Nanotoxicity: emerging concerns regarding nanomaterial safety and occupational hard metal (WC-Co) nanoparticle exposure

Abstract

As the number of commercial and consumer products containing engineered nanomaterials (ENMs) continually rises, the increased use and production of these ENMs presents an important toxicological concern. Although ENMs offer a number of advantages over traditional materials, their extremely small size and associated characteristics may also greatly enhance their toxic potentials. ENM exposure can occur in various consumer and industrial settings through inhalation, ingestion, or dermal routes. Although the importance of accurate ENM characterization, effective dosage metrics, and selection of appropriate cell or animal-based models are universally agreed upon as important factors in ENM research, at present, there is no "standardized" approach used to assess ENM toxicity in the research community. Of particular interest is occupational exposure to tungsten carbide cobalt (WC-Co) "dusts," composed of nano- and micro-sized particles, in hard metal manufacturing facilities and mining and drilling industries. Inhalation of WC-Co dust is known to cause "hard metal lung disease" and an increased risk of lung cancer; however, the mechanisms underlying WC-Co toxicity, the inflammatory disease state and progression to cancer are poorly understood. Herein, a discussion of ENM toxicity is followed by a review of the known literature regarding the effects of WC-Co particle exposure. The risk of WC-Co exposure in occupational settings and the updates of in vitro and in vivo studies of both micro- and nano-WC-Co particles are discussed.

Keywords: cancer; engineered nanomaterial; lung disease; occupational exposure; particle; toxicity.

Figure 1

Routes and potential detrimental effects of nanoparticle exposure.

Figure 2

Cell viability after (A) nano-WC-Co and (B) micro-WC-Co particle exposure and (C) oxidative stress indicated by DCF fluorescence after exposure to 1,000 μg/mL nano- and micro-WC-Co particles. *P<0.05, ^#P<0.001 compared to control, ^‡P<0.05 compared to micro-WC-Co. Note: Reproduced from Armstead AL, Arena CB, Li B. Exploring the potential role of tungsten carbide cobalt (WC-Co) nanoparticle internalization in observed toxicity toward lung epithelial cells in vitro. Toxicol Appl Pharmacol. 2014;278(1):1–8. Abbreviations: DCF, 2′,7′-dichlorofluorescein; WC-Co, tungsten carbide cobalt.

Figure 3

Pulmonary inflammation parameters assessed in the BAL fluid following 24 h exposure to WC-Co and CeO₂ NPs: (A) LDH activity, (B) albumin, and (C) AM chemiluminescence. Values presented as mean ± SD. *P<0.05, ^‡P<0.001 compared to the vehicle control, and ^#P<0.01 compared to WC-Co NP exposed groups. Notes: Reproduced from Armstead AL, Minarchick VC, Porter DW, Nurkiewicz TR, Li B. Acute inflammatory responses of nanoparticles in an intra-tracheal instillation rat model. PLoS One. 2015;10(3):e0118778. Abbreviations: BAL, bronchoalveolar lavage; LDH, lactate dehydrogenase; AM, alveolar macrophage; SD, standard deviation; NP, nanoparticle; WC-Co, tungsten carbide cobalt.