Increased Pulmonary Toxicity of Inhaled Ultrafine Particles: Due to Lung Overload Alone?

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Abstract
Groups of rats were exposed 6 h per day, 5 days per week for 12 weeks as follows: (1) control (filtered air); (2) TiO2-F (∼250 nm particle size); (3) TiO2-D (∼20 nm particle size); and (4) SiO2 (cristobalite, 800 nm particle size). At the end of exposure, retained lung burdens were 6.62 and 5.22 mg for TiO2-F and TiO2-D, respectively, and 0.34 mg for SiO2. Inflammatory parameters in lung lavage fluid (cells, protein, enzymes) were highly increased in the SiO2 and TiO2-D group and only moderately in the TiO2-F group. Long-term lung clearance of 85Sr test particles, instilled or inhaled at the end of the dust exposures, was significantly prolonged in the SiO2 and TiO2-D groups by factors of 28 and 8 and only moderately by a factor of 2 in the TiO2-F group compared to control. Pulmonary retention of TiO2-D particles was likewise highly increased whereas TiO2-F retention was less prolonged despite a slightly higher initial lung dust burden. We conclude, that inhalation of ultrafine particles of nuisance dusts can lead to increased pulmonary toxicity and that TLVs should be revised to take this into account.

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