Skip to main content
Log in

Assessing the first wave of epidemiological studies of nanomaterial workers

  • Review
  • Published:
Journal of Nanoparticle Research Aims and scope Submit manuscript

Abstract

The results of early animal studies of engineered nanomaterials (ENMs) and air pollution epidemiology suggest that it is important to assess the health of ENM workers. Initial epidemiological studies of workers’ exposure to ENMs (<100 nm) are reviewed and characterized for their study designs, findings, and limitations. Of the 15 studies, 11 were cross-sectional, 4 were longitudinal (1 was both cross-sectional and longitudinal in design), and 1 was a descriptive pilot study. Generally, the studies used biologic markers as the dependent variables. All 11 cross-sectional studies showed a positive relationship between various biomarkers and ENM exposures. Three of the four longitudinal studies showed a negative relationship; the fourth showed positive findings after a 1-year follow-up. Each study considered exposure to ENMs as the independent variable. Exposure was assessed by mass concentration in 10 studies and by particle count in six studies. Six of them assessed both mass and particle concentrations. Some of the studies had limited exposure data because of inadequate exposure assessment. Generally, exposure levels were not very high in comparison to those in human inhalation chamber studies, but there were some exceptions. Most studies involved a small sample size, from 2 to 258 exposed workers. These studies represent the first wave of epidemiological studies of ENM workers. They are limited by small numbers of participants, inconsistent (and in some cases inadequate) exposure assessments, generally low exposures, and short intervals between exposure and effect. Still, these studies are a foundation for future work; they provide insight into where ENM workers are experiencing potentially adverse effects that might be related to ENM exposures.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

SOD:

Superoxide dismutase

GPX:

Glutathione peroxidase

3-Cl-Tyr:

3-chloro-tyrosine

3-NOTyr:

3-nitrotyrosine

5-OHMeU:

5-Hydroxymethyl uracil

8-isoprostane:

8-Iso-prostaglandin F2α

8-OHG:

8-Hydroxyguanosine

8-OHdG:

8-Hydroxydeoxyguanosine

C6–C12 :

n-alkanes

HNE:

4-Hydroxy-trans-nonenal

HHE:

4-Hydroxy-trans-hexenal

LTs:

Leukotrienes

MDA:

Malondialdehyde

o-tyr:

o-Tyrosine

CC16:

Clara cell protein

FENO:

Fractional exhaled nitric oxide

KL-6:

Krebs Von den Lungen 6

MIP-1beta:

Macrophage inflammatory protein-1β

PFT :

Pulmonary function test

FVC:

Forced vital capacity

FEV1:

Forced expiratory volume at 1 s

MMF:

Maximal mid-expiratory flow

PEFR:

Peak expiratory flow rate

FEF25 %:

Forced expiratory flow at 25 %

FEF50 %:

Forced expiratory flow at 50 %

FEF75 %:

Forced expiratory flow at 75 %

TGF-β1:

Transforming growth factor beta-1

hsCRP:

Highly sensitive C-reactive protein

IL1β:

Interleukin-1β

IL8:

Interleukin-8

IL-6:

Interleukin-6

IL-6sR:

Interleukin-6 soluble receptor

NF-kβ:

Nuclear factor-kappaβ

TNFalpha:

Tumor necrosis factor α

hsCRP:

Highly sensitive C-reactive protein

ICAM:

Intercellular adhesion molecule

IL-6:

Interleukin-6

IL-6sR:

Interleukin-6 soluble receptor

MPO:

Myeloperoxidase

VCAM:

Vascular cell adhesion molecule

HRV :

Heart rate variability

SDNN:

Standard deviation of all normal to normal R–R intervals

RMSSD:

The root mean square of successive differences between adjacent normal cycles

LF/HF:

Low frequency/high frequency ratio

LF:

Low frequency

HF:

High frequency

VLF:

Very low frequency

CNT/CNF:

Carbon nanotube/carbon nanofiber

EBC:

Exhaled breath condensate

ENM:

Engineered nanomaterials

ENP:

Engineered nanoparticles

Mfg:

Manufacturing

NAOO:

Nano-objects, their aggregates and agglomerates

UFP:

