Use of Short-Term Inhalation Study to Obtain Initial Hazard Data and Prepare for Subacute and Subchronic Inhalation Studies, and Toxicokinetic Studies

  • Ki Soo Jeon
  • Jae Seong Yi
  • Il Je YuEmail author
Part of the Current Topics in Environmental Health and Preventive Medicine book series (CTEHPM)


A short-term inhalation study (STIS) protocol that has been specifically developed for testing nanomaterials can be used as an alternative testing choice for acute toxicity testing, and a range-finding study for subacute and subchronic studies. The STIS can also be used to characterize the nanoparticle physicochemical properties and determine the type of exposure and particle monitoring methods in the inhalation chamber for subsequent subacute and subchronic inhalation studies. In addition, importantly, the particle generation method and particle concentration stability can be studied before and during the STIS. Furthermore, combining an STIS with a lung burden analysis, which is now a mandatory requirement for OECD 412 (subacute) and 413 (subchronic) test guidelines, can provide toxicokinetic information, including the biodistribution and lung clearance of nanoparticles.


Short-term inhalation study Inhalation toxicity Toxicokinetics Nanomaterials Nanoparticles 



This research was supported by the Industrial Technology Innovation Program (10052901), Development of highly usable nanomaterial inhalation toxicity testing system in commerce through the Korea Evaluation Institute of Industrial Technology by the Korean Ministry of Trade, Industry & Energy



