Nanofibrillated cellulose causes acute pulmonary inflammation that subsides within a month

Abstract

Nanofibrillated cellulose (NFC) is a renewable nanomaterial that has beneficial uses in various applications such as packaging materials and paper. Like carbon nanotubes (CNT), NFCs have high aspect ratio and favorable mechanical properties. The aspect ratio also rises a concern whether NFC could pose a health risk and induce pathologies, similar to those triggered by multi-walled CNT. In this study, we explored the immunomodulatory properties of four NFCs in vitro and in vivo, and compared the results with data on bulk-sized cellulose fibrils and rigid multi-walled CNT (rCNT). Two of the NFCs were non-functionalized and two were carboxymethylated or carboxylated. We investigated the production of pro-inflammatory cytokines in differentiated THP-1 cells, and studied the pulmonary effects and biopersistence of the materials in mice. Our results demonstrate that one of the non-functionalized NFCs tested reduced cell viability and triggered pro-inflammatory reactions in vitro. In contrast, all cellulose materials induced innate immunity response in vivo 24 h after oropharyngeal aspiration, and the non-functionalized NFCs additionally caused features of Th2-type inflammation. Modest immune reactions were also seen after 28 days, however, the effects were markedly attenuated as compared with the ones after 24 h. Cellulose materials were not cleared within 1 month, as demonstrated by their presence in the exposed lungs. All effects of NFC were modest as compared with those induced by rCNT. NFC-induced responses were similar or exceeded those triggered by bulk-sized cellulose. These data provide new information about the biodurability and pulmonary effects of different NFCs; this knowledge can be useful in the risk assessment of cellulose materials.

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

“…To date, twelve studies from 2011–2018 have been published on the short-term inhalation toxicity of CNs [12,13,14,15,16,17,18,19,20,21,22,23]. These studies use both cellular (in vitro) [16,17,18,19,20,21] and animal (in vivo) [12,13,14,15,16,22,23] models to investigate the effect of CNC and CNF exposure on the lung. The main findings from these studies are summarized here before analyzing the studies using two published approaches for their usefulness for risk assessment purposes.…”

“…A similarly designed study by Ilves et al (2018) examined the cytotoxicity and pro-inflammatory cytokine production in THP-1 cells following exposure to four surface-modified CNFs and compared these responses to conventional cellulose [16]. The authors found that one of the unmodified CNFs reduced cell viability and triggered pro-inflammatory cytokine production; the remaining three CNF materials had no significant changes and were similar to the response observed for bulk-sized cellulose.…”

“…Ilves et al (2018) recently published a study of one-time exposures using pharyngeal aspiration (10 or 40 μg/mouse) to one of four surface-modified CNFs in mice [16]. The authors included two observation timepoints (24 h and 28 days post-exposure), used positive and negative controls, and compared results to relevant reference materials—multiwalled carbon nanotubes (MWCNTs) and bulk-size cellulose.…”

“…Researchers may aim to determine the mechanisms of toxicity (i.e., how are these materials causing their effects at high doses), find the lowest observed adverse effect level (i.e., at what concentration do effects start to occur) or conduct a risk assessment, which considers whether a hazard might cause harm to exposed persons under realistic exposure scenarios. Here, we have adapted the Krug and Wick and Card and Magnuson criteria sets to specifically assess the quality of studies examining short-term CN inhalation for risk assessment purposes and used them to evaluate seven animal (in vivo) studies [12,13,14,15,16,22,23] and six cellular (in vitro) studies [16,17,18,19,20,21] (Table 1). Studies were evaluated that specifically examined exposure to CN using in vivo or in vitro models of inhalation; studies examining inhalation exposure to bulk cellulose were not included, except when included in the study design as reference materials.…”

Biomass Cellulose Nanoparticles Display Considerable Neurotoxicity in Zebrafish

“…Based on the results of toxicity studies of metal nanomaterials, we consider that the research on the toxicity of CNs should be carried out urgently. Till now, the toxicity of these biomass CNs were reported mainly in the inhalation toxicity to the lung in both cellular [20][21][22] and animal [20,23,24] models. These investigations demonstrated CN exposures resulted in in ammatory responses [19].…”