Summary of Findings and Recommendations
In the course of this study the committee reviewed almost 2,000 papers, monographs, abstracts, and technical summaries in search of information regarding the long-term health effects of exposure to mustard agents and Lewisite. The committee found a ''stunted" body of literature, clearly focused on the acute effects of these agents and the prevention or treatment of these effects. Certainly, protection of lives in combat situations is an important and necessary effort. Yet the narrow focus of the literature presented a major barrier to this committee, concerned as it was with surveying the scientific and medical literature to assess the health risks incurred by anyone exposed to these agents, but especially the human subjects in the World War II (WWII) testing programs. Thus, the lack of follow-up health assessments of the human subjects in WWII gas chamber and field tests severely diminished the amount and quality of information that could be applied in the assessment of long-term health consequences of exposure to mustard agents and Lewisite.
The lack of follow-up of these subjects particularly dismayed the committee for a number of reasons. For example, the end point of the chamber and field tests was tissue injury, but it was already known by 1933 that certain long-term health problems resulted from sulfur mustard exposure. Further, it was documented that numerous subjects suffered severe injuries that required up to a month of treatment. Finally, the exposure levels were sufficiently high that even the most efficient gas mask could have leaked enough mustard agent or Lewisite to cause inhalation and eye injuries.
There was, in fact, no long-term follow-up of any of the thousands of individuals exposed to these agents during WWII as evidenced by the accompanying lack of epidemiological studies of chemical warfare production workers, war gas handlers and trainers, and combat casualties of the Bari harbor bombing. The committee was particularly dismayed at this lack of epidemiological and follow-up data from the United States, despite the availability of a large cohort of civilian workers and military personnel who were involved in chemical warfare production and training, as well as the individuals who served as human subjects in chemical warfare testing programs. The committee was forced to rely on studies done in Japan and Great Britain to assess what was known about the long-term health risks from occupational exposure to mustard agents and Lewisite. As demonstrated in Chapters 3 and 7, such occupational data are directly relevant to the assessment of the potential effects of mustard agent and Lewisite exposure in the experimental testing programs, because the levels of exposure to mustard agents or Lewisite experienced by the human subjects may have been much higher than inferred in the summaries of the gas chamber and field tests.
These exposures were likely as high as those estimated for battlefield and occupational exposures, due to cumulative skin exposure compounded by inhalation exposure. Numerous lines of evidence demonstrate that inhalation exposures did indeed occur (see Chapter 3 and 7). First, modern gas masks have efficiency ratings (or PF) between 50 and 100 (a PF of 100 means that 1 percent of the contaminant in the atmosphere will penetrate a mask's filter canister); however, the efficiency achieved in actual use has been demonstrated to be much lower. Even if a much higher PF of 1,000 is assumed for the gas masks used in the WWII testing programs, penetration of sufficient amounts of the agents to cause respiratory and ocular signs and symptoms would have been expected at many of the concentrations used in the experiments. Second, there is documentation in the actual records of these experiments, as well as official histories of production settings, that respiratory and ocular symptoms and injuries did occur, and that problems were encountered with gas masks leaking after repeated use. Third, the specific diaphragm type of gas mask used in the gas chamber tests was eventually shown to be leaky due to penetration of the diaphragm element, independent of the filter canister employed.
The reasons for the lack of follow-up of human subjects and combat casualties, as well as gas production, handling, and training personnel, can only be surmised, but the climate of secrecy within which the WWII chemical warfare production and testing programs were conducted is probably a key factor.
CONCLUSIONS REGARDING THE CAUSAL RELATIONSHIPS OF EXPOSURE TO THE DEVELOPMENT OF SPECIFIC DISEASES
The major conclusions reached by the committee regarding the association of exposure to mustard agents or Lewisite to specific diseases in different organ systems are summarized in Table 12-1. In some cases, the data examined were found to indicate a causal relationship between exposure and a particular disease or health problem. For other health problems, the data were suggestive, but not completely clear. Finally, there were certain health problems for which very little or no data existed regarding the possible contributions of exposure to mustard agents or Lewisite. By the same token, however, there was no condition evaluated that could be removed from consideration as a health consequence of exposure to these agents. Thus, for many diseases and health problems, there remains significant doubt about whether or not exposure to these agents is a key etiological factor.
