Journal of Nanoparticle Research

, 14:1029 | Cite as

Development of risk-based nanomaterial groups for occupational exposure control

  • E. D. Kuempel
  • V. Castranova
  • C. L. Geraci
  • P. A. Schulte
Research Paper
Part of the following topical collections:
  1. Nanotechnology, Occupational and Environmental Health


Given the almost limitless variety of nanomaterials, it will be virtually impossible to assess the possible occupational health hazard of each nanomaterial individually. The development of science-based hazard and risk categories for nanomaterials is needed for decision-making about exposure control practices in the workplace. A possible strategy would be to select representative (benchmark) materials from various mode of action (MOA) classes, evaluate the hazard and develop risk estimates, and then apply a systematic comparison of new nanomaterials with the benchmark materials in the same MOA class. Poorly soluble particles are used here as an example to illustrate quantitative risk assessment methods for possible benchmark particles and occupational exposure control groups, given mode of action and relative toxicity. Linking such benchmark particles to specific exposure control bands would facilitate the translation of health hazard and quantitative risk information to the development of effective exposure control practices in the workplace. A key challenge is obtaining sufficient dose–response data, based on standard testing, to systematically evaluate the nanomaterials’ physical–chemical factors influencing their biological activity. Categorization processes involve both science-based analyses and default assumptions in the absence of substance-specific information. Utilizing data and information from related materials may facilitate initial determinations of exposure control systems for nanomaterials.


Risk assessment Occupational exposure limits Comparative toxicity Hazard groups Exposure control groups Health effects 



We would like to thank Mr. Randall Smith for helpful discussions concerning statistical aspects of this paper.


