ENVIRONMENTAL EXPOSURE REPORT

PESTICIDES

EXECUTIVE SUMMARY

I. PURPOSE

The Office of the Special Assistant for Gulf War Illnesses (OSAGWI) has published an interim report on the results of an investigation into pesticide use and exposure during the Gulf War.^[1] The OSAGWI report is about the pesticides that were used, how they were used, and it addresses the known health effects that may have been experienced by individuals who were exposed to pesticides during their deployment in Operations Desert Shield/Desert Storm. In pursuing each of these issues the investigators attempted to determine the role pesticides might have played in the undiagnosed illnesses reported by some Gulf War veterans. A secondary goal was to examine issues surrounding pesticide use as part of the continuing efforts to advance force health protection issues especially those involving the handling and use of pesticides. The information provided in this document summarizes the findings and conclusions reached during the course of that investigation.

II. BACKGROUND

The requirement for pesticide use in the Kuwait Theater of Operation (KTO) arose due to the prevalence of pests such as filth flies, sand flies, mosquitoes, fleas, and lice indigenous to this part of the Middle East. These insects carry several infectious diseases, including leishmaniasis, sand fly fever, malaria, and typhus. Unabated, these diseases were believed to be capable of incapacitating a large number of the US and Coalition fighting force.

To combat this threat more than 60 different pesticide products and formulations were used during the Gulf War. This total includes a variety of products that include sprays, powders, baits, pest strips, and flypaper. Depending on its intended use and the pest it was formulated to target, most of the pesticide products consisted of at least one active ingredient and one or more inert ingredients. A complete analysis of all pesticides used during the Gulf War was not practical. Therefore, we applied a series of carefully selected screening criteria to reduce the number to those considered to have the greatest potential to cause adverse health effects – those that were considered to be the pesticides of potential concern (POPCs). Precautions in the development of the screening factors were taken to ensure the significance or potential threat of any pesticide was not trivialized and that pesticides that have historically been associated with disease in humans were included in the investigation.

Based on a thorough analysis of the available data, OSAGWI investigators focused on 15 POPCs containing 12 active ingredients. The compounds consist of five organophosphate pesticides (azamethiphos, chlorpyrifos, diazinon, dichlorvos and malathion); three carbamate pesticides (bendiocarb, methomyl, and propoxur); two pyrethroid pesticides (permethrin and d-phenothrin); one organochlorine pesticide (lindane); and one repellent (DEET). Investigators believe these active ingredients posed the greatest potential hazard to US servicemembers due to manner of use, prevalence of use, and toxicity.

Some pesticide products containing these active ingredients were used only on a limited basis, and some were used by only a very small number of US service members. Others received widespread use and were largely available to the general military population. All were considered safe at the time for general use under normal application conditions and when applicators followed instructions for use on the packaging labels.

These or similar pesticide products were available for purchase by the general public at local garden and hardware supply stores and, when used during the Gulf War, were approved by the US Environmental Protection Agency (EPA) and/or the US Food and Drug Administration for general use by the US public. However, in recent years, EPA has moved to limit the uses of some of the active ingredients, due mainly to concerns about possible impacts on the health of children. Some pesticide products, such as the fly bait Snip^� , were purchased in-theater by authorized personnel for unit use or by individuals for their personal use. Some of these locally purchased products were not registered with the EPA.

III. METHODOLOGY

Information contained in the OSAGWI report is the result of several key tasks that comprised the overall investigation; these included:

• review of various databases on background issues associated with the use and application of pesticides;

• review of DoD policies and guidelines on the use and management of pesticides;

• literature review, conducted by RAND, of the health affects associated with pesticide exposure;

• random survey of more than 2,000 Gulf War veterans, also conducted by RAND, to obtain information on the use of and exposure to pesticides used during the Gulf War;

• interviews by OSAGWI investigators with approximately 700 preventive medicine personnel as well as approximately 200 interviews with other personnel to acquire information on pesticide application and management practices; and

• an independently reviewed health risk assessment (HRA) developed in conjunction with the US Environmental Protection Agency that estimates the likelihood that exposures to pesticides during the Gulf War may have been connected to acute effects at the time of exposure.

