Inhalation toxicity study of disk-shaped potassium octatitanate particles (terracess TF) in rats following 90 days of aerosol exposure

Our plain-English summary of Inhalation toxicity study of disk-shaped potassium octatitanate particles (terracess TF) in rats following 90 days of aerosol exposure, by S. Sakai, K. Inada, A.K. Tanaka, et al (Inhalation Toxicology, 2010).

The study

• Authors: S. Sakai, K. Inada, A.K. Tanaka, D.P. Kelly, G.P. Sykes, K.P. Lee
• Journal: Inhalation Toxicology
• Published: 2010;22(1):56-68
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Since fibrous particles such as asbestos and some man-made fibers (MMF) have been known to produce carcinogenic or fibrogenic effects, disk-shaped potassium octatitanate (POT) particles (trade name: Terracess TF) were manufactured as nonfibrous particles. A 90-day inhalation toxicity study of Terracess TF was performed to evaluate comparative inhalation toxicity of the disk shape with a fibrous shape that was previously evaluated. Four groups of 20 male and 15 female rats each were exposed to Terracess TF aerosols at concentrations of 0, 2, 10, or 50 mg/m(3) for 90 days. Ten male and 10 female rats per group were sacrificed at 90 days of exposure. After 90 days of exposure, 5 male rats per group were sacrificed at 3 wk of recovery period and 4-5 male rats per group or 5 female rats per group were sacrificed at 15 wk of recovery for lung clearance and histopathology. The mass median aerodynamic equivalent diameter (MMAED) of the aerosols of test materials ranged from 2.5 to 2.9 microm. There were no test-substance-related adverse effects on clinical observations. At the end of the 90-day exposure, a slight increase in lung-to-body weight ratios was observed at 50 mg/m(3) in male but not in female rats. However, lung weights were within normal limits after 3- or 15-wk recovery periods. Microscopically, inhaled Terracess TF particles were mostly phagocytized by free alveolar macrophages (AMs) in the alveolar airspaces and alveolar walls maintained normal structure at 2 and 10 mg/m(3). At 50 mg/m(3), some alveoli were distended and filled with aggregates of particle-laden AMs. The alveolar walls showed slight type II pneumocyte hyperplasia, but neither proliferative inflammation nor alveolar fibrosis was present at 50 mg/m(3). The clearance half-times for Terracess TF were estimated to be in the order of 6 to 9 mo for the 50-mg/m(3) group and 2 to 3 mo for the 10- and 2-mg/m(3) groups. The lung responses and lung clearance rate were comparable to those of "nuisance" type dusts at these concentrations. Based on interpretation that aggregated particle-laden AMs in alveoli was considered to be an early histopathological sign of lung overloading, an effect level was considered to be 50 mg/m(3) and no-observedadverse- effect level (NOAEL) was 10 mg/m(3). This experiment clearly demonstrated that particle morphology was considered to be an important factor to determine inhaled particle toxicity.

In plain English

This animal experiment tested Terracess TF, a disk-shaped (nonfibrous) form of potassium octatitanate, in rats. It did not test asbestos. Four groups, each of 20 male and 15 female SD rats, breathed 0, 2, 10 or 50 mg/m³ of the particles for 6 hours a day, 5 days a week, for 90 days. Some rats were examined after exposure and others after about 3 or 15 weeks of recovery. No test-substance-related effects were seen on clinical observations, body weights or food consumption. At 50 mg/m³, males had slightly higher lung-to-body weight ratios after exposure, but females did not, and lung weights were normal after recovery. At 50 mg/m³, clumps of particle-filled immune cells (macrophages) filled some air sacs, with slight type II pneumocyte hyperplasia (extra growth of lining cells), but no inflammation or fibrosis. Estimated clearance half-times were 2 to 3 months at 10 mg/m³ and 6 to 9 months at 50 mg/m³. The authors set the no-observed-adverse-effect level at 10 mg/m³. They contrasted the findings with earlier published studies of a fibrous form (TISMO D) and concluded that particle shape was one important factor in inhaled-particle toxicity.

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: 90-day whole-body inhalation toxicity study in rats, with additional groups killed after about 3 and 15 weeks of recovery to measure lung clearance and examine tissues
• Who was studied: Male and female SD rats about 5 weeks old, in four groups of 20 males and 15 females each. The article does not state where or when the exposures were carried out.
• Exposure: Aerosols of Terracess TF, disk-shaped potassium octatitanate particles, at 0, 2, 10 or 50 mg/m³ for 6 hours a day, 5 days a week, for 90 days. The mass median aerodynamic diameter of the particles in the chambers was 2.5 to 2.9 µm.
• Main results:
  • In all exposed groups, no test-substance-related effects were seen on clinical observations, body weights or food consumption, during either exposure or recovery.
  • At 50 mg/m³, males had a slight increase in lung-to-body weight ratio at the end of exposure and females did not. Lung weights were within normal limits after the 3- or 15-week recovery periods.
  • At 10 mg/m³, some air sacs were filled with clumps of particle-laden macrophages in 1 of 10 males and 1 of 10 females.
  • At 50 mg/m³, some air sacs were distended and filled with clumps of particle-laden macrophages. The alveolar walls showed slight type II pneumocyte hyperplasia, but there was no proliferative inflammation or alveolar fibrosis.
  • At 50 mg/m³, the clumps of particle-laden macrophages became fewer and smaller during recovery, but some large clumps remained after 15 weeks.
  • Estimated overall lung clearance half-time was 2 to 3 months for the 10 mg/m³ group and 6 to 9 months for the 50 mg/m³ group.
  • The authors considered 2 or 10 mg/m³ to be the no-observed-adverse-effect level (NOAEL). They treated 50 mg/m³ as an effect level because of distended air sacs packed with particle-laden macrophages, which they interpreted as an early sign of lung overloading.
  • Comparison with earlier published studies (not this study): the authors contrasted these results with previously reported studies of TISMO D, the fibrous form of potassium octatitanate, in which the lung response included fibrosis.
• The authors' conclusion: The authors concluded that particle shape (morphology) was one important factor in determining the toxicity of inhaled particles. They based this on their view that the disk-shaped and fibrous forms of potassium octatitanate had the same physical and chemical properties except for shape.
• Limitations the authors state:
  • Lung titanium data at the lowest concentration (2 mg/m³) were variable and not precise enough to measure the small amount of titanium present accurately.
  • Because of this variability, a definitive clearance half-time over the whole recovery period could not be calculated for the 2 mg/m³ group. Using only the 3- to 15-week period gave about 2 to 3 months.

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenic, Fibrogenic, Histopathology, Alveolar Macrophage, Alveoli, Inflammation, Fibrosis, NOAEL.

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