Toxicology metabolic aspects

Machin, A.F. et al. (1975). Metabolic aspects of the toxicology of diazinonl Hepatic metabolism in the sheep, cow, guinea-pig, rat, turkey, chicken, and duck. Pesticide Science 6, 461 73. 

RN Wixtrom, BD Hammock. In D Zakim, DA Vessey, eds. Biochemical Pharmacology and Toxicology Methodological Aspects of Drag Metabolizing Enzymes, Vol. 1. New York John... 

Sorbic acid is metabolized to carbon dioxide and water ia the same way as other fatty acids, releasiag 27.6 kj/g sorbate (6.6 kcal/g) (165). As a result of the favorable toxicological and physiological aspects, the World Health Organization (WHO) has allowed sorbic acid at the highest acceptable daily iatake of all food preservatives, 25 mg/kg body weight (178). 

Hodgson, E. and Levi, P. (1994). A multiauthor text dealing in depth with some aspects of biochemical toxicology highly relevant to the present topic. Examples of metabolism and mode of action of insecticides, and PAHs. 

This biennial report is oriented strongly towards the chemical aspects It will be of special interest to workers in the fields of metabolic and toxicological evaluation of foreign compounds. This volume has a 10-year period of coverage 4SSpp 11 (X)... 

The are several clearance and toxicological aspects that have to be considered in the drug discovery process such as metabolic stability, enzyme selectivity, CYP inhibition and type of inhibition. Among these factors, the prediction of the site of metabolism has become one of the most successful parameters for prediction. The knowledge of the site of metabolism enhances the opportunity to chemically modify the molecule to improve the metabolic stability. There are several approaches based on database mining, chemical reactivity, protein interaction or both that have been developed for the prediction of this property, with different degree of success and applicability. 

Maurel, P. (1996) The CYP3A family, in Cytochrome P450 Metabolic and Toxicological Aspects, (ed. Ioannides C.) CRC Press, Boca Raton, FL, pp. 241-270. 

These various examples underline various aspects of the metabolism and disposition of lactones in connection with their pharmacological or toxicological activities. Other cases also exist, namely the lactone prodrugs to be presented in Chapt. 8. 

A number of practical considerations affect the choice of experimental approaches to address a specific question. In general, these practical considerations tend to have a greater impact on applications to toxicology (where specific endpoints may not be measurable in all cell types) than studies of xenobiotic metabolism (where the principal requirement is enzyme activity). However, applications to toxicology should be considered when making a choice of an experimental approach as specific toxicological issues may develop from the metabolism studies or in other aspects of the safety assessment processes. 

However, apart from absolute specificity, foreign compounds may also be substrates for enzymes involved in endogenous pathways, often with toxicological consequences. Thus, for example, with VPA (see above), fluoroacetate, and galactosamine (see chap. 7) involvement in endogenous metabolic pathways is a crucial aspect of... 

Tarloff JB, Goldstein RS, Hook JB. Xenobiotic bio transformation by the kidney pharmacological and toxicological aspects. In Gibson GG, ed. Progress in Drug Metabolism. Vol. 12. London Taylor Francis, 1990. 

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