The investigation was hampered by the lack of quantitative data on the amount of pesticides used during the Gulf War, and the levels of pesticides present in the air and on surfaces to which US troops were exposed. The investigation also lacked information from veterans’ hospital and medical records. Collectively this lack of data resulted in significant uncertainties in the findings and conclusions of the HRA. To reduce these uncertainties and better characterize the risk from pesticide exposure, further research is needed in several key areas, including: the effects of low-level pesticide exposures; pesticide interactions with other chemical compounds, such as pyridostigmine bromide; record searches of more than 28,000 patient records for evidence of pesticide poisoning and overexposure; and epidemiological studies involving pesticide applicators.

In the absence of sampling data and information about actual pesticide application rates that we otherwise would have used, we relied in part on the results of the RAND survey and approximately 700 interviews with preventive medicine personnel to determine exposure levels. Of these interviews, 252 provided specific information related to exposure (e.g., frequency with which a pesticide was applied, application rates, personal protective equipment worn, etc.). An additional 60 provided more general information without specifics relating to issues of exposure. Investigators also interviewed approximately 200 non-preventive medicine personnel regarding lindane use in delousing enemy prisoners of war, and the use of fly baits.

As noted above, information contained in this report refers to the results of two RAND studies. The first study presents the results of a medical and scientific literature review on the health effects associated with pesticide exposure.^[2] The literature review reports in detail on the health effects of the 12 POPC active ingredients, identified by OSAGWI, contained in pesticide products used during the Gulf War. The second study presents the results of a survey of 2,005 Gulf War veterans, focusing on how pesticides were used during the Gulf War.^[3]

The OSAGWI report is organized into three parts. Part A is the Environmental Exposure Report with information on the background issues associated with pesticide use, handling, management, and training during the Gulf War. Part A also summarizes the recognized health effects associated with exposure to pesticides and contains a non-technical summary of the health risk assessment that was prepared to provide an estimate of the likelihood that various short-term effects occurred during deployment due to exposure to pesticides. Part B is the complete health risk assessment, which is a highly technical report. Part C contains information used to support or expand the discussion of selected topics presented in Parts A and B, including a description of DoD guidance on the use, application, and management of pesticides; additional information on fly baits and delousing operations; procurement, storage, and distribution practices used in handling pesticides during the Gulf War; and benchmark toxicological data on selected pesticides.

IV. PESTICIDE USE

We know from information received during veteran interviews and from Department of Defense (DoD) guidance and policy documents that US forces used pesticides in areas where they worked, slept, and ate throughout the KTO. US military personnel used pesticides for several reasons:

• personal use on the skin and uniforms as an insect repellent;

• as area sprays, surface applications, and fogs to kill crawling and flying insects;

• in pest strips and fly baits to attract and kill flying insects; and

• as delousing agents applied to enemy prisoners of war.

These widespread, commonly reported uses further supported the decision to investigate pesticide exposures.

The Army, the Navy (which supported the Marine Corps), and the Air Force each had specially trained and certified personnel (applicators) to apply pesticides. In addition to these certified applicators, some Army personnel were assigned duty as pesticide applicators during all or part of their deployment. These individuals served as members of field sanitation teams or as military police. To reduce disease and non-battle injury, and to assist unit commanders in protecting their units’ health, the field sanitation teams provided individual Army units with limited preventive medicine capabilities. To prevent the outbreak of typhus, military police used the insecticide lindane to conduct delousing operations in enemy prisoner of war camps. Lindane was also authorized for use by the general military population to control body lice on an as-needed basis.

The report documents several cases of apparent pesticides misuse. It is important to note that in the cases where pesticides were improperly used, personnel involved in the incidents did not follow instructions for use on the product label. Other personnel unnecessarily exposed themselves and those around them by ignoring published guidance on pesticide use provided by the services, or did not wear appropriate personal protective equipment. However, some personnel reported to us that they did not have access to adequate personal protective equipment.

