Toxic site

In seawater, silver nitrate is less toxic than in freshwater (Wood et al. 1995 Wood et al. 1999). This difference is probably due to the low concentration of free Ag+ (the toxic moiety in freshwater) in seawater, the high levels of chloride, and the predominance of negatively charged silver-chloro complexes. However, high levels of silver nitrate are toxic to marine invertebrates despite the absence of Ag+, and this is attributed to the bioavailability of stable silver-chloro complexes (Wood et al. 1995 Ratte 1999). In seawater, in contrast to freshwater, plasma Na+ and Cl- rise rather than fall, and death may result from the elevated Na+ and Cl concentrations combined with dehydration (Hogstrand and Wood 1998). Osmoregulatory failure occurs in marine teleosts exposed to high concentrations of Ag+, and the intestine is the main toxic site of action (Wood et al. 1999). 

On high toxicity sites even with a very small amount of material escaping from the site, may have extreme consequences. Military Agents are high toxicity compounds which are designed to be lethal in very very small quantities. They are also extremely stable and hard to destroy. A number of industrial chemicals, particularly pesticides also fall into this category. Chlorinated solvents, PCB s and some pesticides, herbicides, and biocides fall into this category. 

When we are dealing with a high toxicity site, there are environmental exposure criteria as well as the questions about the soils and the technology, and we must be able to answer two very important questions ... 

This refers to the distribution and elimination of the DC, excluding transport to the target site (and toxicity site, as shown in Figure 13.4). In general, it is desirable that the DC is not rapidly eliminated from the circulation. This is necessary both to minimize the exposure of... 

Hunt et al. [6] also introduced the Drug Targeting Index, which was defined as the ratio of drug delivered to the target and toxicity sites when the drug-carrier conjugate is administered, divided by the same ratio when the active drug is administered intravenously and is formulated as follows. 

The concept of DTI is based on a pharmacokinetic model analogous to the model shown in Figure 13.4. Boddy and Aarons [44] used a simplified model, corresponding to Figure 13.3, in which the toxicity sites are included in the systemic (non-target) tissues, and the formula for DTI should be modified accordingly. 

Once inside the body, extremely hydrophilic compounds tend to be excreted more readily by the kidney. That could be useful, because it lowers toxicity. Additionally, chemical classes and functional groups known to be toxic—as well as those that can be bioactivated into toxic substances—should be avoided when designing chemical products. Chemicals can also be designed to shield active toxic sites or to facilitate metabolic degradation to nontoxic metabolites. 

Anderton DL, Oakes JM, Egan KL (1997) Environmental equity in Superfund. Demographics of the discovery and prioritization of abandoned toxic sites. Eval Rev, 21 3-26. 

Metal chelate complexes should be excreted rapidly in the faeces or urine with no redistribution of iron from relatively non-toxic sites such as the liver, to more harmful ones such as the heart. Complexes formed intracellularly should not accumulate within cells, but should leave cells freely. In the case of liver cells this should result in significant excretion of iron in the bile. Clearly this biliary iron-chelator complex should not then be reabsorbed from the gut. 

Type of toxicity Site of effect Examples of effects... 

In addition to potential metal toxicity, sites with multiple contaminants have difficulty meeting regulatory cleanup levels within acceptable time frames. It is important to note that at these highly contaminated sites, one remedial approach will not be able to address all of the contaminants and media. The key will be to employ remedial treatments that can be easily adapted as a part of the treatment train. 

PE is a single-chain protein with a molecular mass of 66 kDa composed of three distinct domains (Fig. 2). In the PE protein, domain I (1-252) binds to the PE receptor on normal animal cells, which has been identified as the a2-macroglobulin receptor. Domain II (253-364) mediates translocation of domain III (400-613) into the cytosol. The translocation domain contains a proteolytic cleavage site within a disulfide loop, which, after proteolytic cleavage, leaves the cell-binding site (I) and translocation domain (II) bound to the catalytic/toxic site (III) by a disulfide bond (Fig. 2). Following reduction of this bond in the cytosol, the ADP-ribosylation activity of domain III inactivates elongation factor (EF2) and causes inhibition of protein synthesis and cell death. 

When an organism is placed in an aqueous solution of a toxicant, pseudo-steady-state partitioning takes place between the toxic site of action and the aqueous phase. For organisms in which air is extracted from the water by means of gills, exchange of toxicant takes place mainly via this route, and the rate of uptake is controlled by the cross-sectional area, and the rate of blood flow across the gills. 

Groundwater, test well approx. 100 ft east of toxic site... 

Almost aU publications on the metabolites of marine reptiles are devoted to snake venoms. Like their terrestrial homologs, these venoms are mixtures of proteins. The most studied are netirotoxins, particularly erabutoxins A and B, isolated from species of the genus Laticauda, the amino acid sequences of which have been determined (Gttinea, Tamiya, and Cogger, 1983 Tamiya et al., 1983). The toxic sites of snake neurotoxin molecules from marine and land snakes always include a number of invariant amino adds (Menez et al., 1986). 

Figure 2. Schematic diagram of botulinum neurotoxin showing its light and heavy chains. The two different domains of the heavy chain shaded with different patterns indicate the N-terminal and C-terminal halves (about 50 kDa each). These two domains are believed to play different functional roles during the intoxication process. The light chain has been shown to contain the toxic site.

---