The effect of lung burden on biopersistence and pulmonary effects in rats exposed to potassium octatitanate whiskers by intratracheal instillation

Our plain-English summary of The effect of lung burden on biopersistence and pulmonary effects in rats exposed to potassium octatitanate whiskers by intratracheal instillation, by T. Oyabu, H. Yamato, A. Ogami, et al (Journal of Occupational Health, 2006).

The study

• Authors: T. Oyabu, H. Yamato, A. Ogami, Y. Morimoto, I. Akiyama, S. Ishimatsu, H. Hori, I. Tanaka
• Journal: Journal of Occupational Health
• Published: 2006;48(1):44-8
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In our previous inhalation studies on health effects of the asbestos substitute, potassium octatitanate whiskers (POW), we showed that an excess amount of POW deposition in the rat lung increased biopersistence resulting in fibrotic changes. The critical deposition amount which induced the higher biopersistence was estimated to lie between 1.5 mg and 2.4 mg. In order to find the exact amount, the relationship between the lung POW burden and biopersistence was investigated by the intratracheal instillation method. The chemical formula of POW is K2Ti8O17 and the geometric mean fiber diameter (geometric standard deviation, GSD) and geometric mean fiber length (GSD) are 0.35 microm (1.6) and 4.4 microm (2.7), respectively. Rats were intratracheally instilled with 0.5 mg, 1.0 mg, 2.0 mg or 5.0 mg of POW and sacrificed at 1 day and 1, 3, 6 and 12 months after the instillation. The POW amount in each lung was chemically analyzed by ICP-AES after microwave digestion and the biological half time (BHT) of each POW dose was calculated. The BHTs of each group were 10, 15, 20 and 42 months for 0.5, 1.0, 2.0 and 5.0 mg of POW, respectively, and BHT showed a linear dose-dependent increase, but without a threshold within the range of 0.5 mg to 5.0 mg, which was recognized in our earlier inhalation studies. In the histopathological photograph just after the instillation, many macrophages, which had phagocytized many more fibers, existed around the bronchiole compared with the earlier inhalation study at almost the same deposited amount. The relationship between POW amount and biopersistence in this intratracheal instillation study was different from that of our previous inhalation studies, probably due to the unnatural method of the fiber introduction to the lung, which in turn led to a different fiber distribution. It is suggested that an intratracheal instillation study is not an appropriate method for estimating excess deposition amounts of POW and an inhalation study will be needed. However, this intratracheal instillation study clarified that the clearance of POW was delayed as compared with previous inhalation studies at similar deposition amounts and this result has importance for the hazard assessment of dusts in animal experiments.

In plain English

This animal experiment examined potassium octatitanate whiskers (POW), which the authors describe as an asbestos substitute. Asbestos itself was not tested. The authors placed 0.5, 1.0, 2.0 or 5.0 mg of POW directly into the windpipes of 140 male rats (intratracheal instillation). They measured lung fiber amounts from 1 day to 12 months later. The biological half time (time for half the fiber to clear) was 10, 15, 20 and 42 months for the four doses, rising linearly with dose. Within the tested 0.5 to 5.0 mg range, the authors found no threshold in the link between lung POW amount and biopersistence, unlike their earlier inhalation studies. At comparable lung amounts, clearance was slower than in those inhalation studies. Lungs were heavier at higher doses, and fibrotic changes seemed more obvious as dose increased. The authors suggested the differences from inhalation were probably due to the unnatural method of introducing fibers, which led to a different fiber distribution. They concluded that an inhalation study will be necessary to estimate the excess exposure amount inducing higher biopersistence and lung injury.

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 (intratracheal instillation in rats)
• Who was studied: 140 male Kud:Wistar rats, aged 10 weeks. At 1 day and at 1, 3, 6 and 12 months, 5 rats per dose group were sacrificed for lung burden measurement, plus 1 or 2 for pathology.
• Exposure: Potassium octatitanate whiskers (K2Ti8O17, JFM reference sample PT1), at doses of 0.5, 1.0, 2.0 or 5.0 mg per rat lung. Geometric mean diameter was 0.35 µm and geometric mean length 4.4 µm.
• Main results:
  • Biological half times were 10, 15, 20 and 42 months for the 0.5, 1.0, 2.0 and 5.0 mg groups, respectively.
  • The biological half time increased linearly with the instilled dose.
  • No threshold lung amount was found between 0.5 and 5.0 mg in this study, unlike the authors' previous inhalation studies.
  • At comparable lung amounts, clearance was slower in this instillation study than in the authors' previous inhalation studies.
  • At 1 day and 1 month, wet lung weights in the 1.0, 2.0 and 5.0 mg groups were significantly higher than in the 0.5 mg group. After 3 months, only the 5.0 mg group remained significantly higher.
  • There were no significant differences among the four groups in body weight or other organ weights; only lung weight differed.
  • At 12 months, fibrotic changes around fiber clusters and thickening of the alveolar wall seemed more obvious as dose increased.
  • One day after instillation of 1.0 mg, many macrophages had taken up many fibers that had accumulated around the bronchiole.
• The authors' conclusion: The authors concluded that, because no threshold was seen with instillation (unlike earlier inhalation studies), an inhalation study will be necessary to estimate the excess exposure amount that induces higher biopersistence and lung injury.
• Limitations the authors state:
  • The authors suggested the differences from inhalation results were probably due to the unnatural method of introducing fibers, which led to a different fiber distribution.
  • The authors state that fibers are difficult to distribute uniformly in the alveolar space by instillation, so inhalation exposure is likely necessary to estimate the excess exposure amount.

Topics

Medical terms in this study, explained in our Lexicon: biopersistence, Deposition, Fiber Length, Macrophage.

Related studies

• The effect of lung burden on biopersistence and pulmonary effects in rats exposed to potassium octatitanate whiskers by inhalation — T. Oyabu, H. Yamato, et al. (2004)
• Histopathological changes in rat lung following intratracheal instillation of silicon carbide whiskers and potassium octatitanate whiskers — A. Ogami, Y. Morimoto, et al. (2007)
• Expression of heme oxygenase-1 in the lungs of rats exposed to potassium octatitanate whiskers — Y. Obata, Y. Morimoto, et al. (2011)
• Pulmonary effects and biopersistence of deposited silicon carbide whisker after 1-year inhalation in rats — I. Akiyama, A. Ogami, et al. (2007)
• Pulmonary and pleural toxicity of potassium octatitanate fibers, rutile titanium dioxide nanoparticles, and MWCNT-7 in male Fischer 344 rats — M. Abdelgied, A.M. El-Gazzar, et al. (2019)
• Potassium octatitanate fibers induce persistent lung and pleural injury and are possibly carcinogenic in male Fischer 344 rats — M. Abdelgied, A.M. El-Gazzar, et al. (2018)

Browse more research in Journal of Occupational Health, or return to medical research.