Toxicological studies within the GLP regimen and in accordance with the OECD methods

 

Test No. 405:

Acute Eye Irritation/Corrosion

 

OECD Guidelines for the Testing of Chemicals

EU B.5, OECD 405

This method provides information on health hazard likely to arise from exposure to test substance (liquids, solids and aerosols) by application on the eye.

 

This Test Guideline is intended preferably for use with albino rabbit. The test substance is applied in a single dose in the conjunctival sac of one eye of each animal. The other eye, which remains untreated, serves as a control. The initial test uses an animal; the dose level depends on the test substance nature. A confirmatory test should be made if a corrosive effect is not observed in the initial test, the irritant or negative response should be confirmed using up to two additional animals. It is recommended that it be conducted in a sequential manner in one animal at a time, rather than exposing the two additional animals simultaneously. The duration of the observation period should be sufficient to evaluate fully the magnitude and reversibility of the effects observed. The eyes should be examined at 1, 24, 48, and 72 hours after test substance application. The ocular irritation scores should be evaluated in conjunction with the nature and severity of lesions, and their reversibility or lack of reversibility. The individual scores do not represent an absolute standard for the irritant properties of a material, as other effects of the test material are also evaluated.

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Test No. 404:

Acute Dermal Irritation/Corrosion

OECD Guidelines for the Testing of Chemicals

EU B.4, OECD 404

This method provides information on health hazard likely to arise from exposure to liquid or solid test substance by dermal application. This Test Guideline recommends sequential testing strategies, which include the performance of validated and accepted in vitro or ex vivo tests for corrosion/irritation.

The albino rabbit is the preferable laboratory animal. The substance to be tested is applied in a single dose to a small area of skin (approximately 6 cm²) of an experimental animal; untreated skin areas of the test animal serve as the control. The exposure period is 4 hours. Residual test substance should then be removed. The dose is 0.5ml (liquid) or 0.5g (solid) applied to the test site. The method consists of two tests: the initial test and the confirmatory test (used only if a corrosive effect is not observed in the initial test). All animals should be examined for signs of erythema and oedema during 14 days. The dermal irritation scores should be evaluated in conjunction with the nature and severity of lesions, and their reversibility or lack of reversibility. When responses persist to the end of the 14-day observation period, the test substance should be considered an irritant.

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Test No. 402:

Acute Dermal Toxicity

OECD Guidelines for the Testing of Chemicals

EU B.3 , OECD 402

This method provides information on health hazard likely to arise from a short-term exposure to solid or liquid test substance by the dermal route.

This Test Guideline is intended primarily for use with rodents (rat, rabbit or guinea pig may be used). For each dose at least 5 animals (of the same sex) are used. The test substance is applied to the skin (not less than 10 per cent of the body surface area) in graduated doses to several groups of experimental animals, one dose being used per group. At least three dose levels should be used, appropriately spaced to produce a dose-response curve. A limit test of at least 2000 mg/kg could be made. The observation period should be at least 14 days. During the first day the animals should be observed frequently and then the observations should be made daily. Necropsy of all animals should be carried out and all gross pathological changes should be recorded. A study of acute toxicity by the dermal route and determination of a dermal LD provides an estimate of the relative toxicity of a substance by the dermal route of exposure and they may serve as a basis for classification and labeling. It is an initial step in establishing a dosage regimen in subchronic and other studies and may provide information on dermal adsorption and the mode of toxic action of a substance by this route.