 Fifth St. N.W. | Washington, D.C. 20001

Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement