Pulmonary toxicity and translocation of gallium phosphide nanowires to secondary organs following pulmonary exposure in mice

Our plain-English summary of Pulmonary toxicity and translocation of gallium phosphide nanowires to secondary organs following pulmonary exposure in mice, by T. Berthing, M. Lard, P.H. Danielsen, et al (Journal of Nanobiotechnology, 2023).

The study

• Authors: T. Berthing, M. Lard, P.H. Danielsen, L. Abariute, K.K. Barfod, K. Adolfsson, K.B. Knudsen, H. Wolff, C.N. Prinz, U. Vogel
• Journal: Journal of Nanobiotechnology
• Published: 2023;21(1):322
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: III-V semiconductor nanowires are envisioned as being integrated in optoelectronic devices in the near future. However, the perspective of mass production of these nanowires raises concern for human safety due to their asbestos- and carbon nanotube-like properties, including their high aspect ratio shape. Indeed, III-V nanowires have similar dimensions as Mitsui-7 multi-walled carbon nanotubes, which induce lung cancer by inhalation in rats. It is therefore urgent to investigate the toxicological effects following lung exposure to III-V nanowires prior to their use in industrial production, which entails risk of human exposure. Here, female C57BL/6J mice were exposed to 2, 6, and 18 µg (0.12, 0.35 and 1.1 mg/kg bw) of gallium phosphide (III-V) nanowires (99 nm diameter, 3.7 μm length) by intratracheal instillation and the toxicity was investigated 1, 3, 28 days and 3 months after exposure. Mitsui-7 multi-walled carbon nanotubes and carbon black Printex 90 nanoparticles were used as benchmark nanomaterials.

Results: Gallium phosphide nanowires induced genotoxicity in bronchoalveolar lavage cells and acute inflammation with eosinophilia observable both in bronchoalveolar lavage and lung tissue (1 and 3 days post-exposure). The inflammatory response was comparable to the response following exposure to Mitsui-7 multi-walled carbon nanotubes at similar dose levels. The nanowires underwent partial dissolution in the lung resulting in thinner nanowires, with an estimated in vivo half-life of 3 months. Despite the partial dissolution, nanowires were detected in lung, liver, spleen, kidney, uterus and brain 3 months after exposure.

Conclusion: Pulmonary exposure to gallium phosphide nanowires caused similar toxicological effects as the multi-walled carbon nanotube Mitsui-7.

© 2023. BioMed Central Ltd., part of Springer Nature.

In plain English

This was an experiment in mice, not a study of asbestos. The authors put gallium phosphide nanowires, tiny fibers developed for electronics, into the lungs of female mice through the windpipe at 2, 6 or 18 µg. They compared them with Mitsui-7 multi-walled carbon nanotubes and Printex 90 carbon black, and examined the mice 1, 3 and 28 days and 3 months later. The nanowires caused short-term lung inflammation with neutrophils and eosinophils, similar in strength to the carbon nanotubes. At 28 days neutrophils were still higher than in controls, but not statistically significantly. DNA strand breaks rose in lung-wash cells at the highest dose on day 1 and at all doses on day 3, but not in lung or liver tissue. The nanowires partly dissolved, becoming thinner, with an estimated half-life of about 3 months. Lung changes had receded by 3 months, yet nanowires were found in the liver, kidney, spleen, brain and uterus of all three treated mice examined then. The authors concluded the effects resembled those of Mitsui-7 and called for long-term studies.

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 instillation (liquid placed into the windpipe) with follow-up at 1, 3 and 28 days and 3 months, preceded by a pilot study at one dose
• Who was studied: Female C57BL/6JRj mice aged 7 weeks from Janvier Labs, France, randomly allocated to groups; 264 mice in total (6–9 per group for inflammation, 6 for genotoxicity, 3–5 for histology/darkfield). Procedures were carried out under Danish animal-experiment law.
• Exposure: Gallium phosphide (GaP) nanowires at 2, 6 or 18 µg per mouse (average 99 nm diameter, 3.7 μm length; 5% longer than 10 μm). Comparison materials were Mitsui-7 multi-walled carbon nanotubes at 6, 18 or 54 µg and Printex 90 carbon black at 162 µg, all given in a vehicle of 2% mouse serum in water. No asbestos was tested.
• Main results:
  • In nanowire-exposed mice, eosinophils in lung-wash (bronchoalveolar lavage) fluid increased with dose on days 1 and 3 after exposure.
  • At 28 days, neutrophils in nanowire-exposed mice were still higher than in the control group, but the difference was not statistically significant.
  • In nanowire-exposed mice, the total deposited nanowire surface area correlated with neutrophil influx at day 1 (R2 = 0.759, p < 0.0001) and day 3 (R2 = 0.9099, p < 0.0001).
  • In lung-wash (BAL) cells of nanowire-exposed mice, DNA strand breaks increased at the highest dose on day 1 and at all doses on day 3. There was no increase at other time points or in lung or liver tissue.
  • The nanowires partly dissolved in the lung, mainly becoming thinner, with an estimated half-life of approximately 3 months in vivo and somewhat less in laboratory fluids.
  • At 28 days, giant cells and areas of alveolar protein debris were seen in all mice given the highest nanowire dose (18 µg). By 3 months these lung changes had receded.
  • At 3 months, nanowires were found in the kidney, liver, spleen, brain and uterus body of 3 of 3 nanowire-exposed mice examined, and in none of the controls. They were also found in the diaphragm (3/3), chest wall (2/3), right ovary (1/3) and left uterus horn (1/2).
  • No tissue damage that could consistently be linked to exposure was seen in the secondary organs examined.
  • The authors described the lung tissue findings as resembling an eosinophilic inflammation, a pattern they said had previously been shown for asbestos and two carbon nanotubes.
• The authors' conclusion: The authors concluded that GaP nanowires caused acute lung inflammation with similar potency as Mitsui-7 carbon nanotubes and caused genotoxicity in lung-wash cells. They said dissolution would be expected to reduce long-term toxicity, and that the combined effect of dissolution and high acute toxicity should be assessed in long-term studies. Based on the acute responses, they recommended precautionary measures against human exposure in production and post-production.
• Limitations the authors state:
  • Dissolution measurements at 3 months in vivo and at day 28 in vitro were more uncertain than those at earlier time points.
  • Nanowire surface area was estimated by calculation rather than measured directly, because too little material was available.
  • The highest carbon nanotube dose was three times the highest nanowire dose, so potency was compared at the 6 and 18 µg doses.
  • Long-term toxicity after repeated occupational exposure was not studied and needs further research.

Topics

Medical terms in this study, explained in our Lexicon: Translocation, Aspect Ratio (Length-to-diameter ratio), Lung Cancer, Genotoxicity, Bronchoalveolar Lavage (BAL), Inflammation.

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