  1. ACGIH (2008) Gallium arsenide. In: Threshold limit values for chemical substances and physical agents and biological exposure indices. American Conference of Governmental Industrial Hygienists, Cincinnati, p 12Google Scholar
  2. Ader AW, Farris JP, Ku RH (2005) Occupational health categorization and compound handling practice systems: roots, application and future. Chem Health Safety, July/Aug:20–24CrossRefGoogle Scholar
  3. ANSES (2010) Development of a specific control banding tool for nanomaterials. Agence nationale de sécurité sanitarie, Maisons-Alfort CedexGoogle Scholar
  4. Attfield MD, Schleiff PL, Lubin JH, Blair A, Stewart PA, Vermeulen R, Coble JB, Silverman DT (2012) The diesel exhaust in miners study: a cohort mortality study with emphasis on lung cancer. J Natl Cancer Inst, 104(11):869–883Google Scholar
  5. BSI (2007) Nanotechnologies, Part 2. PD 6699-2:2007: guide to safe handling and disposal of manufactured nanomaterials. British Standards Institution, LondonGoogle Scholar
  6. Castranova V (2000) From coal mine dust to quartz: mechanisms of pulmonary pathogenicity. Inhal Toxicol 3:7–14CrossRefGoogle Scholar
  7. Castranova V (2011) Overview of current toxicological knowledge of engineered nanoparticles. JOEM 53(6 Suppl):S14–S17Google Scholar
  8. CFR (2001) Limit on exposure to diesel particulate matter, Mine Safety and Health Administration. Code of federal regulations: 30 CFR Section 57.5060. US Government Printing Office, Office of the Federal Register, Washington, DCGoogle Scholar
  9. CIIT, RIVM (2006) Multiple-path particle dosimetry (MPPD V 2.0): a model for human and rat airway particle dosimetry. Research Triangle Park, NC, USA: Centers for Health Research (CIIT) and the Netherlands: National Institute for Public Health and the Environment (RIVM)Google Scholar
  10. Crump KS (1984) A new method for determining allowable daily intakes. Fund Appl Toxicol 4:854–871CrossRefGoogle Scholar
  11. Dolan DG, Naumann BD, Sargent EV, Maier A, Dourson M (2005) Application of the threshold of toxicological concern concept to pharmaceutical manufacturing operations. Regul Toxicol Pharmacol 43:1–9CrossRefGoogle Scholar
  12. Donaldson K, Borm PJ, Oberdörster G, Pinkerton KE, Stone V, Tran CL (2008) Concordance between in vitro and in vivo dosimetry in the proinflammatory effects of low-toxicity, low-solubility particles: the key role of the proximal alveolar region. Inhal Toxicol 20:53–62CrossRefGoogle Scholar
  13. Donaldson K, Murphy FA, Duffin R, Poland CA (2010) Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesothelioma. Part Fibre Toxicol 22(7):5CrossRefGoogle Scholar
  14. Driscoll KE (1996) Role of inflammation in the development of rat lung tumors in response to chronic particle exposure. In: Mauderly JL, McCunney RJ (eds) Particle overload in the rat lung and lung cancer: implications for human risk assessment. Taylor & Francis, Philadelphia, pp 139–152Google Scholar
  15. Duffin R, Tran L, Brown D, Stone V, Donaldson K (2007) Proinflammogenic effects of low-toxicity and metal nanoparticles in vivo and in vitro: highlighting the role of particle surface area and surface reactivity. Inhal Toxicol 19(10):849–856CrossRefGoogle Scholar
  16. Elder A, Gelein R, Finkelstein JN, Driscoll KE, Harkema J, Oberdörster G (2005) Effects of subchronically inhaled carbon black in three species. I. Retention kinetics, lung inflammation, and histopathology. Toxicol Sci 88(2):614–629CrossRefGoogle Scholar
  17. Grieger KD, Linkov I, Hansen SF, Baun A (2012) Environmental risk analysis for nanomaterials: review and evaluation of frameworks. Nanotoxicol 6(2):196–212CrossRefGoogle Scholar
  18. Heinrich U, Fuhst R, Rittinghausen S, Creutzenberg O, Bellmann B, Koch W, Levsen K (1995) Chronic inhalation exposure of Wistar rats and two different strains of mice to diesel engine exhaust, carbon black, and titanium dioxide. Inhal Toxicol 7:533–556CrossRefGoogle Scholar
  19. Hewett P, Logan P, Mulhausen J, Ramachandran G, Banerjee S (2006) Rating exposure control using Bayesian decision analysis. J Occup Environ Hyg 3:568–581CrossRefGoogle Scholar
  20. ICRP (1975) Report of the task group on reference man: a report prepared by a task group of committee 2 of the International Commission on Radiological Protection. Pergamon, ElmsfordGoogle Scholar
  21. ICRP (1994) Human respiratory tract model for radiological protection. International commission on radiological protection publication no. 66. Elsevier, OxfordGoogle Scholar
  22. Invernizzi N (2011) Nanotechnology between the lab and the shop floor: what are the effects on labor? J Nanopart Res. doi: 10.1007/s11051-011-03033-z