In addition we also identified some systemic deficiencies; many of which have been addressed by the services since the war. A key element still not addressed is the lack of training in the use of personal protective measures against pests of military significance (including use of personal pesticides to combat these pests). Including such training at a basic training level and during refresher training will raise the awareness of all personnel and their leaders on the proper use of pesticides.

RAND designed and conducted the veteran survey report to obtain detailed data on pesticides personally used by individuals and pesticides used or observed in the field. RAND obtained the data from telephone interviews with 2,005 veterans who were randomly selected to be statistically representative of the entire Gulf War ground population. The RAND survey results suggest that some symptomatic exposures may have occurred during the deployment. Other interviews, such as those with preventive medicine personnel, also indicate that several instances of symptomatic exposures may have occurred, and that those exposures may have been severe, especially for those assigned to apply organophosphate pesticides. However, most symptomatic exposures, due, for example, to DEET, permethrin, and lindane, most likely resulted in mild and localized reactions of short duration.

V. HEALTH EFFECTS FROM EXPOSURE TO PESTICIDES

As part of a continuing effort to better understand the possible causes of undiagnosed illnesses reported by some Gulf War veterans, OSAGWI commissioned RAND to conduct a review of the scientific literature on the potential health effects of pesticides. The RAND report reviews literature on 12 of the 37 pesticide active ingredients used during the war.

The RAND report summarizes the relevant scientific literature and focuses on reports of known pesticide exposures or doses and related health effects where available. According to the literature the range of short- and long-term health effects from exposure to pesticides varies by pesticide and is a function of the duration of exposure and route of exposure (i.e., dermal, inhalation, ingestion). In general, health findings and short-term symptoms from exposure to pesticides include: acetylcholinesterase inhibition, headache, nausea, vomiting, restlessness, ataxia (loss of muscular coordination), tremor, dizziness, anorexia (loss of appetite), shortness of breath, rashes, and itching. More severe short-term health effects include: blood disorders, convulsions, respiratory depression, and coma. Long-term or chronic effects from organophosphates and carbamates include: impaired cognition (memory loss, confusion), fatigue, joint and muscle symptoms, sleep effects, mood effects, and neurological effects. Long-term effects from exposure to pesticides other than organophosphates and carbamates have not been consistently observed.

Several individual differences also complicate analyzing the effect of pesticides on Gulf War veterans. First, genetic differences occur among individuals. For example, some pesticides may be potentially more toxic to people with genetic or acquired differences in susceptibility. Second, many factors may affect the rate and magnitude of pesticide absorption. Protective clothing and differences in skin properties and integrity influence dermal exposure, and inhalation exposure may vary with ventilation rate or as a result of other factors, including properties of airway membranes. Furthermore, the rates at which pesticides are cleared from the body vary by individual.

Results of the RAND literature review include the following:

• RAND considers the organophosphates chlorpyrifos, diazinon, malathion, dichlorvos; the carbamate, bendiocarb; and the organochlorine, lindane to represent the greatest risk for adverse health effects.

• RAND uncovered no reports of pesticide over exposure among Gulf War veterans during their literature review; however, OSAGWI investigators found one documented case in medical records of a pesticide exposure resulting in short-term adverse health effects. Follow-up interviews with this veteran revealed that he is not currently suffering from any long-term symptoms associated with this exposure. Information obtained through interviews conducted by OSAGWI investigators suggests that some veterans experienced symptoms of overexposure to pesticides during the war. Investigators were unable, however, to corroborate these accounts with documentation (e.g., hospital and medical records) generated during the Gulf War.

• RAND suggests exposure to some pesticides, especially the acetylcholinesterase (AChE) inhibitors, organophosphates and carbamates, could be among potential contributing agents to some of the undiagnosed illnesses reported by Gulf War veterans.

• RAND found significant uncertainties exist in showing pesticides cause undiagnosed illnesses. More research is needed to confirm or deny a causal link between pesticides and other agents, and illness among Gulf War veterans.

