Combined Exposures to Hydrogen Cyanide and Carbon Monoxide in Army Operations: Final Report (2008)

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Summary Military personnel in weaponized armored vehicles are exposed to combustion by-products gen- erated from propellants used to fire the vehicle’s guns. Personnel may also be exposed concurrently to other substances, such as diesel exhaust, present in the vehicle compartment, despite the use of mechani- cal ventilation. In response, the U.S. Army assessed possible additive or synergistic toxic effects from potentially harmful substances. Specific attention was given to the combined effects of simultaneous low- level exposures to carbon monoxide (CO) and hydrogen cyanide (HCN), because both gases produce similar adverse effects.1 Weapons emissions evaluated by the Health Hazard Assessment (HHA) Program of the Army’s Center for Health Promotion and Preventive Medicine (CHPPM) include CO, HCN, and other gases. These chemicals are typically evaluated on an individual basis against medical criteria, which may in- clude military-specific standards. However, additive or synergistic toxic effects among the chemicals were also considered. Because it found an increased potential for adverse effects on personnel simultane- ously exposed to HCN and CO, CHPPM prepared a report titled Assessment of Combined Health Effects of Hydrogen Cyanide and Carbon Monoxide at Low Levels for Military Occupational Exposures. The report provides guidance to assess combined exposures in HHAs of military systems. The Army found that the weight of available evidence indicates that the adverse effects of CO and HCN at lethal and incapacitating concentrations inhaled over periods of about 30 minutes or less are additive. However, for exposures occurring at lower and varying concentrations over periods of several weeks to perhaps several years, it is not known whether military personnel, while also in the presence of other combustion gases, may experience similar additive effects. No relevant chronic or low-level expo- sure studies were found in the literature. In 1981, a military standard established the Army’s carboxyhe- moglobin (COHb) limits of 5% for aviation crew members to protect against adverse visual effects and 10% for all other military personnel. The Army uses the Coburn-Forster-Kane (CFK) equation to estimate the percentage of COHb in the blood of military personnel in armored vehicles based on measurements of CO in the air inside of the vehicles. The exposure criterion for HCN is the current American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value (TLV) ceiling of 4.7 parts per million (ppm) on the basis of anoxia, central-nervous-system irritation, and lung and thyroid effects. In addition to single evaluations of CO and HCN, the following hazard quotient (HQ) approach using single benchmarks was used in the Army’s HHA report. COHb% 15 - min avg. HCN (ppm) + = HQ. 10% 4.7 ppm The HHA assumed the effects at low levels were additive. An HQ equal to or greater than 1.0 indicated an overexposure. The U.S. Department of Defense (DOD) requested that the National Research Council (NRC) as- sess the Army’s proposed guidance for assessing the adverse effects resulting from the combined simulta- 1 Both compounds can induce hypoxia in human tissue, and the primary targets are the brain and heart. 3 

Combined Exposures to HCN and CO in Army Operations: Final Report neous exposures to low levels of CO and HCN in weaponized armored vehicles. The NRC was asked to prepare two reports. In response, it convened the Committee on Combined Exposures to Hydrogen Cya- nide and Carbon Monoxide in Army Operations under the oversight of the Committee on Toxicology to assess the Army’s proposed guidance. THE COMMITTEE’S INITIAL REPORT In its first report, Combined Exposures to Hydrogen Cyanide and Carbon Monoxide in Army Op- erations: Initial Report, completed in 2008, the committee evaluated whether the adverse effects from combined exposure to HCN and CO at low levels warrant their combined assessment or whether the indi- vidual assessment of each chemical is sufficiently protective. If the combined exposure assessment of HCN and CO at low levels is warranted, the committee would determine whether the HQ approach is a reasonable method of assessment and whether it should be modified or improved. The committee concluded the following in its initial report: • The toxic effects of CO and HCN are probably additive, and, therefore, the effects from com- bined exposures to these chemicals should be assessed as a mixture and not individually. • Until further findings suggest otherwise, the use of the HQ approach proposed by the Army is reasonable in establishing exposure limits for personnel simultaneously exposed to CO and HCN. • The use of the CFK equation for the prediction of COHb levels related to air concentrations of CO is appropriate. • The CFK equation has not been adequately evaluated in environments with dynamically changing air concentrations, such as in a weaponized armored vehicle. • The use of an air concentration for HCN in the HQ equation, as opposed to a blood concentra- tion, is reasonable. The committee recommended that the Army assess the validity of the CFK equation in the con- text of weaponized armored vehicles using instantaneous measured data and various running averages. It also recommended that the Army conduct further neurologic 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 to assess more-subtle ef- fects of interest to the Army. Finally, the committee recommended that the Army consider concurrent ex- posures to other chemicals (for example, other combustion products and diesel exhaust), which may have additional effects on the armored-vehicle crew. THE COMMITTEE’S FINAL REPORT For this, its second report, the committee was asked to address whether the approach discussed in the technical context section of the Army’s proposed guidance is appropriate or whether an alternative assessment method should be developed and validated through either field or laboratory study. The com- mittee was also asked to provide recommendations for making improvements in the Army's proposed method for assessing these combined exposures. The committee was asked to recommend methods for obtaining more precise measurements of gases that might be useful in exposure assessment and to rec- ommend approaches for developing exposure limit guidelines for combined exposures to these chemicals. As stated in its first report, the committee concludes that consideration should be given to the po- tential interaction between HCN and CO that could affect crew performance and health. This conclusion is based primarily on the possible additivity of the effects of both chemicals on attentiveness and reaction 4 

