Toxic Effects on Animals

Most irreversible enzyme inhibitors combine covalently with functional groups at the active sites of enzymes. These inhibitors are usually chemically reactive, and many of them show some specificity in terms of the amino acid groups which they react with. Diisopropyl fluorophosphate (DFP), for example, forms a covalent adduct with active site serine residues, such as in the serine proteases, and in acetylcholinesterase, which explains its toxic effect on animals. Irreversible enzyme inhibition can be used to identify important active site residues. A special case of irreversible enzyme inhibition is the effect of suicide inhibitors, which are generally chemically unreactive compounds that resemble the substrate of the target enzyme and bind at the active site. The process of enzyme turnover begins, but the inhibitor is so... 

Toxic effects on animals from inhalation exposure include anesthetic effects and decreased blood pressure. The 4h inhalation lethal concentration 50% in rats is 164 000 ppm (16.4%). Cardiac sensitization occurred in dogs exposed to concentrations of 20% or greater. 

The ultimate concern with wastes has to do with their toxic effects on animals, plants, and microbes. Virtually all hazardous waste substances are poisonous to a degree, some extremely so. The toxicity of a waste is a function of many factors, including the chemical nature of the waste, the matrix in which it is contained, circumstances of exposure, the species exposed, manner of exposure, degree of exposure, and time of exposure. The toxidties of some of the substances found in hazardous wastes are discussed in more detail in Chapter 2. 

The second type of material includes spores, which may or may not produce disease symptoms but which can germinate in the insect gut and give rise to vegetative bacterial cells which in turn may produce, and exoenzymes such as phospholipases (lecithinases) or hyaluronidase. The phospholipases may produce direct toxic symptoms owing to their action on nervous or other phospholipid-containing tissue. Hyaluronidase breaks down hyaluronic acid and produces effects on animal tissue which are morphologically similar to the breakdown of insect gut wall in the presence of microbial insecticide preparations. 

House, W.B. 1964. Tolerance criteria for continuous exposure inhalation exposure to toxic materials. III. Effects on animals of 90-d exposure to hydrazine, unsymmetrical dimethylhydrazine (UMDH), decaborane, and nitrogen dioxide. ASD-TR-61-519 (iii). Wright-Patterson AFB, OH. 84 pp. 

No information is available on the adverse health effects of hexachloroethane in humans. Animal studies revealed that hexachloroethane primarily causes liver and kidney toxicity. Effects on the nervous system and lungs have also been reported. The mechanism by which these effects are mediated is not well characterized. Reductive metabolism by cytochrome P-450 and production of a free radical intermediate have been suggested as factors in hexachloroethane-induced hepatotoxicity (Nastainczyk et al. 1982a Thompson et al. 1984 Town and Leibman 1984). Accordingly, one possible approach may be to reduce free radical injury. To that end, oral administration of N-acetylcysteine can be used as a means of reducing free radical injury. Also, oral administration of vitamin E and vitamin C may be of value since they are free radical scavengers. 

On the basis of this concept, one might expect a poison to be relatively uniform in its toxic effect on a series of intact animals because, in the different animals, many different tissues and organs would be involved and the chance exists that the resistance of one tissue might be compensated for by the susceptibility of another. Since from our previous discussions we realize that every individual animal is made up of a coordinated set of organs and tissues, each distinctive (quantitatively) in size, composition, and enzymic make-up, we should expect the greatest interindividual differences to be observed when single tissues from different animals are tested in parallel. This exemplifies the principle which appears to be an important one for our discussions. We expect to find the most striking evidences for biochemical individuality when we look at details, rather than at crude summations. 

Sandage C. 1961. Tolerance criteria for continuous inhalation exposure to toxic material. I. Effects on animals of 90-day exposure to phenol, CC14 and a mixture of indole, skatole, H2S and methyl mercaptan. Wright- Patterson Air Force Base, OH. U.S. Air Force systems command, Aeronautical Systems Division, ASD technical report 61-519(1). 

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