BECAUSE OF WIDESPREAD CONCERN over possible use of biologic warfare (BW) by a foreign power against the United States and its allies, President Roosevelt in 1942 established the U.S. Biological Warfare Program. The policy of the United States concerning BW between 1941 and 1973 was, first, to deter its use against the United States and its allies and, second, to retaliate by using pathogenic agents if deterrence failed (U.S. Army 1977). The stockpile of offensive BW agents was destroyed in 1973 in accordance with a directive issued by President Nixon in 1969.
The potential tactical use of BW agents required the development of tables of munitions requirements (the quantities of materials required to achieve particular military objectives) for the strategic use of BW agents against specific cities. To obtain some estimate of the amount of BW material required to meet certain objectives in given cities, an indirect approach was used: to simulate the BW agents, and run tests with the simulants in suitable locations. The U.S. Army used both biologic and non-
biologic simulants in its tests. Biologic simulants are defined as living microorganisms that are not normally capable of causing infection, that represent the physical and biologic characteristics of potential pathogenic microbiologic agents, and that were considered medically safe for operating personnel and the general public. Nonbiologic simulants are nonliving inert (usually inorganic) materials; they are formed to resemble the size of BW agents for dispersion in the air in a manner similar to BW agents, but they are not themselves BW agents.
The biologic simulants used included Serratia marcescens, Bacillus globigii, Bacillus subtilis, and Aspergillus fumigatus; all these were considered by the Army to be safe at the time of their use (U.S. Army 1977). (More recent research indicates that the organisms are generally nonpathogenic or of low virulence in normal populations, but some could become pathogenic in immunocompromised persons.) The nonbiologic simulants used included zinc cadmium sulfide (ZnCdS) and sulfur dioxide (SO), the former of which is the subject of this report. Although some of the Army's tests involved exposures to ZnCdS at the same time as biologic agents, such as Serratia marcescens, the subcommittee did not assess the implications of such coexposures, because that was beyond its charge and ability. Information on interactions between biologics and chemicals can be found in the Institute of Medicine's 1996 report entitled ''Interactions of Drugs, Biologics, and Chemicals in the U.S. Military Forces.'' Appendix A provides greater detail on the U.S. BW program and the selection of biologic and nonbiologic simulants.
ZNCDS DISPERSION TESTS
During the 1950s and 1960s, Stanford University and other contractors for the U.S. Army Chemical Corps conducted dispersion tests with fluorescent particles of ZnCdS as part of the BW program in Minneapolis, MN; Corpus Christi, TX; St. Louis, MO; Fort Wayne, IN; and 29 other urban and rural locations in the United States and Canada. Tables 5-1 and B-1 show the locations, dates, and amounts of ZnCdS released. Appendix A provides greater detail on and the reasons for the selection of the test cities or other test locations.
ZnCdS is a sintered chemical (it is formed by heating a mixture of zinc sulfide, ZnS, and cadmium sulfide, CdS) composed of 80% ZnS and 20% CdS. It was considered to be desirable as a nonbiologic simulant for several reasons: (1) it fluoresces under ultraviolet (UV) light and therefore can be easily detected, (2) its particle size (0.5-6.25 µm), which is similar to that of several microorganisms, makes it easily dispersible (Leighton 1955), (3) it was economically feasible, (4) it was perceived to be nontoxic to humans, animals, and plants, and (5) it is stable in the atmosphere.
The ZnCdS tests were initially conducted in Minneapolis, St. Louis, and Winnipeg. These cities were selected because of their similarity-in meteorologic, terrain, population, and physical characteristics—to such cities in the former Soviet Union as Moscow and St. Petersburg (formerly Leningrad). As the field testing program progressed, it was recognized that data were needed for other geographical areas. Tests with single and multiple munitions were conducted in forests—in mountainous areas of Targhee National Forest in Idaho; in moderately to heavily covered flat land in Florida, and tropical islands off the Panama coast. In addition, numerous field tests were conducted by the British in India and Australia which added to the variety of terrain and geographical variables. When all of these tests were completed, there was an abundance of information showing directly how various biologic agents behaved under a variety of conditions which were either representative of or bracketed the conditions experienced in areas of combat.
Operation LAC (for Large Area Coverage) was the largest test program ever undertaken by the Army's Chemical Corps. The test area covered the United States from the Rockies to the Atlantic, from Canada to the Gulf of Mexico. The tests proved the feasibility of covering large areas (thousands of square miles) of a country with BW agents based on ZnCdS particles as simulants.
