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Date:11/15/2005
Session:109th Congress (First Session)
Witness(es):Lynn Goldman and Samuel Potolicchio
Credentials:  Lynn Goldman, MD, MPH, Professor, Bloomberg School of Public Health, Johns Hopkins University, Baltimore; and Chair, Committee on Gulf War and Health: Review of the Medical Literature Relative to Gulf War Veterans Health; Chair, Committee on Gulf War and Health: Fuels, Combustion Products, and Propellants; and Member, Committee on Gulf War and Health: Insecticides and Solvents, Board on Health Promotion and Disease Prevention, Institute of Medicine, The National Academies

Samuel Potolicchio, MD
, Professor and Clinical Neurologist, The George Washington School of Medicine, Washington, D.C.; and Member Committee on Gulf War and Health: Review of the Medical Literature Relative to Gulf War Veterans Health; Member, Committee on Gulf War and Health: Fuels, Combustion Products, and Propellants; Member, Committee on Gulf War and Health: Insecticides and Solvents; Member, Committee on Gulf War and Health: Depleted Uranium, Pyridostygmine Bromide, Sarin, Vaccines; and Member Committee on Gulf War and Health: Update Literature Review of Sarin, Board on Health Promotion and Disease Prevention, Institute of Medicine, The National Academies
Chamber:House
Committee:National Security, Emerging Threats, and International Relations Subcommittee, Committee on Government Reform, U.S. House of Representatives
Subject:Gulf War Veterans Act Oversight

(PLEASE NOTE: Dr. Potolicchio’s testimony immediately follows Dr. Goldman’s.)

Gulf War and Health – Institute of Medicine Reports

Testimony of

Lynn Goldman, MD, MPH
Professor, Bloomberg School of Public Health
Johns Hopkins University
Baltimore, Maryland

and

Chair, Committee on Gulf War and Health: Review of the Medical Literature Relative to Gulf War
Veterans Health
and
Chair, Committee on Gulf War and Health: Fuels, Combustion Products, and Propellants
and
Member, Committee on Gulf War and Health: Insecticides and Solvents
Board on Health Promotion and Disease Prevention
Institute of Medicine
The National Academies

before the

Subcommittee on National Security, Emerging Threats, and International Relations
Committee on Government Reform
U.S. House of Representatives

November 15, 2005

Good morning Mr. Chairman and members of the subcommittee. Thanks to Congressman Shays, Congressman Kucinich and members of the house Subcommittee on National Security, Emerging Threats and International Relations for your concern about veteran’s health. My name is Lynn Goldman. I am a professor of environmental health sciences and epidemiology at the Bloomberg School of Public Health at Johns Hopkins University in Baltimore and chair of our program in applied public health. Prior to joining Hopkins in 1999 I served for six years at the US Environmental Protection Agency (EPA) as Assistant Administrator for the Office of Prevention, Pesticides and Toxic Substances. My primary training is in pediatrics and epidemiology. I also have served as Chair of two Institute of Medicine (IOM) Gulf War committees: the committee that is currently working on the report Gulf War and Health: Review of the Medical Literature Relative to Gulf War Veterans Health, and the committee that produced the report Gulf War and Health: Fuels, Combustion Products, and Propellants. Additionally, I was a member of the committee that produced Gulf War and Health: Insecticides and Solvents. Because of my experience, the IOM requested that I testify about the approach taken by those committees, as well as other Gulf War and Health committees and Vietnam Veterans and Agent Orange (VAO) committees.

Those reports are part of a series of studies conducted by the IOM, a division of The National Academies, which have investigated the health effects of exposures that might have occurred during the Gulf War. They continue a long history of the IOM applying its and its volunteers’ scientific expertise to assist the Department of Veterans Affairs by evaluating scientific evidence and drawing conclusions regarding health effects associated with exposures to which our nation’s veterans might have been exposed. On the basis of my own experience, it is my personal opinion that members of the committee take their responsibility to assess the scientific data in a fair and unbiased manner very seriously.

Today I would like to focus on two main points. First, from the perspective of a committee member and chair, how the IOM committee process works and the independence of IOM committees and second, the approach taken by the Gulf War committees, in particular the use of animal data.

