Immediate signs and symptoms of nerve agent poisoning. OP nerve agents are designed to incapacitate and kill humans. Inhalation exposure to these agents leads to immediate effects, including miosis, runny nose, and increased salivation. Immediate effects following skin exposure include local sweating and muscle twitching. Eye exposure rapidly produces miosis, which often is associated with eye pain, headache, and blurred vision.264 In fact, miosis is the most sensitive and specific immediate response to acute poisoning in humans, and this reaction has served as the basis for establishing allowable occupational concentrations for CW nerve agents. Higher doses of these agents cause more severe effects, including convulsions, neuromuscular blockage, profuse airway obstruction and apnea-developing within one to two minutes of exposure.77 Death occurs due to respiratory paralysis. The effects of nerve agent poisoning (figure 4-1) are virtually identical to those of severe OP-pesticide poisoning.

Data on human effects of CW nerve agent poisoning derive largely from human experiments carried out by the U.S. Army from the 1940s to the 1960s. Table 4-2 illustrates the type of information on immediate poisoning effects from low-level exposures to the OP nerve agent sarin.

Immediate signs and symptoms of mustard agent poisoning. With mustard agents, poisoning symptoms are severe irritation and tissue damage to eyes, skin, and respiratory and gastrointestinal (GI) tracts. Usually the onset of symptoms is delayed for some hours after exposure.

One report of Iraqi use of mustard agent against Iranian troops in 1984 documented health effects in more than 5,000 Iranian casualties. Affected individuals had first to third degree burns over 20 to 70 percent of the total skin surface. Eye exposure caused tearing, severe conjunctivitis, and temporary loss of vision. Corneal abrasion was nearly always present, and photophobia and blurred vision developed in some cases. Upper airway involvement due to chemical burning of the throat led to pharyngitis and tracheobronchitis. These effects were quite severe, and this group suffered approximately 15 percent mortality. Those who survived the initial symptoms later experienced various GI complaints, including nausea, vomiting, and diarrhea. After five to seven days, hematologic problems were the greatest health threat to survivors.105

Long-term health effects of exposure to CW nerve agents. Two NRC reports addressed possible long-term morbidity and mortality in about 1,400 servicemen intentionally exposed to CW nerve agents in experiments conducted over a 20-year period ending in 1975. The possibilities of excess cancer risk and adverse mental, neurologic, hepatic, and reproductive effects were reviewed. Both NRC analyses concluded that no evidence exists that CW nerve agents cause long-term, adverse human health effects at the doses tested. The doses were nonlethal, but were high enough to cause clinical effects (such as miosis). NRC reported that both analyses had the power to detect any major health effects had they been present. A statistically significant increase in admissions to VA hospitals for malignant neoplasms was detected, with the caveat that admission numbers were small, showed no dose relationship, and no clustering of specific chemicals in relation to tumor site.174,175

Numerous studies in humans and animals report that survival from severe, immediate poisoning by OP nerve agents (including OP pesticides) can be associated with measurable, long-term neurological effects. One study of 77 industrial workers exposed to levels of sarin that caused immediate toxicity showed slight alterations in electroencephalograms (EEGs) one year after exposure. The study also reported, however, that trained experts could not distinguish an individual EEG from an exposed individual from an EEG of a person who had not been exposed, and that no clear relationship existed between alterations in EEG frequency spectrum and alterations in brain function.22 A 1975 review by Lohs of the effects of CW agents in humans similarly reported long-lasting effects following severe, immediate OP pesticide and CW agent poisoning.140

CW nerve agents do not show OPIDN toxicity as measured in EPA's standardized hen bioassay for evaluating OP pesticides, except with extremely high doses (10 to 100 times the lethal dose) where immediate and severe toxic effects, including death, are seen.117 Because OP CW nerve agents are chemically similar to OP pesticides and affect the same enzyme system in the body, similar long-term health effects would likely occur in the aftermath of immediate, severe poisoning with sarin, soman, or VX-i.e., the subtle, but measurable, neurophysiological and neuropsychological effects described earlier in this chapter. Again, these health effects did not occur in populations that had been exposed to subclinical amounts of OP pesticides. Current scientific evidence suggests that subclinical exposure to OP CW nerve agents does not result in long-term neurophysiological and neuropsychological health effects. Ongoing research at the Boston and Portland Environmental Hazards Research Centers is investigating the possibility of such effects in Gulf War veterans.

Long-term health effects of exposure to mustard agents. Based on epidemiologic research, humans exposed to mustard agent are at increased risk for lung cancer.98,287 Several other reviews of human exposure to mustard agent during World War I (WWI) and other wars also indicate veterans exposed to mustard agents during the Gulf War could experience other respiratory problems as well.98,287

During World War II (WWII), more than 60,000 U.S. service members were used as human test subjects and exposed to mustard agents, including at least 4,000 individuals exposed to high concentrations of these agents.98 An Institute of Medicine (IOM) review concluded that several specific chronic diseases are causally associated with mustard agent exposure. These include various respiratory cancers, skin cancer, chronic skin ulceration and scar formation, chronic respiratory disease including asthma, chronic bronchitis, emphysema, chronic eye diseases, and various psychological disorders including PTSD. IOM also found suggestive evidence (weaker than the associations for the conditions just mentioned) that exposure to mustard agent was associated with leukemia. Finally, IOM also analyzed two studies that examined the link between mustard and reproductive dysfunction, but determined that the database could not be used to make conclusions about human reproductive health effects.98

Current scientific literature indicates that when exposure to OP CW agents results in immediate and severe poisoning, long-term, subtle neuropsychological and neurophysiological effects could occur. Available scientific evidence does not indicate that such long-term effects occur in humans following low-level exposures, but the amount of data from either human or animal research on low-level exposures is minimal. Long-term effects in humans exposed to mustard agents include an elevated risk of lung cancer beginning decades after exposure. Based on available data, it is unlikely the health effects reported by Gulf War veterans today are the result of exposure to OP or mustard CW agents during the Gulf War. Ongoing or planned federally-funded studies focused specifically on low-level exposures and delayed neurotoxicity of CW agents should elucidate gaps in knowledge and eliminate uncertainty and/or identify new directions for research.