Detoxication mechanisms

R. T. Williams, Detoxication Mechanisms, Chapters 7 to 14. Chapman and Hall, London, 1959,... 

Many pesticides are not as novel as they may seem. Some, such as the pyre-throid and neonicotinoid insecticides, are modeled on natural insecticides. Synthetic pyrethroids are related to the natural pyrethrins (see Chapter 12), whereas the neo-nicotinoids share structural features with nicotine. In both cases, the synthetic compounds have the same mode of action as the natural products they resemble. Also, the synthetic pyrethroids are subject to similar mechanisms of metabolic detoxication as natural pyrethrins (Chapter 12). More widely, many detoxication mechanisms are relatively nonspecific, operating against a wide range of compounds that... 

As far as fruit and vegetables are concerned Ripper proposes the following tolerances. At these dosage rates no detectable response or injury is manifested since the detoxicating mechanisms of the human body are able to inactivate the insecticide ... 

Williams RT. 1959. The metabolism of halogenated aromatic hydrocarbons. In Detoxication mechanisms. 2nded. New York, NY John Wiley and Sons, 237-258. 

Wdbams, R.T. (1959) Detoxication mechanisms the metabolism and detoxication of drugs, toxic substances and other organic compounds, 2nd edn. Chapman Hall, London. 

Resource restriction. If chemical defenses vary quantitatively within or between individual plants, then some tissues may be defended while others are not. As a result, insects have available to them the evolutionary option of avoidance they may develop the ability to recognize poor quality food and avoid it, rather than evolving detoxication mechanisms (12,18). This should result in feeding activity concentrated on a restricted set of tissues or plant individuals. There are two important consequences of this. First, contact rates with defenses can be lowered by avoiding them. Hence, the evolution of detoxication is less li)cely or less rapid (18). Second, and perhaps more important, the effectiveness of natural enemies may be enhanced (below). 

A systematic modification of the structure was performed to make the substituent R bulkier and bulkier to protect against the possible hydrolytic detoxication mechanism. In the course of the structural modification, the QSAR analyses were utilized to get informations for structural factors to optimize the activity. The analysis for a set of 41 derivatives where R varies from simple alkyls to such congested groups as i-Pr(Me)2C and t-Bu(Cl)CH gave Eq. 34 31>,... 

Williams R.T. (1947) Detoxication Mechanisms the Metabolism of Drugs and Allied Organic Compounds, John Wiley Sons, Inc., New York. 

Williams RT. Detoxication Mechanisms. The Definitive First Complete, Comprehensive Text on Drug Metabolism. London Chapman Hall, 1959. 

Hydroxysteroid sulfotansferase also appears to exist in several forms. This reaction is now known to be important, not only as a detoxication mechanism but also in the synthesis and possibly the transport of steroids. Hydroxysteroid sulfotransferase will react with hydroxysterols and primary and secondary alcohols but not with hydroxyl groups in the aromatic rings of steroids. 

Figure 2. Detoxicative mechanisms imparting organo-phosphorus-resistance (e.g. to methyl parathion)...

The majority of xenobiotics that enter the body tissues are lipophilic, a property that enables them to penetrate lipid membranes and to be transported by lipoproteins in body fluids. The metabolism of xenobiotics, carried out by a number of relatively nonspecific enzymes, usually consists of two phases. During phase I, a polar group is introduced into the molecule and although this increases the molecule s water solubility, the most important effect is to render the xenobiotic a suitable substrate for phase II reactions. In phase II reactions, the altered compounds combine with an endogenous substrate to produce a water-soluble conjugation product that is readily excreted. Although this sequence of events is generally a detoxication mechanism, in some cases the intermediates or final products are more toxic than the parent compound, and the sequence is termed an activation or intoxication mechanism. See Chapter 20 for discussion of activation and toxicity. 

This exercise addresses the question Is burping (belching) part of a detoxication mechanism Does the upper GI tract function in ridding the body of potentially toxic plant compounds Specifically, does burping serve in removing plant volatiles from ingested spicy food ... 

Williams, R.T., Detoxication Mechanisms The Metabolism and Detoxication of Drugs, Toxic Substances and Other Organic Compounds, Chapman HaU, London, 1959 Prochaska, H.J., Santamaria, A.B., and Talalay, R, Rapid detection of inducers of enzymes that protect against carcinogens, Proc. Natl. Acad. Sci. USA., 89, 2394—2398, 1992. 

Williams RT. Detoxication mechanisms. London Chapman and Hall Ltd 1959. p. 796. 

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