addition to the limitations of the Seabees study population described above, is the lack of clinical validity of measures used to infer neurological damage.

A more recent study (Haley et al., 1999) investigated genetic polymorphisms of PON1 and BuChE in 45 subjects (cases and controls), who had been reported by Haley and colleagues in the previously described case-control study. The authors measured serum activity levels of various allozymes to test the hypothesis that differences in allozyme levels might have put some Gulf War veterans at higher risk of neurological damage from exposure to environmental chemicals that require these enzymes for detoxification. The study found that ill veterans with the neurological symptom complexes described were more likely to have the R allele of the PON1 gene (heterozygous QR or homozygous R) than to be homozygous Q. They found that low activity of the PON1-type Q arylesterase allozyme distinguished ill veterans from controls better than the PON1 genotype alone or the activity levels of the type R arylesterase allozyme, total arylesterase, total paraoxonase, or BuChE. The authors found that a history of advanced acute toxicity after taking PB was also correlated with low PON1-type Q arylesterase activity.

A major criticism of this study is that type Q, the allozyme of PON1 that most efficiently hydrolyzes several organophosphates (sarin, soman, and diazinon), does not hydrolyze PB (unpublished data from their laboratories cited by the authors); thus, the interpretation of lowered levels of this enzyme is uncertain insofar as it relates to PB use in ill Gulf War veterans.

A study of U.K. servicemen who served in the Gulf War (Unwin et al., 1999) addressed PB exposure. This cross-sectional postal survey of Gulf War veterans (n = 4,248), Bosnia conflict veterans (n = 4,250), and those serving during the Gulf War but not deployed there (n = 4,246) found a greater perception of worse physical health in the Gulf War cohort. Gulf War veterans reported all symptoms and disorders more commonly than the comparison cohort. All of the self-reported exposures showed associations with all outcome measures in the three cohorts. Three exposures were reported more frequently by Gulf War veterans than by the other cohorts: exposure to burning oil-well smoke, vaccination against biological warfare agents, and CW protection measures. Very small proportions of the Bosnia and nondeployed Gulf War era veterans reported exposure to PB, 1.9 percent and 5.2 percent, respectively, compared to 81.6 percent of deployed Gulf War veterans. Nevertheless, the association of symptoms with self-reported PB use was not different between the three cohorts with elevated odds ratios observed for the three principal health outcome measures in all three cohorts.


Acute Effects

A large number of clinical studies report acute transient cholinergic effects in normal volunteers and patients with a wide variety of clinical disorders given PB as a diagnostic test of hypothalamic pituitary function and patients with my-

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