Some individuals who recover from immediate and severe OP poisoning show long-term (lasting more than a year), subtle, neuropsychological abnormalities that can be detected using a battery of standardized neuropsychological tests. In an epidemiologic study of such long-term effects, severely poisoned individuals showed clear but subtle differences in intellectual functioning, academic skills, abstraction and flexibility of thinking, and simple motor skills. For example, about a five point difference in IQ was measured in severely poisoned versus control subjects.

Neurophysiologic effects were less apparent; abnormalities were found only in measurements of memory, abstraction, and mood and on one test of motor reflexes.221 These effects could not be detected, however, in a subset of the same worker population that had been exposed to doses of OP pesticides that were too low to cause the symptoms of immediate and severe poisoning.241 Other studies of low-level occupational exposures reinforce the finding that these types of long-term effects present solely in the aftermath of severe and immediate OP agent poisoning.4,241

Some OP pesticides that are no longer sold in the United States have been associated with human cases of a second type of delayed toxic effect called organophosphate-induced delayed neurotoxicity (OPIDN, sometimes referred to as delayed neuropathy). Initial symptoms are muscular incoordination progressing to numbness, tingling, fatigue or a cramp-like pain in the calf muscles, and even moderate to severe muscular weakness and paralysis.7,117 Typically, effects occur 7 to 14 days following recovery from immediate and severe poisoning by the OP pesticide and involve neuropathologic lesions and degeneration of the nerve axon and myelin nerve sheath in both the central and peripheral nervous systems;117 these effects are easy to measure in a clinical setting. In general, OPIDN caused by OP pesticide poisoning is associated with immediate poisoning symptoms.

All OP pesticides sold in the United States today are routinely screened for OPIDN toxicity with a standardized hen assay used by EPA; the hen is a laboratory animal especially sensitive to OPIDN effects. For some OP agents, these effects only can be observed by giving the hen extremely high doses that would rapidly lead to death, but then keeping the hen alive through the use of protective drugs such as atropine. Many investigators conclude any OP agent theoretically could cause this effect at sufficiently high doses, but that, in fact, immediate toxic effects cause death before delayed effects can be seen.117 None of the pesticides DOD shipped to the Gulf War test positive for OPIDN in standard EPA screens.

A National Research Council (NRC) subcommittee that reviewed possible health problems for military personnel wearing permethrin-treated military clothing concluded it is unlikely that soldiers using such uniforms would experience adverse health effects at the suggested exposure levels. The subcommittee concluded, "the weight of evidence shows that permethrin is unlikely to be a skin irritant or skin sensitizer for military personnel who are exposed to it dermally from wearing permethrin impregnated [uniforms]." The estimated "no observable adverse effect level" for immediate neurotoxic effects in humans from daily exposure is 200 milligram (mg)/kilogram, which is approximately three million times greater than estimated dermal exposure from permethrin treated uniforms.171 NRC's worst-case estimate of lifetime carcinogenicity risk for humans wearing permethrin treated uniforms was less than 2 in 1,000,000.

In laboratory animal studies, dermal absorption of permethrin is low, although scientists observe neurotoxic effects if the substance is injected.171,301 Most, but not all, studies have reported permethrin does not cause damage to genetic material in a wide variety of standard measurement systems. Permethrin is neurotoxic to laboratory animals at high oral doses. Rats fed permethrin at 6,000 mg/kg for 14 days showed fragmented and swollen sciatic nerve axons and myelin degeneration. However, nerve conduction studies in 23 permethrin workers showed no evidence of nerve impairment associated with permethrin exposure.171 Rodent bioassays of chronic exposure to permethrin showed carcinogenic effects, such as liver and lung adenomas and lung carcinomas in mice, but data on human carcinogenicity of permethrin are lacking.

Some pregnant laboratory animals orally treated with the maximum tolerated dose (the dose just below that causing immediate and severe toxicity) showeda statistical increase in the number of fetuses with extra limbs, indicating that lindane is a teratogen for this laboratory animal strain. Lindane has not been shown to be a human carcinogen, although long-term oral exposure of lindane to certain species and strains of laboratory rodents has been reported to cause liver cancer.283 Hence, DHHS has determined that lindane should be viewed as a human carcinogen.

Rats continuously fed DEET up to the maximum tolerated dose over three generations showed a slight increase in the high-dose animals in a single neurological abnormality-a slight increase in exploratory locomotor activity-and no histopathologic central nervous and peripheral nervous system changes of significance.190 Other reports indicate that rats fed the maximum tolerated dose of DEET can show severe and often fatal prostration accompanied by a brain myelinopathy.320

According to DOD, after-action reports from in-theater medical personnel did not reveal any U.S. troops reporting symptoms that would indicate pesticide poisoning. Evidence from studies of humans poisoned by OP pesticides suggests that low-level exposures that do not cause signs and symptoms of immediate and severe poisoning will not result in long-term health effects.

Thus, the Committee concludes it is unlikely that health effects and symptoms reported today by Gulf War veterans are the result of exposure to pesticides during the Gulf War. Lindane is an animal liver carcinogen, but it is too early to see an elevated liver cancer rate in Gulf War veterans.