Transformation processes substance toxicity

Table 20.5 lists the partition and transformation processes applicable in the deep-well environment and indicates whether they significantly affect the toxicity or mobility of hazardous wastes. None of the partition processes results in detoxification (decomposition to harmless inorganic constituents), but all affect mobility in some way. All transformation processes except complexation can result in detoxification however, because transformation processes can create new toxic substances, the mobility of the waste can be critical in all processes except neutralization. 

Adsorption is a physicochemical process whereby ionic and nonionic solutes become concentrated from solution at solid-liquid interfaces.3132 Adsorption and desorption are caused by interactions between and among molecules in solution and those in the structure of solid surfaces. Adsorption is a major mechanism affecting the mobility of heavy metals and toxic organic substances and is thus a major consideration when assessing transport. Because adsorption is usually fully or partly reversible (desorption), only rarely can it be considered a detoxification process for fate-assessment purposes. Although adsorption does not directly affect the toxicity of a substance, the substance may be rendered nontoxic by concurrent transformation processes such as hydrolysis and biodegradation. Many chemical and physical properties of both aqueous and solid phases affect adsorption, and the physical chemistry of the process itself is complex. For example, adsorption of one ion may result in desorption of another ion (known as ion exchange). 

Examples of the Effects of Transformation Processes on the Toxicity of Substances... 

The transformation of toxic substances in soil can have a profound effect on their potential for human exposure and accumulation by biota. Transformation processes in soil include physical processes such... 

Metabolism, or biotransformation, is the process of ehemical transformation of a toxicant to different structures, called metabolites, which may possess a different toxicity profile than the parent compound. Biotransformation affects both endogenous chemicals exogenous (xenobiotic) entities. Metabolism can result in a transformation product that is less toxie, more toxic or equitoxic but in general more water soluble and more easily excreted. Chemical modification can alter biological effects through toxication of a substance, also called bioactivation, which refers to the situation where the metabolic process results in a metabolite that is more toxic than the parent. If the metabolite demonstrates lower toxicity than the parent compound, the metabolic process is termed detoxication. These processes can involve both enzymatic and non-enzymatic processes, all of which should be familiar to undergraduate and graduate chemists. 

Bioremediation A process that uses naturally occurring or genetically engineered micro-organisms to transform harmful substances into less toxic or non-toxic compounds. 

Toxicokinetics describes the biokinetics of toxic substances. It includes the kinetic processes for toxic substances which govern the movement into, within, and from the bodies of human populations. The overall lead toxicoki-netic process includes (1) the uptake, i.e., absorption rate, of lead into the bloodstream from various body compartments such as the lung or G1 tract (2) movement within the bloodstream followed by transport internally to target tissues and their cellular components (3) retention within one or more tissues and finally (4) excretion from the body by various systemic pathways. Older literature made incorrect reference to lead toxicokinetics as lead metabolism, but the latter term is more correctly employed with toxic substances undergoing actual chemical transformation within such processes as addition or removal of chemical groups and oxidative or reductive changes. 

Toxicity tests exist which have been carried out on bacteria that are specific to the soil compartment. They investigate the long-term adverse effects of substances on carbon (OECD 217, [58]) or nitrogen (OECD 216, [59]) transformation processes over a period of no less than 28 days. 

The transformation of toxic substances in soil can have a profound effect on their potential for transport and accumulation at different soil depths. The rate of transformation processes impact the effective penetration depth of contaminants in soil, which in turn determines the length scale needed to define the soil compartment dimensions in mass transfer models. Transformation processes in soil include chemical conversions such as photolysis, hydrolysis, and oxidation/reduction biological processes such as microbial transformations and physical processes such as radioactive decay. 

Thus, a substance may be in a solid form or in solution (described by the precipitation-dissolution process), but its toxicity remains unaltered regardless of form. The form or state of a substance, however, influences the transformation and transport processes that can occur. For this reason, partition processes are important to define in a fate assessment. 

The widely used insecticide carbaryl (FD50=270 mg/kg) transforms in oxidizing processes into 5-oxynaphthyl-N-methylcarbamate, a substance that is as toxic as carbaryl itself (FD50=297 mg/kg) [30, 33]. One of the metabolites of the fungicide benomyl, the methyl ester carbamino acid (BMK, carbendazim), is also toxic to fungi [33]. 

Environmental fate Chemicals released in the environment are suscephble to several degradahon pathways, including chemical (i.e., hydrolysis, oxidation, reduction, dealkylahon, dealkoxylation, decarboxylahon, methylation, isomerization, and conjugation), photolysis or photooxidahon and biodegradation. Compounds transformed by one or more of these processes may result in the formation of more toxic or less toxic substances. In addihon, the transformed product(s) will behave differently from the parent compound due to changes in their physicochemical properties. Many researchers focus their attention on transformahon rates rather than the transformahon products. Consequently, only limited data exist on the transitional and resultant end products. Where available, compounds that are transformed into identified products as weh as environmental fate rate constants and/or half-lives are listed. 

