Effects of prenatal exposure to surface-coated nanosized titanium dioxide (UV-Titan). A study in mice

Background: Engineered nanoparticles are smaller than 100 nm and designed to improve or achieve new physicochemical properties. Consequently, also toxicological properties may change compared to the parent compound. We examined developmental and neurobehavioral effects following maternal exposure to a nanoparticulate UV-filter (UV-titan L181). Methods: Time-mated mice (C57BL/6BomTac) were exposed by inhalation 1h/day to 42 mg/m(3) aerosolized powder (1.7.10(6) n/cm(3); peak-size: 97 nm) on gestation days 8-18. Endpoints included: maternal lung inflammation; gestational and litter parameters; offspring neurofunction and fertility. Physicochemical particle properties were determined to provide information on specific exposure and deposition. Results: Particles consisted of mainly elongated rutile titanium dioxide (TiO2) with an average crystallite size of 21 nm, modified with Al, Si and Zr, and coated with polyalcohols. In exposed adult mice, 38 mg Ti/kg was detected in the lungs on day 5 and differential cell counts of bronchoalveolar lavage fluid revealed lung inflammation 5 and 26-27 days following exposure termination, relative to control mice. As young adults, prenatally exposed offspring tended to avoid the central zone of the open field and exposed female offspring displayed enhanced prepulse inhibition. Cognitive function was unaffected (Morris water maze test). Conclusion: Inhalation exposure to nano-sized UV Titan dusts induced long term lung inflammation in time-mated adult female mice. Gestationally exposed offspring displayed moderate neurobehavioral alterations. The results are discussed in the light of the observed particle size distribution in the exposure atmosphere and the potential pathways by which nanoparticles may impart changes in fetal development.