Risk Analysis of Cellulose Nanomaterials by Inhalation: Current State of Science

Our plain-English summary of Risk Analysis of Cellulose Nanomaterials by Inhalation: Current State of Science, by J.D. Ede, K.J. Ong, M. Goergen, et al (Nanomaterials, 2019).

The study

• Authors: J.D. Ede, K.J. Ong, M. Goergen, A. Rudie, C.A. Pomeroy-Carter, J.A. Shatkin
• Journal: Nanomaterials
• Published: 2019;9(3)
• Type of article: Review
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Cellulose nanomaterials (CNs) are emerging advanced materials with many unique properties and growing commercial significance. A life-cycle risk assessment and environmental health and safety roadmap identified potential risks from inhalation of powdered CNs in the workplace as a key gap in our understanding of safety and recommended addressing this data gap to advance the safe and successful commercialization of these materials. Here, we (i) summarize the currently available published literature for its contribution to our current understanding of CN inhalation hazard and (ii) evaluate the quality of the studies for risk assessment purposes using published study evaluation tools for nanomaterials to assess the weight of evidence provided. Our analysis found that the quality of the available studies is generally inadequate for risk assessment purposes but is improving over time. There have been some advances in knowledge about the effects of short-term inhalation exposures of CN. The most recent in vivo studies suggest that short-term exposure to CNs results in transient inflammation, similarly to other poorly soluble, low toxicity dusts such as conventional cellulose, but is markedly different from fibers with known toxicity such as certain types of multiwalled carbon nanotubes or asbestos. However, several data gaps remain, and there is still a lack of understanding of the effects from long-term, low-dose exposures that represent realistic workplace conditions, essential for a quantitative assessment of potential health risk. Therefore, taking precautions when handling dry forms of CNs to avoid dust inhalation exposure is warranted.

In plain English

This was a review, not a new experiment. The authors examined published studies (2011 to 2018) on breathing in cellulose nanomaterials, tiny plant-derived materials made as nanocrystals or nanofibrils. They scored seven animal studies and six cell studies with two published quality tools to judge how useful each was for risk assessment. They found the materials were generally poorly characterized. Animal study design scores were low, from 1 to 11 out of 20 on the Krug and Wick scale. Studies from 2017 and 2018 scored higher (7 to 11) than those from 2014 to 2016 (1 to 3). Most animal studies delivered high doses all at once to the lungs by pharyngeal aspiration rather than by inhalation. Many tested only one or two doses. In one reviewed mouse study (Park et al. 2018), crocidolite asbestos produced a response indicating chronic inflammation, while the cellulose nanomaterials produced much weaker responses. The authors concluded that the studies give only limited evidence for risk assessment and that long-term studies at realistic levels are lacking. They also concluded that preventing or minimizing inhalation exposure remains the safest course.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review of published studies, including a quality evaluation of each study for risk assessment purposes using two published scoring approaches (Krug and Wick 2011; Card and Magnuson 2010)
• Who was studied: Twelve published studies (2011–2018) on short-term inhalation toxicity of cellulose nanomaterials. The authors evaluated seven animal (in vivo) studies in mice and rats and six cellular (in vitro) studies. One study (Ilves et al. 2018) counts in both groups.
• Exposure: Cellulose nanomaterials: cellulose nanocrystals (CNC) and cellulose nanofibrils (CNF). Some reviewed studies used comparison materials: crocidolite asbestos, single-walled and multiwalled carbon nanotubes, and bulk or conventional cellulose.
• Main results:
  • Across the reviewed studies, the authors found the physical and chemical characterization of the cellulose nanomaterials was generally inadequate.
  • Under the Krug and Wick approach, study design scores for the animal studies were generally low, ranging from 1 to 11 out of a possible 20.
  • Animal study design scores improved over time: studies from 2014–2016 scored 1–3, and studies from 2017 and 2018 scored 7–11 (Krug and Wick approach).
  • Under the Card and Magnuson approach, none of the animal studies met a mandatory minimum criterion on whether the study design was appropriate for risk assessment.
  • Most of the animal studies used pharyngeal aspiration to deliver high doses to mouse lungs all at once (bolus doses), rather than by inhalation.
  • Many of the animal studies tested only one or two doses.
  • In the reviewed Park et al. (2018) mouse study, crocidolite asbestos produced an immune response indicating chronic inflammation. Single-walled carbon nanotubes, CNF and CNC produced much weaker responses.
  • In the reviewed Ilves et al. (2018) mouse study, only modest immune reactions were seen 28 days after CNF exposure. These were reduced compared with 24 hours after exposure and similar to those from bulk cellulose.
  • The authors judged that the available studies provide only a limited weight of evidence for risk assessment, but that study quality is improving.
• The authors' conclusion: The authors concluded that, given the remaining uncertainties, the safest course is still a precautionary approach that prevents or minimizes the potential for inhaling dry cellulose nanomaterials.
• Limitations the authors state:
  • The authors state that the scoring criteria do not judge whether a study is good or bad, only whether it was designed in a way usable for risk assessment.
  • The authors state that the user of these evaluation approaches bears responsibility for critically judging the relevance of the information.
  • The authors note that no long-term studies at realistic exposure levels by inhalation exist, which leaves significant uncertainty about health effects.
  • The authors note that no longer-term animal study comparing CNC with conventional cellulose had been reported.

Topics

Medical terms in this study, explained in our Lexicon: Short-Term Exposure, Inflammation.

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