Toxicology

Toxicology

Toxycology

Toxicology is the scientific discipline concerned with the detection, the effects and mechanisms of action of poisons and toxic chemicals. Toxicity is a relative phenomenon which depends on the structure and properties of a chemical compound, as well as its dose. Dose-response curves are usually obtained in animals exposed to different concentrations of a chemical. Exogenous chemicals are absorbed following ingestion, inhalation or skin contact, and then distributed to different organs. The chemicals are metabolized frequently, often through multiple pathways, resulting in products that may be more or less toxic than the original chemical. Later, one or more of these products can interact with the target macromolecule, resulting in a toxic effect. The point of toxicity is usually the body where the metabolism or excretion of toxic metabolites. The administered dose (external dose) may not be the same as the effective dose reaching the biological body and the target macromolecule. The basic principles of xenobiotic metabolism are:

Most xenobiotics are lipophilic, facilitating their transport by blood lipoproteins and their ability to cross lipid membranes. Toxic lipophilic to hydrophilic metabolites are metabolized in two steps. In the reactions of phase I, a polar functional group is added to the original compound. Reactions usually lead to oxidation and reactive intermediates and electrophiles as primary

One dilemma that always faces a toxicologist is to what extent the results of animal studies generated by testing programs can be extrapolated to a particular human exposure situation. Name five potential differences between human populations and animals in toxicity tests that may alter the reliability of an extrapolation. Briefly explain (one sentence may be all that is necessary) why this difference can produce a species-selective (species-specific) toxicity.

Principles of Toxicology

Extrapolation of research center animal data to gather human cancer danger is right now a key segment of regulatory choice making. The legitimacy of this approach obviously hinges on upon the significance of the trial animal model to people. Vast contrasts in cancer-causing reaction between experimental animals are not surprising. For instance, mice are profoundly impervious to the hepatocarcinogenic impacts of the contagious poison aflatoxin B 1 . Dietary dosages as high as 10,000 parts for every billion (ppb) neglected to process liver disease in mice, while in rats dietary measurements as low as 15 ppb transformed a noteworthy expand in liver tumors (p. 27). The unthinking premise for this dramatic contrast accordingly has all the earmarks of being fully identified with species contrasts in the interpretation of a specific type of glutathione S - transferase (mgsta3-3) that has uncommonly high synergist movement at the cancer-causing epoxide of aflatoxin. Mice express this chemical constitutively, though rats nor- mally express a nearly identified structure with significantly less detoxifying action to aflatoxin epoxide. In this manner, dietary medicine can breathtakingly change the affectability of an animal groups to a cancer-causing agent.

Explain what is meant by the term “ultimate toxicant.” (5 pts) Define in your own words a “target molecule.” (5 pts) List the three types of effects (not types of ...