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Combined Exposures to Hydrogen Cyanide and Carbon Monoxide in Army Operations: Initial Report 7 Conclusions and Recommendations In requesting that this project be carried out, the major concern of the army is the health of personnel during certain military operations, particularly the firing of guns in tanks which can result in the generation of toxic gases. The most relevant of these are carbon monoxide (CO) and hydrogen cyanide (HCN). The questions being asked are whether the adverse effects of these chemicals are additive or synergistic in nature and whether an assessment of their combined risk can be calculated using the hazard quotient approach (HQ) with the equation: If so, this approach would be used to establish limits of exposure for these personnel; that would be important in the design and operation of the tanks. As noted above, the mechanisms by which CO and HCN exert their toxic effects are multiple, have been well studied as individual agents, and continue to be investigated. While their exact mechanisms and characteristics for absorption, distribution, metabolism and excretion may be different, nevertheless, it is not unreasonable to suspect that the effects of these two chemicals on oxygen delivery and utilization would have an additive effect. Based on the extensive review of the literature of studies in animals on this interaction, the committee concluded based on the weight of evidence that the effects of the two chemicals were additive. The committee recommends that the hazard quotient approach be utilized. However, one of the limitations in making this conclusion is that most of the studies were carried out in animals using high levels of cyanide, which were greater than 100 ppm or high levels of CO that were in the range of one to several thousand parts per million compared with low levels of interest with cyanide at less than 5 ppm or CO at less than 100 ppm and extreme end points, such as incapacitation or death. Thus there needs to be a caveat in the extrapolation of these results to low levels of exposure (less than 5 ppm for HCN and less than 100 ppm for CO) and more subtle effects such as decrements in performance of the tank crew. While a theoretical case could be made perhaps for a less than additive effect based on, for example, changes in respiration and gas uptake, the committee believes that it is prudent to expect that the additive effect of the combined exposure observed with high concentrations would occur if subjects were exposed to low concentrations (less than 4 ppm for HCN and concentrations of CO producing carboxyhemoglobin [COHb] levels of 10%). While there have been a number of reports on the interaction of cyanide and CO and the potential interaction has been well recognized in respect to fires, the human literature is not helpful in defining adverse blood levels of cyanide alone or in combination with CO. In most cases, either the exposures were very high and/or the measurements of exposure, particularly cyanide, were questionable. It is difficult to find studies which carefully correlated exposures, blood levels and adverse effects. Furthermore, available studies do not address subtle effects, such as decrements in performance, relevant to setting guidelines for human exposure. While guidelines for limiting exposure to CO and cyanide have
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Combined Exposures to Hydrogen Cyanide and Carbon Monoxide in Army Operations: Initial Report been published by governmental and professional groups, they have the same limited databases, especially for the interaction. As noted, since the actions of the two toxicants apparently are additive, the use of the hazard quotient approach proposed by the army is appropriate. The use of the Coburn-Foster-Kane (CFK) model for the prediction of COHb levels related to air concentrations appears to have a solid scientific basis. Since the spikes observed in air levels of CO within the tank during firing scenarios were of such short duration taking into account respiratory rate and tidal volume, the committee concluded that it was not overly concerned about them in comparison with longer, possibly increasing, COHb levels. However, because of conditions where ambient CO concentrations are changing rapidly, it is recommended that the use of CFK equation to calculate COHb levels needs to be verified with blood COHb measurements. It was also noted by the Army that their monitoring data from gun firing scenarios would suggest that cyanide levels would be expected to be below levels of concern most of the time. That, is they would normally not be expected to add substantially to the hazard quotient. An ancillary question was whether or not the blood level of cyanide, rather than air exposure, should be used in the hazard quotient calculation. The committee concluded that use of a blood level would be problematical based on the lack of good data to support a model such as the CFK model for CO. Furthermore, there is no simple method for determining cyanide levels in blood, and there are a number of technical difficulties in obtaining and handling blood samples. In addition, the rapid metabolism of cyanide makes correlation of air levels and blood levels difficult. Finally there are a host of confounding environmental factors which may influence cyanide levels. The committee, therefore, recommends that the Army continue to use the air level for cyanide rather then a blood level. 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, which makes extrapolation to the low-levels of exposure and more subtle toxicity end points of interest to the Army is difficult. Therefore, the Army should conduct neurological studies of sensory and motor performance at lower concentrations of HCN and CO. In conducting its review and evaluation, the committee provides the following additional recommendations for the army to consider. One is to search relevant military documents regarding exposure and biological monitoring that may not be in the open, published literature, especially with regard to cyanide levels. A second is that the Army should consider that, while the binary system is important, other potential exposures such as exposure to diesel combustion products may need to be considered with respect to health of the tank crew.