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Toxic effects of various modifications of a nanoparticle following inhalation

This project aimed at comparing the toxic effects of the triple TiO2 UV TITAN M262, TiO2 UV TITAN M212 and TiO2 P25 coded in the European nanomaterials repository with NM-103, NM-104 and NM-105. These differ in crystal structure (rutile; rutile; 80 % anatase/20 % rutile) and surface modifications (with silicone -> hydrophobic; with glycerol -> hydrophilic; untreated -> hydrophilic, respectively) suggesting a different toxic potential after uptake in lungs. Wistar rats were exposed to aerosol concentrations of 3, 12 and 48 mg/m3 mimicking exposure scenarios at workplaces (6 hours/day, 5 days/week for 28 days) while controls inhaled clean air. This dosing scheme induced a non-, partial, and complete lung overload, respectively.

Endpoints investigated upon cessation of exposure after 3 days, 1.5 and 3 months of recovery were i.) analysis of bronchoalveolar lavage fluid (BALF); ii.) histopathology; iii.) transmission electron microscopy (TEM) analysis; and iv.) chemical analysis of test item retention in lungs, liver, and brain.

Results: Lung wet weights showed dose-dependent increases for all three TiO2. PMN in BALF as inflammation indicator resulted in the low dose groups for NM-105 in a level similar to clean air controls, whereas NM-103 and NM-104 induced a slight inflammation reaching approx. 10% PMN. After 45 and 94 days of recovery in clean air, NM-103-treated animals also returned to normal; in contrary, NM-104-treated animals remained in the significant 5-8% range. In the mid and high dose groups, NM-105 showed a weaker inflammatory effect than NM-103 and NM-104.

Retention analysis data reflected well the different grades of clearance retardation due to the various lung loads and fitted to the values predicted by the MPPD model.

The soluble moiety of the test items (5.5 %, 2.2 % and 0.9 % in the low, mid and high dose groups) suggests that solubility of test items is limited by a given maximum under the conditions of the lung ambience. The translocation potential was very small.

Histopathology revealed a similar dose-dependent character of changes between NM-103, NM-104 and NM-105. In addition, all three groups exhibited a similar mode of deposition and distribution of particles in the respiratory tract. Although marginal differences in the degree of some changes exist, no obvious differences between the particles in terms of degree and character of induced lesions were observable.

TEM analysis showed intraalveolar macrophages as the most prominent compartment of particle detection. In the low/mid dose groups, the second important compartment were pneumocytes type I, whereas, in the high dose groups intraalveolar free particles were the second important compartment.

Experimental and predicted NOAEL values (according to Pauluhn, 2011) were 3 and 5 mg/m3, respectively. A preliminary ranking on the basis of the induction of PMN influx and other endpoints is: NM-104 > NM-103 > NM-105. Pronounced differences in toxicity were not observed between the three test items.

Bibliographic information

O. Creutzenberg:
Toxic effects of various modifications of a nanoparticle following inhalation. 
1. edition. Dortmund: Bundesanstalt für Arbeitsschutz und Arbeitsmedizin 2013. pages 404, Project number: F 2246, PDF file

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Research Project

Project numberF 2246 StatusCompleted Project Toxic effects of different modifications of a nanoparticle after inhalation

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