Repeated Inhalation Toxicity 14- and 28-Day Study

For evaluating the toxic characteristics of an inhalable material (e.g., gas, volatile chemical, or aerosol/particulate material), animals are subjected to repeated exposures after initial information on material toxicity has been obtained by acute testing. It provides information on health hazards likely to arise from repeated exposure via the inhalation route over a limited period of time. Hazards of inhaled chemicals are influenced by inherent toxicity and physical factors, such as volatility and particulate size. 

There is similarity in the conduct of a 28-day or 14-day repeated-dose inhalation study. This similarity allows the use of one guideline to cover both test durations. The main differences, however, lie in the time over which dosing takes place and the extent of clinical and pathologic investigations, which might be appropriate for shorter test duration. 

Several groups of animals are exposed daily to the test chemical for a defined period in graduated concentrations (one concentration per group) for a period of 28 days. When a vehicle is used to help generate an appropriate concentration of the test chemical in the atmosphere, a vehicle control group should be used. 

During the exposure period, animals are observed daily to detect signs of toxicity. Animals that die during the test are necropsied, and animals that have survived at the conclusion of the test are sacrificed and necropsied. 

Test System To conduct a repeated-dose inhalation toxicity study, different species may be used. However, this guideline is intended primarily for use with rodents. When a rodent is required, the preferred species is the rat. Commonly used laboratory strains of young, healthy animals should be employed. At the commencement of the study, the weight variation of animals should not exceed 20% of the mean body weight. When a repeated-dose inhalation study is conducted as preliminary to a long-term study, the same species should be used in both studies. 

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