Incorporation of particle size differences between animal studies and human workplace aerosols for deriving exposure...

Inhalation animal studies usually employ homogeneous aerosols of small particle diameter. By contrast, workers are usually exposed to coarser and more heterogeneous aerosols. The particle size distribution of an aerosol will determine the deposited fraction of inhaled particles in the various regions of the respiratory tract in rodents and humans. The deposited, and subsequently retained, doses in these regions correlate closely with long-term toxic effects. Yet, differences in deposited doses between animals and humans due to particle size differences of aerosols have not been consistently taken into account in risk assessment. This paper describes an approach to calculate equivalent human concentrations (EHC) for respiratory tract effects after inhalation using workplace particle size information. Worker's exposure to the EHC results in the same deposited dose in the respiratory tract as achieved in animals exposed to the experimental particle size distribution. Example data for nickel compounds demonstrate that exposure levels used in the rat studies are equivalent to 4-11-fold higher levels of human workplace exposures. This approach is equally applicable to other metal/inorganic particulates that exert adverse effects on the respiratory tract after inhalation. Dosimetric extrapolation should be a first step in the derivation of limit values based on animal local respiratory effects.