Summary

The U.S. Army’s Health Hazard Assessment (HHA) Program is a Medical Department initiative that supports the Army acquisition process by evaluating potential health hazards during the design and development of materiel systems. Weapons emissions evaluated by the program include carbon monoxide (CO), hydrogen cyanide (HCN), oxides of nitrogen, sulfur dioxide, ammonia, and carbon dioxide. Typically, these chemicals are evaluated on an individual basis against their respective medical criteria that may include military-specific standards. However, additive or synergistic toxic effects among the chemicals must also be considered. Therefore, the Army is considering the simultaneous exposures of crew members in enclosed vehicles to CO and HCN generated from firing of conventional munitions from a 30-mm cannon.

Both CO and HCN are well known toxicants with established guidelines for safe levels of exposure. Adherence to these guidelines for either of these toxicants alone leads to engineering designs, administrative controls, and use of personal protective devices to ensure an acceptable working environment. However, safe levels of exposure to each of the toxicants may need to be lower if the combined effects of exposure are additive or more than additive. Hypothetically, the design requirements could be based upon the toxicologic mechanisms of CO and HCN being independent, additive, or synergistic. The three different scenarios would lead to differences in the resulting designs for ventilation systems, etc.

The potential for combined exposures results from firing of guns in enclosed (but ventilated) spaces in a military environment such as armored tanks. Because of concerns for the health effects of the personnel simultaneously exposed to HCN and CO, the U.S. Army’s Center for Health Promotion and Preventive Medicine prepared a report titled Assessment of Combined Health Effects of Hydrogen Cyanide and Carbon Monoxide at Low Levels for Military Occupational Exposures. That report provides guidance to assess combined exposures in HHAs of military systems.

The weight of available evidence indicates that the toxic effects of inhaled CO and HCN at lethal and incapacitating levels are additive. Whether similar additive effects hold true at lower concentrations and longer time periods that military personnel may experience, while also in the presence of other combustion gases, is not known. No relevant chronic or low-level exposure studies were found in the literature. In 1981, a military standard established the Army’s COHb limits of 5% for aviation crew members to protect against visual effects and 10% for all other military personnel. The exposure criterion for HCN is the current American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value (TLC) ceiling of 4.7 ppm on the basis of anoxia, central-nervous-system, irritation, lung, and thyroid effects.

In addition to singular or individual evaluations of CO and HCN, the following hazard quotient (HQ) approach using singular benchmarks was employed in the Army’s HHA report.



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Summary The U.S. Army’s Health Hazard Assessment (HHA) Program is a Medical Department initiative that supports the Army acquisition process by evaluating potential health hazards during the design and development of materiel systems. Weapons emissions evaluated by the program include carbon monoxide (CO), hydrogen cyanide (HCN), oxides of nitrogen, sulfur dioxide, ammonia, and carbon dioxide. Typically, these chemicals are evaluated on an individual basis against their respective medical criteria that may include military-specific standards. However, additive or synergistic toxic effects among the chemicals must also be considered. Therefore, the Army is considering the simultaneous exposures of crew members in enclosed vehicles to CO and HCN generated from firing of conventional munitions from a 30-mm cannon. Both CO and HCN are well known toxicants with established guidelines for safe levels of exposure. Adherence to these guidelines for either of these toxicants alone leads to engineering designs, administrative controls, and use of personal protective devices to ensure an acceptable working environment. However, safe levels of exposure to each of the toxicants may need to be lower if the combined effects of exposure are additive or more than additive. Hypothetically, the design requirements could be based upon the toxicologic mechanisms of CO and HCN being independent, additive, or synergistic. The three different scenarios would lead to differences in the resulting designs for ventilation systems, etc. The potential for combined exposures results from firing of guns in enclosed (but ventilated) spaces in a military environment such as armored tanks. Because of concerns for the health effects of the personnel simultaneously exposed to HCN and CO, the U.S. Army’s Center for Health Promotion and Preventive Medicine prepared a report titled Assessment of Combined Health Effects of Hydrogen Cyanide and Carbon Monoxide at Low Levels for Military Occupational Exposures. That report provides guidance to assess combined exposures in HHAs of military systems. The weight of available evidence indicates that the toxic effects of inhaled CO and HCN at lethal and incapacitating levels are additive. Whether similar additive effects hold true at lower concentrations and longer time periods that military personnel may experience, while also in the presence of other combustion gases, is not known. No relevant chronic or low-level exposure studies were found in the literature. In 1981, a military standard established the Army’s COHb limits of 5% for aviation crew members to protect against visual effects and 10% for all other military personnel. The exposure criterion for HCN is the current American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value (TLC) ceiling of 4.7 ppm on the basis of anoxia, central-nervous-system, irritation, lung, and thyroid effects. In addition to singular or individual evaluations of CO and HCN, the following hazard quotient (HQ) approach using singular benchmarks was employed in the Army’s HHA report. COHb% + 15-min avg. HCN (ppm) HQ. = 10% 4.7 ppm 1

