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. 2017 Oct 4;11(10):10623–10624. doi: 10.1021/acsnano.7b06327

Correction to“Inhaled Nanoparticles Accumulate at Sites of Vascular Disease”

Mark R Miller ✉, Jennifer B Raftis, Jeremy P Langrish, Steven G McLean, Pawitrabhorn Samutrtai, Shea P Connell, Simon Wilson, Alex T Vesey, Paul H B Fokkens, A John F Boere, Petra Krystek, Colin J Campbell, Patrick W F Hadoke, Ken Donaldson, Flemming R Cassee, David E Newby, Rodger Duffin, Nicholas L Mills
PMCID: PMC8504789  PMID: 28976185

The authors submit the following corrections. A mislabeling of the units was found in Figure 2D. The y-axes of both graphs should read: “concentration of gold (ng gold/L)” not “(ng gold/mL)”. Similarly, in Supplementary Figure S4 the urine concentration on the y-axis should also read: “concentration of gold (ng gold/L)”.

This error affects the estimate of % mass translocation in the Discussion, which also contained inconsistencies. We have now corrected these errors and refined our exposure estimates for this calculation. Thus, we would like to revise the following text on page 4546:

“Based on the exposure characteristics of our first study (2 h exposure of ∼116 μg/m3 under light exercise), we calculate the total inhaled dose of particulate to be ∼690 mg. If ∼80 μg of gold was cleared by the kidneys over 24 h (average volume of urine collected: 2.4 L containing 35 ng/mL), and, therefore, if this was the sole route of clearance, we estimate that at least 0.2% of inhaled gold nanoparticles translocated from the lung into circulation”.

This should be replaced with:

“Based on the exposure characteristics of our first study (2 h exposure of ∼116 μg/m3 intermittent rest [6 L/min for 4 × 15 min] and moderate exercise [47.5 L/min for 4 × 15 min]), we calculate the total inhaled dose of the particulate to be ∼383 μg. If ∼84 ng of gold was cleared by the kidney over 24 h (average volume or urine collected: 2.4 L containing 35 ng/L; Figure 1D), we estimate that at least 0.02% of inhaled gold nanoparticles translocated from the lung into the circulation”.

We emphasize that this calculation is for illustrative purposes and represents only a defined 24 h period in time. The estimate is likely to be conservative and does not take into account the proportion of alveolar deposition and the slow return of respiratory rate to resting levels after exercise and is based on the assumption that the urine is the sole route of clearance.

While this estimate is an order of magnitude lower than that stated in the original manuscript, the proportion of translocated particles still fits with prior findings. Early studies in rodents provided rough estimates that <1% mass of nanoparticles with a diameter of <50 nm will translocate.1 Subsequent studies broadened this range from 0.01 to 10%, although estimates are most frequently around 0.3% or less for a given tissue at 24 h post-exposure.2−11 Studies in man are hampered by technical limitations,12,13 although, on the assumption that translocation can occur in man, current findings suggest a very low rate of translocation.14−16 Thus, the estimate of 0.02% translocation in the present study concurs with that of previous work.

Differences in the species, method of exposure, particle size, particle physicochemistry, post-exposure sampling period, method of measurement and tissue sample(s) used, all make direct comparisons between these studies challenging. In most instances (especially where values are close to the threshold of detection), the relative amount of gold in exposed versus non-exposed tissues (within the same study) has arguably greater value than the actual concentration of gold per se. However, the calculation has qualitative value in that it confirms or strengthens several key messages about the translocation process:

  • (1)

    A very low proportion of nanoparticles translocate from the lung to the blood in both animals and man.

  • (2)

    The body has several routes of clearance of translocated nanoparticles (including, but not limited to, the urine and via the liver) that will affect systemic levels of nanoparticles. Nevertheless, translocated nanoparticles accumulate in several tissues. The individual biokinetics of these routes requires further research.

  • (3)

    Particles are retained in the lung for long periods of time, thus, there appears to be an ongoing slow translocation of low amounts of nanoparticles into the blood (from the lung and/or other organs they may have originally accumulated in).

These corrections do not affect any other findings of the paper or the conclusions drawn. The important observation in the current study is that translocated nanoparticles reach and accumulate at areas of disease that may be most susceptible to their physicochemical properties. Thus, the preferential accumulation in regions of susceptibility suggests that translocated nanoparticles could cause significant biological actions that promote the disease process.

Acknowledgments

We would like to thank Dr. Wolfgang Kreyling for his time and insightful input. The authors acknowledge the following funders: British Heart Foundation Programme Grant (RG/10/9/28286), British Heart Foundation Project Grants (PG/10/042/28388, PG/12/8/29371), British Heart Foundation Senior Research Fellowship (FS/16/14/32023), British Heart Foundation Special Project Grant (SP/15/8/31575), British Heart Foundation Chair Award (CH/09/002), Colt Foundation Project Grant (CF/07/11), Dutch Ministry of Infrastructures and Environment (M/630196), and Department of Health (UK) Project Grant (PR-NT-0208-10025).