IOM committees are comprised of expert volunteers and function independent of government oversight. At no time during the conduct of the Gulf War studies on which I was involved has anyone outside of the National Academies, including the Department of Veterans Affairs and the Department of Defense, and veterans, influenced the committee deliberations or the outcomes of the studies. Indeed the only outside guidance we have received has been in the form of (1) the legislation enacted by congress and signed into law by the President mandating that these studies be conducted, and (2) the scope of work that was established for each individual committee. Those items are indicated in the charge to the committee which is included in each report.

For each of the Gulf War reports, the expert committee members evaluated and interpreted literally thousands of peer-reviewed scientific publications that were identified through searches of databases. On the basis of their analyses and deliberations, the committees reached consensus conclusions on the potential associations between health outcomes and the agents of concern.

To fulfill the goals of the legislation, the approach taken to conduct the Gulf War studies is modeled after the approach taken for the Veterans and Agent Orange series of reports. At the same time, each newly-formed committee has needed to grapple with tailoring an approach to the challenges posed by the specific scientific issues put forward in the scope of work. Also, one difference between the Agent Orange studies and the Gulf War studies is the addition of a category of association, one of causality, to clarify that there is a difference scientifically between an association of an agent with a health outcome and an agent causing a health outcome. This category enhanced the scientific clarity of the committees’ reports but did not change the criteria set forth by Congress. In practice, that category has rarely been invoked.

Each committee has needed to determine how to evaluate the various kinds of scientific evidence that are available. That decision is scientifically-based and is made by the committee with no external restrictions. When available and of acceptable quality, epidemiology studies that have evaluated health effects in human populations exposed to chemicals of concern have been of great relevance to the work of all of these committees. However, for some outcomes and exposures, for example, contact dermatitis from exposure to certain chemicals, clinical case reports have played an important role; in most other circumstances such case reports have not been deemed acceptable.

Tables summarizing the committees’ conclusions are presented in the Executive Summary of each Gulf War report. I submitted those tables as an appendix to the written portion of this testimony (see Appendix A).

We are aware that you are concerned about whether and how animal data have been utilized in our evaluations. Because of my previous involvement in a regulatory agency, I am well aware of the primary importance of such data in toxicological risk assessments for many chemicals, pesticides and radioactive materials. However, the various IOM committees, which have included toxicologists, have consistently agreed that, in general, animal data should not be used as a sole basis for drawing conclusions regarding health outcomes in humans. Why should this be the case? There are three reasons.

First, although animal data may indicate which category of health outcomes might occur in humans, it does not answer questions about specific medical diagnoses. Take vinyl chloride, a known human carcinogen. In humans it causes a rare cancer called angiosarcoma of the liver. But in laboratory rats it causes an array of other cancers as well, including cancer of the zymbal gland, an organ that humans do not even possess. While such animal studies would be expected to give a more accurate determination of the potency of such a chemicals (given the lack of precise exposure measurements in human studies of vinyl chloride workers) it is only the human study that would provide the level of detail that is needed to conclude about specific health outcomes in humans. This issue is especially relevant to health outcomes like cancer and birth defects.

Second, animal studies may be carried out in ways that are not relevant to the Gulf War experience. Whereas the exposures in the Gulf were short term exposures to relatively low levels of chemicals and pesticides, most animal studies involve chronic doses to high levels of chemicals over much of a lifetime of an animal. These models are not appropriate to the experience in the Gulf.

Third, the Gulf War committees have often relied on pre-existing toxicology reviews for their reports. The Gulf War committees have been faced with evaluating the potential health effects of dozens of compounds that might have been used in the Gulf War. In some cases, prior expert committees have conducted extensive, peer-reviewed evaluation processes; these include reviews sponsored by: the Agency for Toxic Substances and Disease Registries (ATSDR), the EPA, the National Toxicology Program (NTP) and the World Health Organization (WHO). In such cases, where the effects of those chemicals in animals are well established and not contentious, Gulf War committees have relied heavily on those summaries rather than consulting the thousands of original toxicology articles. If a toxicology study was particularly critical, such as an animal carcinogenicity study and the committee wanted more detail regarding the study than provided in a review document, the committee would evaluate the original study. In their reports, committees refer readers to summaries and reviews of the toxicology literature and provide details of any particularly relevant studies.