  1. 1.
    ISO/TR 19601. Nanotechnologies—Aerosol generation for Nano-objects and their aggregates and agglomerates (NOAA) air exposure studies. Geneva: ISO; 2017.Google Scholar
  2. 2.
    OECD. OECD guidelines for testing of chemicals, Test Guideline (TG) 403. Acute Inhalation Toxicity. Paris: OECD; 2009.Google Scholar
  3. 3.
    OECD. OECD guidelines for testing of chemicals, Test Guideline (TG) 433. Acute inhalation toxicity: Fixed concentration procedure. Paris: OECD; 2017.Google Scholar
  4. 4.
    OECD. OECD guidelines for testing of chemicals, Test Guideline (TG) 436. Acute Inhalation Toxicity—Acute Toxic Class Method. Paris: OECD; 2009.CrossRefGoogle Scholar
  5. 5.
    OECD. OECD guidelines for testing of chemicals, Test Guideline (TG) 412. Subacute Inhalation Toxicity: 28-Day Study. Paris: OECD; 2009.Google Scholar
  6. 6.
    OECD. OECD guidelines for testing of chemicals, Test Guideline (TG) 413. Subchronic Inhalation Toxicity: 90-day Study. Paris: OECD; 2009.Google Scholar
  7. 7.
    OECD. OECD guidelines for testing of chemicals, Test Guideline (TG) 412. Subacute Inhalation Toxicity: 28-Day Study, vol. 201. Paris: OECD.Google Scholar
  8. 8.
    OECD. OECD guidelines for testing of chemicals, Test Guideline (TG) 413. Subchronic Inhalation Toxicity: 90-day Study. Paris: OECD; 2018.Google Scholar
  9. 9.
    Ma-Hock L, Burkhardt S, Strauss V, Gamer AO, Wiench K, van Ravenzwaay B, Landsiedel R. Development of a short-term inhalation test in the rat using nano-titanium dioxide as a model substance. Inhal Toxicol. 2009;21:102–18.CrossRefGoogle Scholar
  10. 10.
    OECD. A steering group 7 case-study for hazard identification of inhaled nanomaterials: An integrated approach with short-term inhalation studies. ENV/CHEM/NANO(2011)6/REV1. Paris: OECD; 2013.Google Scholar
  11. 11.
    OECD. Guidance document on acute inhalation toxicity testing, series on testing and assessment No. 39, ENV/JM/MONO(2009)28/REV1. 2nd ed. Paris: OECD; 2018.Google Scholar
  12. 12.
    UN. United Nations Globally Harmonized System of Classification and Labelling of Chemicals (GHS), ST/SG/AC.10/30, New York: UN; 2017. Available:
  13. 13.
    Ahn K, Ensor D, Shama M, Ostraat M, Ramsden J, Kanno J, Ghazi-Khansari M, Lazos R, Gulumian M, Cassee FR, De Jong WH, Jeon K, Yu IJ. Development of International Standard on Nano Aerosol Generation for Inhalation Toxicology Study. Toxicol Open Access. 2017;3(2)
  14. 14.
    ISO/TR 13014. Nanotechnologies—Guidance on physico-chemical characterization of engineered nanoscale materials for toxicologic assessment. Geneva: ISO; 2012.Google Scholar
  15. 15.
    ISO 29701. Nanotechnologies—endotoxin test on nanomaterial samples for in vitro systems—Limulus amebocyte lysate (LAL) test. Geneva: ISO; 2010.Google Scholar
  16. 16.
    Ech RK, Han L, Ensor DS, Foarde KK. Endotoxin contamination of engineered nanomaterials. Nanotoxicology. 2009;4(1):73–83.Google Scholar
  17. 17.
    Schindler S, von Aulock S, Daneshian M, Hartung T. Development, validation and applications of the monocyte activation test for pyrogens based on human whole blood. ALTEX. 2009;26(4):265–77.CrossRefGoogle Scholar
  18. 18.
    Lee JH, Kwan M, Ji JH, Kang CS, Ahn KH, Han JH, Yu IJ. Exposure assessment of workplace manufacturing nanosized TiO2 and silver. Inhal Toxicol. 2011;23(4):226–36.CrossRefGoogle Scholar
  19. 19.
    Shin JH, Han SG, Kim JK, Kim BW, Hwang JH, Lee JS, Lee JH, Baek JE, Kim TG, Kim KS, Lee HS, Song NW, Ahn K, Yu IJ. 5-Day repeated inhalation of 28-day post-exposure study of graphene. Nanotoxicology. 2015;9(8):1023–31. Scholar
  20. 20.
    Kim JK, Shin JH, Lee JS, Hwang JH, Lee JH, Baek JE, Kim TG, Kim BW, Kim JS, Lee GH, Ahn K, Han SG, Bello D, Yu IJ. 28-Day inhalation toxicity of graphene nanoplates in sprague-dawley rats. Nanotoxicology. 2016;10(7):891–901. Scholar
  21. 21.
    Kim YH, Jo MS, Kim JK, Shin JH, Baek JE, Park HS, An HJ, Lee JS, Kim BW, Kim HP, Ahn KH, Jeon K, Oh SM, Lee JH, Workman T, Faustman EM, Yu IJ. Short-term inhalation study of graphene oxide nanoplates. Nanotoxicology. 2018;12(3):224–38. Scholar
  22. 22.
    An K, Lee S, Sung J, Kim H, Lee J, Song K. A 90-day subchronic inhalation toxicity study of graphene oxide powder in F344 rats. Toxicologist. 2017;150(1):2727.Google Scholar
  23. 23.
    Han SG, Lee JS, Ahn K, Kim YS, Kim JK, Lee JH, Shin JH, Jeon KS, Cho WS. Size-dependent clearance of gold nanoparticles from lungs of Sprague-Dawley rats after short-term inhalation exposure. Arch Toxicol. 2015;89(7):1083–94. Scholar
  24. 24.
    Sung JH, Ji JH, Park JD, Song MY, Song KS, Ryu HR, Yoon JU, Jeon KS, Jeong J, Han BS, Chung YH, Chang HK, Lee JH, Kim DW, Kelman BJ, Yu IJ. Subchronic inhalation toxicity of gold nanoparticles. Part Fibre Toxicol. 2011;8:16.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.HCTm Co. Ltd.IcheonRepublic of Korea

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