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Cancer Sci. 2018 Jul;109(7):2164-2177. doi: 10.1111/cas.13643. Epub 2018 Jun 22.

Potassium octatitanate fibers induce persistent lung and pleural injury and are possibly carcinogenic in male Fischer 344 rats.

Author information

1
Nanotoxicology Project, Nagoya City University, Nagoya, 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
Core Laboratory, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
6
Division of Risk Assessment, National Institute of Health Sciences, Tokyo, Japan.
7
Division of Cellular and Molecular Toxicology, National Institute of Health Sciences, Tokyo, Japan.
8
Japan Industrial Safety and Health Association, Japan Bioassay Research Center, Kanagawa, Japan.

Abstract

Potassium octatitanate fibers (K2 O·8TiO2 , POT fibers) are widely used as an alternative to asbestos. We investigated the pulmonary and pleural toxicity of POT fibers with reference to 2 non-fibrous titanium dioxide nanoparticles (nTiO2 ), photoreactive anatase (a-nTiO2 ) and inert rutile (r-nTiO2 ). Ten-week-old male F344 rats were given 0.5 mL of 250 μg/mL suspensions of POT fibers, a-nTiO2 , or r-nTiO2 , 8 times (1 mg/rat) over a 15-day period by trans-tracheal intrapulmonary spraying (TIPS). Rats were killed at 6 hours and at 4 weeks after the last TIPS dose. Alveolar macrophages were significantly increased in all treatment groups at 6 hours and at 4 weeks. At week 4, a-nTiO2 and r-nTiO2 were largely cleared from the lung whereas a major fraction of POT fibers were not cleared. In the bronchoalveolar lavage, alkaline phosphatase activity was elevated in all treatment groups, and lactate dehydrogenase (LDH) activity was elevated in the a-nTiO2 and POT groups. In lung tissue, oxidative stress index and proliferating cell nuclear antigen (PCNA) index were elevated in the a-nTiO2 and POT groups, and there was a significant elevation in C-C motif chemokine ligand 2 (CCL2) mRNA and protein in the POT group. In pleural cavity lavage, total protein was elevated in all 3 treatment groups, and LDH activity was elevated in the a-nTiO2 and POT groups. Importantly, the PCNA index of the visceral mesothelium was increased in the POT group. Overall, POT fibers had greater biopersistence, induced higher expression of CCL2, and provoked a stronger tissue response than a-nTiO2 or r-nTiO2 .

KEYWORDS:

inhalation toxicity; potassium octatitanate fiber; rat; titanium dioxide nanoparticle; trans-tracheal intrapulmonary spraying

PMID:
29774637
PMCID:
PMC6029824
DOI:
10.1111/cas.13643
[Indexed for MEDLINE]
Free PMC Article

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