In closing I want to reiterate the main points of this testimony. First, the IOM committees that prepared the Gulf War reports work independently and decide as a committee how to approach the charge that they are given. Committees have a great deal of latitude in the interpretation and approach to its charge. Second, each committee decides how it will use epidemiology and toxicology data. In general, where adequate epidemiology data have been available, committees have decided that those data are the most appropriate on which to draw conclusions regarding the relationship of exposures to specific chemicals and potential health outcomes in humans. This process has been a productive one in that it has provided the Veteran’s Administration with a wealth of information about the potential associations between agents in the Gulf War and the likelihood of subsequent adverse health effects in veterans. At the same time, as I noted in the preface to the last report that I chaired, which is attached (Appendix B), this is a process that is deserving of careful reassessment to assure that the scientific expertise of the country is effectively engaged in the mission of assuring the health and wellbeing of our veterans.

I would like to thank you for inviting me to testify before this Subcommittee on National Security, Emerging Threats, and International Relations. Your careful scrutiny of this process is most welcome, I would be happy to answer any questions you have.

***********

APPENDIX A:

Summary of Conclusions from Gulf War and Health Reports

TABLE 1 - Gulf War and Health Conclusions from Vols. 1, 2, 3 and Sarin Update

TYPE OF CONCLUSION

GW&H
Volume #

AGENT

HEALTH EFFECT

Sufficient Evidence of a Causal Relationship

2

Benzene

Acute leukemia

Aplastic anemia

 

1, Sarin

Sarin

Dose-dependent acute cholinergic syndrome that is evident seconds to hours subsequent to sarin exposure and resolves in days to months

       

Sufficient Evidence of an Association

1

Anthrax vaccination

Transient acute local and systemic effects

 

2

Benzene

Adult leukemia

 

1

Botulinum toxoid vaccination

Transient acute local and systemic effects

 

3

Combustion products

Lung cancer

 

2

Propylene glycol

Allergic contact dermatitis

 

1

Pyridostigmine bromide

Transient acute cholinergic effects in doses normally used in treatment and for diagnostic purposes

 

2

Solvents

Acute leukemia

       

Limited/Suggestive Evidence of an Association

2

Benzene

Non-Hodgkin’s lymphoma

 

2

Carbamates

Non-Hodgkin’s lymphoma

Limited/Suggestive Evidence of an Association (continued)

3

Combustion products

Bladder cancer

Cancers of the nasal cavity and nasopharynx

Cancers of the oral cavity and oropharynx

Incident asthma

Laryngeal cancer

Low birthweight/intrauterine growth retardation and exposure during pregnancy

Preterm birth and exposure during pregnancy

 

3

Hydrazines

lung cancer

 

2

Insecticides

Allergic contact dermatitis

 

2

Organophosphorus insecticides

Adult leukemia

Non-Hodgkin’s lymphoma

OP poisoning and long-term neurobehavioral effects (that is, abnormal results on neurobehavioral test batteries and symptom findings)

 

1

Sarin at doses sufficient to cause acute cholinergic signs

Symptoms and subsequent long-term health effects

 

Sarin

Sarin at doses sufficient to cause acute cholinergic signs

Symptoms and a variety of subsequent long-term neurological effects

 

2

Solvents

Adult leukemia

Bladder cancer

Chronic glomerulonephritis

Hepatic steatosis

Multiple myeloma

Myelodysplastic syndromes

Neurobehavioral effects (that is, abnormal results on neurobehavioral test batteries and symptom findings)

 

2

Tetrachloroethylene and dry-cleaning solvents

Bladder cancer

Kidney cancer

       

Inadequate/
Insufficient Evidence to Determine Whether an Association Exists

2

Benzene

Myelodysplastic syndromes

 

3

Combustion products

Colon cancer

Esophageal cancer

Female breast cancer

Female genital cancers (cervical, endometrial, uterine, and ovarian cancers)

Hepatic cancer

Hodgkin’s disease

Kidney cancer

Leukemia

Male breast cancer

Melanoma

Multiple myeloma

Myelodysplastic syndrome

Nervous system cancers

Non-Hodgkin’s lymphoma

Ocular melanoma

Pancreatic cancer

Prostatic cancer

Rectal cancer

Stomach cancer

Testicular cancer

Inadequate/
Insufficient Evidence to Determine Whether an Association Exists (continued)

