Repeated Dose Dermal Toxicity 21/28 days study. OECD 410: 1981.
Test with the Certificate of Good Laboratory Practices (GLPs).
This test provides information on possible health risks that may arise from repeated exposures of a product via dermal route. The test according to OECD Guideline 410 provides information on the effects of repeated exposure and may indicate the need for longer-term studies, as well as provide information on the dose levels that should be used in them. The extrapolation of the results of the study to man is valid to a limited degree but can provide useful information on the degree of percutaneous absorption of a substance.
In this procedure, adult rats, rabbits or guinea pigs can be used. The test chemical is applied daily on at least 10% of the body surface for several hours a day, for a period of 21/28 days. It should be applied in graduated doses on the skin of several groups of experimental animals, using one dose per group. For each dose level, at least 10 animals (5 females and 5 males) with healthy skin are used. A minimum of three dose levels should be used, with a control, and when appropriate a vehicle control. While the higher dose level should produce toxic effects, but not produce an incidence of deaths that precludes a meaningful evaluation, the lower dose level should not produce evidence of toxicity. In addition, an additional group or satellite of treated animals can be used that will be maintained for 14 days without treatment to study the recovery or persistence of the toxic effects. Also, for substances for which no toxicity is expected based on the existing data of structurally related compounds, a limit test can be performed. For this, the chemical must be tested at a dose level of at least 1,000 mg/kg of body weight per day.
During the application period, animals are observed daily for signs of toxicity. Both the animals that die or are sacrificed during the test, and the surviving animals that are slaughtered at the end of the study are necropsied. At the end of the trial period, a haematological examination, clinical biochemistry determinations, and pathological anatomy studies (necropsy and histopathology) should be performed.