The evidence indicates a causal relation between sulfur mustard exposure and the occurrence of excess respiratory and skin cancer, and possibly leukemia. This conclusion is based upon estimates of exposure to sulfur mustard during the chamber tests, which may have approximated the battlefield exposure of surviving World War I (WWI) soldiers and WWII production workers in Japan and Great Britain. Inadequate exposure information, however, limits precise estimation of the cancer excesses that may be expected. The evidence is insufficient to indicate a causal relationship for Lewisite carcinogenesis.
Mustard agents are DNA-alkylating agents and are extremely cytotoxic at low doses. DNA alkylation is probably responsible for the mutagenicity of mustard agents. These agents also alkylate RNA and proteins and can, at moderate to high doses, produce nonrepairable DNA lesions (genotoxicity). The sulfur mustards induce a wide variety of genetic lesions in many types of mammalian cells in vitro in a dose-related fashion. They also induce genetic damage in vivo in peripheral blood lymphocytes from exposed individuals at low doses. The toxicology of Lewisite has been poorly studied.
Chamber exposure to sulfur mustard has produced skin malignancies in rats, and intravenous injection has produced a significant increase in pulmonary tumors in highly susceptible strain A mice. Subcutaneous injection of sulfur mustard has been shown to cause sarcomas and other tumors at the injection site in C3H, C3Hf, and strain A mice, but did not produce an increase of tumors at other sites.
Nitrogen mustard, particularly HN2, has been more widely tested than sulfur mustard and has been found to be a carcinogen, producing
TABLE 12-1 Summary of Findings Regarding Specific Health Problems
Evidence Indicates Causal Relationship to Mustard Agent Exposure a
Pigmentation abnormalities of the skin
Chronic skin ulceration and scar formation
Leukemia (typically acute nonlymphocytic type, nitrogen mustard only)
Chronic respiratory diseases (also Lewisite)
chronic obstructive pulmonary disease
Recurrent corneal ulcerative diseaseb
Delayed recurrent keratitis of the eye
Bone marrow depression and immunosuppressionc
anxiety disorders (including post-traumatic stress disorder)
other traumatic stress disorder responses
Evidence Suggestive of Causal Relationship to Mustard Agent Exposure
Leukemia (sulfur mustard)
Reproductive dysfunction (genotoxicity, mutagenicity, etc.)
Insufficient Evidence of Causal Relationship to Mustard Agent Exposure
Reproductive dysfunction (Lewisite)
a Includes Lewisite only when indicated.
b Includes corneal opacities; acute severe injuries to eye from Lewisite will persist.
c An acute effect that may result in greater susceptibility to serious infections with secondary permanent damage to vital organ systems.
d These may result from traumatic or stressful features of the exposure experience, not a toxic effect of the agents themselves.
e Scrotal and penile scarring may prevent or inhibit normal sexual performance or activity. Decreased sexual function may adversely affect reproductive success.
f Except when caused by serious infection (e.g., rheumatic fever) closely following an exposure that produced bone marrow depression and immunosuppression.
pulmonary tumors from both intravenous and intraperitoneal injections in strain A mice. Subcutaneous exposures produced injection site tumors and pulmonary tumors in selected strains of mice. The carcino-
genic potency of nitrogen mustard appears to be similar to sulfur mustard. In addition, nitrogen mustard has been shown to be one of the most potent carcinogens amongst the alkylating agents tested in the strain A bioassay program of the National Cancer Institute.
Studies of these agents in humans have involved occupational, battlefield, and therapeutic exposures. Occupational exposure to sulfur mustard has been associated with respiratory tract cancer. The data from battlefield exposures, however, have been somewhat more equivocal: an excess of lung cancer was observed, but the excess was not statistically significant. Follow-up of cancer patients treated with nitrogen mustard derivatives has clearly indicated a causal association with skin cancer and leukemia, particularly the acute nonlymphocytic type. Although an excess of skin cancer or leukemia was not evident in the occupational or battlefield studies, the discrepancy may result from differences in amount of exposure; the leukemias or skin cancer may have occurred prior to the start of observation of the occupational and battlefield cohorts; or nonfatal cases of skin cancer may not have been detected in mortality studies. It is also possible that skin cancers did not occur in the studied populations, or that there was a difference in effects between sulfur and nitrogen mustards. Although nitrogen mustard-associated leukemia and skin cancer occur usually within a decade of therapeutic exposure, the occurrence of an excess of such cases among the WWII human subjects, Bari casualties, or workers would not be surprising.
