Acute biological effects of intratracheally instilled titanium dioxide whiskers compared with nonfibrous titanium dioxide and amosite in rats

Our plain-English summary of Acute biological effects of intratracheally instilled titanium dioxide whiskers compared with nonfibrous titanium dioxide and amosite in rats, by Y. Ishihara, H. Kyono, N. Kohyama, et al (Inhalation Toxicology, 1999).

The study

• Authors: Y. Ishihara, H. Kyono, N. Kohyama, N. Otaki, F. Serita, T. Toya, J. Kagawa
• Journal: Inhalation Toxicology
• Published: 1999;11(2):131-49
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The dimensions of man-made mineral fiber whiskers are similar to those of some kinds of asbestos. Thus these mineral fibers raise the concern for potential health hazard for workers exposed in the occupational environments. This study was designed to define acute biological effects of intratracheally administered titanium dioxide whiskers (TO1) compared with nonfibrous titanium dioxide (TOP) and UICC amosite (Ams), and their relations to acute lung inflammation in rats. The observed geometric mean length (microm) and width (microm) and geometric standard deviation are: TO1(2.1[2.0], 0.14[1. 53]); Ams (4.3[3.3], 0.31[1.9]); and TOP (50 nm, 1-2 microm aggregates). Ten-week-old Wistar-Jcl male rats received a single tracheal injection of test materials at doses between 0.05 and 1.0 mg/rat. Control animals were injected with the same volume of saline. Lung tissue and bronchoalveolar lavage (BAL) fluid were collected from rats on days 1, 3, and 7 after administration. In the group injected with TO1, total protein, cytokine-induced neutrophil chemoattractant (CINC)/growth-regulated gene product (GRO), interleukin (IL) 1beta, and tumor necrosis factor (TNF) alpha increased on day 1. Subsequently, total elastolytic activity and fucose levels in BAL increased by day 3. All parameters, except for fucose in BAL, recovered to the normal levels. Animals in the Ams group showed increased total protein and CINC/GRO and decreased total elastolytic activity in a dose-dependent manner on day 1. The fucose level increased on day 3 in the Ams group. All parameters returned to their control levels on day 7. Animals in the TOP group did not show significant changes any of parameters during the experimental period. Gene expression of TNF-alpha and monocyte chemoattractant protein (MCP) 3 in the lung increased dose-dependently in the animals treated with the three materials. The mRNAs for eotaxin and MIP-1alpha were overexpressed in the lung of animals treated with Ams and TO1, while RANTES mRNA was overexpressed dose-dependently in the lung of animals treated with Ams on day 1. Onset of inflammatory response was more rapid in the Ams group than the TO1 group. Recovery of the fucose level in BAL was slower in the TO1 group than in the Ams group, though we observed similar histopathological changes in the lung of animals with TO1 or Ams. We conclude that whisker-induced acute biological effects in the lung may be related to the shape of the whiskers and not to their chemical composition or surface crystal structure, showing biological effects similar to those of UICC amosite.

In plain English

This animal experiment compared the short-term lung effects of three materials in rats: titanium dioxide whiskers (a man-made fiber), non-fibrous titanium dioxide particles, and UICC amosite asbestos. The study used 132 male rats aged 10 weeks. Treated rats each received a single dose of 0.05 to 1.0 mg of one material injected into the windpipe; control rats received saline. Lung fluid and lung tissue were examined 1, 3 and 7 days later. The whiskers and amosite both raised lung-inflammation markers, such as total protein and the signal CINC/GRO, mostly at the 1.0 mg dose. The non-fibrous titanium dioxide caused no significant changes in the lung-fluid measures. In lung tissue, however, it increased expression of two inflammation-related genes, TNF-alpha and MCP-3, as all three materials did. Inflammation began earlier with amosite. One marker, fucose, stayed raised longer with the whiskers. The authors concluded that the whiskers' effects may be linked to their fiber shape rather than their chemistry, and that long-term inhalation studies are needed. They noted that they studied only acute, not chronic, effects.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: animal experiment: single intratracheal (windpipe) injection in rats, with lung fluid and tissue examined 1, 3 and 7 days later
• Who was studied: 132 male Wistar-Jcl rats, 10 weeks old, divided into groups of 4; control animals were injected with saline
• Exposure: Titanium dioxide whiskers (TO1, geometric mean length 2.1 µm, width 0.14 µm), non-fibrous globular titanium dioxide particles (TOP), and UICC amosite (geometric mean length 4.3 µm, width 0.31 µm), at doses between 0.05 and 1.0 mg per treated rat; controls received the same amount of saline
• Main results:
  • On day 1, total protein in lung fluid was significantly increased only in the 1.0 mg whisker (TO1) group among whisker-treated rats. Amosite-treated rats showed a significant, dose-dependent increase.
  • Fucose in lung fluid was significantly increased on days 3 and 7 in rats given 0.2 and 1.0 mg of whiskers. In amosite-treated rats it was significantly increased only at 1.0 mg on day 3.
  • On day 3, total elastolytic (tissue-degrading enzyme) activity was significantly increased in rats given 1.0 mg of whiskers or amosite. On day 1 it was decreased in a dose-dependent way in the amosite group.
  • On day 1, TNF-alpha in lung fluid increased in a dose-dependent way in the whisker group. The non-fibrous titanium dioxide and amosite groups showed only a tendency to increase, which was not statistically significant.
  • CINC/GRO in lung fluid was significantly increased on day 1 at 1.0 mg of whiskers and at 0.2 and 1.0 mg of amosite. It was still significantly high at 1.0 mg of amosite on day 7.
  • Non-fibrous titanium dioxide caused no significant changes in the lung-fluid measures during the experiment.
  • Expression (mRNA levels) of the TNF-alpha and MCP-3 genes in lung tissue rose in a dose-dependent way on days 1 and 3 with all three materials, and returned to normal by day 7. Eotaxin mRNA rose with whiskers or amosite. RANTES mRNA rose with 1.0 mg of amosite on day 1.
  • Inflammation, as shown by the rise in total protein, began earlier with amosite than with whiskers. Recovery of fucose levels was slightly delayed with whiskers.
• The authors' conclusion: The authors concluded that lung injury from the titanium dioxide whiskers may be associated with the whiskers' shape rather than their chemical composition or surface crystal structure. They also concluded that long-term inhalation studies are required to assess the health hazards of whisker fibers.
• Limitations the authors state:
  • Only acute (short-term), not chronic, effects were studied.
  • The precision of the RT-PCR gene-expression technique should be considered when interpreting those results.
  • The mechanism of eosinophil accumulation and the role of eosinophils were not worked out in this study.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Amosite.

Medical terms in this study, explained in our Lexicon: Amosite, Mineral Fiber, UICC, Inflammation, Bronchoalveolar Lavage (BAL), Cytokine, Necrosis, Crystal Structure.

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