3

Fuels

Bladder cancer

Cancers of the nasal cavity and nasopharynx

Cancers of the oral cavity and oropharynx

Colon cancer

Esophageal cancer

Female breast cancer

Female genital cancers (cervical, endometrial, uterine, and ovarian cancers)

Hepatic cancer

Hodgkin’s disease

Kidney cancer

Laryngeal cancer

Lung cancer

Male breast cancer

Melanoma

Multiple myeloma

Myelodysplastic syndromes

Nervous system cancers

Non-Hodgkin’s lymphoma

Nonmelanoma skin cancer

Pancreatic cancer

Prostatic cancer

Rectal cancer

Stomach cancer

Testicular cancer

Inadequate/
Insufficient Evidence to Determine Whether an Association Exists (continued)

2

Insecticides

Aplastic anemia

Brain and other central nervous system cancers

Kidney cancers

Lung cancer

Pancreatic cancer

Prostate, testicular, or bladder cancers

Soft tissue sarcomas

 

2

Insecticides and solvents

Amyotrophic lateral sclerosis

Alzheimer’s disease

Hepatobiliary cancers

Hodgkin’s disease

Irreversible cardiovascular outcomes

Male or female infertility after cessation of exposure

Multiple myeloma

Parkinson’s disease

Peripheral neuropathy

Persistent respiratory symptoms or impairment after cessation of exposure

 

2

Insecticides (parental preconception exposure)

Childhood leukemias, brain and other central nervous system cancers, and non-Hodgkin’s lymphoma

Congenital malformations

Spontaneous abortion or other adverse pregnancy outcomes

 

2

Lindane and solvents

Breast cancer

 

1

Pyridostigmine bromide

Long-term adverse health effects

 

1

Sarin at low doses insufficient to cause acute cholinergic signs

Symptoms and subsequent long-term adverse health effects

 

Sarin Update

Sarin at low doses insufficient to cause acute cholinergic signs

Subsequent long-term cardiovascular effects

Symptoms and subsequent long-term adverse neurological health effects

Inadequate/
Insufficient Evidence to Determine Whether an Association Exists (continued)

2

Solvents

Alterations in liver function tests after cessation of exposure

Bone cancer

Chronic pancreatitis and other persistent gastrointestinal outcomes

Cirrhosis

Long-term hearing loss

Long-term reduction in color discrimination

Long-term reduction in olfactory function

Melanoma or nonmelanoma skin cancer

Multiple sclerosis

Oral, nasal, or laryngeal cancer

Ovarian or uterine cancer

Prostate cancer

Stomach, rectal, or pancreatic cancer

Systemic rheumatic diseases: scleroderma, rheumatoid arthritis, undifferentiated connective tissue disorders, and systemic lupus erythematosus

 

2

Solvents other than tetrachloroethylene and dry-cleaning solvents

Esophageal cancer

Bladder cancer

Lung cancer

 

2

Solvents other than trichloroethylene

Cervical cancer

 

2

Solvents other than trichloroethylene and mixtures of benzene, toluene, and xylene

Colon cancer

 

2

Solvents, parental preconception exposure

Congenital malformations

Neuroblastoma and childhood brain cancers

Spontaneous abortion or other adverse pregnancy outcomes

Inadequate/
Insufficient Evidence to Determine Whether an Association Exists (continued)

2

Solvents: specific, other than benzene

Acute and adult leukemia

Aplastic anemia

Brain and other central nervous system cancers

Non-Hodgkin’s lymphoma

 

1

Uranium

Bone cancer

Cardiovascular effects

Dermal effects

Effects on hematological parameters

Gastrointestinal disease

Genotoxic effects

Hepatic disease

Immune-mediated disease

Lymphatic cancer

Musculoskeletal effects

Nervous system disease

Nonmalignant respiratory disease

Ocular effects

Reproductive or developmental dysfunction

 

1

Uranium at higher levels of cumulative exposure (>200 mSv or 25 cGy)

Lung cancer

 

1

Vaccination: anthrax

Long-term adverse health effects

 

1

Vaccination: botulinum toxoid

Long-term adverse health effects

 

1

Vaccinations: multiple

Long-term adverse health effects

       

Limited/Suggestive Evidence of No Association

1

Uranium at cumulative internal dose levels lower than 200 mSv or 25 cGy

Lung cancer

 

1

Uranium

Clinically significant renal dysfunction

       