Summary times. However, there is not enough evidence available at this time for the committee to make a conclu- sive assessment. In addition, the assessment is complicated by the presence of other combustion products released both from weapons firing and from use of vehicle fuel, and the committee recognizes that the potential toxic effects of those other products, especially in combination with CO and HCN, may also be important. Hence, although the committee still considers the HQ approach to risk assessment valid, and it reiterates its recommendation that the approach be used until further findings suggest otherwise, the committee concludes that additional information is needed to better understand possible synergisms be- tween CO, HCN, and other combustion products that could help refine this risk assessment. From a practical standpoint, to deal with the problem of possible synergy with respect to decre- ments in performance, it is necessary to understand how low concentrations of CO and HCN would act individually. This understanding will require additional information from studies specifically designed to examine such effects as attentiveness and reaction times. The information could then be used as a frame- work for follow-up studies on combinations of the two agents to determine whether there are interactions involving any of those effects. The exposure information provided to the committee by CHPPM focused mainly on CO. As noted in the committee’s initial report, the Army reported that exposures to HCN appear to be low most of the time, indicating that HCN may not contribute substantially to the HQ calculation for HCN and CO. As a result, the committee focused much of its consideration on CO with the understanding that actual exposures involve a multi-chemical mixture. Major Conclusions and Recommendations Portable Multi-Agent Monitors To determine whether the air quality inside armored-vehicle cabins can meet exposure guidelines under deployment conditions, the Army test fires the vehicles’ weapons and measures the concentrations of potentially harmful gases resulting under various operational scenarios. Samples are collected by using an innovative autosampling device consisting of long probes that draw a sample from infantry equipment into a nearby building for rapid analysis using spectrophotometry. As an alternative to the current use of fixed gas-monitoring instruments, portable gas monitoring instruments convey numerous advantages, in- cluding availability of real-time results and lower cost. Portable instruments are specifically available for measuring CO and HCN and are routinely used for measuring these chemicals in confined spaces. The direct-reading instruments can provide data transfer to a laptop computer, which would calculate potential COHb concentrations as well as an HQ index. The results of the direct-reading instruments would need to be verified periodically to determine whether the results were reasonably accurate and free of interfer- ences. The instruments would also need to be carefully assessed in terms of sensitivity. Assessing the Validity of the CFK Equation The committee concluded that, although use of the CFK equation is appropriate in the context of weaponized armored vehicles, it has not been adequately evaluated in environments with dynamically changing CO concentrations. The committee recommends that the Army conduct experiments on human subjects to address the effects of rapid changes in inspired CO concentration at a constant rate of ventila- tion; rapid changes in ventilation at a constant inspired CO concentration; and simultaneous increases in inspired CO concentration and ventilation on CO uptake, venous blood COHb, and COHb predicted by the CFK equation. These experiments will assess the validity of the CFK equation at low or spiking levels of CO or under conditions of rapid changes in human ventilation. 5 

Combined Exposures to HCN and CO in Army Operations: Final Report Possible Human Performance Degradation Resulting from CO Exposure In view of the lack of sufficient neuropsychological data and the inconsistencies in existing data, the committee recommends that the Army consider controlled experiments on human subjects using sce- narios and concentrations of CO relevant to combat conditions. The experiments could be done best with vehicle simulators in an atmospheric chamber (or less desirably with face-delivery systems) where sce- narios, CO concentrations, temperature, and humidity could be individually controlled. Such experiments should be designed to seek a dose-response relationship between CO and COHb so that levels of blood COHb are less than 10%. The experiments should examine neuropsychological end points, such as visual and reaction-time decrements, relevant to real-life scenarios in armored vehicles. Alternatively, experiments could be done in an actual vehicle with standardized measures of per- formance under battlefield conditions. Such experiments, however, are unlikely to give definitive results because of multiple uncontrollable variables, such as heat, workload, and stress. Possible Human Performance Degradation Resulting from Combined Exposures to CO and HCN As more data become available on the actual combined exposure concentrations of CO and HCN and the durations of such exposures, the Army should consider the possibility that exposures to other chemicals, including ammonia, particulate matter, and components of diesel exhaust, might affect the in- teraction of CO and HCN. It should arrange for review of the information by an independent body to as- sist in setting priorities on such interactions, including those that may be synergistic. Other Possible Deleterious Effects from CO and HCN Exposures Both CO and HCN are known to affect respiratory rates, and the presence of these agents could result in an increased uptake of CO and other toxic gases. The data on such complex mixtures are insuffi- cient to ascertain whether any such effects are functionally relevant to battle conditions. The Army should consider close and systematic surveillance of vehicle crews to identify any exacerbation of conditions affecting pulmonary efficiency (for example, asthma) or any increased risk of sudden death, myocardial infarction, or other significant medical problems. Seeking Advice from Additional Perspectives The Army performs an important role in ensuring that the health of personnel in armored vehicles is not compromised by co-exposures to CO and HCN during weapons firing. CHPPM’s activity related to the development of new models for armored vehicles and the use of test-firing scenarios to mimic possi- ble crew exposures to CO, HCN, and other gases could benefit substantially from greater communication with and feedback from groups involved with personnel training and field deployment. Such groups in- clude the Army’s Human Factors Engineering Program, instructors associated with training armored- vehicle crews in the field, crew members themselves, and health personnel involved with those crews dur- ing actual deployment. These groups could serve as valuable resources regarding the signs and symptoms associated with actual experiences in the different uses of these vehicles and under varying ventilation conditions. 6 

Summary Human Subjects Research The committee’s recommendations given in this report include experiments that would expose humans to CO concentrations that are within the range of typical conditions encountered by military per- sonnel when firing weapons from inside armored vehicles. It is important to note that these studies in- volving research on human subjects must comply with federal and other applicable regulations for the protection of human subjects of research. Protocols for research involving human subjects should receive approval by a certified Institutional Review Board. 7