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A Practical Approach to Toxicological Investigations by Alan Poole, George B. Leslie

By Alan Poole, George B. Leslie

First released in 1989, this ebook recognizes that new medications, foodstuff ingredients and different compounds must be rigorously screened for poisonous side-effects. the majority of this examine is dedicated to the sensible questions of 'what toxicological experiences may still we perform?' and 'how should still we practice them?' Compounds which endure toxicity checking out should be very easily categorized as these that are meant for management to guy and people which aren't. the previous comprise prescribed drugs for use medicinally or prophylactically and chemical compounds that are further to our nutrition, beverages or drugs to enhance their balance, visual appeal or palatability. because it is on prescribed drugs that the main entire toxicological reviews are commonly played, this ebook has been directed basically in the direction of to toxicological evaluate of capability new medicinal drugs. the rules and technique of toxicological overview of different kinds of compounds are primarily comparable.

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Clinical trials should provide: Pharmacology data: dose-response relationships, therapeutic index, optimum dose, etc. Pharmaco kinetic data: absorption, bioavailability, distribution, metabolism, protein binding, excretion, etc. Drug interactions: important for drugs with high protein binding, metabolised extensively in the liver (effect of metabolic inducers). Effect of concomitantly prescribed drugs on blood levels of test material. Therapeutic efficacy: well designed, double blind trials, controlled with a placebo and/or another approved drug.

Such 'social problems' can be overcome by caging animals individually. While this is obviously necessary in reproductive studies it is often a disadvantage in most other types of long term studies since singly housed animals are usually more aggressive and can be more difficult to handle and dose. Another disadvantage of single caging is that it uses more space in an animal facility and is more labour intensive. Although in some strains of mice the males may fight when put together, this problem can be minimised if they are group housed when they are very young.

G. clinical chemistry parameters (see Chapter 5), thereby possibly giving a false indication of a toxicological response. It is also not uncommon tofindthat rodents learn to separate the drug from their diet and avoid eating it, although this problem can sometimes be resolved by formulating the drug/diet mixture into pellets. Another problem is that drug-contaminated dust can be generated from such drug/diet mixtures, which may be inhaled or ingested by other animals, including controls, present in the facility.

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