Reaction mechanisms toxicology

Another area rarely dealt with in previous literature is the how-to of ozone experiments. This information is usually hard-earned by doctoral candidates and laboratory staff, and either not considered as appropriate information for a scientific treatise or considered as proprietary information that belongs to expertise. This lack of information has motivated us to write a book that contains not only fundamental information about the toxicology of ozone, its reaction mechanisms, and full-scale applications of ozonation (Part A Ozone in... 

Research on aromatic hydroxylation by cytochrome P450 provides an example of how quantum chemical calculations on small models can help in developing structure-reactivity relationships. Hydroxylation of C-H bonds is a particularly important class of reaction in drug metabolism,185 which can activate pro-drugs, or affect the bioavailability of pharmaceuticals. For the reliable prediction of pharmaceutical metabolism and toxicology (ADME/ TOX) properties, a key aim is the development of structure-activity relationships to predict conversions of drugs. Earlier work has shown that structure-activity relationships based on the structures and properties of substrates alone are of limited utility. There is a need for more detailed models, which can include effects of the reaction mechanism and specificity of different cytochrome P450 isozymes. 

SELGRADE, M.K., ZEISS, C.R., KAROL, M.H., SARLO, K KIMBER, I., TEPPER, J.S. HENRY, M.C. (1994) Workshop on the status of test methods for assessing potential mechanisms of chemicals to induce respiratory allergic reactions. Inhalation Toxicology, 6, 303-319. 

We examine here a number of reaction pathways for nitric oxide, with the emphasis on assessing their biological relevance. To date, the fastest reaction for nitric oxide with clear toxicological significance is that with superoxide to produce ONOO" (Huie and Padmaja, 1993). Thus, the chemistry and reactivity of ONOO" are discussed at length. In addition, the interaction between ONOO" and nitric oxide is examined with respect to its effects on nitric oxide half-life as well as effects on peroxynitrite reactivity toward phenol. Reaction mechanisms are proposed to account for the nitrated, hydroxylated, and nitrosated phenolic products seen. 

Linking Chemical Reaction Mechanisms with Mechanistic Toxicology... 

An expert system is loosely defined as a program that captures a human expert s knowledge and can apply that to problems in order to provide expert level advice. There are hundreds of expert systems in chemistry, including toxicological systems, structure elucidation, and reaction mechanism analysis. In fact, the field is so large that it will be covered in a separate article in this encyclopedia. 

A mechanism of action describes the molecular sequence of events (covalent or non-covalent) that lead to the manifestation of a response. The complete elucidation of the reactions and interactions among and between chemicals, include very complex and varied situations including biological systems (macromolecular receptors, physical phenomena (thermodynamics of explosions) or global systems (ozone depletion). Unfortunately, this level of mechanistic detail is often unavailable but recent advances in molecular toxicology and others hazards, at the molecular level, have provided valuable information that elucidates key steps in a mechanism or mode of action. ... 

The mechanism of sulfite-induced asthma is not well-understood. Reactions to sulfited foods probably depend on the sulfite residue level in the food, the sensitivity threshold of the individual, the type of food consumed, and whether sulfite exists in the free (more toxic) form or combined (less toxic) form. The toxicology of sulfites has been reviewed by Madhavi and Salunkhe (1995). Sulfite sensitivity is not a true allergic reaction (Taylor et al., 1988). The FDA initially estimated that more than 1 million Americans are sensitive to sulfites, but more recent estimates lowered the number of asthmatics who may be sulfite sensitive to 80,000-100,000 (Bush et al., 1986). 

As we have seen, a great deal is known about emission sources and strengths, ambient levels, and mutagenic/carcinogenic properties of the particle-phase PAHs in airborne POM. However, because of the tremendous physical and chemical complexity of the aerosol surfaces on which photolysis, photooxidations, and gas-particle interactions take place in real polluted ambient air, much less is known about the structures, yields, and absolute rates and mechanisms of formation of PAH and PAC reaction products, especially for the more polar PACs. This is one area in which there exists a major gap in our knowledge of their atmospheric chemistry and toxicology. 

A critical aspect of toxicological chemistry is that which deals with the biochemical mechanisms and reactions by which xenobiotic compounds and their metabolites interact with biomolecules to cause an adverse toxicological effect.6 7 The remainder of this chapter addresses the major aspects of biochemical mechanisms and processes of toxicity. 

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