90-Day Dermal Toxicity – EPA-OPPTS 870-3250: 1998

 

Test with the Certificate of Good Laboratory Practices (GLPs)

 

The subchronic dermal toxicity test allows the determination of the dose level without observable effect (NOAEL) and the toxic effects associated with continuous or repeated exposure to a test substance over a period of 90 days. The extrapolation of the test results to humans is only valid to a limited extent, but it can provide useful information about the degree of percutaneous absorption, the target organs and the possibilities of accumulation. In addition, it is useful to select the dose level for chronic studies and to establish safety criteria for human exposure.

The test can be performed in rats, rabbits or guinea pigs. At least groups of three dose levels, one control, and solvent control should be used if necessary, with 20 animals each (10 of each sex). The animals should be treated with the test substance at least 6 hours a day and for a period of at least 90 days. The highest dose should produce toxic effects, while the lowest dose should not show adverse effects. Additionally, a satellite or additional group of 20 animals with treatment and 20 control animals can be included to study the reversibility or persistence, and the delayed appearance of the toxic effects during a post-treatment period of not less than 28 days. This guideline also contemplates the possibility of carrying out a limit test with a concentration of 1.000 mg/Kg of body weight.

Animals should be evaluated daily to assess mortality and morbidity. A detailed clinical analysis should be done weekly. At the end of the study, reactivity to stimuli and motor activity should be evaluated. An ophthalmological, hematological, and clinical chemistry analysis should also be performed. In addition, all animals, including control and high-dose animals, must undergo a necropsy and complete histopathology.