Lethal toxicity

Considerable caution is necessary in making quantitative comparisons between different materials, even when considering the same toxic end point. This can be conveniendy illustrated using, as an example, death in response to a single exposure, ie, acute lethal toxicity. Studies to determine acute lethal toxicity by a particular route are usually conducted as described below. 

When making comparisons of lethal toxicity, it must be remembered that different mechanisms may be iavolved with different materials, and these need to be taken iato account. Also, comparisons of acute toxicity should take note of differences ia time to death, siace marked differences ia times between dosiag and death may influence ha2ard evaluation procedures and thek implications. In a few kistances, it may be possible to calculate two LD q values for mortaUty one based on early death due to one mechanism, and a second based on delayed deaths due to a different mechanism (69). 

Although acute lethal toxicity has been used as an example, the principles discussed apply ia general to other forms of toxicity capable of being quantitated ia terms of dose—response relationships. 

Environmental. The toxicity of cyanide in the aquatic environment or natural waters is a result of free cyanide, ie, as HCN and CN . These forms, rather than complexed forms such as iron cyanides, determine the lethal toxicity to fish. Complexed cyanides may revert to free cyanide under uv radiation, but the rate is too slow to be a significant toxicity factor. Much work has been done to estabhsh stream and effluent limits for cyanide to avoid harmful effects on aquatic life. Fish are extremely sensitive to cyanide, and the many tests indicate that a free cyanide stream concentration of 0.05 mg/L is acceptable (46), but some species are sensitive to even lower concentrations. 

Because there are neither flanges, nor packed or gasketed joints inside the shell, potential leak points are eliminated, making the design suitable for higher-pressure or potentially lethal/toxic service. However, because the tube bundle carmot be removed, the shellside of the exchanger (outside the tubes) can only be cleaned by chemical means. 

Figure 4-114. Determination of lethal toxicity from the dose-response curve [32A]. (Courtesy SPE.)...

As discussed earlier, selectivity is the consequence of the interplay between toxicokinetic and toxicodynamic factors. Some examples are given in Table 2.8, which will now be briefly discussed (data from Walker and Oesch 1983, and Walker 1994a,b). These and other examples will be described in more detail under specific pollutants later in the text. In the table, comparisons are made between the median lethal doses or concentrations for different species or strains. Comparisons are made of data obtained in lethal toxicity tests where the same route of administration was used for species or strains that are compared. The degree of selectivity is expressed... 

The inhibition of brain cholinesterase is a biomarker assay for organophosphorous (OP) and carbamate insecticides (Chapter 10, Section 10.2.4). OPs inhibit the enzyme by forming covalent bonds with a serine residue at the active center. Inhibition is, at best, slowly reversible. The degree of toxic effect depends upon the extent of cholinesterase inhibition caused by one or more OP and/or carbamate insecticides. In the case of OPs administered to vertebrates, a typical scenario is as follows sublethal symptoms begin to appear at 40-50% inhibition of cholinesterase, lethal toxicity above 70% inhibition. 

With improvements in scientific knowledge and related technology, there is an expectation that more environmentally friendly pesticides will continue to be introduced, and that ecotoxicity testing procedures will become more sophisticated. There is much interest in the introduction of better testing procedures that work to more ecologically relevant end points than the lethal toxicity tests that are still widely used. Such a development should be consistent with the aims of organizations such as FRAME and ECVAM, which seek to reduce toxicity testing with animals. Mechanistic biomarker assays have the potential to be an important part of... 

Newman, M. S., Guo, L., McCalden, T. A., Levy, M., Porter, J., Wong, A., and Fielding, R. M. (1989). A colloidal dispersion of amphotericin B with reduced lethality and non lethal toxicity, Proc. AAPS Western Regional Meet., February 26-March 1, 1989. 

Other toxins that show low lethal toxicity to laboratory test animals include lipopolysaccharide endotoxin produced as part of the cell wall by all cyanobacteria 11) and certain toxins of some cyanobacteria suspected of causing contact irritation in recreational water supplies 4,12 Carmichael and Codd, unpublished results). 

Mefenamic is a nonsteroidal anti-inflammatory drug used to treat pain, including menstrual pain. Hata et al. [11] treated that drug with P. sordida, and obtained a 90% reduction in mefenamic acid concentration (initial concentration 24 mg L ) after 6 days. The system produced four metabolites, identified as 3 -hydroxymethyl-mefenamic acid, 3 -hydroxymethyl-5-hydroxymefenamic acid, 3 -hydroxmethyl-6 -hydroxymefenamic acid, and 3 -carboxymefenamic acid. Moreover, the authors confirmed that the fungus almost completely removed the acute lethal toxicity of mefenamic towards the freshwater crustacean Thamnocephalus platyurus after 6 days of treatment, suggesting that the metabolites are less toxic than the parental compound. 

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

Haun et al. (1970) also assessed the acute lethal toxicity of rats. Groups of 10 Sprague-Dawley rats were exposed to monomethylhydrazine (30, 60, 120, or 240 ppm) for 30, 60, 120, or 240 min. Similar to the results of Jacobson et al. (1955) the exposure-response curve was steep. The study authors calculated 30-, 60-, 120-, and 240-min LC50 values of427,244, 127, and 78 ppm, respectively. 

Thain, J.E. 1984. Effects of mercury on the prosobranch mollusc Crepidula fornicata acute lethal toxicity and effects on growth and reproduction of chronic exposure. Mar. Environ. Res. 12 285-309. 

Alabaster, J.S., D.G. Shurben, and M.J. Mallett. 1983. The acute lethal toxicity of mixtures of cyanide and ammonia to smolts of salmon, Salmo salar L. at low concentrations of dissolved oxygen. Jour. Fish Biol. 22 215-222. 

McGeachy, S.M. and G. Leduc. 1988. The influence of season and exercise on the lethal toxicity of cyanide of rainbow trout (Salmo gairdneri). Arch. Environ. Contam. Toxicol. 17 313-318. 

Oikari, A.O.J. 1987. Acute lethal toxicity of some reference chemicals to freshwater fishes of Scandinavia. Bull. Environ. Contam. Toxicol. 39 23-28. 

---