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Introduction

The U.S. Army’s Center for Health Promotion and Preventive Medicine (CHPPM) evaluates health hazards of materiel systems and considers that information in the design and development of materiel systems. CHPPM evaluates weapons emissions, including carbon monoxide (CO), hydrogen cyanide (HCN), oxides of nitrogen (NOX), sulfur dioxide (SO2), ammonia (NH3), and carbon dioxide (CO2). Generally, these emission gases are evaluated on an individual basis. CHPPM also considers additive or synergistic toxic effects among the chemicals. The Army is specifically concerned about the combined exposures to low-levels of CO and HCN of crew members in an enclosed armored vehicles from the firing of 30 mm cannons.

The literature (Levin et al. 1987; Levin et al. 1988; Chaturvedi et al. 1995) indicates that the toxic effects of inhaled CO and HCN are additive at lethal and incapacitating levels. Whether similar additive effects hold true at the lower concentrations and for longer time periods (lasting from several weeks to several years in worst-case scenarios) 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. CO is assessed as an individual chemical in HHAs using the Coburn-Forster-Kane (CFK) equation (Smith et al. 1996) for predicting the percent of carboxyhemoglobin (COHb) in blood. A 1981 military standard (DOD 1981) established the U.S. Army’s COHb limits of 5% for aviation crew members to protect against visual effects and 10% for other effects. This level was considered to be a safe level for healthy young people and had previously been used by the American Conference of Governmental Industrial Hygienists (ACGIH) (Smith et al. 1996; DOD 1972). Adverse motor neuron effects such as decreased coordination, tracking, and driving ability, were not present when COHb was below 10% of hemoglobin (ACGIH 2002). The exposure criterion for HCN is the current ACGIH Threshold Limit Value (TLV) ceiling of 4.7 ppm to minimize the potential for headache; nausea; nasal, throat, and pulmonary irritation; and enlargement of the thyroid gland, which can result from low concentration exposure (ACGIH 2001).

The following hazard quotient (HQ) approach using the singular benchmarks was employed, which assumed the effects at low levels were additive. An HQ equal or greater than 1.0 indicated an overexposure.

When evaluating an actual test scenario using the stream of test data, the COHb level was calculated at the end of each data interval (3 or 5 seconds) using the instantaneous CO level and the COHb concentration from the end of the previous interval. The 15-minute HCN average was a running average calculated at the end of each data interval.

The 15-minute HCN average concentration was used because HCN exposures were observed to be transient and to quickly clear after a round is fired. CO concentrations exhibit a spike when a round is fired and also quickly decline but will begin to accumulate in the blood of exposed subjects after several rounds.



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1 Introduction The U.S. Army’s Center for Health Promotion and Preventive Medicine (CHPPM) evaluates health hazards of materiel systems and considers that information in the design and development of materiel systems. CHPPM evaluates weapons emissions, including carbon monoxide (CO), hydrogen cyanide (HCN), oxides of nitrogen (NOX), sulfur dioxide (SO2), ammonia (NH3), and carbon dioxide (CO2). Generally, these emission gases are evaluated on an individual basis. CHPPM also considers additive or synergistic toxic effects among the chemicals. The Army is specifically concerned about the combined exposures to low-levels of CO and HCN of crew members in an enclosed armored vehicles from the firing of 30 mm cannons. The literature (Levin et al. 1987; Levin et al. 1988; Chaturvedi et al. 1995) indicates that the toxic effects of inhaled CO and HCN are additive at lethal and incapacitating levels. Whether similar additive effects hold true at the lower concentrations and for longer time periods (lasting from several weeks to several years in worst-case scenarios) 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. CO is assessed as an individual chemical in HHAs using the Coburn-Forster-Kane (CFK) equation (Smith et al. 1996) for predicting the percent of carboxyhemoglobin (COHb) in blood. A 1981 military standard (DOD 1981) established the U.S. Army’s COHb limits of 5% for aviation crew members to protect against visual effects and 10% for other effects. This level was considered to be a safe level for healthy young people and had previously been used by the American Conference of Governmental Industrial Hygienists (ACGIH) (Smith et al. 1996; DOD 1972). Adverse motor neuron effects such as decreased coordination, tracking, and driving ability, were not present when COHb was below 10% of hemoglobin (ACGIH 2002). The exposure criterion for HCN is the current ACGIH Threshold Limit Value (TLV) ceiling of 4.7 ppm to minimize the potential for headache; nausea; nasal, throat, and pulmonary irritation; and enlargement of the thyroid gland, which can result from low concentration exposure (ACGIH 2001). The following hazard quotient (HQ) approach using the singular benchmarks was employed, which assumed the effects at low levels were additive. An HQ equal or greater than 1.0 indicated an overexposure. COHb% + 15-min avg. HCN (ppm) = HQ. 10% 4.7 ppm When evaluating an actual test scenario using the stream of test data, the COHb level was calculated at the end of each data interval (3 or 5 seconds) using the instantaneous CO level and the COHb concentration from the end of the previous interval. The 15-minute HCN average was a running average calculated at the end of each data interval. The 15-minute HCN average concentration was used because HCN exposures were observed to be transient and to quickly clear after a round is fired. CO concentrations exhibit a spike when a round is fired and also quickly decline but will begin to accumulate in the blood of exposed subjects after several rounds. 4