PUBLIC CONCERN IN RESPONSE TO ZNCDS DISPERSION TESTS
On learning of the dispersion tests in the early 1990s, government officials and citizens in several places, such as Minneapolis, MN, Corpus Christi,
TX, and Fort Wayne, IN, raised concerns about the thousands of people who might unknowingly have been exposed to ZnCdS. After information on the tests became public, some people living in areas where the tests were conducted attributed various illnesses, including cancer and reproductive difficulties, to exposure to the chemical.
In response to the public concern, the AEHA prepared reports that assessed the health risk to humans exposed to ZnCdS in Minneapolis, Corpus Christi, Fort Wayne, and St. Louis (AEHA 1994, 1995a,b). The assessments were based on a review of the toxicity of cadmium because little information on the toxicity of ZnCdS was available in the scientific literature or in Army files and because AEHA considered cadmium to be the most toxic component of ZnCdS. Cadmium, a toxic metal, is present in the ambient environment (in food, air, and water). Zinc is an essential nutrient (NRC 1980) and is toxic only at high doses; AEHA did not believe that zinc would contribute to any toxicity that ZnCdS might have. In the AEHA reports, human exposure to cadmium was estimated from the ZnCdS-exposure monitoring data recorded at the time of the releases. AEHA concluded: "Conservative evaluation of the available data using EPA risk assessment methodology and comparisons with available standards, ambient air data, and health effects information indicates that the measured concentrations in the test areas should not have been associated with any adverse health effects for residents in the test areas. The estimated excess cancer risks are much less than the risk levels generally considered acceptable by the EPA. These comparisons and evaluations indicate that the ZnCdS tests posed negligible health threats to residents of the test areas" (AEHA 1994, 1995a,b).
TASKS OF THE SUBCOMMITTEE
In July 1994, the Army asked the National Research Council to review the AEHA reports assessing the health risks for Corpus Christi, TX, and Minneapolis, MN (AEHA 1994), determine the reasonableness of the conclusions, and, if necessary, suggest recommendations for improving the assessments. In the fiscal year 1995 Department of Defense appropriations, Congress responded to growing public-health concerns by directing the
secretary of defense to request an in-depth independent study by the Research Council of the possible adverse health effects of human exposure to ZnCdS as a result of the Army's dispersion tests. Consequently, the Army asked that the Research Council study on ZnCdS already under way be expanded substantially to determine the health risks associated with exposure to ZnCdS in all exposed U.S. locations, hold public meetings in selected cities where ZnCdS tests were conducted, and review the environmental fate of ZnCdS.
The Research Council assigned the project to the Committee on Toxicology (COT) of the Board on Environmental Studies and Toxicology in the Commission on Life Sciences. COT convened the Subcommittee on Zinc Cadmium Sulfide, which prepared this report. The subcommittee members were chosen for their recognized expertise in toxicology, medicine, pathology, epidemiology, pharmacology, chemistry, environmental health, environmental fate, industrial hygiene, ecology, biostatistics and mathematical modeling, risk assessment, risk communication, and interpretation of technical information. The subcommittee was charged with the following tasks:
Determine the appropriateness of using cadmium-toxicity data as a surrogate for ZnCdS-toxicity data in the AEHA's risk-assessment reports.
Assess the transport and environmental fate (but not ecologic effects) of ZnCdS.
Assess the adequacy of the AEHA estimates of exposures to ZnCdS in Minneapolis, Corpus Christi, Fort Wayne, and other test areas.
Review the toxicokinetics of ZnCdS and its surrogate, cadmium.
Assess the toxicity of ZnCdS and cadmium (or cadmium compounds), including effects on sensitive human populations, toxicologic interactions of zinc and cadmium, and the toxicologic implications of the variable composition of ZnCdS.
Determine the utility and feasibility of conducting an epidemiologic study of the ZnCdS exposures in question.
Review the comments of the U.S. Environmental Protection Agency, Centers for Disease Control and Prevention, and Agency for Toxic Substances and Disease Registry on AEHA's risk-assessment reports on ZnCdS.
Identify research gaps in the available information and develop priorities for research.
The subcommittee's task was to produce three reports: (1) an interim report, which was published in September 1995 (NRC 1995) and contains the subcommittee's preliminary health risk assessment of ZnCdS exposures, (2) a comprehensive final technical report (the present report), which addresses all the 8 issues listed above, and (3) a nontechnical summary report to disseminate the findings to the general public, which is published separately (NRC 1997).
Although some tests involved simultaneous exposures to ZnCdS and biologic simulants, such as Serratia marcescens or Bacillus globigii , the subcommittee did not assess the implications of such coexposures, because that was beyond its charge and expertise. The subcommittee also did not address whether testing of the simulants without the knowledge of the American public was ethical or violated the public trust; this question is also important but is beyond the subcommittee's charge and expertise.
