Acute oral toxicity.
The purposes of acute toxicity testing are to obtain information on the biologic activity of a chemical and gain insight into its mechanism of action. The information on acute systemic toxicity generated by the test is used in hazard identification and risk management in the context of production, handling, and use of chemicals. The LD50 value, defined as the statistically derived dose that, when administered in an acute toxicity test, is expected to cause death in 50% of the treated animals in a given period, is currently the basis for toxicologic classification of chemicals. For a classical LD50 study, laboratory mice and rats are the species typically selected. Often both sexes must be used for regulatory purposes. When oral administration is combined with parenteral, information on the bioavailability of the tested compound is obtained. The result of the extensive discussions on the significance of the LD50 value and the concomitant development of alternative procedures is that authorities today do not usually demand classical LD50 tests involving a large number of animals. The limit test, the fixed-dose procedure, the toxic class method, and the up-and-down methods all represent simplified alternatives using only a few animals. Efforts have also been made to develop in vitro systems; e.g., it has been suggested that acute systemic toxicity can be broken down into a number of biokinetic, cellular, and molecular elements, each of which can be identified and quantified in appropriate models. The various elements may then be used in different combinations to model large numbers of toxic events to predict hazard and classify compounds.
Walum
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Cell and Molecular Biology, Research Department, Pharmacia & Upjohn, Stockholm, Sweden. erik.walum@eu.pnu.com
D000284:Administration, Oral; D000826:Animal Testing Alternatives; D000818:Animals; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008954:Models, Biological; D011237:Predictive Value of Tests; D051381:Rats