The RAND literature review also notes that it is unlikely that exposure to these pesticides alone explains the myriad health problems reported by Gulf War veterans, as few veterans’ symptoms are uniquely characteristic of pesticide exposure only. For example, pyridostigmine bromide (PB), a widely used drug during the Gulf War to counteract the effects of the nerve agent soman, is also an AChE inhibitor and may or may not be a contributing factor to undiagnosed illnesses.

Furthermore, veterans may have been exposed to several different potentially toxic substances, making it difficult to attribute findings specifically to one pesticide or another, and pesticides combined with other factors may exert effects different from those experienced with pesticides alone. RAND found no retrospective studies in the literature that positively identify pesticides as causing the symptoms associated with Gulf War illnesses.

The important question regarding organophosphate and carbamate pesticides is: If individuals had no signs or symptoms at the time of exposure, how likely is it that such exposures could result in adverse health effects months or years later? There is no simple answer we can give with a high level of confidence as there is conflicting information in the literature on this subject. The relevant information comes mainly from published studies of civilian pesticide handlers in the US and foreign countries. There are reports in the literature that suggest unless individuals had signs and symptoms of serious pesticide poisoning or toxicity at the time of the initial exposure, health effects months or years later are unlikely. However, according to the RAND literature review for pesticides, there is also evidence of modest long-term effects following asymptomatic exposures (i.e., no symptoms) to organophosphate pesticides.

VI. HEALTH RISK ASSESSMENT

OSAGWI prepared a health risk assessment (HRA) as part of this investigation. Developed in conjunction with the EPA and peer-reviewed by subject matter experts and members of the academic community, the HRA’s purpose is twofold: to help identify those who may have been at higher risk of pesticide exposure and to estimate the likelihood of certain specific effects from those exposures. Such effects would have been limited to the time of deployment, and may or may not have implications for long-term health effects.

Developing the HRA was hampered by the lack of quantitative data on the amount of pesticides used during the Gulf War, and the levels of pesticides present in the air and on surfaces to which US military personnel were exposed. For example, during the Gulf War, military personnel may have used 37 different types of pesticide active ingredients, but the amounts used are undocumented. Because the military kept no records on what pesticides it dispensed, it was impossible for investigators to determine the total quantity of pesticides used in the Gulf. In addition, the non-specialized personnel who applied these pesticides were not adequately trained and monitored, raising concerns that they may have improperly applied the pesticides and thereby created unsafe conditions. In combination, the lack of information in several key areas regarding use and application has resulted in a fairly high degree of uncertainty about the results of the HRA. Despite these limitations, the HRA provides the best estimate available to attempt to determine potential exposures.

The HRA relies on exposure scenarios to estimate the likelihood and magnitude of health effects. Exposure scenarios are based on commonly known application procedures and deployment-specific data (e.g., area spraying by certified applicators and enemy prisoner of war delousing by military police) determined through interviews and the RAND survey; however, we do not know the application rates and doses received by the applicators. Therefore, we were obliged to estimate the range of exposure potential to complete the HRA. Since the HRA relies on many assumptions with varying degrees of uncertainty, the risk estimates may indicate areas of potential concern for large groups (e.g., area sprayers or field sanitation teams) but cannot with any certainty predict the hazards and risks to individuals.

OSAGWI investigators estimated that a large minority of the roughly 3,500 to 4,500 veterans whose assignments included the handling and application of pesticides, may have been at elevated risk for short-term health effects. In addition, OSAGWI estimates, based in part on the RAND survey, that approximately 30,500 members of the general military population may also have been at elevated risk for short-term health effects because of their exposure to pest strips. A third group, numbering about 7,000 of the general military population, may have been over exposed to pesticides applied during area spraying operations.  The following table summarizes the exposures for the general military population that exceeded the levels of concern.