Consensus Not Reached on Category of Association

2

Tetrachloroethylene and dry-cleaning solvent

Esophageal cancer

Lung cancer

 

2

Trichloroethylene

Colon cancer

Cervical cancer

 

2

Mixtures of benzene, toluene, and xylene

Colon cancer

 

2

Solvents

Kidney cancer

 

2

Benzene and solvents

Brain and other central nervous system cancers

 

2

Solvents, Parental preconception exposure

Childhood leukemia

 

2

Organophosphorous insecticide exposure without OP poisoning

long-term neurobehavioral effects (that is, abnormal results on neurobehavioral test batteries and symptom findings)

APPENDIX B:

Preface from: Gulf War and Health, Volume 3: Fuels, Combustion Products, and Propellants

PREFACE

As this report goes to press and our country is engaged in a war in Iraq, it is important to recall the 1990-1991 Gulf War. Engaging around 700,000 US military personnel, the Gulf War was of brief duration and entailed very few casualties among US troops. Yet, as they say, “war is hell”, and our troops were exposed to numerous traumatic events and a multitude of hazardous substances. Not long after the war ended, many of its veterans reported a variety of chronic symptoms. Numerous studies were conducted, most of which corroborated reports of higher rates of signs and symptoms among these veterans. Some of the signs and symptoms have clearly been associated with identifiable medical diagnoses such as post-traumatic stress disorder and depression; others are outside current medical diagnostic classifications.

Veterans have been deeply concerned about whether exposures in the gulf were associated with chronic health problems after the end of the war. In response to their concerns, the Department of Veterans Affairs (VA) and Congress secured the assistance of the Institute of Medicine (IOM) in evaluating the scientific literature regarding exposures that may have occurred in the Gulf War. In a sense, this approach followed a model developed for the Vietnam War, after which there was concern about the possible health effects of exposure to dioxins in Agent Orange. In that case, the work of IOM has played a key role in informing VA decisions regarding compensation for dioxin-related chronic health effects. Following that model, Congress enacted legislation that specifically directed IOM to evaluate the effects of 33 agents; this report covers a small number of the agents: hydrazines, red fuming nitric acid, hydrogen sulfide, oil-fire byproducts, and diesel-heater fumes. In addition, VA requested that we assess potential exposures to fuels that were used in the Gulf War (gasoline, jet fuel, diesel fuel, and kerosene) and their combustion products.

Although we had a relatively small number of substances to review, the scientific literature on air pollutants from fuel combustion, as well as from exposure to fuels, is extensive. IOM appointed a committee with knowledge in the toxicology and epidemiology of fuels and combustion products; it included experts in combustion chemistry, rocket propellants, immunology, pulmonology, cancer, neurosciences, dermatology, and reproductive and developmental toxicology. The committee did not limit itself to studies of Gulf War veterans but rather reviewed all relevant literature with regard to chronic medical effects of exposure. Although the committee focused on epidemiologic studies, which are likely to identify associations between specific exposures and diagnoses in people, it also placed weight on toxicologic studies and on clinical case series that were informative about specific exposure-disease relationships. Along the lines of earlier Gulf War reports, the committee has framed its conclusions in categories of strength of association. Despite the extensive challenge of reviewing the literature and the diversity of expertise and views among committee members, the committee was able to reach consensus on all conclusions. For that, I am most grateful.

The committee identified several associations between exposures to rocket propellants and combustion products and disease. However, there is some concern among our members about the direction that the process has taken. Many of the substances to which there was potential exposure in the gulf are unique to war service (for example, nerve agents, mustard agents, and rocket propellants), but others are not and may be at least as likely to occur in noncombat military service or in civilian life as in war (for example, fuels, air pollutants, and the solvents and pesticides reviewed in Gulf War and Health, Volume 2: Insecticides and Solvents). Therefore, as the process has evolved from an examination of exposures unique to wartime to exposures that are ubiquitous and may be even greater in civilian life, what are VA and Congress to do with the results of this study? A second troubling issue is the lack of exposure information for individual veterans; given that many risks are clearly exposure-related, it is difficult to use the results of our review to assess whether veterans’ illnesses are due to such exposures. Third, it is important to interpret the results of our review in a larger context of public health and prevention; for example, the committee found some evidence of an association between hydrazine exposure and lung cancer, but there obviously are much larger and better-established associations between lung cancer and other exposures, such as smoking and exposure to radon and asbestos. Given those circumstances, this report cannot answer the question of whether service in the gulf was associated with such exposures and whether specific health outcomes are due to the exposures. Despite those limitations, the committee hopes that its report will be helpful to all who may have been exposed to the substances in question and to those who are considering further research in the subject.

