Gordon E. Hartzell

Modeling of Toxicological Effects of Fire Gases: Ii. Mathematical Modeling of Intoxication of Rats By Carbon Monoxide and Hydrogen Cyanide

Research in combustion toxicology over the past few years has led to a reason able understanding and even quantification of some of the effects of fire effluent toxicants and, with the availability of a modest amount of both non-human primate and human exposure data, the combustion toxicologist is gaining increasing capability to assess and predict the toxicological effects of smoke inhalation.

Effects of Combustion Gases on Escape Performance of the Baboon and the Rat

In postcrash aircraft fires, only a few minutes are often available for egress. To assess the potential of selected combustion gases (CO, acrolein and HCl) to impair human escape, a signalled avoidance task was developed for use with the juvenile African Savannah baboon. After a 5-minute exposure, the animal was required to select and depress the correct lever to open an escape door and then to exit into the adjacent compartment of a shuttlebox. With CO, the EC50 for escape failure was 6850 ppm. Acrolein (12 to 2780 ppm) neither prevented escape nor affected escape times, despite irritant effects at all concentrations. Similar results were obtained with HCI (190 to 17,200 ppm) in that, despite severe irritant effects, all animals successfully performed the escape task. With a comparable shuttlebox and escape paradigm for rats, the EC50 of CO was 6780 ppm. Five-minute exposures to HCI (11,800 to 76,730 ppm) did not prevent escape but severe post-exposure respiratory effects and lethality occurred at 15,000 ppm and higher. In both species, escape time was not affected by HCI but a concentration-related increase in intertrial responses was evident. The data suggest that laboratory test methods for measurement of incapacitation of rodents may be useful in evaluating potential effects of atmospheres containing CO or irritant gases on human escape capability.

Modeling of Toxicological Effects of Fire Gases: I. Incapacitating Effects of Narcotic Fire Gases

Common fire gas toxicants fall into two major classes, narcosis-producing agents and irritants. It is desirable to model, mathematically, the effects of these common toxicants on humans exposed in a fire, and therefore, obviate the use of large numbers of laboratory animals in smoke toxicity testing. From a review of methodologies for assessment of the incapacitating effects of the nar cotic fire gases, it appears that rats are sensitive to approximately the same range of accumulated doses as may be deemed potentially hazardous to human subjects. This paper introduces an approach as a first approximation to the modeling of the incapacitating effects of the narcotic toxicants based on correla tion of observed effects with accumulated doses to which subjects are exposed.

Modeling of Toxicological Effects of Fire Gases: V. Mathematical Modeling of Intoxication of Rats By Combined Carbon Monoxide and Hydrogen Cyanide Atmospheres:

Mathematical modeling methods for the intoxication of rats by carbon mon oxide and hydrogen cyanide are extended to accommodate combined at mospheres of these fire gas toxicants. Predictions using the Fractional Effective Dose model for both incapacitation and lethality show no significant differences from animal bioassay data. Use of the model is suggested as a potential substitute for live animal testing for the toxicity of smoke produced from burning materials. The model is further shown to have potential utility in the assessment of toxic hazard tenability limits using analytical data from full-scale fires.

Modeling of Toxicological Effects of Fire Gases: Iii. Quantification of Post-Exposure Lethality of Rats From Exposure To HCl Atmospheres

This paper, the third in a series of publications on the modeling of tox icological effects of fire gases, addresses the quantification of post-exposure lethality of rats from exposure to hydrogen chloride atmospheres. Experimental L(Ct)50 values for HCl varied from about 80,000 ppm-min (5-minute exposure to 16,000 ppm) to about 170,000 ppm-min (60-minute exposure to 2800 ppm). Rele vant data involving non-human primate exposures are cited, which suggest the comparability of the rat and the primate for the purpose of assessing lethal doses of HCl.

Toxic products from fires.

The role of toxic combustion products in causing fire deaths has received considerable public attention in recent years. This paper outlines critical aspects of the problem, including the identification of common combustion products, the toxicological effects of these products and the dependence of their formation on the combustion process itself. The significance of escape as the key to survival in a fire is particularly emphasized. This paper then focuses on the development of test methods for assessment of toxic hazards produced by burning materials, with the objective being to enable decisions to be made as to whether the use of one material, as opposed to another, would result in any significant difference in hazard to life safety in a fire. It is argued that smoke toxicity test methods which determine only lethal toxicological potency under “worst case” conditions do not satisfactorily address the critical issue of relative hazard, including time-to-escape and tenability limits resulting from the fi...

Modeling of Toxicological Effects of Fire Gases: VI. Further Studies on the Toxicity of Smoke Containing Hydrogen Chloride

Studies of rodent lethality due to exposure to HCl, as well as to mixtures of HCl and CO, have shown different apparent toxicological effects at low and at high concentrations of HCl. At low concentrations of HCl, sensory irritation causes a decrease in respiratory minute volume, with somewhat slower loading of CO and a delay in incapacitation. This effect is observable only at low con centrations of CO. At much higher HCl concentrations, pulmonary irritant ef fects are observed leading to postexposure lethality. An empirical analysis of the data for mixtures of HCl and CO suggests that exposure doses leading to lethality may be additive. The lethal toxic potency (LC50) of PVC smoke may be largely, but not entirely, accounted for by the HCl produced. However, PVC smoke exhibits a greater in cidence of early postexposure deaths. The early deaths, which may be partially attributable to a combined effect of CO and HCl, may also be linked to the pattern of respiratory penetration by the smoke. There is evidence that com ponents other than HCl are present which cause PVC smoke to be more irri tating than HCl alone.

Prediction of the Toxic Effects of Fire Effluents

A major thrust in the assessment of the toxicity of fire effluents has been in the development of mathematical models for predicting toxic ef fects from appropriate data on the composition of the fire gases. The objectives of these efforts are two-fold. Assessment of smoke toxicity from analytical data could obviate much of the use of live animals in conventional bioassay method ology. Furthermore, providing that both qualitative and quantitative dif ferences in toxicological effects between laboratory animals and man are understood, such modeling methodology could also be used for estimating the time to development of a toxic hazard in either real or simulated fire scenarios. This paper presents a state-of-the-art review of the predictive modeling of tox icological effects from exposure to fire effluent atmospheres. Also included are compilations of data for individual fire gases which may be used as input for such modeling.

Toxicity and the smoke problem

Abstract The production and toxicological effects of selected, major fire gases are reviewed. These gases include carbon monoxide, hydrogen cyanide, carbon dioxide, irritants and oxygen depletion, among others. The measurement of the toxicity of smoke is discussed relative to the parameters which need to be measured, in addition to some selected, existing test methods. These test methods are reviewed relative to their relevance to “real” fires, utility and appropriateness as standard tests.

Modeling of Toxicological Effects of Fire Gases: VII. Studies on Evaluation of Animal Models in Combustion Toxicology

This study evaluated the potential use of the guinea pig as an animal model in conducting combustion toxicology experiments in which lethality is the end point. The guinea pig was found to be approximately three times as sensitive as the rat upon exposure to hydrogen chloride, presumably due to its tendency for bronchoconstriction. Compared to the rat, the guinea pig was relatively in sensitive to carbon monoxide. Lethal effects of mixtures of carbon monoxide and hydrogen chloride showed additivity only at relatively high concentrations of carbon monoxide. The lethal toxic potency of hydrogen cyanide was about the same for both the rat and the guinea pig. Based on comparisons of available toxicity data for humans and nonhuman primates, it was concluded that the rat is the better model when lethality studies are used. However, it is uncertain which animal model would be better when sublethal exposures, particularly to irritants, are considered.