Table 1. General military population exposures which exceeded the levels of concern

The results of the HRA alone do not prove either that overexposures occurred during deployment, or that any connection exists between pesticide exposures and chronic health effects months or years after exposure. However, the HRA contends that some groups had the potential to be exposed to concentrations of pesticides exceeding conservatively derived, risk-based levels of concern. While not conclusive, these results provide justification to consider some pesticide exposures as possible contributing factors to the unexplained illnesses reported by some veterans. Moreover, as the result of the overall lack of data with which to conduct a rigorous analysis, there is insufficient evidence to completely rule out possible long-term effects resulting from exposures to pesticides during the Gulf War.

VII. ADDITIONAL RESEARCH

The OSAGWI report notes several areas where further research is required to more accurately characterize exposures, more fully identify exposed populations, and determine the potential for long-term health effects. Key areas of future research include the following:

• Conduct a more in-depth review of the diagnoses contained in the approximately 28,000 Gulf War veterans’ inpatient records maintained at the National Personnel Records Center and analyze in detail any records with diagnoses that might be pesticide-related. Follow up with personnel who were hospitalized for possible pesticides exposures to determine their current health.

• Review chlorpyrifos exposure, biomonitoring, and health outcome data available from various databases such as those of the Environmental Protection Agency, Office of Pesticide Programs and the California EPA. Compare with chlorpyrifos results in the HRA and use as surrogate data for comparison to other pesticides.

• Compare in detail the HRA exposure assessment results with estimates and measurements from other published pesticide studies.

• Collect and analyze data on contemporary pesticide military use, and conduct an epidemiological study of current and past military pesticide applicators, assessing levels of pesticide exposure and reported health effects.

VIII. CONCLUSIONS

The report reflects the current body of knowledge on the use of pesticides, the levels of exposure experienced by select groups of Gulf War veterans, and the potential health effects associated with these exposures. While there is a high level of uncertainty in some areas of the investigation and conservative assumptions were used in the HRA, the investigation and health risk assessment methodology are both based on methodologies developed in conjunction with the US Environmental Protection Agency, Office of Pesticide Programs. Overall the analysis improves our understanding of several issues about pesticide use during the Gulf War, reasonably attempts to characterize exposures given the data available, and begins to address the question of the possible long-term effects from pesticide exposures. The following are the key findings and conclusions developed as a result of this investigation:

• The lack of data and information in several key areas has complicated the investigation and led to a fairly high degree of uncertainty with respect to the overall results. Additional research is recommended to more accurately characterize pesticide exposures and improve estimates on the likelihood of long-term health effects.

• While there was one documented instance of acute health problems from pesticide exposure, there is no evidence of widespread pesticide poisonings during the Gulf War. However, there does appear to have been some incidents of exposure that resulted in symptoms at the time. Details on these incidents are based largely on the results of veteran interviews and are not supported by hospitalization and medical records. Nevertheless, because of pesticides’ potential to induce long-term health effects and the lack of studies in the literature indicating otherwise, RAND suggests that it is inappropriate to rule out pesticides as a potential cause of long-term effects.

• The HRA basically agrees with RAND’s conclusion. The HRA demonstrates that military personnel who worked as field sanitation team members, preventive medicine specialists, military police, and servicemembers who were exposed to pest strips may have been exposed to concentrations of pesticides that placed them at a higher risk for short-term health effects. These exposures are largely the result of personal misuse of pesticides and systemic failure to comply with existing guidance on pesticide use and management within the military. As a result, and because of the lack of data and evidence to the contrary, OSAGWI also concludes that the possibility for the onset of long-term symptoms cannot be ruled out.

END NOTES

[1]  Special Assistant for Gulf War Illnesses, "Environmental Exposure Report - Pesticides," January 2001, web site http://www.gulflink.health.mil.

[2] Cecchine, G., BA Golomb, LH Hilborne, DM Spektor, and C.R. Anthony, A Review of the Scientific Literature as it Pertains to Gulf War Illnesses: Pesticides, RAND, Volume 8: June 2000. http://www.gulflink.health.mil

[3] Fricker, RD, E Reardon, DM Spektor, SK Cotton, J. Hawes-Dawson, JE Pace, and S D Hosek, Pesticide Use During the Gulf War: A Survey of Gulf War Veterans, RAND, July 2000. http://www.gulflink.health.mil

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