Biopersistence and Translocation to Extrapulmonary Organs of Titanium Dioxide Nanoparticles after Subacute Inhalation Exposure to Aerosol in Adult and Elderly Rats

The increasing industrial use of nanoparticles (NPs) has raised concern about their impact on human health. Since aging and exposure to environmental factors are linked to the risk for developing pathologies, we address the question of TiO2 NPs toxicokinetics in the context of a realistic occupational exposure. We report the biodistribution in healthy young adults (12-13-week-old) and in elderly rats (19-month-old) exposed to 10 mg/m3 of a TiO2 nanostructured aerosol 6 hours/day, 5 days/week for 4 weeks. We measured Ti content in major organs using inductively coupled plasma mass spectrometry immediately and up to 180 days after the end of exposure. Large amounts of titanium were initially found in the lungs which were slowly cleared during the post-exposure period. From day 28, a small increase of Ti was found in the spleen and liver of young adults exposed rats. Such an increase was however never found in blood, kidneys or brain. In the elderly group, translocation to extra-pulmonary organs was significant at day 90. Ti recovered in spleen and liver of elderly exposed rats was higher than in exposed young adults. These data suggest that TiO2 NPs may translocate from the lungs to extra-pulmonary organs where they could eventually promote systemic side effects.