References

  1. Kreyling W. G.; Semmler M.; Erbe F.; Mayer P.; Takenaka S.; Schulz H.; Oberdorster G.; Ziesenis A. Translocation of ultrafine insoluble iridium particles from lung epithelium to extrapulmonary organs is size dependent but very low. J. Toxicol. Environ. Health, Part A 2002, 65, 1513–1530. 10.1080/00984100290071649. [DOI] [PubMed] [Google Scholar]
  2. Semmler M.; Seitz J.; Erbe F.; Mayer P.; Heyder J.; Oberdorster G.; Kreyling W. G. Long-term clearance kinetics of inhaled ultrafine insoluble iridium particles from the rat lung, including transient translocation into secondary organs. Inhalation Toxicol. 2004, 16, 453–459. 10.1080/08958370490439650. [DOI] [PubMed] [Google Scholar]
  3. Semmler-Behnke M.; Kreyling W. G.; Lipka J.; Fertsch S.; Wenk A.; Takenaka S.; Schmid G.; Brandau W. Biodistribution of 1.4- and 18-nm gold particles in rats. Small 2008, 4, 2108–2111. 10.1002/smll.200800922. [DOI] [PubMed] [Google Scholar]
  4. Chen J.; Tan M.; Nemmar A.; Song W.; Dong M.; Zhang G.; Li Y. Quantification of extrapulmonary translocation of intratracheal-instilled particles in vivo in rats: effect of lipopolysaccharide. Toxicology 2006, 222, 195–201. 10.1016/j.tox.2006.02.016. [DOI] [PubMed] [Google Scholar]
  5. Lipka J.; Semmler-Behnke M.; Sperling R. A.; Wenk A.; Takenaka S.; Schleh C.; Kissel T.; Parak W. J.; Kreyling W. G. Biodistribution of PEG-modified gold nanoparticles following intratracheal instillation and intravenous injection. Biomaterials 2010, 31, 6574–81. 10.1016/j.biomaterials.2010.05.009. [DOI] [PubMed] [Google Scholar]
  6. Furuyama A.; Kanno S.; Kobayashi T.; Hirano S. Extrapulmonary translocation of intratracheally instilled fine and ultrafine particles via direct and alveolar macrophage-associated routes. Arch. Toxicol. 2009, 83, 429–437. 10.1007/s00204-008-0371-1. [DOI] [PubMed] [Google Scholar]
  7. Kreyling W. G.; Semmler-Behnke M.; Takenaka S.; Möller W. Differences in the biokinetics of inhaled nano- versus micrometer-sized particles. Acc. Chem. Res. 2013, 46, 714–722. 10.1021/ar300043r. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kreyling W. G.; Hirn S.; Möller W.; Schleh C.; Wenk A.; Celik G.; Lipka J.; Schaffler M.; Haberl N.; Johnston B. D.; Sperling R.; Schmid G.; Simon U.; Parak W. J.; Semmler-Behnke M. Air-blood barrier translocation of tracheally instilled gold nanoparticles inversely depends on particle size. ACS Nano 2014, 8, 222–233. 10.1021/nn403256v. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Geiser M.; Stoeger T.; Casaulta M.; Chen S.; Semmler-Behnke M.; Bolle I.; Takenaka S.; Kreyling W. G.; Schulz H. Biokinetics of nanoparticles and susceptibility to particulate exposure in a murine model of cystic fibrosis. Part. Fibre Toxicol. 2014, 11, 19. 10.1186/1743-8977-11-19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kreyling W. G. Discovery of unique and ENM- specific pathophysiologic pathways: Comparison of the translocation of inhaled iridium nanoparticles from nasal epithelium versus alveolar epithelium towards the brain of rats. Toxicol. Appl. Pharmacol. 2016, 299, 41–46. 10.1016/j.taap.2016.02.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kreyling W. G.; Holzwarth U.; Haberl N.; Kozempel J.; Wenk A.; Hirn S.; Schleh C.; Schaffler M.; Lipka J.; Semmler-Behnke M.; Gibson N. Quantitative biokinetics of titanium dioxide nanoparticles after intratracheal instillation in rats: Part 3. Nanotoxicology 2017, 11, 454–464. 10.1080/17435390.2017.1306894. [DOI] [PubMed] [Google Scholar]
  12. Nemmar A.; Hoet P. H.; Vanquickenborne B.; Dinsdale D.; Thomeer M.; Hoylaerts M. F.; Vanbilloen H.; Mortelmans L.; Nemery B. Passage of inhaled particles into the blood circulation in humans. Circulation 2002, 105, 411–414. 10.1161/hc0402.104118. [DOI] [PubMed] [Google Scholar]
  13. Mills N. L.; Amin N.; Robinson S. D.; Anand A.; Davies J.; Patel D.; de la Fuente J. M.; Cassee F. R.; Boon N. A.; Macnee W.; Millar A. M.; Donaldson K.; Newby D. E. Do inhaled carbon nanoparticles translocate directly into the circulation in humans?. Am. J. Respir. Crit. Care Med. 2006, 173, 426–431. 10.1164/rccm.200506-865OC. [DOI] [PubMed] [Google Scholar]
  14. Wiebert P.; Sanchez-Crespo A.; Falk R.; Philipson K.; Lundin A.; Larsson S.; Möller W.; Kreyling W. G.; Svartengren M. No significant translocation of inhaled 35-nm carbon particles to the circulation in humans. Inhalation Toxicol. 2006, 18, 741–747. 10.1080/08958370600748455. [DOI] [PubMed] [Google Scholar]
  15. Kreyling W. G.; Semmler-Behnke M.; Seitz J.; Scymczak W.; Wenk A.; Mayer P.; Takenaka S.; Oberdorster G. Size dependence of the translocation of inhaled iridium and carbon nanoparticle aggregates from the lung of rats to the blood and secondary target organs. Inhalation Toxicol. 2009, 21, 55–60. 10.1080/08958370902942517. [DOI] [PubMed] [Google Scholar]
  16. Geiser M.; Kreyling W. G. Deposition and biokinetics of inhaled nanoparticles. Part. Fibre Toxicol. 2010, 7, 2. 10.1186/1743-8977-7-2. [DOI] [PMC free article] [PubMed] [Google Scholar]

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