Kuwahara (1981) exposed rats to various combinations of CO and HCN concentrations and recorded the C × T values when animal deaths occurred; the results also led these authors to conclude that the combined effects were additive.
Several studies were carried out by the Civil Aerospace Medical Institute (CAMI) of the Federal Aviation Administration (Oklahoma City, OK); Sanders et al. (1994) and Chaturvedi et al. (1995) reported that the Ti for combined CO + HCN exposure in rodents was shortened compared with the Ti for individual gas exposures; these observations led the authors to conclude that the combined effects were additive. The results of an earlier study conducted at CAMI led Smith et al. (1974) to come to the same conclusion.
Higgins et al. (1971) observed no additive toxicity in animals exposed to CO followed by HCN. However, additive lethal effects might not have been detected because of the great variation in the data points; the large confidence limits may have prevented detection of the combined biological effects of CO + HCN.
Moore’s group concluded that the combined lethal effects in CO-exposed mice given lethal doses of cyanide salt by intraperitoneal injection were synergistic (Norris et al. 1986). However, the fact that the two compounds were given by different routes, resulting in different toxicokinetics, coupled with the fact that the data were not rigidly analyzed. A similar study by Moore’s group examining biochemical variables in blood showed that some results were additive and others were synergistic (Moore et al. 1991). Pitt et al. (1979) studied effects of CO and cyanide on cerebral blood flow (CBF) and oxygen consumption in anesthetized and CO-exposed dogs, to which cyanide was given by slow intravenous infusion. The exposure concentrations were comparable to those that produce physical incapacitation. These authors concluded that the combined effects of co-exposure on CBF and cerebral conductance were additive.
The weight of evidence on combined exposures to CO and HCN supports the conclusion that the effects of these toxic gases are additive. However, the exposure concentrations that were used to investigate the combined effects were high in efforts to observe lethality or physical incapacitation. As pointed out above, the U.S. Army is concerned about the potential for the combined effects of exposures to low concentrations of these gases to produce performance decrements. In assessing the toxicity of these two compounds, it is prudent to expect that the additive effects of combined exposure observed with high concentrations would occur in subjects exposed to low concentrations. The hazard quotient or hazard index should be used for calculating the risk of the CO+HCN combined exposures.
where [CO]exp and [HCN]exp are exposure concentrations, and [CO]al and [HCN]al are allowable concentrations.
For the blood, COHb% and the 15-min average [HCN] are the variables measured and 10% COHb and 4.7 ppm HCN are the Army’s current allowable values, and the equation becomes
The appropriateness of the Army’s current level of 10% for CoHb and 4.7 ppm for HCN will be evaluated in the committee’s final report, which is likely to be finalized in September 2008.