In the assessment and evaluation of the toxic characteristics of a chemical, the determination of sub-chronic oral toxicity using repeated doses may be carried out after initial information on toxicity has been obtained from acute or repeated dose 28-day toxicity tests. The 90-day study provides information on the possible health hazards likely to arise from repeated exposure over a period of rapid growth and into young adulthood. The study will provide information on the major toxic effects, indicate target organs and the possibility of accumulation, and can provide an estimate of a no-observed-adverse-effect level of exposure which can be used in selecting dose levels for chronic studies and for establishing safety criteria for human exposure. The revised guideline allows for the identification in non-rodent species of adverse effects of chemical exposure and should only be used :
− where effects observed in other studies indicate a need for clarification/characterisationin a second, non-rodent species, or
− where toxicokinetic studies indicate that the use of a specific non-rodent species is themost relevant choice of laboratory animal, or
− where other specific reasons justify the use of a non-rodent species
PRINCIPLE OF THE TEST:
The test substance is orally administered daily in graduated doses to several groups of experimental animals, one dose level per group for a period of 90 days. During the period of administration the animals are observed closely for signs of toxicity. Animals which die or are killed during the test are necropsied and at the conclusion of the test surviving animals are also killed and necropsied.