Toxicology toxicokinetic mechanisms

Peter Lacouture, Associate Director, Clinical Research, The Purdue Frederick Company, Norwalk, Connecticut Dr. Fumio Matsumura, Associate Director, Toxic Substances Program, Institute of Toxicology and Environmental Health, University of California, Davis, California Dr. Frederick Oehme, Director, Comparative Toxicology Laboratories, Kansas State University, Manhattan, Kansas and Dr. Jack Radomski, Private Consultant, Jonesport, Maine. These experts collectively have knowledge of heptachlor and heptachlor epoxide s physical and chemical properties, toxicokinetics, key health end points, mechanisms of action, human and animal exposure, and quantification of risk to humans. All reviewers were selected in conformity with the conditions for peer review specified in Section 104(i)(13) of the Comprehensive Environmental Response, Compensation, and Liability Act, as amended. 

This group of compounds have a 4-hydroxycoumarin ring with different side-chain substituents at the 3-position. Commonly used superwarfarin anticoagulant rodentieides in this group are bromadiolone, brodifacoum, coumate-tralyl, coumafuryl, and difenacoum. Brodifacoum, difena-coum and bromadiolone are three of the most commonly used rodentieides around the world. Brodifacoum is the most frequently used rodenticide in the USA. These rodentieides share most of their physical and chemical characteristics, as well as their toxicokinetics, toxicody-namics, and mechanism of toxicity, and the medical toxicological management is the same for all superwarfarins. 

Epidemiology Mechanisms of Toxicity Medical Sun/eil-lance Molecular Toxicology-Recombinant DNA Technology Pharmacokinetic Models Pharmacokinetics/ Toxicokinetics Risk Assessment, Human Health. 

See also Absorption Analytical Toxicology Biotransformation Distribution Exposure Mechanisms of Toxicity Mixtures, Toxicology and Risk Assessment Pharmacoki-netics/Toxicokinetics Resistance to Toxicants. 

Toxicology is the subdiscipline of pharmacology concerned with adverse effects of chemicals on living systems. Toxic effects and mechanisms of action may be different from therapeutic effects and mechanisms for the same drug. Similarly, at the high dose of drugs at which toxic effects may be produced, rate processes are frequently altered compared with those at therapeutic doses. For these reasons, the terms toxicodynamics and toxicokinetics are now applied to these special situations. 

Along with the regulatory development, EPA prepares criteria documents which provide technical support for the final rules. These criteria documents identify fundamental information regarding health effects of contaminants in drinking water. Health-effects-related data such as physical and chemical properties, toxicokinetics, human exposure, health effects in animals and humans, mechanisms of toxicity, and quantification of toxicological effects are evaluated and serve as supporting documentation for the MCLGs. ... 

SubceUular distribution of Pb in human soft tissues appears to mainly involve the mitochondria and nuclei, two organelles known to either be affected toxicologically by lead or be involved in Pb sequestration and toxicokinetics. Intranuclear inclusion bodies, for example, have long been known to form as a transitory protective mechanism for averting or delaying lead toxicity. Lead in relatively large amounts is sequestered in nuclear inclusions and the biochemical and structural characteristics of these bodies have been described (Carroll et al., 1970 Moore et al., 1973). Cramer et al. (1974) showed the formation of intranuclear inclusions as an early response to Pb in kidney proximal tubule cells in new lead workers. 

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