I am deeply appreciative of the expert work of our committee members, and it has been a privilege and a pleasure to work with the IOM staff. Without them, this report would not have been possible.

Lynn Goldman, MD, MPH, Chair

*********

Gulf War and Health: Updated Literature Review of Sarin

Testimony of

Samuel Potolicchio, MD
Professor and Clinical Neurologist
The George Washington School of Medicine
Washington, DC

and

Member, Committee on Gulf War and Health: Review of the Medical Literature Relative to Gulf War
Veterans Health
and
Member, Committee on Gulf War and Health: Fuels, Combustion Products, and Propellants
and
Member, Committee on Gulf War and Health: Insecticides and Solvents
and
Member, Committee on Gulf War and Health: Depleted Uranium, Pyridostygmine Bromide, Sarin,
Vaccines
and
Member, Committee on Gulf War and Health: Update Literature Review of Sarin
Board on Health Promotion and Disease Prevention
Institute of Medicine
The National Academies

before the

Subcommittee on National Security, Emerging Threats, and International Relations
Committee on Government Reform
U.S. House of Representatives

November 15, 2005

Good morning Mr. Chairman and members of the subcommittee. I am Dr. Samuel Potolicchio. I am a clinical neurologist with The George Washington University Hospital. In addition, I have been a volunteer member of the committees that produced or are currently preparing the following four Institute of Medicine (IOM) reports: Gulf War and Health: Review of the Medical Literature Relative to Gulf War Veterans Health; Gulf War and Health: Fuels, Combustion Products, and Propellants, Gulf War and Health: Insecticides and Solvents; Gulf War and Health: Depleted Uranium, Pyridostygmine Bromide, Sarin, Vaccines; and Gulf War and Health: Updated Literature of Sarin. Because of my experience on those committees and, in particular, my work on the sarin report, the IOM requested that I testify on the work of the sarin committee. I appreciate this opportunity to speak with you about the sarin report.

The sarin report was conducted following a request from the Department of Veterans Affairs (VA) to update an earlier report on the potential human health effects of sarin. That request followed the publication of a series of toxicology studies in rats looking at the effects of relatively low concentrations of sarin. Sarin is a highly toxic nerve agent produced for chemical warfare. Sarin can be fatal within minutes to hours. It is a member of a class of chemicals known as organophosphorous compounds. In humans and other animals, exposure to high doses of sarin produces a well-characterized syndrome, the acute cholinergic syndrome, featuring a wide variety of signs and symptoms, including: increased salivation, lacrimation (increased tears) and perspiration, “bloody tears”, blurring of vision, nausea, vomiting, diarrhea and fecal incontinence, excessive secretions in the bronchi (respiratory system), tightness in chest, cough, tachycardia (quickened heart rate), increased blood pressure, drowsiness and lethargy, mental confusion, headache, coma and convulsions. It is important to remember that the acute cholinergic syndrome is a very serious effect that requires medical attention and can lead to death.

I would like to note that, as with the committees discussed by Dr. Goldman, at no time during the preparation of Gulf War and Health: Updated Literature Review of Sarin, did anyone outside of the committee process influence the work, deliberations or outcomes of the studies.

In drawing its conclusions, the sarin update committee evaluated relevant studies that were identified in searches of databases that identified approximately 250 articles that were potentially relevant to the committee’s charge. Those articles included studies in humans and animals. On the basis of those studies the committee reached its conclusions.

The committee, as with previous Gulf War and Health committees, made conclusions regarding the existence of the acute cholinergic syndrome following sarin exposure, the existence of long-term effects in individuals exposed to sarin who had the acute cholinergic syndrome, and the existence of long-terms effects in individuals exposed to sarin who did not have any signs of having had the acute cholinergic syndrome.

The first conclusion is that there is sufficient evidence of a causal relationship between exposure to sarin and a dose-dependent (effect seen at high doses) acute cholinergic syndrome that is evident seconds to hours after sarin exposure and resolves in days to months. That conclusion is based on data from humans exposed to sarin and is supported by data in animals and on organophosphorous pesticides, which are related chemically to sarin.