The evidence indicates a causal relation between exposure to sufficient concentrations of sulfur mustard (and presumably nitrogen mustard and Lewisite) and chronic nonreversible respiratory effects in humans.
Follow-up of WWI battlefield casualties has demonstrated the association between exposure to sulfur mustard and development of chronic bronchitis, emphysema, and asthma. Chronic respiratory effects have also been shown in workers from WWII chemical weapons factories and casualties of the Iran-Iraq war. These results are well supported by studies in laboratory animals. Given the concentrations of mustard agents and Lewisite used in the WWII experiments, prior research predicts the development of chronic nonreversible lung diseases. Further, indirect evidence, based on a review of the relationships between acute and chronic effects caused by other substances, suggests that these long-term respiratory effects may occur in the absence of an acute respiratory response.
The evidence indicates a causal relation between exposure to sulfur mustard and recurrent corneal ulcerative disease (including corneal opacities), delayed recurrent keratitis, and chronic
intractable conjunctivitis. Evidence in laboratory animals indicates no causal relation between exposure to Lewisite and any long-term ocular disease process. However, any corneal scarring or vascularization that occurs soon after injury from Lewisite will persist.
There is an extensive base of knowledge from studies in laboratory animals and humans regarding the long-term effects of mustard agents on the eye. Thus, acute, severe injury of the eye with sulfur mustard, resulting in corneal scarring among other effects, can result in recurrent corneal ulcerative disease. The maximum incidence of this disease occurs 15 to 20 years after the injury. Acute severe injury from sulfur mustard has also been shown to result in the development of delayed recurrent keratitis and corneal opacities. The conjunctiva of the eye has been shown to be more vulnerable than the cornea to sulfur mustard exposure, explaining the development of intractable, prolonged conjunctivitis even in the absence of severe injury to the cornea.
The evidence indicates a causal relation between acute, severe exposure to mustard agents and increased skin pigmentation and depigmentation, chronic skin ulceration, scar formation, and the development of cancer in human skin. A causal relationship also exists between chronic exposure to minimally toxic, and even subtoxic, doses and skin pigmentation abnormalities and cutaneous cancer. There is insufficient evidence, however, to establish a causal relationship between Lewisite exposure and long-term adverse effects on skin.
There has been much research on the toxic mechanisms of acute skin injury from mustard agents, especially in laboratory animals and tissue cultures. Injuries from mustard agents have been shown in these models to result in a complex cascade of biochemical reactions that cause cell death and genotoxicity. Studies of carcinogenesis were positive in laboratory animals, but these studies employed outdated methods and are relatively crude by today's standards. Studies in humans after battlefield or occupational exposure also vary tremendously in quality.
Nevertheless, skin cancers have been observed in many of these studies. That fact, coupled with documented and plausible biological mechanisms, indicates cancer as a likely consequence of acute, severe (or chronic, mild to moderate) mustard agent injury to the skin. Scar formation and chronic ulceration of the skin following mustard agent exposure have been well documented in the literature. Genital regions are especially sensitive to exposure, and scarring of the scrotum and penis can seriously impair sexual performance and capability. In those studies in which pigmentation abnormalities were reported, including recent observations in casualties of the Iran-Iraq war, the abnormalities
are completely consistent with known effects of skin damage. Despite data highly suggestive of a link between skin diseases and arsenic exposure, very little data exist that can be directly extrapolated to exposure to the organic arsenical Lewisite and its consequences in the skin.
The evidence indicates a causal relationship between exposure to mustard agents and bone marrow depression and immune system dysfunction. These acute effects would render individuals highly susceptible to infections, including pneumonia, rheumatic fever, and tuberculosis, which in severe cases may cause permanent damage to vital organs. There is insufficient evidence with which to draw conclusions regarding the effects of Lewisite on immune system function.
Animal studies clearly demonstrate a causal relationship between exposure to mustard agents and immunotoxicity. Evidence from observations in humans indicates a causal relationship between mustard agent exposure and acute bone marrow toxicity expressed as leukopenia, pancytopenia, and aplastic or hypoplastic bone marrow. However, underrepresented in human studies is information on chronic or delayed effects. The data examined, however, indicate that clinical studies as a whole support a close parallelism between animal experiments and observations in humans regarding the immunosuppressive properties of mustard agents.