  23. Jones RM, Nicas M (2006) Margins of safety provided by COSHH essentials and the ILO chemcial control toolkit. Ann Occup Hyg 50(2):149–156CrossRefGoogle Scholar
  24. Kuempel ED, Tran CL, Castranova V, Bailer AJ (2006) Lung dosimetry and risk assessment of nanoparticles: evaluating and extending current models in rats and humans. Inhal Toxicol 18(10):717–724CrossRefGoogle Scholar
  25. Kuempel ED, Geraci CL, Schulte PA (2007) Risk assessment approaches and research needs for nanoparticles: an examination of data and information from current studies. Proceedings of the NATO Advanced Research Workshop on Nanotechnology: Toxicological Issues and Environmental Safey, Varna, Bulgaria, August 12–17, 2006. In: Simeonova P, Opopol N, Luster M (eds) Nanotechnology: toxicological issues and environmental safety. Springer, New York, pp 119–145Google Scholar
  26. Kuempel ED, Smith RJ, Dankovic DA, Stayner LT (2009) Rat- and human-based risk estimates of lung cancer from occupational exposure to poorly-soluble particles: a quantitative evaluation. J Phys Conf Series 151:012011CrossRefGoogle Scholar
  27. Lee KP, Trochimowicz HJ, Reinhardt CF (1985) Pulmonary response of rats exposed to titanium dioxide (TiO2) by inhalation for 2 years. Toxicol Appl Pharmacol 79:179–192CrossRefGoogle Scholar
  28. Linkov I, Satterstrom FK, Steevens J, Ferguson E, Pleus RC (2007) Multi-criteria decision analysis and environmental risk assessment for nanomaterials. J Nanopart Res 9(4):543–554CrossRefGoogle Scholar
  29. Linkov I, Steevens J, Adlakha-Hutcheon F, Bennett E, Chappell M, Colvin V, Davis M, Davis T, Elder A, Hansen SF, Hakkinen PB, Hussain SM, Karkan D, Korenstein R, Lynch I, Metcalfe C, Ramadan AB, Satterstrom FK (2009) Emerging methods and tools for environmental risk assessment, decision-making, and policy for nanomaterials: summary of NATO advanced research workshop. J Nanopart Res 11:513–527CrossRefGoogle Scholar
  30. Mauderly JL (1997) Relevance of particle-induced rat lung tumors for assessing lung carcinogenic hazard and human lung cancer risk. Environ Health Perspect 105(Suppl 5):1337–1346CrossRefGoogle Scholar
  31. Maynard AD (2007) Nanotechnology: the next big thing, or much ado about nothing? Ann Occup Hyg 51(1):1–12CrossRefGoogle Scholar
  32. Maynard AD, Kuempel E (2005) Airborne nanostructured particles and occupational health. J Nanoparticle Res 7(6):587–614CrossRefGoogle Scholar
  33. Melnick RL, Bucher JR, Roycroft JH, Hailey JR, Huff J (2003) Carcinogenic and toxic effects of inhaled, nonfibrous, poorly soluble particulates in rats and mice contradict threshold lung cancer hypotheses that are dependent on chronic pulmonary inflammation. Eur J Oncol 8(3):177–186Google Scholar
  34. Morrow PE (1988) Possible mechanisms to explain dust overloading of the lungs. Fund Appl Toxicol 10(3):369–384CrossRefGoogle Scholar
  35. Muhle H, Bellmann B, Creutzenberg O, Dasenbrock C, Ernst H, Kilpper R, MacKenzie JC, Morrow P, Mohr U, Takenaka S, Mermelstein R (1991) Pulmonary response to toner upon chronic inhalation exposure in rats. Fund Appl Toxicol 17:280–299CrossRefGoogle Scholar
  36. Muller J, Huaux F, Moreau N, Misson P, Heilier JF, Delos M, Arras M, Fonseca A, Nagy JB, Lison D (2005) Respiratory toxicity of multi-wall carbon nanotubes. Toxicol Appl Pharmacol 207(3):221–231CrossRefGoogle Scholar
  37. Murray AR, Kisin ER, Tkach AV, Yanamala N, Mercer R, Young S-H, Fadeel B, Kagan VE, Shvedova AA (2012) Factoring-in agglomeration of carbon nanotubes and nanofibers for better prediction of their toxicity versus asbestos. Particle Fibre Toxicol 9:10Google Scholar
  38. Nakanishi J (2011) Risk Assessment of Manufactured Nanomaterials: Carbon Nanotubes (CNT). Final report issued on August 12, 2011. New Energy and Industrial Technology Development Organization (NEDO) project (P06041) "Research and Development of Nanoparticles Characterization Methods." National Institute of Advanced industrial Science and Technology (AIST). Available at
  39. Naumann BD, Sargent EV, Starkman BS, Fraser WJ, Becker GT, Kirk GD (1996) Performance-based exposure control limits for pharmaceutical active ingredients. Am Ind Hyg Assoc J 57:33–42CrossRefGoogle Scholar
  40. Nikula KJ, Snipes MB, Barr EB, Griffith WC, Henderson RF, Mauderly JL (1995) Comparative pulmonary toxicities and carcinogenicities of chronically inhaled diesel exhaust and carbon black in F344 rats. Fundam Appl Toxicol 25:80–94CrossRefGoogle Scholar
  41. NIOSH (2005) NIOSH pocket guide to chemical hazards and other databases. DHHS (NIOSH) Publication No. 2005-149. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, CincinnatiGoogle Scholar