The second conclusion is that there is limited/suggestive evidence of an association between exposure to sarin at doses sufficient to cause the acute cholinergic signs and symptoms and a variety of subsequent long-term neurologic effects.1 As with the previous conclusion, that conclusion is based on data from humans exposed to sarin and is supported by data in animals and data on organophosphorous pesticides.

Finally, the committee concluded that there is inadequate/insufficient evidence of an association between exposure to sarin at low doses insufficient to cause acute cholinergic signs and symptoms and subsequent long-term adverse health effects (specifically, neurologic and cardiovascular effects). That conclusion was based on a lack of data in humans or animals. I will focus on this last conclusion, as the first two conclusions are relatively well established and not controversial.

As with other Gulf War and Health committees, the sarin update committee first reviewed the human studies. There were data from studies of U.S. and U.K. servicemen who several decades ago (1958 through 1984) volunteered to be exposed to chemical weapons, including sarin; industrial workers with documented acute, high-dose exposures to sarin, victims of the sarin terrorist attacks in Japan, and studies of Gulf War veterans. All of those studies, with the exception of the studies of Gulf War veterans, focused on the effects in individuals who had shown the signs and symptoms of the acute cholinergic syndrome and, therefore, do not provide information on the effects of sarin at concentrations below those that cause the acute cholinergic syndrome.

The studies conducted in Gulf War veterans—including U.S., U.K., Danish, and Canadian veterans—were not very useful in making specific conclusions regarding the health effects of sarin because many do not have objective assessments of exposure to sarin (e.g., many rely on self-reports of exposures in surveys taken years after the war or are in individuals not deployed to the Gulf War until after any of the potential exposures to sarin are thought to have occurred) or have other problems with the exposure assessment. In addition, no health outcomes were consistently seen in those studies.

Given the limitations of the epidemiology studies, the committee then reviewed the available toxicology data, focusing on those studies conducted with doses below those that cause the signs and symptoms of the acute cholinergic syndrome to draw conclusions related to lower exposure to sarin and health effects. Although few studies have evaluated the effects of such doses, a recent series of studies by Dr. Rogene Henderson, which are the studies that prompted the IOM sarin update, have evaluated the effects of low-dose sarin exposure in rats. Those studies did show some alterations in some subtypes of a specific family of receptors in certain areas of the rats’ brains, but no consistent and long-term effects were seen in the levels of the neurotransmitters and on behavioral parameters in the rats. The data on receptors indicate further research areas, but are not correlated with any particular health outcome in rats, let alone humans. Those data on receptor density, therefore, are not sufficient to indicate an association with a human health effect, especially given the fact that behavioral effects were not seen in rats treated with sarin at the same concentration. Animal studies by other researchers looking at low-dose effects also showed inconsistent, if any, effects.

In summary, the committee concluded that there is sufficient evidence of a causal relationship between exposure to high amounts of sarin and the acute cholinergic syndrome and there is limited/suggestive evidence of an association between exposure to sarin at those high levels that cause the acute cholinergic syndrome and a variety of subsequent long-term neurologic effects. However, given the few epidemiology studies, the limitations of those studies that look at the effects of exposure to low concentrations of sarin (i.e., below those that cause the acute cholinergic syndrome), and the limited number of relevant toxicology studies and their inconsistent results, the committee concluded that there was inadequate/insufficient evidence to determine if there is an association between exposure to sarin at levels that do not cause the acute cholinergic syndrome and any human health effects. Those conclusions were based on available scientific data and they were made by the committee without any external pressures or interference.

With that, I would once again like to thank you for inviting me to testify before this subcommittee. I appreciate the work of this Subcommittee on National Security, Emerging Threats, and International Relations and am happy for your interest in this important area of veteran’s health. I look forward to answering any questions you might have.

******

Endnotes

1. Many health effects are reported in the literature to persist after sarin exposure: fatigue, headache, visual disturbances (asthenopia, blurred vision, and narrowing of the visual field), asthenia, shoulder stiffness, and symptoms of PTSD. Sarin exposure has been followed by abnormal test results, of unknown clinical significance, on the digit symbol test of psychomotor performance, EEG records of sleep, event-related potential, visual evoked potential, and computerized posturography.

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