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

Abstract

BackgroundEngineered 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).MethodsTime-mated mice (C57BL/6BomTac) were exposed by inhalation 1h/day to 42 mg/m3 aerosolized powder (1.7·106 n/cm3; 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.ResultsParticles 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).ConclusionInhalation 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.

The potential health risk of titania nanoparticles

“…In fact, TNPs were shown to be transferred from pregnant mice to their pups [70][71][72][73]. When pregnant mice were treated with TNPs via subcutaneous injection, the genital and cranial nerve systems of the male offspring were affected [70].…”

“…When pregnant mice were treated with TNPs via subcutaneous injection, the genital and cranial nerve systems of the male offspring were affected [70]. When time-mated female mice were treated with TNPs, their offspring showed moderate neurobehavioral alterations, although cognitive function was not affected [71]. This finding can be explained by changes in the expression of genes associated with CNS development and function [72].…”

“…treated with uncoated rutile TNPs, anatase TNPs, and SiO 2 NPs [22]. UV Titan (rutile TiO2 modified with Al, Si, Zr and coated with polyalcohol) is reported to produce prolonged lung inflammation in dams and developmental neurotoxicity in pups [71]. In addition, it causes acute-phase immune and inflammatory responses by altering gene expression [121].…”

Transport of Nanoparticles through the Placental Barrier

“…However King-Heiden et al (2009) observed QD induced necrosis and yolk sac and tail malformation, which were not characteristic to Cd 2+ evoked effects, indicating that nanostructure exhibits new qualities that are not prominent in their components. Hougaard et al (2010) observed adverse effects on neurobehavior and fertility of the offspring's of TiO 2 exposed rats. The research highlighted that the maternal NP exposure can lead to indirect effects on embryogenesis without NP accumulation in the fetus.…”

Human health hazards of persistent inorganic and carbon nanoparticles

“…Potential effects on the lungs include damage to membranes, cytotoxicity, genotoxicity, apoptosis (induced programmed cell death), necrosis (cell death due to toxic interference with vital cell functions), inflammation, fibrosis, and cancer [1-3, and references therein]. Inhaled nanoparticles may penetrate the alveolar-capillary barrier between the respiratory and circulatory system, and thus be translocated from the lungs [2,3,[30][31][32][33][34][35][36][37][38][39][40][41][42], and references therein]. When the nanoparticles translocate to the circulatory system, other organs may also be affected [1-3, 15, 16, 30-32, 39-42].…”