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

Abstract

Background: Engineered nanoparticles are smaller than 100 nm and designed to improve or achieve new physico-chemical 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.

Figure 1

TEM image of TiO₂ crystallites. Transmission electron microscopy image showing the typical equidimensional to elongated morphology of the TiO₂ crystallites in UV-Titan L181. Bar = 50 nm.

Figure 2

Characteristics of the exposure atmosphere. A) Particle number size distribution of the UV-Titan L181 in the exposure chamber. Data are based on nine one-hour exposure measurements. Mean ± SD. B) Accumulated number and mass concentration of particle concentrations in the exposure chamber. It is assumed that the optical and mobility particle sizes can be directly compared and data gap is filled by linear interpolation.

Figure 3

Differential cell count in bronchoalveolar lavage fluid. The total number of cells in BAL subdivided by cell type. A: time-mated mice that had not achieved pregnancy, 5 days after termination of exposure (n = 8-9). B: littering time-mated dams after weaning, 26-27 days after exposure (n = 10-14). Mean ±SEM. *p < 0.05, **p < 0.01, and ***p < 0.001 vs. controls.

Figure 4

Open field. Open field performance during a 3-min observation period in male and female offspring from dams exposed to ambient air or TiO₂ during gestation. (A) Ambulation. (B) Visits to the central zone of the open field. Time spent in central zone of the open field (C). Mean ± SEM, n = 12-14. *p < 0.05, **p < 0.01, vs. same gender controls.

Figure 5

Prepulse inhibition. Prepulse inhibition in male (A) and female (B) offspring from dams exposed to ambient air or TiO₂ during gestation, at four different levels of prepulse. Mean ± SEM, n = 10-14. (*) 0.05 <p < 0.1; *p < 0.05 vs. controls at same level of prepulse.

Figure 6

Time-to-first F2 litter. Littering curves for male offspring of control and UV-titan exposed pregnant mice. As adults, male C57BL offspring were mated to naïve CBA/J mice and time-to-first-delivery of F2 litter was recorded.