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Arch Toxicol. 2019 Apr;93(4):909-920. doi: 10.1007/s00204-019-02410-z. Epub 2019 Feb 13.

Pulmonary and pleural toxicity of potassium octatitanate fibers, rutile titanium dioxide nanoparticles, and MWCNT-7 in male Fischer 344 rats.

Author information

1
Nanotoxicology Project, Nagoya City University, 3-1 Tanabe-Dohri, Mizuho-ku, Nagoya, 466-8603, Japan.
2
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
3
Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, Egypt.
4
Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt.
5
Nanotoxicology Project, Nagoya City University, 3-1 Tanabe-Dohri, Mizuho-ku, Nagoya, 466-8603, Japan. dalexand@phar.nagoya-cu.ac.jp.
6
Core Laboratory, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
7
Division of Risk Assessment, National Institute of Health Sciences, Tokyo, Japan.
8
Division of Cellular and Molecular Toxicology, National Institute of Health Sciences, Tokyo, Japan.
9
Japan Bioassay Research Center, Japan Industrial Safety and Health Association, Kanagawa, Japan.
10
Department of Biochemistry, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
11
Department of Biochemistry, Faculty of Veterinary Medicine, Beni-Suef University, Beni Suef, Egypt.
12
Nanotoxicology Project, Nagoya City University, 3-1 Tanabe-Dohri, Mizuho-ku, Nagoya, 466-8603, Japan. htsuda@phar.nagoya-cu.ac.jp.

Abstract

Potassium octatitanate (K2O·8TiO2, POT) fibers are used as an alternative to asbestos. Their shape and biopersistence suggest that they are possibly carcinogenic. However, inhalation studies have shown that respired POT fibers have little carcinogenic potential. We conducted a short-term study in which we administered POT fibers, and anatase and rutile titanium dioxide nanoparticles (a-nTiO2, r-nTiO2) to rats using intra-tracheal intra-pulmonary spraying (TIPS). We found that similarly to other materials, POT fibers were more toxic than non-fibrous nanoparticles of the same chemical composition, indicating that the titanium dioxide composition of POT fibers does not appear to account for their lack of carcinogenicity. The present report describes the results of the 3-week and 52-week interim killing of our current 2-year study of POT fibers, with MWCNT-7 as a positive control and r-nTiO2 as a non-fibrous titanium dioxide control. Male F344 rats were administered 0.5 ml vehicle, 62.5 µg/ml and 125 µg/ml r-nTiO2 and POT fibers, and 125 µg/ml MWCNT-7 by TIPS every other day for 2 weeks (eight doses: total doses of 0.25 and 0.50 mg/rat). At 1 year, POT and MWCNT-7 fibers induced significant increases in alveolar macrophage number, granulation tissue in the lung, bronchiolo-alveolar cell hyperplasia and thickening of the alveolar wall, and pulmonary 8-OHdG levels. The 0.5 mg POT- and the MWCNT-7-treated groups also had increased visceral and parietal pleura thickness, increased mesothelial cell PCNA labeling indices, and a few areas of visceral mesothelial cell hyperplasia. In contrast, in the r-nTiO2-treated groups, none of the measured parameters were different from the controls.

KEYWORDS:

Inhalation toxicity; Intra-tracheal intra-pulmonary spraying; MWCNT-7; Potassium octatitanate fibers; Titanium dioxide nanoparticles

PMID:
30759267
DOI:
10.1007/s00204-019-02410-z

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