  42. NIOSH (2010a) Strategic plan for NIOSH nanotechnology research and guidance filling the knowledge gaps. DHHS (NIOSH) Publication No. 2010–105. U.S. Department of Health and Human Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, CincinnatiGoogle Scholar
  43. NIOSH (2010b) Current intelligence bulletin: occupational exposure to carbon nanotubes and nanofibers. Draft for public comment. NIOSH Docket Number: NIOSH 161-A. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, CincinnatiGoogle Scholar
  44. NIOSH (2011) Current intelligence bulletin 63: occupational exposure to titanium dioxide. NIOSH (DHHS) Publication No. 2011-160. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, CincinnatiGoogle Scholar
  45. NRC (2009) Science and decisions: advancing risk assessment. Committee on improving risk analysis approaches used by the U.S. EPA, Board on Environmental Studies and Toxicology, Division on Earth and Life Studies, National Research Council of the National AcademiesGoogle Scholar
  46. NTP (1996–2000) National Toxicology Program, Technical Report Series: Toxicology and carcinogenesis in F344/N rats and B6C3F1 mice (inhalation studies). US Department of Health and Human Services, National Institutes of Health (NIH), Research Triangle Park, NC. Reports referenced include: Cobalt sulfate heptahydrate (NIH 1998, Pub. No. 98-3961, NTP TR 471); gallium arsenide (NIH 2000, Pub. No. 00-3951, NTP TR 492); nickel oxide (NIH 1996, Pub. No. 96-3367, NTP TR 451); nickel subsulfide (NIH 1996, Pub. No. 96-3369, NTP TR 453); and molybdenum trioxide (NIH 1997, Pub. No. 97-3378, NTP TR 462)Google Scholar
  47. Oberdörster G, Yu CP (1990) The carcinogenic potential of inhaled diesel exhaust: a particle effect? J Aerosol Sci 21(Suppl 1):S397–S401CrossRefGoogle Scholar
  48. Oberdörster G, Ferin J, Lehnert BE (1994) Correlation between particle size, in vivo particle persistence, and lung injury. Environ Health Perspect 102(Suppl 5):173–179CrossRefGoogle Scholar
  49. Oberdörster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick J, Ausman K, Carter J, Karn B, Kreyling W, Lai D, Olin S, Monteiro-Riviere N, Warheit D, Yang H (2005a) Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Report of the international life sciences institute research foundation/risk science institute nanomaterial toxicity screening working group. Part Fibre Toxicol 2:8CrossRefGoogle Scholar
  50. Oberdörster G, Oberdörster E, Oberdörster J (2005b) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113(7):823–839CrossRefGoogle Scholar
  51. OECD (2007) Guidance on grouping of chemicals. Series on testing and Assessment, No. 80. ENV/JM/MONO(2007)28 Organization for Economic Cooperation and Development, Environmental Health and Safety Publications Google Scholar
  52. OECD (2010a) List of manufactured nanomaterials and list of endpoints for phase one of the sponsorship programme for the testing of manufactured nanomaterials: revision. No. 27. ENV/JM/MONO(2010)46. Organization for Economic Cooperation and Development, Series on the Safety of Manufactured NanomaterialsGoogle Scholar
  53. OECD (2010b) Guidance manual for the testing of manufactured nanomaterials: OECD’s sponsorship programme; first revision. ENV/JM/MONO(2009)20/REVGoogle Scholar
  54. Pauluhn J (2010) Subchronic 13-week inhalation exposure of rats to multiwalled carbon nanotubes: toxic effects are determined by density of agglomerate structures, not fibrillar structures. Toxicol Sci 113(1):226–242CrossRefGoogle Scholar
  55. Pauluhn J (2011) Poorly soluble particulates: searching for a unifying denominator of nanoparticles and fine particles for DNEL estimation. Toxicology 279(1–3):176–188CrossRefGoogle Scholar
  56. Rom WN, Markowitz S (2006) Environmental and occupational medicine. Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
  57. Rushton EK, Jiang J, Leonard SS, Eberly S, Castranova V, Biswas P, Elder A, Han X, Gelein R, Finkelstein J, Oberdorster G (2010) Concept of assessing nanoparticle hazards considering nanoparticle dosemetric and chemical/biological response metrics. J Toxicol Environ Health A 73:445–461CrossRefGoogle Scholar
  58. Sargent LM, Shvedova AA, Hubbs AF, Salisbury JL, Benkovic SA, Kashon ML, Lowry DT, Murray AR, Kisin ER, Friend S, McKinstry KT, Battelli L, Reynolds SH (2009) Induction of aneuploidy by single-walled carbon nanotubes. Environ Mol Mutagen 50(8):708–717CrossRefGoogle Scholar
  59. Sargent LM, Hubbs AF, Young SH, Kashon ML, Dinu CZ, Salisbury JL, Benkovic SA, Lowry DT, Murray AR, Kisin ER, Siegrist KJ, Battelli L, Mastovich J, Sturgeon JL, Bunker KL, Shvedova AA, Reynolds SH (2011b) Single-walled carbon nanotube-induced mitotic disruption. Mutat Res 745(1–2):28–37Google Scholar