Ultrafine particles

References

  • Bekker C, Brouwer DH, Tielemans E, Pronk A (2013) Industrial production and professional application of manufactured nanomaterials-enabled end products in Dutch Industries: potential for exposure. Ann Occup Hyg 57:314–327

    Article  Google Scholar 

  • Bergamaschi E, Poland C, Canu IG, Prina-Mello A (2015) The role of biological monitoring in nano-safety. NanoToday 10:274–277

    Article  Google Scholar 

  • Borm PJ, Robbins D, Haubold S, Kuhlbusch T, Fissan H, Donaldson K, Schins R, Stone V, Kreyling W, Lademann J, Krutmann J, Warheit D, Oberdörster E (2006) The potential risks of nanomaterials: a review carried out for ECETOC. Part Fibre Toxicol 3:11–45

    Article  Google Scholar 

  • Chang CC, Kuo CC, Liou SH, Yang CY (2013) Fine particulate air pollution and hospital admissions for myocardial infarction in a subtropical city: Taipei, Taiwan. J Toxicol Environ Health A 76:440–448

    Article  Google Scholar 

  • Cui L (2013) Exposure assessment and inflammatory response among workers producing calcium carbonate nanomaterials. Ph D. Dissertation. University of Washington

  • Dahm MM, Evans DE, Schubauer-Berigan MK, Birch ME, Fernback J (2012) Occupational exposure assessment in carbon nanotube and nanofiber primary and secondary manufacturers. Ann Occup Hyg 56:542–556

    Google Scholar 

  • Dahm MM, Evans DE, Schubauer-Berigan MK, Birch ME, Deddens JA (2013) Occupational exposure assessment in carbon nanotube and nanofiber primary and secondary manufacturers: mobile direct-reading sampling. Ann Occup Hyg 57:328–344

    Article  Google Scholar 

  • Dahm MM, Schubauer-Berigan MK, Evans DE, Birch ME, Fernback JE, Deddens JA (2015) Carbon nanotube and nanofiber exposure assessments: an analysis of 14 site visits. Ann Occup Hyg 59:705–723

    Article  Google Scholar 

  • Erdely A, Dahm M, Chen BT, Zeidler-Erdely PC, Fernback JE, Birch ME, Evans DE, Kashon ML, Deddens JA, Hulderman T, Bilgesu SA, Battelli L, Schwegler-Berry D, Leonard HD, McKinney W, Frazer DG, Antonini JM, Porter DW, Castranova V, Schubauer-Berigan MK (2013) Carbon nanotube dosimetry: from workplace exposure assessment to inhalation toxicology. Part Fibre Toxicol 10:53

    Article  Google Scholar 

  • Fatkhutdinova LM, Khaliullin TO, Zalyalov RR, Mustafin IG, Birch EM, Kisin ER, Shvedova AA (2013) Biological markers relevant to realistic occupational exposures to multiwalled carbon nanotubes. 2nd International School-conference on nanotechnology and nanotoxicology. Book of Abstract, pp 23–24

  • Glass D, Sim M, Abramson M, Plebanski M, Priestly B, Dennekamp M, Mahzar M (2013) An investigation of the immunological and respiratory effects among workers exposed to engineered nanoparticles. Accessed at http://www.coeh.monash.org/nanoparticles on Dec 15, 2013

  • Guseva Canu I, Boutou-Kempf O, Delabre L, Ducamp S, Iwatsubo Y, Marchand JL, Imbernon E (2013) Medical surveillance and epidemiologic studies of engineered nanomaterials (enm) workers in France. Occup Environ Med 70(Suppl 1):A66

    Google Scholar 

  • Hesterberg TW, Long CM, Bunn WB, Sax SN, Lapin CA, Valberg PA (2009) Non-cancer health effects of diesel exhaust: a critical assessment of recent human and animal toxicological literature. Crit Rev Toxicol 39:195–227

    Article  Google Scholar 

  • Hesterberg TW, Long CM, Lapin CA, Hamade AK, Valberg PA (2010) Diesel exhaust particulate (DEP) and nanoparticle exposures: what do DEP human clinical studies tell us about potential human health hazards of nanoparticles? Inhal Toxicol 22:679–694