In many cases, the subsurface is contaminated by a mixture of toxic chemicals with components having different physical and chemical properties. Therefore, a contaminant undergoes transformations controlled by the properties of each substance, the characteristics of the subsurface, and the ambient conditions. Physicochemically mediated and biologically mediated degradation are the main processes involved in such transformations. 

Polymerization, or conjugation, is the process in which toxic organic molecules undergo microbially mediated transformation by oxidative coupling reactions. In this case, a contaminant or its intermediate product(s) combines with itself or other organic molecules (e.g., xenobiotic residues, naturally occurring compounds) to form larger molecular polymers that can be incorporated in subsurface humic substances. 

The enzymatic route which a drug or poison follows in its metabolism is very specific to the xenobiotic itself. Substances with the same type of structures need not go through the same pathway. And the "active" form of the drug or the "toxic" form of the poison may occur either at the beginning or during the course of transformation. Usually synthetic combinations are not active or toxic but many of their precursors are. The following diagram illustrates the possibilities of a biotransformation process. 

In mammalian liver microsomes, cytochrome P-450 is not specific and catalyzes a wide variety of oxidative transformations, such as (i) aliphatic C—H hydroxylation occurring at the most nucleophilic C—H bonds (tertiary > secondary > primary) (ii) aromatic hydroxylation at the most nucleophilic positions with a characteristic intramolecular migration and retention of substituents of the aromatic ring, called an NIH shift,74 which indicates the intermediate formation of arene oxides (iii) epoxidation of alkenes and (iv) dealkylation (O, N, S) or oxidation (N, S) of heteroatoms. In mammalian liver these processes are of considerable importance in the elimination of xenobiotics and the metabolism of drugs, and also in the transformation of innocuous molecules into toxic or carcinogenic substances.75 77... 

Metabolism is especially important in toxicological chemistry for two reasons (1) interference with metabolism is a major mode of toxic action, and (2) toxic substances are transformed by metabolic processes to other materials that are usually, though not invariably, less toxic and more readily eliminated from the organism. This chapter introduces the topic of metabolism in general. Specific aspects of the metabolism of toxic substances are discussed in Chapter 7. 

In view of the fact that we have evolved in a manner in which we obtain our energy primarily by way of the gastrointestinal (GI) system, this route also became the most likely portal for the inadvertent introduction of toxic substances. Therefore, as a survival necessity, the body had to evolve a strategy for the early interception and processing of potentially lethal xenobiotic substances. Anatomically, this is accomplished by the hepatic-portal venous system, which delivers substrates absorbed from the gut directly to a succession of chemical-transforming enzyme systems located in the liver. 

Another typical source of uncertainty in mixture assessment is the potential interaction between substances. Interactions may occur in the environment (e.g., precipitation after emission in water), during absorption, transportation, and transformation in the organism, or at the site of toxic action. Interactions can be either direct, for example, a chemical reaction between 2 or more mixture components, or indirect, for example, if 1 mixture component blocks an enzyme that metabolizes another mixture component (see Chapters 1 and 2). Direct interactions between mixture components are relatively easy to predict based on physical-chemical data, but prediction of indirect interactions is much more difficult because it requires detailed information about the processes involved in the toxic mechanisms of action. One of the main challenges in mixture risk assessment is the development of a method to predict mixture interactions. A first step toward such a method could be the setup of a database, which contains the results of mixture toxicity tests. Provided such a database would contain sufficient data, it could be used to predict the likelihood and magnitude of potential interaction effects, that is, deviations for CA and RA. This information could subsequently be used to decide whether application of an extra safety factor for potential interaction effects is warranted, and to determine the size of such a factor. The mixture toxicity database could also support the search for predictive parameters of interaction effects, for example, determine which modes of action are involved in typical interactions. 

Fig. 10.8. Simple biogeochemical model for metal mineral transformations in the mycorhizosphere (the roles of the plant and other microorganisms contributing to the overall process are not shown). (1) Proton-promoted (proton pump, cation-anion antiport, organic anion efflux, dissociation of organic acids) and ligand-promoted (e.g. organic adds) dissolution of metal minerals. (2) Release of anionic (e.g. phosphate) nutrients and metal cations. (3) Nutrient uptake. (4) Intra- and extracellular sequestration of toxic metals biosorption, transport, compartmentation, predpitation etc. (5) Immobilization of metals as oxalates. (6) Binding of soluble metal species to soil constituents, e.g. clay minerals, metal oxides, humic substances.

If, following absorption, medications were undisturbed by the body, we would need to take only one dose for an eternal effect. Of course, this is not the case. As soon as drugs enter the bloodstream, the process of metabolism ensues. The body recognizes the drug as a foreign substance and eliminates it outright (say, via the kidneys, as in the case of lithium) or transforms it chemically, using a complex enzyme mechanism located in the liver. This chemical transformation enables the medication to be eliminated from the body. In some cases, the chemical transformation produces a new compound that may also have therapeutic effects (or, in some rare instances, a toxic effect). For example, fluoxetine (trade name Prozac) is transformed into norfluoxetine, which is also an antidepressant. A similar situation occurs with the old tricyclic antidepressants (amitriptyline—trade name Elavil—to nortriptyline the latter, in fact, is... 

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