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Example text

Q16. The structure shown below is a potential rodenticide. Rodent pests will eat the compound in food. Suggest ways in which the compound might be metabolised and the enzymes responsible. Indicate any possible toxic metabolites which may be formed. Figure: Question 16. Q17. The chemical structure shown below is a potential fungicide being developed by a company. Toxicologists in the safety evaluation department need to know the likely metabolic fate of the compound before carrying out ecotoxicological studies.

C) Phase 3 metabolism is the further metabolism of products of phase 2 metabolism. These are normally conjugates. For example, glutathione conjugates are further metabolised by removal of the glutamyl and glycinyl moieties. The remaining cysteine is then acetylated. The further metabolism of some cysteine conjugates by the enzyme CS lyase may produce toxic products. For example, the industrial chemical hexachlorobutadiene undergoes this route of metabolism and causes kidney toxicity as a result.

Thus if a chemical is removed from the blood by an organ such as the liver (metabolism) or the kidney (excretion), then the blood flow is an important determinant of the clearance. Indeed clearance by an organ cannot be greater than the blood flow to that organ. (b) The bioavailability of a chemical is the proportion of the dose of the drug or other chemical which reaches the systemic circulation and is therefore available to the organism following absorption from a particular site. It can be determined experimentally by comparing the AUC after oral and after intravenous dosing and is often expressed as a percentage: Thus a chemical which is well absorbed from the gastrointestinal tract would have a bioavailability of perhaps 90%.

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