Toxic potency

As a class of compounds, the two main toxicity concerns for nitriles are acute lethality and osteolathyrsm. A comprehensive review of the toxicity of nitriles, including detailed discussion of biochemical mechanisms of toxicity and stmcture-activity relationships, is available (12). Nitriles vary broadly in their abiUty to cause acute lethaUty and subde differences in stmcture can greatly affect toxic potency. The biochemical basis of their acute toxicity is related to their metaboHsm in the body. Following exposure and absorption, nitriles are metabolized by cytochrome p450 enzymes in the Hver. The metaboHsm involves initial hydrogen abstraction resulting in the formation of a carbon radical, followed by hydroxylation of the carbon radical. MetaboHsm at the carbon atom adjacent (alpha) to the cyano group would yield a cyanohydrin metaboHte, which decomposes readily in the body to produce cyanide. Hydroxylation at other carbon positions in the nitrile does not result in cyanide release. 

Animals which are fed extensively can encounter a vast array of compounds of varying medicinal and toxic potency and susceptibilities to degradation or detoxihcation a number of texts can be consiilted. ... 

In rat liver slices, evidence also supports the roles of QMs in mediating the toxicity of a series of 4-methylphenols.24 The potency correlates with rates of QM formation in the order 2-bromo-4-methylphenol > 4-methylphenol = DMP > TMP > 2-methoxy-4-methylphenol. None of these compounds contain two bulky ortho substituents, so as discussed earlier the corresponding QMs are expected to be highly reactive. The authors suggested that differences in the reactivities of these QMs determine their relative toxic potencies as electron-donating substituents on the ring stabilize the QM and thereby reduce its toxicity (e.g., 2-methoxy-4-methylphenol is less toxic than DMP) and conversely, electron-withdrawing substituents destabilize QMs and enhance toxicity (e.g., 2-bromo-4-methylphenol is more potent than DMP). 

Mizutani, T. Ishida, I. Yamamoto, K. Tajima, K. Pulmonary toxicity of butylated hydroxytoluene and related alkylphenols structural requirements for toxic potency in mice. Toxicol. Appl. Pharmacol. 1982, 62, 273-281. 

Mizutani, T. Satoh, K. Nomura, H. Hepatotoxicity of eugenol and related compounds in mice depleted of glutathione structural requirements for toxic potency. Res. Commun. Chem. Pathol. Pharmacol. 1991, 73, 87-95. 

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 ... 

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. 

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). 

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

LEVIN GANN Toxic Potency of Fire Smoke... 

The calculation of the fire s outcome in the third step includes the distribution of heat, smoke, and toxic gases throughout the building of concern. It allows the introduction of people into that building and monitors their movement in response to the fire. They may escape safely or fail to escape due to heat or the inhalation of toxic smoke. The benefits of changing some component of the defined fire problem is observed in the change in the number of deaths predicted, rather than by direct comparison of the toxic potencies of the different smokes. This mirrors the complexity of real-life fires. 

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. 

Table I. Lethal Toxic Potencies of Hydrogen Chloride (LCM Values in ppm)...

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,... 

Fire safety can be improved by decreasing fire hazard, but is unlikely to be affected by small changes in toxic potency of smoke, since the toxic potency of most materials is very similar. 

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. 

The toxic potency of the smoke of most common materials (natural or synthetic) is very similar (see Figure 1). In fact, the difference between the toxic potency of almost all combustible materials is less than one order of magnitude. Therefore, the relative rankings of materials are heavily dependent on the exact composition of the smoke being tested, i.e. on the combustion procedure being used. 

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. 

Categories of toxicity are classically distinguished by differences in orders of magnitude. The toxic potency of the smoke of most common materials is very similar, and thus, the toxicity of smoke is usually governed simply by the amount of material burnt per unit time. 

Toxic potency of smoke data can be used as one of the inputs in fire hazard assessment. In particular, they can be combined with average mass loss rates and times to ignition to obtain a quick estimate of toxic fire hazard. 

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). 

Other papers in this volume address the importance of a variety of fire properties on fire hazard, in particular the relative importance (or lack of it) of toxic potency of smoke (e.g. Ref. [1]). 

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. 

The relevance of all this to the present paper is that the toxic potency of PVC smoke or of HC1 are fairly similar to those of other smoke or of carbon monoxide (CO) respectively. 

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]. 

Table III presents the results of calculating the "time to lethal concentration" for each one of the PVC products investigated. The toxic potency values used for all the materials are based on 30 min exposures in the NBS cup furnace toxicity test, in the Non-Flaming mode, the one most relevant to this scenario.

The same calculation procedure has also been applied to other products in the same scenario. In particular, it has been used for PTFE wire coating in one of the scenarios being considered here [28, 29]. The results showed that, even if the toxic potency of the product in the plenum is extremely high, it is extremely unlikely to contribute significantly to fire hazard in the habitable areas if it has very good fire performance. 

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