  60. Schoeny RS, Margosches E (1989) Evaluating comparative potencies: developing approaches to risk assessment of chemical mixtures. Toxicol Indust Health 5(5):825–837Google Scholar
  61. Schulte PA, Salamanca-Buentello F (2007) Ethical and scientific issues of nanotechnology in the workplace. Environ Health Perspect 115(1):5–12CrossRefGoogle Scholar
  62. Schulte P, Geraci C, Zumwalde R, Hoover M, Kuempel E (2008) Occupational risk management of engineered nanoparticles. JOEH 5:239–249Google Scholar
  63. Schulte PA, Murashov V, Zumwalde R, Kuempel ED, Geraci CL (2010) Occupational exposure limits for nanomaterials: state of the art. J Nanopart Res 12:1971–1987CrossRefGoogle Scholar
  64. Shvedova AA, Kisin ER, Mercer R, Murray AR, Johnson VJ, Potapovich AI, Tyurina YY, Gorelik O, Arepalli S, Schwegler-Berry D, Hubbs AF, Antonini J, Evans DE, Ku BK, Ramsey D, Maynard A, Kagan VE, Castranova V, Baron P (2005) Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. Am J Physiol Lung Cell Mol Physiol 289:L698–L708CrossRefGoogle Scholar
  65. Sobels FH (1993) Approaches to assessing genetic risks from exposure to chemicals. Environ Health Perspect 101(Suppl 3):327–332CrossRefGoogle Scholar
  66. Stayner L, Kuempel E, Gilbert S, Hein M, Dement J (2008) An epidemiological study of the role of chrysotile asbestos fibre dimensions in determining respiratory disease risk in exposed workers. Occup Environ Med 65(9):613–619CrossRefGoogle Scholar
  67. Stefaniak AB, Virji MA, Day GA (2011) Dissolution of beryllium in artificial lung alveolar macrophage phagolysosomal fluid. Chemosphere 83(8):1181–1187CrossRefGoogle Scholar
  68. Sutter JR (1995) Molecular and cellular approaches to extrapolation for risk assessment. Environ Health Perspect 103:386–389CrossRefGoogle Scholar
  69. Tervonen T, Linkov I, Figueira FR, Steevens J, Chappell M, Merad M (2009) Risk-based classification system of nanomaterials. J Nanopart Res 11:757–766CrossRefGoogle Scholar
  70. Tran CL, Buchanan D, Cullen RT, Searl A, Jones AD, Donaldson K (2000) Inhalation of poorly soluble particles. II. Influence of particle surface area on inflammation and clearance. Inhal Toxicol 12(12):1113–1126CrossRefGoogle Scholar
  71. U.S. EPA (1987) Recommendations for and documentation of biological values for use in risk assessment. Environmental criteria and assessment office, office of health and environmental assessment, office of research and development, U.S. Environmental Protection Agency, August, CincinnatiGoogle Scholar
  72. U.S. EPA (2010) Benchmark dose software, version 2.1.2. U.S. Environmental Protection Agency, National Center for Environmental Assessment, WashingtonGoogle Scholar
  73. U.S. Supreme Court (1980) Industrial Union Department, AFL-CIO v. American Petroleum Institute et al., Case Nos. 78-911, 78-1036. Supreme Court Reporter 100:2844–2905Google Scholar
  74. Wang L, Mercer RR, Rojanasakul Y, Qiu A, Lu Y, Scabilloni JF, Wu N, Castranova V (2010) Direct fibrogenic effects of dispersed single-walled carbon nanotubes on human lung fibroblasts. J Toxicol Environ Health Part A 73(5):410–422CrossRefGoogle Scholar
  75. Warheit DB, Hoke RA, Finlay C, Donner EM, Reed KL, Sayes CM (2007) Development of a base set of toxicity tests using ultrafine TiO2 particles as a component of nanoparticle risk management. Toxicol Lett 171:99–110CrossRefGoogle Scholar
  76. Zalk DM, Nelson DI (2008) History and evolution of control banding: review. J Occup Environ Hyg 5:330–346CrossRefGoogle Scholar
  77. Zalk DM, Paik SY, Swuste P (2009) Evaluating the control banding nanotool: a qualitative risk assessment method for controlling nanoparticle exposures. J Nanopart Res 11:1685–1704CrossRefGoogle Scholar
  78. Zhang H, Ji Z, Xia T, Meng H, Low-Kam C, Liu R, Pokhrel S, Lin s, Wang X, Liao YP, Wang M, Li L, Rallo R, Damoiseaux R, Telesca D, Mädler L, Cohen Y, Zink JI, Nel AE (2012) Use of metal oxide nanoparticle band gap to develop a predictive paradigm for oxidative stress and acute pulmonary inflammation. ACS Nano 6(5):4349–4368Google Scholar

Copyright information

© Springer Science+Business Media B.V. (outside the USA) 2012

Authors and Affiliations

  • E. D. Kuempel
    • 1
  • V. Castranova
    • 2
  • C. L. Geraci
    • 1
  • P. A. Schulte
    • 1
  1. 1.Education and Information Division NTRCNanotechnology Research Center (NTRC), National Institute for Occupational Safety and Health (NIOSH)CincinnatiUSA
  2. 2.Health Effects Laboratory Division and NTRCNIOSHMorgantownUSA

Personalised recommendations