There is insufficient evidence to demonstrate a causal relationship between exposure to mustard agents and the development of long-term gastrointestinal, hematologic, or neurological diseases or dysfunctions, other than those secondary to other conditions related to exposure to mustard agents. In addition, there is insufficient information to link Lewisite with long-term health effects on the hematological, gastrointestinal, and neurological systems.
Gastrointestinal, hematological, and neurological effects are common after acute high exposures to mustard agents and can be attributed primarily to the known toxicological effects of these agents and secondarily to effects on other organ systems (e.g., from shock or burns). However, effects on these organ systems have not been a focus of any follow-up studies of humans exposed to mustard agents or Lewisite.
There is insufficient evidence to demonstrate a causal relationship between exposure to mustard agents or Lewisite and toxicity to the reproductive system.
The database is too small and uncertain to allow a clear understanding of human reproductive risk from exposure to sulfur mustards.
However, there is evidence to suggest a causal relationship between sulfur mustard exposure and reproductive toxicity in laboratory animals. Reproductive success, however, can be adversely affected by impaired sexual function caused by scarring of penile tissue.
The studies of the reproductive toxicity of Lewisite in laboratory animals are negative. Such data, however, are not complete and thus are insufficient to support or deny a causal relationship between exposure and adverse reproductive outcomes.
The evidence indicates a causal relationship between characteristic aspects of the chamber and field experiences and the development of adverse psychological effects. These effects may be highly individual, but diagnosable, and may include long-term mood and anxiety disorders, PTSD, or other traumatic stress disorder responses. Data are insufficient, however, to associate the presence of adverse psychological disorders with any physiological disease or dysfunction.
Many elements of the gas chamber and field experiments were highly stressful. These include lack of prior knowledge about what to expect, the duration and conditions of the chamber trials, the experience of skin injury from the exposures, the threats of punishment if the experiments were revealed, and other elements. Any stress reaction from the experiences may have well been magnified by subsequent secrecy, fears about the health risks, and institutional denials. Data from studies of chemical and biological warfare environments and environmental exposures to toxic chemicals or radiation support the assertion that, in certain individuals, these experiences would have been sufficient to cause adverse psychological effects, resulting in long-term dysfunction. It is likely that such effects also occurred in some production workers, gas handlers and trainers, and Bari harbor survivors as a result of traumatic episodes including explosions, accidents, personal exposure injury, or the witnessing of severe injury or death of others. Current investigations of the physiological concomitants of psychological disorders are compelling and of great interest for future research. However, it is not possible to predict from these studies what adverse physiological effects may be attributable to long-standing psychological problems.
GAPS IN THE LITERATURE REGARDING MUSTARD AGENTS AND LEWISITE
Clearly the most important gap in studies assessing the effect of agent exposure on humans is the lack of epidemiological studies of occupa-
tional exposure. Only limited cohorts of workers in Japan and Great Britain have been studied, and the value of these studies has been diminished by a lack of precise exposure information. The few exposure measurements made were usually from specific plant regions or during particularly troublesome parts of the manufacturing process. More useful would have been exposure information according to specific job categories. Finally, no attempts were made in such studies to determine the likely dose-response relationships. Such prediction would require quantitative risk assessments for which adequate data are not available.
The focus on carcinogenicity in epidemiological studies also left large gaps in the literature pertinent to the development of nonmalignant diseases. Although sufficient studies exist to associate the development of nonmalignant respiratory diseases, eye damage, and certain skin diseases with exposure, little to nothing is known regarding the effect of exposure on the development of gastrointestinal, immunological, and neurological diseases in humans. Further, no human data exist concerning the possible adverse reproductive effects of exposure to mustard agents or Lewisite.
The most extensively studied organ systems in terms of human pathology are the eye and the skin. Much of this research is quite old and, for the skin, research into the long-term effects in humans of exposure is still lacking. The recent casualties of sulfur mustard exposure, such as those injured in the Iran-Iraq war, are now being followed to assess long-term cutaneous effects of acute sulfur mustard exposure. Yet, observation periods as long as 35-45 years may be required to produce meaningful human data. Because these studies are only in their fourth or fifth year, conclusive results will probably not be available for another 15 to 20 years. In the short term for this cohort, however, investigative application of modern methods of ophthalmological treatment, such as the use of soft contact lenses to reduce the effects of chronic relapsing keratitis of the eyes, may yield some benefits. There are also human data derived from patients previously treated in Russian and Eastern European studies of the sulfur mustard-containing agent psoriasin that may be useful in determining the delayed effect of short term administration of sub-erythema dosages of sulfur mustard. Because these studies began 20 to 25 years ago, follow-up of the psoriasin-treated patients now, if properly done, would be of invaluable help in determining delayed effects of acute sulfur mustard exposure.
