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Toxic effects of various modifications of a nanoparticle following inhalation

: Creutzenberg, Otto; Voss, Jens-Uwe; Mangelsdorf, Inge; Tillmann, Thomas; Pohlmann, Gerhard; Hansen, Tanja; Kock, Heiko; Schaudien, Dirk

Naunyn-Schmiedebergs archives of pharmacology 387 (2014), Supplement 1, pp.S6, A017
ISSN: 0028-1298
ISSN: 1432-1912
Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie (Annual Meeting) <80, 2014, Hannover>
Journal Article, Conference Paper
Fraunhofer ITEM ()

The toxic effects of the dust triple TiO2 UV TITAN M262, TiO2 UV TITAN M212 and TiO2 P25 (coded NM-103, NM-104 and NM-105, respectively, in the JRC repository) were compared in a 28-day inhalation test. Differences in crystal structure (rutile vs. anatase) or surface modification (hydrophobic vs. hydrophilic) suggested 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). This dosing scheme induced a non-, partial, and complete lung overload, respectively. Endpoints investigated after end of exposure (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. - PMN in BALF as inflammation indicator resulted in the low dose groups for NM-105 at control levels, whereas NM-103 and NM-104 induced 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. – Test item 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. A very low translocation potential of particles from lungs was detected. - Histopathology revealed a similar dosedependent character of changes between NM-103, NM-104 and NM-105. - TEM analysis showed intraalveolar macrophages as the most prominent compartment of particle detection. - Experimental and predicted NOAEL values (according to Pauluhn, 2011) were 3 and 5 mg/m3, respectively. A preliminary toxicity ranking on the basis of the induction of PMN influx and other endpoints is: NM-104 > NM-103 > NM-105. However, pronounced differences in toxicity were not observed between the three test items. The project was funded by the Federal Institute for Occupational Safety and Health (BAuA), Dortmund, Germany.