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Introduction In addition to evaluating test data, the Army also provides predictions for proposed training and operational scenarios. The predictions are used for adjusting the proposed training and operational scenarios. The predictions are used for adjusting the proposed firing rates and patterns to keep weapons emissions exposure below the desired levels or verifying the need for use of personnel protective equipment. The predictions are based on the worst-case CO exposure levels per round (expressed in ppm-minutes) from the proposed hatch position/ventilation configuration. The build-up and decay of COHb is calculated over the course of the scenario. The HQ is then calculated with the highest estimated COHb value and highest value of the 15-minute running HCN average from the relevant scenario. In summary, the Army used three criteria to evaluate the data. If one or both 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 as the third criterion. The method employed allowed the HQ results to be consistent with the singular results. Although the Army assumes a linear relation between biological effects and COHb and HCN concentrations that may not be true, it was successful in providing an additional degree of protection above the singular benchmarks. In 2005, the Department of Defense requested that the National Research Council assess the Army’s proposed guidance for assessing the adverse effects resulting from the combined simultaneous exposures to low-levels of CO and HCN. The potential for combined exposures results from routine firing of guns in enclosed but ventilated spaces in the military environment such as armored tanks. In response, the National Research Council convened the Committee on Combined Exposures to Hydrogen Cyanide and Carbon Monoxide in Army Operations under the oversight of the Committee on Toxicology to assess the Army’s proposed guidance. Both CO and HCN are well known intoxicants with established guidelines for safe levels of exposure. Adherence to these guidelines for either of these intoxicants alone would lead to engineering designs, administrative controls, and use of personal protective devices. These controls would ensure an acceptable working environment. Safe levels of exposure to each of the intoxicants may be lower if the combined effects of exposure are additive to more than additive. Hypothetically the design requirements could be predicated based upon the toxicological mechanisms of CO and HCN being independent, additive, or synergistic. The three different scenarios would lead to variation in the resulting designs for ventilation systems, etc. The committee’s Statement of Task is as follows: A committee of the National Academies’ Committee on Toxicology will assess potential toxic effects from combined exposures to low-levels of CO and HCN and evaluate the Army’s proposed guidance on assessing combined exposures in Health Hazard Assessments (HHAs) of military systems. The committee will specifically determine the following: • 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 of health? • If the combined exposure assessment of HCN and CO is warranted at low levels, is the HQ 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)? • 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? 5

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Combined Exposures to Hydrogen Cyanide and Carbon Monoxide in Army Operations • The committee will also provide recommendations for making improvements 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. THE COMMITTEE’S FIRST REPORT The committee divided its work into two reports. In the first report due by September 2007, the committee considers whether the hazards presented from combined exposures at low levels warrant a combined assessment. The committee then considers whether the HQ approach is a reasonable approach to assessment of the combined exposures. The committee approached its task by reviewing the toxicity data on CO and HCN singularly and in combination. The committee also heard presentations from representatives of academe, EPA, and ATSDR. The committee relied primarily on published peer reviewed data. THE COMMITTEE’S SECOND REPORT In the second report, 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? 6