Acute toxicity testing purpose

Zbinden, G. (1984). Acute toxicity testing, purpose. In Acute Toxicity Testing Alternative Approaches (Goldberg, A., Ed.). Mary Ann Liebert, New York, pp. 5-22. 

How close do the above estimates relate to the actual LD50 Studies have shown that the approximate lethal dose for 86% of those chemicals tested in this manner were within 30% of the known LD50 values determined by the classical approach. The method is not infallible for example, some 14% of chemicals were outside this range and no dose-response or slope information can be obtained. International agreement has been reached that the up-and-down procedure could replace the conventional acute toxicity test for the purposes of hazard classification and label (including color-coding) production. 

It is necessary to determine the toxicity of a drug. The maximum tolerable dose and area under curve are established in rodents and non-rodents. There are two types of toxicity studies single dose and repeated dose. Single dose acute toxicity testing is conducted for several purposes, including the determination of repeated doses, identification of organs subjected to toxicity, and provision of data for starting doses in human clinical trials. 

Identifying the LD50 is not the only purpose of the acute toxicity study. The LD50 provides a reasonably reliable indication of the relative acute toxicities of chemicals, and this is obviously important. But an even more important reason exists for conducting such tests, and that is to prepare the way for more extensive study of subchronic and chronic exposure. 

Norway has a standardized test program for permit derivation, comprising the Ames mutagenicity test, acute and chronic toxicity tests, and a biodegradation test. For monitoring purposes, it is advised to start screening the toxicity of an effluent with a comparatively large... 

The guidance document offers a comparison of TG 420 (Fixed Dose Method), TG 423 (Acute Toxic Class Method), and TG 425 (Up-and-Down Procedure). The purpose of this Guidance Document is to provide information to assist with the choice of the most appropriate Guideline to enable particular data requirements to be met while reducing the number of animals used and animal suffering. The Guidance Document also contains additional information on the conduct and interpretation of test guidelines 420, 423, and 425. 

Following the determination of its acute toxicity, the pesticide is then evaluated in subchronic studies (Table 1). Subchronic exposure usually lasts for 90 days and its objective is to generally evaluate and characterize the effects of the test substance when administered to laboratory animals on a daily basis. EPA requires that subchronic studies be performed in two species, the rat and dog, and at several dosage levels. The test substance is normally administered to the animals in their diet. However, when pesticide use involves purposeful application to or prolonged exposure of human skin, or if... 

Data requirements for new chemicals are tied to the quantity of chemical actually placed on the market. The Base Set consists of chemistry, production details, proposed uses and handling precautions, acute toxicity, skin and eye irritation, in vitro mutagenicity, and environmental fate [3]. Base Set data are required for chemicals sold in quantities of <1 tonne a chemicals used in small quantities, for research and development purposes only, may be excused. Further tests are added to the base set requirements as the quantity sold increases up to the highest level of 1000 tonnes a /manufacturer, or 5000 tonnes total. 

The LD50 may be either oral or dermal , depending on the method of exposure. Lethal doses with respect to inhalation of chemicals in the form of a gas or aerosol can also be tested. In this case, the concentration of gas or vapor that kills half the animals is known as the lethal concentration for 50%, or the LC50. The LD50 and LC50 are very widely used as indices of toxicity. The criteria shown in Table 8.1 are often used for purposes of classification of acute toxic effects in animals. In order to classify the acute toxicity of chemicals to humans, the scale shown in Table 8.2 can be used (see also IPGS 1996). 

A comparison of some of the above-mentioned preliminary prescreening results with those of a regular 4-hour test of acute inhalation toxicity (see Section 5.1.2.1.) demonstrates the reliability of this inexpensive and rapid method for orientation purposes in most cases (Table 18). 

Colchicine provides dramatic relief from acute attacks of gout. The effect is sufficiently selective that the drug has been used for diagnostic purposes, but the test is not infallible. Colchicine also has an established role in preventing and aborting acute attacks of gout. However, its toxicity and the availability of alternative agents that are less toxic have substantially lessened its usefulness. 

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