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Factors influencing the variability of results in the assessment of acute toxicity

B. Svetličić ; Zavod za farmakologiju i toksikologiju Veterinarskog fakulteta u Zagrebu
M. Vandekar ; Institut za medicinska istraživanja Jugoslavenske akademije znanosti ·i umjetnosti, Zagreb

Puni tekst: hrvatski pdf 13.933 Kb

str. 11-24

preuzimanja: 197



The significance of newly synthetized compounds with regard to their toxicity and health hazards both for humans and domestic animals is discussed. It is pointed out that the extrapolation of experimental toxicity data on humans and domestic animals is not possible without a thorough understanding of the mechanism of the action of the substances tested. The factors influencing the variability of results in the assessment of acute toxicity are presented, with special reference to the determination of the toxicity of organophosphorus compounds. The autors' discussion is based on literature data and their own experience. The factors influencing the variability of results are divided into those relating (1) to the test substance, (2) to the experimental animal, and (3) to the route of administration. Amongst the factors relating to the test substance, the presence of impurities and the conversion of the sample in the course of its preparation and storage are specially emphasized. With regard to the factors relating to the experimental animal, the effect of the species, age, sex, and genetic factors is discussed. as well as the effect of the factors influencing the condition of the experimental animal. In this connection it is pointed out that in the assessment of results the treatment of animals under observation plays an important part. Different routes of administration may also be the cause of great variability of the results. They determine how long it will take the poison to attain a certain level in the blood, what kind of the detoxifying mechanism will be put in action and to what extent, and by which route and rate the poison will be eliminated from the body. The vehicle used in the application of the test substance may also produce a considerable effect on the absorption rate of the poison. The authors conclude that experimental data on the acute toxicity of .a compound cannot be considered satisfactory, unless besides basic statistical data they contain all the information on the experimental conditions that may be of significance either to the substance tested, or the experimental animal, or the route of administration.

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