Recommendations for the Conduct of Acute Inhalation Limit Tests

This paper reviews the scientific issues related to exposureconcentrations and particle sizes used in acute inhalation limittests. The current United States Environmental Protection Agency(USEPA) recommended exposure concentration for such tests is5 mg/liter, while this level is very high, it is often achievable.On the other hand, its toxicological relevance is questionable.The USEPA recommendation that 25% of the particle distributionbe less than 1 µm is a more difficult issue to address.Physical laws for aerosol particle generation and behavior limitthe minimum size of particles in an exposure atmosphere at aconcentration of 5 mg/liter. Particle size also influences depositionsite in the respiratory tract. Since damage to any region ofthe respiratory tract can produce lethality, and it is not possibleto predict, a priori, the most responsive region of the tractor the most harmful particle size of an untested agent, acutelimit testing should employ particles in a size range that depositsthroughout the entire rodent respiratory tract. Particles between1 and 4 µm mass median aerodynamic diameter (MMAD) arewell suited for such studies. It is, therefore, recommendedthat the limit test concentration should be the highest concentration(up to 5 mg/liter) that can be achieved while still maintaininga particle size distribution having an MMAD between 1 and 4µm.