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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.

Animal Studies

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



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