    Article  Google Scholar 

  • Huang CH, Tai CY, Huang CY, Tsai CJ, Chen CW, Chang CP, Shih TS (2010) Measurements of respirable dust and nanoparticle concentrations in a titanium dioxide pigment production factory. J Environ Sci Health A Tox Hazard Subst Environ Eng 45:1227–1233

    Article  Google Scholar 

  • IARC (1999) Cancer epidemiology: principles and methods. I. Dos Santos Silva (Ed). Chapter 5. Overview of study designs. International Agency for Research on Cancer, WHO

  • Ichihara S, Li WH, Omura S, Fujitani Y, Liu Y, Wang QY, Hiraku Y, Hisanaga N, Ding XC, Kobayashi T, Ichihara G (2013) Effects on respiratory and cardiovascular systems in workers handling titanium dioxide particles. The 6th international symposium on nanotechnology, occupational and environmental health (NanOEH), Book of abstracts. O-30-B-36, pp 47

  • Institute of Occupational Safety and Health (2012) Applications of the newly developed nanoparticles exposure assessment techniques to workplaces in nanoindustries (II). IOSH 101-H322

  • International Agency for Research on Cancer (2012) IARC: Diesel engine exhaust carcinogenic. (Press Release No. 213). Accessed at http://press.iarc.fr/pr213_E.pdf Jan 15, 2013

  • International Agency for Research on Cancer (2014) Volume 111: Fluoro-edenite, silicon carbide fibres and whiskers, and single-walled and multi-walled carbon nanotubes. IARC Working Group. Lyon. IARC Monogr Eval Carcinog Risk Chem Hum (in press)

  • Koivisto AJ, Lyyränen J, Auvinen A, Vanhala E, Hämeri K, Tuomi T, Jokiniemi J (2012) Industrial worker exposure to airborne particles during the packing of pigment and nanoscale titanium dioxide. Inhal Toxicol 24:839–849

    Article  Google Scholar 

  • Lee JH, Kwon M, Ji JH, Kang CS, Ahn KH, Han JH, Yu IJ (2011) Exposure assessment of workplaces manufacturing nanosized TiO2 and silver. Inhal Toxicol 23:226–236

    Article  Google Scholar 

  • Lee JH, Mun J, Park JD, Yu IJ (2012) A health surveillance case study on workers who manufacture silver nanomaterials. Nanotoxicology 6:667–669

    Article  Google Scholar 

  • Lee JS, Choi YC, Shin JH, Lee JH, Lee Y, Park SY, Baik JE, Ahn K, Yu IJ (2015) Health surveillance study of workers who manufacture multi-walled carbon nanotubes. Nanotoxicology 9:802–811

    Article  Google Scholar 

  • Liao HY, Chung YT, Lai CH, Lin MH, Liou SH (2014a) Sneezing and allergic dermatitis were increased in engineered nanomaterial handling workers. Ind Health 52:199–215

    Article  Google Scholar 

  • Liao HY, Chung YT, Tsou TC, Wang SL, Li LA, Chiang HC, Li WF, Lai CH, Lee HL, Lin MH, Hsu JH, Ho JJ, Chen CJ, Shih TS, Lin CC, Liou SH (2014b) Six-month follow-up study of health markers of nanomaterials among workers handling engineered nanomaterials. Nanotoxicology 8(Suppl):100–110

    Article  Google Scholar 

  • Liou SH, Tsou TC, Wang SL, Li LA, Chiang HC, Li WF, Lin PP, Lai CH, Lee HL, Lin MH, Hsu JH, Chen CR, Shih TS, Liao HY, Chung YT (2012) Epidemiological study of health hazards among workers handling engineered nanomaterials. J Nanopart Res 14:878–892

    Article  Google Scholar 

  • Liou S, Liao H, Chung Y, Lai C, Wang S, Chiang H, Li L, Tsou T, Lin M, Lin C, Li W, Lee H (2013) Four-year follow-up study of health hazards among workers handling engineered nanomaterials. Occup Environ Med 70(Suppl 1):A62

