Toxicity and specificity

The high toxicity and specific biological activity of 1-arylsilatranes was discovered about 15 years ago1, 2 At that time, these substances belonged to an almost unknown class of heterocyclic derivatives of 5-coordinate silicon with general formula I (Fig. 1). 

The processes of metabolism and excretion try to protect the body against the possible adverse effects of chemicals. If so, why are chemicals sometimes toxic and specifically damaging to one organ One reason is that the process of metabolism sometimes produces chemicals that are more poisonous than the original. Whether or not a chemical or its metabolic products causes any damage depends on its chemical properties, how much of it is present, and where it goes in the body. This will be discussed further in later chapters, but some illustrations here may show how the sequence of events is crucial in determining what toxic effects occur and where. 

The competent authority may choose to allow communication of certain hazard information for carcinogens, reproductive toxicity and specific target organ systemic toxicity through repeated exposure on the label and on the SDS, or through the SDS alone (see speeific ehapters for details of relevant cut-offs for these classes). 

The ability to produce antibiotics is common among the actinomycetes and much of the interest in these filamentous bacteria in recent years may be attributed to this fact. This interest has been manifest chiefly in research connected directly or indirectly with medicine. Soil samples from all over the world have been examined in the search for new species and strains that may produce a new antibiotic suitable for medical use. Hundreds of these antibiotics have been isolated but only a few have been found to be sufficiently non-toxic and specific for use in disease control. Among the best known of these that are in use are streptomycin, terramycin, aureomycin, cycloheximide, chlortetracycline, oxytetracycline, chloramphenicol and neomycin. Some of these have been used to a limited extent in disease control in plants. Their use for this purpose is limited by cost, by difficulty in getting the antibiotic into the plant, and by toxicity when used at concentrations adequate to be effective. The limited time that they are effective is also an important factor (Brian, 1957 Zaumeyer, 1958 Pramer, 1959). The role of antibiotics in soils and their effect on microbial ecology is considered in Chapter 18. 

The analysis in Turner et al. (1983) of correlations between acute toxicity and specific properties of metal ions has been generalized here to a multiparameter analysis. In addition, metal ions have been divided into two main groups as defined by Kaiser (1980) on the basis of the electronic structure of the ions. Unlike the earlier study (Turner etal. 1983), in which the fit of the data depended on the particular set of metal ions used in the toxicity studies, the W that we derived here are representative of all metals in either group. Furthermore, the W are the least redundant linear combinations of a set of five chosen parameters that are available in handbooks for any metal. As a logical extension to the method of Turner et al. (1983), equations (8 and 9) for group (1) and equations (10 to 12) for group (2) are the optimum parameters to use for fitting data to any linear combinations of the five physical quantities listed in TABLE 2. 

A particular mode of neurotoxicity was discovered for tricresyl phosphate that correlated with the presence of the o-cresyl isomer (or certain other specific aLkylphenyl isomers) in the triaryl phosphates. Many details of the chemistry and biochemistry of the toxic process have been elucidated (139,140,143—146). The use of low ortho-content cresols has become the accepted practice in industrial production of tricresyl phosphate. Standard in vivo tests, usually conducted with chickens sensitive to this mode of toxicity, have been developed for premarket testing of new or modified triaryl phosphates. As of 1992, the EPA called for extensive new toxicity and environmental data on this group of products (147). The Vederal e ster AoQ xm. ci. calling for this... 

In general, the PCTFE resins have been found to be low in toxicity and irritation potential under normal handling conditions. Specific toxicological information and safe handling procedures are provided by the manufacturer of specified PCTFE products upon request. 

Phosphonothioate Esters of Phenols. Phosphonates with a single P—C bond are highly toxic and persistent iasecticides but have not been used extensively because some compounds produce delayed neuropathy leading to irreversible paralysis ia higher animals, including humans. Such compounds specifically inhibit an enzyme, neurotoxic esterase, that is responsible for the growth and maintenance of long nerve axons (31,32). 

Prior to the 1990s phenyhnercuric acetate was the primary bactericide and fungicide in latex and waterborne paints. Because of the increasing concerns of mercury toxicity and the potential for high consumer and occupational exposures to mercury when present in paints, the U.S. Environmental Protection Agency (EPA) induced U.S. manufacturers of PMA and other mercury compounds to withdraw their registrations for use of these substances as biocides in paints (see AIercury). Mercury compounds are used only for very limited, specific purposes, such as the use of phenyhnercuric mXx.2LX.e[55-68-5] as a bactericide in cosmetic eye preparations (see Cosmetics). 

Caro s acid is highly corrosive and a powerfiil oxidant. Its acidic properties are similar to those of sulfuric acid of equivalent strength. A strong irritant, it is toxic and should always be handled accordingly. No specific toxicological data are available. 

Most general-purpose release agents have been developed for this market in part because of their low toxicity and chemical inertness and do not usually present health and safety problems. Some of the solvent dispersions require appropriate care in handling volatile solvents, and many supphers are offering water-based alternatives. Some of the sohds, particularly finely divided hydrophobic sohds, can also present inhalation problems. Some of the metallic soaps are toxic, although there is a trend away from the heavier, more toxic metals such as lead. The reactive type of release coating with monomers, prepolymers, and catalysts often presents specific handling difficulties. The potential user with health and safety questions is advised to consult the manufacturer directly. 

Selection of the most suitable machine for a given requirement is an extremely complex process. Added to variations in the properties of the different materials, many of the machines involved have been specifically developed or adapted to perform only particular tasks. The principal factors which must be addressed are toughness/britdeness, hardness, abrasiveness, feed size, cohesity, particle shape and stmcture, heat sensitivity, toxicity, explodability, and specific surface. 

With the aid of cytosine permease, flucytosine reaches the fungal cell where it is converted by cytosine deaminase into 5-fluorouracil [51-21-8]. Cytosine deaminase is not present in the host, which explains the low toxicity of 5-FC. 5-Fluorouracil is then phosphorylated and incorporated into RNA and may also be converted into 5-fluorodeoxyuridine monophosphate, which is a potent and specific inhibitor of thymidylate synthetase. As a result, no more thymidine nucleotides are formed, which in turn leads to a disturbance of the DNA-synthesis. These effects produce an inhibition of the protein synthesis and cell repHcation (1,23,24). 5-Fluorouracil caimot be used as an antimycotic. It is poorly absorbed by the fungus to begin with and is also toxic for mammalian cells. 

Sodium chlorite has also been used for treatment and removal of toxic and odorous gases such as hydrogen sulfide and mercaptans. Chlorine dioxide from chlorite is also useful for microbial and slime control in paper mills and alkaline paper machine systems (164,165). The use of sodium chlorite in textile bleaching and stripping is well known. Cotton is not degraded by sodium chlorite because the oxidation reactions are specific for the hemiceUulose and lignin components of the fibers. 

Neoprene latexes contain 0.5 to 0.02% residual chloroprene depending on the specific latex type. The amount of free alkaH in the water phase of latexes varies from 0.1 to 0.08% depending on type and age of the material. Eye protection and appropriate skin protection have been recommended for use in situations where splashes or spills are possible. Toxicity and safe handling practices have been recommended for Du Pont types (171). Since compositions may vary with other manufacturers, specific information should be obtained for other products. 

Biological sui veys shall be fuUy integrated with toxicity and chemical-specific assessment methods in state water-quahty programs. ... 

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