Toxic potency measurement

A second approach to the problem of toxic potency measurement has been to expose laboratory animals, usually rodents, to the smoke from the combustion of small samples of a burning material. Measurement of their response to the smoke leads to one of several biological endpoints, such as the LC50 (the concentration of smoke lethal to 50% of the test animals). In this approach, the animals respond to all the toxicants that are present in the smoke. It presumes that rodent mortality can be related to human mortality or, more simplistically, that the relative toxicity of the smokes will be similar in humans and rodents. However, since the relative contributions of the individual toxic chemicals in the smoke are not determined, a quantitative relationship between man and rodent is impossible using this approach. 

Thus, there remain a small number of discrete, highly important technical issues to be researched in the field of toxic potency measurement ... 

This discussion indicates that toxic potency measurements are a small portion of the overall toxicity picture. They may serve a useful purpose only in identifying those materials (or products) with a toxic potency outside that of the majority of other products. Such materials (or products) may well have to be looked at somewhat more closely. 

Babrauskas, V., Levin, B., Gann, R., Paabo, M., Harris, R., Peacock, R., and Yusa, S., Toxic Potency Measurements for Fire Hazard Analysis, Special Publication 827, National Institute of Standards and Technology Gaithersburg, MD, 1991. 

As these strategies are brought to fruition, there remains one related issue the determination of a smoke s potential harm per mass of material burned, i.e., the toxic potency of smoke. Accurate measurement of this key characteristic of fire smoke permits a more quantitative determination of the fire s toxic hazard which includes other factors as discussed below. Toxic potency assessment also tells us whether a small fire will produce smoke so toxic that only a small amount will kill. The presence of such "supertoxicants" has been a major topic of discussion within the fire community. 

All fire smoke is toxic. In the past two decades, a sizable research effort has resulted in the development of over twenty methods to measure the toxic potency of those fire smokes (6). Some methods have been based on determinations of specific chemical species alone. Values for the effect (e.g., lethality) of these chemicals on humans are obtained from (a) extrapolation from preexisting, lower concentration human exposure data or from (b) interpretation of autopsy data from accident and suicide victims. The uncertainty in these methods is large since ... 

The toxic potencies of many materials have been measured using a variety of the toxicity test methods. Comparison of toxic potency results between the various methods is, in most cases, meaningless. The frequent lack of agreement between methods is due to different methods of combustion, species of animals, and experimental apparatus (i.e., open or closed devices also referred to as dynamic or static systems). 

Knowing the impact of smoke toxic potency on escape from a fire is of sufficient importance that it has been the subject of research for over twenty years. As a result, we now have a realistic picture of proper contexts for the use of toxic potency data and a series of first-generation tools for measuring it. We also have a vision of the key technical issues to be resolved developing a proper small-scale fire simulator, relating rodent results to people, and validating the small-scale data. 

A large number of small-scale tests have been designed to measure the toxic potency of the smoke of materials. These tests differ in many respects the consequence of this is that the relative toxic potencies of smoke resulting from these various tests are different. The tests are not useful,... 

During the 1970 s and early 1980 s a large number of test methods were developed to measure the toxic potency of the smoke produced from burning materials. The ones most widely used are in refs. 29-32. These tests differ in several respects the conditions under which the material is burnt, the characteristics of the air flow (i.e. static or dynamic), the type of method used to evaluate smoke toxicity (i.e. analytical or bioassay), the animal model used for bioassay tests, and the end point determined. As a consequence of all these differences the tests result in a tremendous variation of ranking for the smoke of various materials. A case in point was made in a study of the toxic potency of 14 materials by two methods [33]. It showed (Table I) that the material ranked most toxic by one of the protocols used was ranked least toxic by the other protocol Although neither of these protocols is in common use in the late 1980 s, it illustrates some of the shortcomings associated with small scale toxic potency of smoke tests. 

In recent years there has been much controversy surrounding the impact of smoke toxicity following a fire. This has included discussions regarding means to measure toxic potency, by one of a variety of small-scale methods, and how to use these results to evaluate fire hazard. There has been, in particular, much speculation regarding the hazards due to certain plastics, typically poly(vinyl chloride) (PVC). 

Undoubtedly, fire hazard is partially associated with the toxicity of the smoke itself. The smoke of a variety of common materials, as measured e.g. by the NBS cup furnace toxicity test [10], has recently been compared with the intrinsic toxic potency of other poisons and of toxic gases, as well as with toxicity categories [11]. It has been shown that toxicity is a relatively minor factor because there is very little difference between the intrinsic toxic potency of the smoke of the majority of common materials, with very few exceptions. 

These considerations are included here because in the discussion that follows HC1 decay will be ignored, to facilitate the calculations. HC1 decay is also important when measuring PVC toxic potency, because the walls of exposure chambers are made of non-sorptive materials, where such decay is minimised. In this connection it is worth pointing out that the highest concentration of HCl found when fire fighters entered buildings actually on fire was ca. 280 ppm [25, 26]. 

If the biological effect of a chemical is related to its dose, there must be a measurable range between concentrations that produce no effect and those that produce the maximum effect. The observation of an effect, whether beneficial or harmful, is complicated by the fact that apparently homogeneous systems are, in fact, heterogeneous. Even an inbred species will exhibit marked differences among individuals in response to chemicals. An effect produced in one individual will not necessarily be repeated in another one. Therefore, any meaningful estimation of the toxic potency of a compound will involve statistical methods of evaluation. 

Figure 4.5 Acute lethality values of some commonly used nitriles. Nitrile toxic potency is measured in mice, and expressed as oral median lethal dose (LD50) in millimoles of the nitrile per kilogram body weight [7].

Roghair, C.J., J. Struijs, and D. de Zwart. 1997. Measurement of Toxic Potency in Freshwaters in the Netherlands. Part A. Methods. RIVM Report 607504 004. the Netherlands National Institute of Public Health and Environment. 

Usually in the context of environmental remediation, human potential hazard, or/and comparison of dioxin-like compounds, DLC, an estimation of the toxic potency of the whole sample is desired, rather than the concentrations of the sample s components. One such measure, the toxic equivalents, TEQ, is obtained from the analytical data by using Toxic Equivalency Factors, TEFs, relating the potency of DLC X to the potency of TCDD, taken as a reference toxicant (TEF = 1). In this TEF scheme, the toxicity of any PCDD or PCDF congener is related, using animal data, to the amount ofTCDD that would have equal toxicity (Table 3). 

EPA critically evaluated the quality and quantity of the blood and brain ChE data and determined that the female brain ChE inhibition was the most appropriate data for developing RPFs. The brain ChE data typically have tighter confidence limits compared to RBC ChE data and therefore eonfer less uncertainty on cumulative risk e.stimates. Brain ChE inhibition also represents a direct measure of the common mechanism of toxicity as opposed to using surrogate measures. The toxic potencies and PoDs for brain cholinesterase inhibition for these OPs are generally similar to the RBC data for the oral, inhalation, and dermal exposures (EPA, 2002c). For some OPs, female rats are more sensitive than male rats. 

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