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Combined Exposures to Hydrogen Cyanide and Carbon Monoxide in Army Operations It assumed the effects at low levels were additive. An HQ equal to or greater than 1.0 indicated an overexposure. The Army used the following criteria to evaluate the data involving combined exposures to CO and HCN: if both or either of the 10% COHb and 4.7 ppm HCN limits is exceeded, then the scenario fails and the HQ calculation is essentially not applicable. If COHb and HCN are within acceptable limits, then the HQ calculation is performed. In 2005, the Department of Defense requested that the National Research Council evaluate the Army’s proposed guidance for assessing the adverse effects resulting from combined exposures to low- levels of HCN and CO, and recommend exposure limit guidelines for combined exposures to these chemicals. In response, the National Research Council convened the Committee on Combined Exposures to Hydrogen Cyanide and Carbon Monoxide in Army Operations with oversight from the Committee on Toxicology to address the task assigned to it. The committee’s Statement of Task is as follows: An ad hoc committee under the oversight of the standing Committee on Toxicology (COT) will assess potential toxic effects from combined exposures to low-levels of HCN and CO. In its first report (i.e., this report), the committee will evaluate the Army's proposed guidance on assessing combined exposures. The ad hoc committee will specifically determine the following in its initial report: 1. Does the hazard presented from combined exposure to HCN and CO at low levels warrant their combined assessment or is the individual assessment of each chemical sufficiently protective? 2. If the combined exposure assessment of HCN and CO is warranted at low levels, is the hazard quotient approach, discussed in the technical context section, a reasonable method of assessment? Should it be modified or improved (i.e., use of a blood CN benchmark instead of the ACGIH TLV-C)? In its second report, to be completed next year, the committee will determine the following: 1. Is the approach discussed in the technical context section appropriate or an alternative assessment method should be developed and validated through either field or laboratory study? 2. What improvements are needed in the Army's proposed methodology for assessing these combined exposures? The committee will also provide recommendations that will yield more precise measurements of gases which might be useful in hazard assessment. 3. What exposure limit guidelines are appropriate for combined exposures to these chemicals? THE COMMITTEE’S MAJOR CONCLUSIONS AND RECOMMENDATIONS OF THE INITIAL REPORT After receiving a briefing from the Army and evaluating published literature on the adverse effects of CO and HCN, both individually and in combination, in animals and in humans, the committee arrived at the following overall conclusions and recommendations for its initial report. 2

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Summary Conclusions • Based on the mechanisms of action of toxicity of CO and HCN and the supporting literature, it is likely that the toxicities of these two chemicals are additive, and therefore, the hazard presented from combined exposures to these chemicals should be assessed as a mixture and not singularly or individually. • The use of the HQ approach proposed by the Army is reasonable in establishing exposure limits for personnel simultaneously exposed to CO and HCN. • CO is assessed as an individual chemical in HHAs using the Coburn-Forster-Kane (CFK) equation for predicting the percent of COHb in blood. The use of the CFK model for the prediction of COHb levels related to air concentrations of CO is justified. The CFK model has been validated; however it has not been tested in environments with dynamically changing air concentrations, such as in an armored vehicle. • The use of an air concentration for HCN in the HQ equation, as opposed to a blood level, is reasonable. Recommendations • The Army should conduct further neurological studies on sensory and motor performance at lower concentrations of HCN and CO because most studies on the combined toxicity of CO and HCN have been carried out at high concentrations and have focused on lethality and/or incapacitation; this makes it difficult to use those data to extrapolate to low-levels of exposures and more subtle toxicity end points of interest to the Army. The committee recommends that the Army assess the validity of the CFK model in the context of armored vehicles both using instantaneous measured data and various running averages. • While the toxicity of combined exposures to HCN and CO is important to understand, the Army should also consider concurrent exposures to other chemicals, e.g., other combustion gases, diesel exhaust, which may have additional effects on the tank crew. 3