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Derivation of PM10 size-selected human equivalent concentrations of inhaled nickel based on cancer and non-cancer effects on the respiratory tract

Abstract Nickel (Ni) in ambient air is predominantly present in the form of oxides and sulfates, with the distribution of Ni mass between the fine (particle aerodynamic diameter < 2.5 µm; PM2.5) and coarser (2.5–10 µm) size-selected aerosol fractions of PM10 dependent on the aerosol's origin. When deriving a long-term health protective reference concentration for Ni in ambient air, the respiratory toxicity and carcinogenicity effects of the predominant Ni compounds in ambient air must be considered. Dosimetric adjustments to account for differences in aerosol particle size and respiratory tract deposition and/or clearance among rats, workers, and the general public were applied to experimentally- and epidemiologically-determined points of departure (PODs) such as no(low)-effect concentrations, for both cancer and non-cancer respiratory effects. This approach resulted in the derivation of threshold-based PM10 size-selected equivalent concentrations (modified PODs) of 0.5 µg Ni/m3 based on workers' cancer effects and 9–11 µg Ni/m3 based on rodent respiratory toxicity effects. Sources of uncertainty in exposure extrapolations are described. These are not reference concentrations; rather the derived PM10 size-selected modified PODs can be used as the starting point for the calculation of ambient air reference concentrations for Ni. The described approach is equally applicable to other particulates.