    Article  Google Scholar 

  • McDonnell WF, Nishino-Ishikawa N, Petersen FF, Chen LH, Abbey DE (2000) Relationships of mortality with the fine and coarse fractions of long-term ambient PM10 concentrations in nonsmokers. J Expo Anal Environ Epidemiol 10:427–436

    Article  Google Scholar 

  • National Institute for Occupational Safety and Health (2011) NIOSH Current Intelligence Bulletin 63. Occupational exposure to titanium dioxide. DHHS (NIOSH) Publication No. 2011–160

  • National Institute for Occupational Safety and Health (2013) NIOSH Current Intelligence Bulletin 65: Occupational Exposure to Carbon Nanotubes and Nanofibers. DHHS (NIOSH) Publication No. 2013–145

  • Nowak D, Kalucka S, Białasiewicz P, Krl M (2001) Exhalation of H2O2 and thiobarbituric acid reactive substances (TBARs) by healthy subjects. Free Radic Biol Med 30:178–186

    Article  Google Scholar 

  • Oberdörster G, Oberdörster E, Oberdörster J (2005) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113:823–839

    Article  Google Scholar 

  • Paik SY, Zalk DM, Swuste P (2008) Application of a pilot control banding tool for risk level assessment and control of nanoparticle exposures. Ann Occup Hyg 52:419–428

    Article  Google Scholar 

  • Pelclova, D, Fenclova Z, Vlckova Stepanka, Zdimal V, Schwarz J, Pusman J, Zikova N, Syslova K, Kuzma M, Navratil T, Zakharov S, Kacer P (2012) Markers of oxidative stress are elevated in workers exposed to nanoparticles. NANOCON 2012, Conference Proceedings, pp 654–658. http://www.nanocon.eu/files/proceedings/04/reports/628.pdf

  • Pelclova D, Fenclova Z, Navratil T, Vlckova S, Syslova K, Kuzma M, Zdimal V, Schwarz J, Pusman J, Zikova N, Zakharov S, Kacer P (2013) Urine and exhaled breath condensate markers of oxidative stress in workers exposed to aerosol containing TiO2 nanoparticles. 2nd QNano integrating conference. Abstract Book, pp 71

  • Pelclova D, Fenclova Z, Navratil T, Vlckova S, Syslova K, Kuzma M, Zdimal V, Schwarz J, Makes O, Zikova N, Zakharov S, Machajova M, Kacer Petr (2014a) Markers of oxidative stress in exhaled breath of workers exposed to iron oxide (nano) particles are elevated. Abstracts from 19th Interdisciplinary Toxicological Conference TOXCON. Interdisciplinary Toxicology 7(Suppl 1):69–70

  • Pelclova D, Fenclova Z, Navratil T, Vlckova S, Syslova K, Kuzma M, Zdimal V, Schwarz J, Pusman J, Zikova N, Zakharov S, Machajova M, Kacer P (2014b) Markers of oxidative stress in exhaled breath condensate are significantly increased in workers exposed to aerosol containing TiO2 nanoparticles. Abstracts of the 50th Congress on the European Society of Toxicology (EUROTOX) Edinburgh September 7–10, 2014. Toxicol Lett 229(Suppl):S12

    Article  Google Scholar 

  • Peters A, von Klot S, Heier M, Trentinaglia I, Hörmann A, Wichmann HE, Löwel H, Cooperative Health Research in the Region of Augsburg Study Group (2004) Exposure to traffic and the onset of myocardial infarction. N Engl J Med 351:1721–1730

    Article  Google Scholar 

  • Rudnicka AR, Rumley A, Lowe GDO, Strachan DP (2007) Diurnal, seasonal, and blood-processing patterns in levels of circulating fibrinogen, fibrin d-dimer, c-reactive protein, tissue plasminogen activator, and von Willebrand factor in a 45-year-old population. Circulation 115:996–1003

    Article  Google Scholar 

  • Schubauer-Berigan MK, Dahm MM, Yencken MS (2011) Engineered carbonaceous nanomaterials manufacturers in the United States: workforce size, characteristics, and feasibility of epidemiologic studies. J Occup Environ Med 53(Suppl):S62–S67

