Intrinsic toxicity

The metaboHsm of a material may result in the formation of a transformation product of lower intrinsic toxicity than the parent molecule ie, a process of detoxification has occurred. In other cases, the end result is a metaboHte, or metaboHtes, of intrinsically greater toxicity than the parent molecule, ie, metaboHc activation has occurred. Some examples of detoxification and metaboHc-activation processes are given in Table 2. 

Biocides are by their nature intrinsically toxic, in this respect any adventitious release to the environment requires an assessment of the relative risk posed. The 5th Environmental Action Plan of the EU is committed to a substantial reduction in the use of biocides. In particular, the Biocidal Products Directive (98/08/EC) is concerned with controlling biocidal products in the market place. Compliance with this directive is required from all member states by 14th May 2000. In this context, a strategy to control the release of biocides is timely, if continued protection is to be afforded to industry and consumer alike. One approach to controlling the release of biocide is to encapsulate in an inert inorganic framework, prior to incorporation in the coating.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. 

Lingappa, S., A. Jagadish, K. Shivaramu, and H.P Prabhuswamy. 1985. Relative intrinsic toxicity of seven insecticides to foragers of the Indian hive bee, Apis cerana indica F. Insect Sci. Applica. 6 567-568. 

Finally, it should be noted that for some agents (contrary to the general rule), decreasing the concentration of chemical in a vehicle may increase its apparent intrinsic toxicity. 

Some intrinsically toxic processes cannot be changed or modified. In these situations, isolation of the process can be considered. Isolation requires that the process or equipment be separated in some manner from nearby workers. The separation can take the form of an actual physical barrier that prevents an unprotected worker from approaching, or a distance barrier whereby the process can be operated by remote control, or even a time barrier whereby physical presence of the worker is only required for short periods during the working day. 

The toxic effect produced by a chemical agent on a susceptible organism depends on the nature and magnitude of its interactions with the vital processes which it disrupts (which may be termed its intrinsic toxicity) and on the amounts which reach the sites of interaction. Both these determinants of toxic effect are expressions of biophysical and physico-chemical factors. The effectiveness of the lethal interaction which is equivalent to the intrinsic toxicity... 

Cyanation of aldehydes and ketones is an important chemical process for C C bond formation." " Trimethylsilyl cyanide and/or HCN are commonly used as cyanide sources. The intrinsic toxicity and instability of these reagents are problematic in their applications. Acetyl cyanide and cyanoformates were used as cyanide sources in the enantioselective cyanation of aldehydes catalyzed by a chiral Ti complex and Lewis base (Scheme 5.31)." The Lewis base was necessary for the good yields and selectivities of these reactions. The desired products were obtained in the presence of 10mol% triethyl amine and 5mol% chiral titanium catalyst (Figure 5.14). Various aliphatic and aromatic aldehydes could be used in these reactions. 

A second form of storage iron is haemosiderin (Weir et al., 1984). This is deposited in humans as a response to the condition of iron overload. Haemosiderin forms as insoluble granules with electron dense cores surrounded by a protein shell. It exists in two forms primary haemosiderin is the result of iron overload due to excessive adsorption of iron in the gut, whereas the secondary form is caused by the numerous blood transfusions which are used to treat thallassaemia (a form of anaemia). Electron diffraction indicated that the iron core in primary haemosiderin is a 3-line ferrihydrite with magnetic hyperfine splitting only below 4 K and, in the secondary form, consists of poorly ordered goethite. As goethite is less soluble in ammonium oxalate buffer solution (pH 3) it has a lower intrinsic toxicity (Mann et al., 1988). 

It is necessary to distinguish between the intrinsic toxicity of a chemical and the hazard it poses. While a chemical may have high intrinsic toxicity, it may pose little or no hazard if exposure is low. In contrast, a relatively nontoxic chemical may be quite hazardous if exposure is large or the route of exposure is not physiological. 

In conclusion, neurosteroid-based anxiolytics with low intrinsic toxicity may represent an exciting new pharmacological development with potential advantages over existing classes of anxiolytics with regard to tolerance, dependence, and abuse liability. 

Fluoroacetate does not cause direct tissue damage and is not intrinsically toxic but requires metabolism to fluoroacetyl CoA (Fig. 7.61). Other fluorinated compounds that are metabolized to fluoroacetyl CoA therefore produce the same toxic effects. For instance,... 

The term potentiation is then reserved for those cases where both compounds have appreciable intrinsic toxicity, such as in the case of malathion and EPN. Malathion has a low mammalian toxicity due primarily to its rapid hydrolysis by a carboxylesterase. EPN (Figure 9.6) another organophosphate insecticide, causes a dramatic increase in malathion toxicity to mammals at dose levels, which, given alone, cause essentially no inhibition of acetylcholinesterase. The increase in toxicity as a result of coadministration of these two toxicants is the result of the ability of EPN, at low concentrations, to inhibit the carboxylesterase responsible for malathion degradation. 

As indicated by the current subclassifications of existing waste classes summarized above, a variety of waste properties could be used to develop meaningful subclassifications of broadly defined waste classes. These properties include, for example, waste volumes, levels of decay heat and external radiation, and the long-term persistence of the hazard posed by waste constituents. Subclassifications of waste classes also could be based on the presence of particular hazardous substances. However, if the broadly defined waste classes are based on risk, as in the classification system proposed in this Report, the intrinsic toxicity of hazardous substances normally would not provide a basis for subclassification, because this property already is accounted for in determining the basic classification of any waste. Examples of possible approaches to subclassifying the basic waste classes are discussed in the following paragraphs. 

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