The most critical gap in animal studies is the lack of more extensive carcinogenicity and toxicity studies of mustard agents and Lewisite. Particularly lacking are studies, employing modern methods, of the
long-term effects of varying levels of exposure to these agents. For example, investigations of the systemic toxicity of short-term exposures to these agents to the gastrointestinal, immunological, and neurological systems are nonexistent. Further studies of the mechanisms of long-term damage to the respiratory system would also be useful. Despite intensive research on the mechanisms of sulfur mustard injury to the skin in animal models, little data exist regarding the long-term consequences of such injury.
In addition, the mechanisms of eye injury from sulfur mustard remain to be elucidated. For example, research on the effect of sulfur mustard on the ciliary body would disclose any changes in its vascular, nutritive, and transport functions. Research to determine the effect of sulfur mustard and Lewisite on limbal stem cells might be useful in determining whether stem cell replacement could reverse some of the adverse effects of injury. Finally, research directed at protection of the stromal component of the cornea might reduce the incidence of ulceration and perforation so common after chemical injuries to the eyes.
Although data exist on the reproductive toxicity of sulfur mustards in more than one animal species, it would be useful to have additional studies to examine the extent of the variability between species. More inhalation and cutaneous exposure studies would also be very helpful, as these exposure results would more accurately mimic human exposure. Certainly studying larger numbers of animals would provide a more sensitive measure of the possible magnitude of any reproductive risk associated with exposure to sulfur mustards. Short-term, high-dose exposures might also be helpful in attempting to examine any dose-rate effects.
The gaps in our knowledge of the toxicity and carcinogenicity of Lewisite based on animal studies are especially prominent, even in the most basic types of research. There is little information available in the literature concerning the reactions of Lewisite with biologically important molecules. Studies on the carcinogenicity or noncarcinogenicity of Lewisite need to be broadened and pursued with greater intensity. Much of the information obtained from these studies, unlike studies of sulfur mustard exposure, will have broad application in industry, farming, and medicine, because arsenic-containing chemicals are in wide use today.
There are also numerous gaps in the literature relative to the acute and long-term effects of Lewisite skin exposure. Very little is known regarding its specific effect on skin; data on such basic areas as absorption, disposition, and excretion after skin exposure are minimal. In addition, the morphological sites vulnerable to Lewisite are not known. Microscopic examination of affected skin has yet to be pursued in depth, although most studies have been impaired, as has
been work on sulfur mustard exposure, by the lack of good animal model systems.
Serious gaps also exist in our knowledge concerning the potential of Lewisite to cause reproductive problems. The reproductive toxicity of Lewisite in males is unclear. Our ability to extrapolate from the animal studies to humans is limited. The kinetics of absorption through the skin are unclear, as is the potential of this exposure to induce long-term storage of potentially teratogenic arsenic in doses high enough to induce reproductive problems later in life. Even the form of arsenic that is a potent teratogen in animals, and the ability of Lewisite to yield this form as a metabolite in man, are not entirely clear. More studies of multiple species would be helpful in understanding the potential reproductive toxicity of this compound.
With the immense gaps in the knowledge base about the long-term health risks associated with exposure to mustard agents and Lewisite, and after serious consideration of the historical analyses of the WWII testing programs and the likely exposure levels to the human subjects involved, this committee believes certain recommendations are necessary and justified. First, the committee recommends that the Department of Veterans Affairs (VA) institute a program to identify each human subject in the WWII testing programs (chamber and field tests, and to the degree possible, patch tests), so that these individuals can be notified of their exposures and the likely health risks associated with those exposures. Further, all subjects so identified, if still living, should be medically evaluated and followed by the VA as to their health status in the future. These individuals should also, if they request it, be treated by the VA for any exposure-related health problems discovered. Morbidity and mortality studies should be accomplished by the VA, comparing chamber, field, and patch test cohorts to appropriate control groups, in order to resolve some of the remaining questions about the health risks associated with exposure to these agents.