    Article  Google Scholar 

  • Schubauer-Berigan KM, Dahm MM, Deddens JA et al (2013) From the very small to the very large: challenges in conducting epidemiologic studies of U.S. workers exposed to carbon nanotubes. Occup Environ Med 70(Suppl 1):A64

    Google Scholar 

  • Schulte PA, Smith A (2011) Ethical issues in molecular epidemiologic research. In: Rothman N et al (eds) Molecular epidemiology: principles and practices. IARC, Lyon, pp 9–22

    Google Scholar 

  • Schulte PA, Trout D, Zumwalde RD, Kuempel E, Geraci CL, Castranova V, Mundt DJ, Mundt KA, Halperin WE (2008) Options for occupational health surveillance of workers potentially exposed to engineered nanoparticles: state of the science. J Occup Environ Med 50:517–526

    Article  Google Scholar 

  • Schulte PA, Schubauer-Berigan MK, Mayweather C, Geraci CL, Zumwalde R, McKernan JL (2009) Issues in the development of epidemiologic studies of workers exposed to engineered nanoparticles. J Occup Environ Med 51:323–335

    Article  Google Scholar 

  • Seal S, Karn B (2014) Safety aspects of nanotechnology based activity. Saf Sci 63:217–225

    Article  Google Scholar 

  • Stern ST, McNeil SE (2008) Nanotechnology safety concerns revisited. Toxicol Sci 101:4–21

    Article  Google Scholar 

  • Törner A, Duberg AS, Dickman P, Svensson A (2010) A proposed method to adjust for selection bias in cohort studies. Am J Epidemiol 171:602–608

    Article  Google Scholar 

  • Törner A, Dickman P, Duberg AS, Kristinsson S, Landgren O, Björkholm M, Svensson A (2011) A method to visualize and adjust for selection bias in prevalent cohort studies. Am J Epidemiol 174:969–976

    Article  Google Scholar 

  • Tsai CJ, Huang CY, Chen SC et al (2011) Exposure assessment of nano-sized and respirable particles at different workplaces. International Symposium of Occupational Safety and Health on Engineering Nanoparticles, pp 181–196

  • Vermeulen R, Pronk A, Vlaanderen J, Hosgood D, Rothman N, Hildesheim A, Silverman D, Melis A, Spaan S, Voogd E, Hoet P, Godderis L, Lan Q (2014) A cross-sectional study of markers of early immunological and cardiovascular health effects among a population exposed to carbon nanotubes: the CANTES study. Occup Environ Med 71(Suppl 1):A35

    Article  Google Scholar 

  • Wu WT, Liao HY, Chung YT, Li WF, Tsou TC, Lin MH, Ho JJ, Wu TN, Liou SH (2014) Effect of nanoparticles exposure on fractional exhaled nitric oxide (FENO) in workers exposed to nanomaterials. Int J Mol Sci 15:878–894

    Article  Google Scholar 

Download references

Acknowledgments

This study was partly supported by the National Health Research Institutes of Taiwan (Grants 01A1-EOSP03-014) and the Institute of Occupational Safety and Health, Taiwan (Grants IOSH101-M323). The authors also thank project teams P25/1LF/2 and P28/1LF/6, of the Charles University in Prague, Czech Republic, which supported this work.

Contributorship

SHL and CSJT conceived the study. SHL, CSJT, DP, and MKSB searched and checked the databases according to the inclusion and exclusion criteria. PAS helped to develop search strategies. SHL, CSJT, DP, MKSB, and PAS extracted the data and assessed their quality. SHL wrote the draft of the paper. All authors contributed to writing, reviewing, or revising the paper and read and approved the final manuscript.

Disclaimer

The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the U.S. National Institute for Occupational Safety and Health and Taiwan National Health Research Institutes.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Saou-Hsing Liou.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liou, SH., Tsai, C.S.J., Pelclova, D. et al. Assessing the first wave of epidemiological studies of nanomaterial workers. J Nanopart Res 17, 413 (2015). https://doi.org/10.1007/s11051-015-3219-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11051-015-3219-7

Keywords

Navigation