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

• Published in: Archives of toxicology Vol. 93; no. 4; pp. 909 - 920
• Main Authors: Abdelgied, Mohamed, El-Gazzar, Ahmed M., Alexander, David B., Alexander, William T., Numano, Takamasa, Iigou, Masaaki, Naiki-Ito, Aya, Takase, Hiroshi, Abdou, Khaled Abbas, Hirose, Akihiko, Taquahashi, Yuhji, Kanno, Jun, Abdelhamid, Mona, Tsuda, Hiroyuki, Takahashi, Satoru
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2019; Springer Nature B.V
• Subjects: Alveoli; Anatase; Animals; Asbestos; Biocompatibility; Biomedical and Life Sciences; Biomedicine; Carcinogenicity; Carcinogens; Chemical composition; Environmental Health; Fibers; Granulation; Hyperplasia; Inhalation; Inhalation Exposure; Lung - drug effects; Lung - metabolism; Lung - pathology; Lungs; Macrophages; Macrophages, Alveolar - drug effects; Macrophages, Alveolar - metabolism; Macrophages, Alveolar - ultrastructure; Male; Nanoparticles; Nanoparticles - toxicity; Nanotoxicology; Nanotubes, Carbon - toxicity; Occupational Medicine/Industrial Medicine; Organ Size - drug effects; Organic chemistry; Pharmacology/Toxicology; Pleura; Pleura - drug effects; Pleura - metabolism; Pleura - pathology; Potassium; Proliferating cell nuclear antigen; Rats, Inbred F344; Respiration; Rutile; Spraying; Surgical implants; Thickening; Tips; Tissue Distribution; Titanium; Titanium - pharmacokinetics; Titanium - toxicity; Titanium dioxide; Toxicity; Inhalation toxicity; Potassium octatitanate fibers; Intra-tracheal intra-pulmonary spraying; MWCNT-7; Titanium dioxide nanoparticles
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-019-02410-z

Potassium octatitanate (K 2 O·8TiO 2 , 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-nTiO 2 , r-nTiO 2 ) 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-nTiO 2 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.