The only way to answer some of the key remaining questions is to establish a base of knowledge based on human exposures. There is precedent for this recommendation in the later identification and follow-up of veterans exposed to chemicals, including hallucinogenic drugs, in the military testing programs between 1950 and 1975. The committee is also well aware that a half century has now passed and that many of those who might have benefited from a broader understanding of the toxicity and carcinogenicity of mustard agents and Lewisite are already dead. Nevertheless, these individuals' surviving family mem-
bers deserve to know about the testing programs, the exposures, and the potential results of those exposures. For those veterans still living, diseases such as skin and lung cancer may still appear. Treating these cancers with full knowledge of their likely cause should be the responsibility of the VA and may be life-saving; for example, the likelihood of survival from skin cancer is greatly increased by early diagnosis and treatment.
In the case of the human subjects of the WWII testing programs, it is reasonable to assume that the secrecy surrounding the experiments may have kept individuals and entire families from successful resolution and treatment of any adverse psychological effects that may have been caused. Given this possibility and the special problems of ambiguity, health fears, and institutional denials encountered by many of those exposed to these agents, the committee recommends that careful attention be paid by health care providers to the special problems and concerns of the affected veterans and their families. This attention may include the convening of a special task force of experts in stress disorders and risk perception to aid the VA, further than this committee is able, in the establishment of comprehensive guidelines for handling of these cases.
The above recommendations are not meant to ignore the fact that thousands, probably tens of thousands, of other military and civilian personnel were exposed to mustard agents and Lewisite in occupational and training settings, and in combat in the Bari harbor disaster. Some of these exposures will have resulted in one or more of the exposure-related health problems identified in this report. The committee is also aware that some military personnel who served in the Chemical Warfare Service have qualified for service-connected disability as a result of such exposures. However, many more military personnel were exposed to significant levels of mustard agents or Lewisite than is obvious from service records, because of job classifications, inadequate documentation of ''live agent" training and accidents, and other factors. Therefore, the committee additionally recommends that the Department of Defense (DoD) should use all means at its disposal, including public channels, to identify cohorts of chemical warfare production workers (military or civilian) and individuals exposed to mustard agents or Lewisite from gas handling, training, the Bari harbor disaster, or other circumstances. Records of former military personnel could be turned over to the VA for notification, inclusion in morbidity and mortality studies, and health status evaluation. Records of the civilian personnel should be used by the DoD to notify the former workers. These workers should also be advised as to their health risks and options for seeking appropriate compensation for any illnesses that resulted from their exposures.
This committee discovered that an atmosphere of secrecy still exists to some extent regarding the WWII testing programs. Although many documents pertaining to the WWII testing programs were declassified shortly after the war ended, others were not. Of those declassified, many remained "restricted" to the present day and are not released to the public. As a result, the committee often had great difficulty obtaining information. For example, only one of the three major chamber test locations, the Naval Research Laboratory, freely shared technical reports and detailed summaries with the committee from the beginning of the study. For other locations, such information only arrived as the study was in its final stages, despite months of requests and inquiries to a variety of offices. The committee is certain that other relevant information exists that was never obtained. It is also clear that there may be many exposed veterans and workers who took an oath of secrecy during WWII and remain true to that oath even today. Veterans, who had just heard about the study and thought it might now be permissible to reveal their experiences, were still contacting the committee for information up until the very end of the study. Such continuing secrecy, in the committee's view, has impeded well-informed health care for thousands of people. Therefore, the committee recommends that the VA and DoD publicly announce and widely advertise that personnel exposed to mustard agents or Lewisite during their service are released from any oath of secrecy taken at the time. In addition, professional educational materials should be prepared by the DoD or the VA, or both, and made available for physicians who may be treating affected individuals. These materials should incorporate the latest information regarding the long-term health effects of exposure to mustard agents and Lewisite.
There is no doubt that the long-term health consequences of exposure to mustard agents or Lewisite can be serious and, in some cases, devastating. This report has demonstrated that complete knowledge of these long-term consequences has been and still is sorely lacking, resulting in great costs to some of those exposed in WWII. The lack of knowledge, however, has ongoing ramifications as nations will probably continue to use these chemical weapons in battle or begin to grapple with their disposal. Thus, accidental and deliberate human exposures to mustard agents and Lewisite can only be expected to continue in the foreseeable future.