Part 8: Other Issues Related to Cholinesterase Inhibitor Exposure

Upon completion of this section, you should be able to

• Describe the association between cholinesterase inhibitor exposure and
  • Cancer risks.
  • Fetal effects.
  • Gulf War I illness
  • Immune system effects.

Generally, organophosphorus compounds are not thought to be carcinogenic, although there is some controversy about this. (Poisindex Editorial Staff 2005) Although a number of studies have concluded that pesticide exposure increased the risk of some childhood cancers, these studies suffered from significant methodological problems.

These have included:

• Exposure assessments based on parental recall of home exposures (sometimes as far back as 20 years), rather than direct measurement of the actual pesticides.
• Failure of exposure assessments to distinguish between herbicides, insecticides, fungicides, or other types of pesticides, much less cholinesterase inhibitors. (Nurminen 1995; Daniels J 1997; Pagoda and Preston-Martin 1997; Daniels, Olshan et al. 2001)
• Potential biases in the selection of controls.
• Retrospective presumption of exposure based on job title and industry where employed.
• Small sample sizes.

Note: One study of Gulf War Veterans exposed to sarin and cyclosarin from the 1991 explosion of the Khamisiyah chemical munitions cache in Iraq found an almost 2-fold increase in subsequent brain cancer deaths. In this study, exposure was assessed using plume modeling and the location of the soldier’s company at the time of the explosion. However, the investigators noted that neither sarin nor cyclosarin are known carcinogens, so the cancer deaths could have been due to other chemicals released in the explosion. (Bullman, Mahan et al. 2005)

Some organophosphorus compounds have been shown to cross the placenta in animals. However, there is a lack of evidence that fetal toxicity has occurred in the absence of maternal toxicity. The few reported cases in humans where pregnant women were poisoned were managed successfully with standard treatment. (Arbuckle and Sever 1998; Erdman 2004)

Currently, there is a lack of convincing evidence that cholinesterase inhibitors cause birth defects or adverse effects on the reproductive system in humans. Although many studies have been carried out, they suffer from serious methodological problems. There are human case reports on third trimester exposures that did not result in birth defects. Animal data are conflicting. While some animal studies suggest that birth defects could result from exposure to cholinesterase inhibitors, others do not. Thus, the possibility that birth defects could occur has neither been confirmed nor ruled out. (Minton and Murray 1988; Sever 1997; Shaw, Wasserman et al. 1999; Erdman 2004)

Experience with oxime treatment of pregnant patients is almost non-existent. Only six cases have been published describing the findings in pregnant victims of organophosphate poisoning. In only 3 cases did these patients receive oxime treatment. One mother, who received obidoxime, elected to have an abortion. The findings in the aborted fetus were not reported. The other two patients were at 16 weeks and 36 weeks of gestation at the time of exposure, and were treated with 2-PAM and atropine. Both delivered normal term infants. (Bailey 1997)

An extensive review of the literature carried out by the RAND Corporation came to the following conclusions about the association between cholinesterase inhibitors and Gulf War I illness (Cecchine, Golomb et al. 2000)

• Cholinesterase inhibitors can cause some signs and symptoms similar to those found in Gulf War I illness.
• However, based on the evidence available, one cannot explain the myriad health problems reported by Persian Gulf War (I) veterans on the basis of exposure to cholinesterase inhibitors.
• The evidence also does not currently allow us to rule out cholinesterase inhibitors as a contributing factor.

There are a multitude of physiological processes that lead to effective immune system function, and the immunotoxic disruption of any one of them may not necessarily alter host resistance. Studies in laboratory animals have documented immunotoxic effects of organophosphorus compounds, and in some cases have even linked them with altered disease resistance. However, there is a lack of clear-cut evidence to show that exposure to these compounds alters overall immune function in humans. (Galloway and Handy 2003)

• Currently, convincing evidence does not exist to confirm or rule out cancer, birth defects or immune system effects due to exposure to cholinesterase inhibitors.
• Current evidence is also lacking to verify or reject a causal relationship between exposure to cholinesterase inhibitors and the development of Gulf War I illness.