SOURCES OF DATA
The subcommittee held public meetings to gather information in selected cities in which dispersion tests were conducted. Three public meetings were held—in Minneapolis, Fort Wayne, and Corpus Christi. The public was informed about the meetings through advertisements in local newspapers and through the courtesy of local radio and television stations. A total of several hundred persons attended the meetings, and they were covered by television, radio, and newspapers. Information gathered and issues and concerns raised at the public meetings are presented and addressed in Chapter 2, which contains the details of the three public meetings.
The subcommittee reviewed toxicity data on ZnCdS, cadmium, cadmium compounds, and zinc. The ZnCdS data came from reports available in the open literature; reports from the Army's contractors for the ZnCdS tests; material-safety data sheets; and the U.S. Army. The subcommittee is aware that some of the exposure data from the Army's tests on ZnCdS
are missing. The Army was asked to supply the missing data, and it has informed the subcommittee that it is unable to find the missing data because the information being sought is 30-40 years old, and the data on the Army's dispersion tests were not cataloged. Although some exposure data from the Army's ZnCdS dispersion tests are missing, the subcommittee feels confident in the quality of the large amount of data that it reviewed and does not believe it likely that the additional missing data would alter its conclusions. These data provide information on exposures at various locations but not on exposures to individuals, which is important in epidemiologic studies.
The subcommittee reviewed only the unclassified data available on ZnCdS. The Army has assured the subcommittee in writing that all the relevant data on ZnCdS dispersion tests have been declassified and provided to the subcommittee (letter attached in Appendix C). According to the Army, the only information that was not declassified pertains to the LAC study, on which there is information regarding the altitude from which a very small quantity of a BW agent could be dropped and contaminate approximately 500,000 square miles of the country. The Army felt that declassification of this information could affect the national security of this country (Col. Robert Gum, U.S. Army Medical Research Institute of Chemical Defense, personal commun., 1995).
A vast amount of data on cadmium toxicity is available in the open literature; the subcommittee drew heavily on the detailed toxicity reviews conducted by the Agency for Toxic Substances and Disease Registry (ATSDR 1993), International Agency for Research on Cancer (IARC 1993), World Health Organization (IPCS 1992), and Occupational Safety and Health Administration (OSHA 1992).
The subcommittee reviewed the toxicity data on zinc and concluded that it would not be toxic at the low exposure levels associated with ZnCdS dispersion tests. The subcommittee also reviewed the possible interaction of zinc and cadmium (Appendix D). The toxicities of minor components of ZnCdS, such as copper (≈.005%) and silver (≈.005%) were also reviewed (Appendix D).
STRUCTURE OF THE REPORT
The subcommittee assesses the health risk associated with ZnCdS exposures in various U.S. locations by conducting an in-depth review of the toxicity and toxicokinetic data on ZnCdS and its most toxic component—cadmium—by estimating the maximal concentration of cadmium in each test location and by characterizing the risk associated with the estimated maximal cadmium exposures. The subcommittee considered total exposures to cadmium as a consequence of exposure to ZnCdS from all routes—inhalation and ingestion of food and water—in relation to known background exposures to cadmium. The effect of ZnCdS and cadmium on potentially susceptible groups in the human population was also considered. In addition, the subcommittee assessed the environmental fate of ZnCdS and determined the utility and feasibility of conducting an epidemiologic study of populations exposed to it.
Chapter 2 presents the information gathered from the public meetings. Chapter 3 reviews the toxicity and related data on ZnCdS, and Chapter 4 evaluates the toxicity, environmental fate, and epidemiology data of cadmium compounds. Chapter 5 evaluates the exposures to ZnCdS and cadmium, and Chapter 6 contains the subcommittee's risk assessments of ZnCdS for noncancer and cancer effects. Chapter 7 discusses the feasibility of conducting epidemiologic studies of ZnCdS-exposed persons. Chapter 8 contains the subcommittee's conclusions and recommendations. Appendix A reviews the historical background of the U.S. Biological Warfare Program. Appendix B summarizes the doses and concentrations of ZnCdS particles from the Army's dispersion tests. Appendix C contains correspondence with the U.S. Army. Appendix D discusses the interaction of zinc and cadmium and the toxicity of copper and silver. Appendix E provides information concerning public meetings. Appendix F reviews sampling and analytic methods for ZnCdS. Appendix G contains a review of the Army Environmental Hygiene Agency's risk-assessment reports on ZnCdS, and Appendix H reviews the comments of EPA, ATSDR, and CDC on the Army's risk-assessment reports. Appendix I discusses the exposure assessment for cadmium. The final section of the report—the glossary—provides brief descriptions of technical terms used in the report.