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. 2025 Feb 4;15(3):238.
doi: 10.3390/nano15030238.

Life-Cycle Risk Assessment of Second-Generation Cellulose Nanomaterials

James D Ede  1 , Amanda K Charlton-Sevcik  2 , Julia Griffin  1 , Padmapriya Srinivasan  1   3 , Yueyang Zhang  1   4 , Christie M Sayes  2 , You-Lo Hsieh  5 , Nicole Stark  6 , Jo Anne Shatkin  1
Affiliations

Life-Cycle Risk Assessment of Second-Generation Cellulose Nanomaterials

James D Ede et al. Nanomaterials (Basel). .

Abstract

A nanomaterial life-cycle risk assessment (Nano LCRA) was conducted for second-generation functionalized cellulose nanomaterials (CNs) in five case studies, including applications in water filtration, food contact packaging (including as an additive and coating), and food additives, to identify and prioritize potential occupational, health, consumer, and environmental risks. Exposure scenarios were developed and ranked for each product life-cycle stage. A Safer-by-Design Toolbox (SbD Toolbox) representing a compendium of high-throughput physical, chemical, and toxicological new approach methodologies (NAMs) was used for a screening-level hazard assessment. Overall, risks identified for the CN-enabled products were low. Of the exposure scenarios, occupational inhalation exposures during product manufacturing and application ranked the highest. Despite differences in chemistry and morphology, the materials behaved similarly in oral, dermal, and inhalation models, supporting their grouping and read-across. The screening-level hazard assessment identified potential lung inflammation associated with CN exposure, and a review of the literature supported this funding, suggesting CNs behave as poorly soluble, low-toxicity dusts with the potential to irritate the lung. Key research gaps to reduce uncertainty include evaluating long-term, low-dose exposures typical of the workplace, as well as the potential release and toxicity of CN-containing composite particles.

Keywords: cellulose; exposure; hazard; life-cycle; nanomaterial; risk assessment.

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Conflict of interest statement

Authors James D. Ede, Julia Griffin, Padmapriya Srinivasan, Yueyang Zhang and Jo Anne Shatkin were employed by Vireo Advisors, LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Overview of Nano LCRA and role of SbD Toolbox in hazard and exposure assessment.
Figure 2
Figure 2
Exposure scenarios for the product manufacture life-cycle stage (Scenarios 2.1–2.12).
Figure 3
Figure 3
Percent cytotoxicity induced by CN exposure for (A) 15 min and (B) 4 h to SbD lung co-culture model as measured by LDH. Treatments include untreated cells (UT); simulated gastrointestinal fluid (VC: vehicle control); 1% (v/v) Triton X-100 (PC: positive control); unmodified cellulose material (MFC: unmodified cellulose fiber); periodate-chlorite surface-functionalized CNs (PCCNF); sulfonate surface-functionalized CNs (SCNF); and TEMPO surface-functionalized CNs (TCNF). Values corresponding to statistically adverse effects compared to vehicle control are denoted (* p < 0.05).
Figure 4
Figure 4
Inflammation induced by CN exposure for (A) 15 min and (B) 4 h to SbD lung co-culture model as measured by IL-6. Materials include untreated cells (UT); simulated gastrointestinal fluid (VC: vehicle control); 1% (v/v) Triton X-100 (PC: positive control); unmodified cellulose material (MFC: unmodified cellulose fiber); periodate-chlorite surface-functionalized CNs (PCCNF); sulfonate surface-functionalized CNs (SCNF); and TEMPO surface-functionalized CNs (TCNF). Values corresponding to statistically adverse effects compared to vehicle control are denoted (* p < 0.05).
Figure 5
Figure 5
Percent cytotoxicity induced by CN exposure for (A) 15 min and (B) 4 h to SbD dermal co-culture model as measured by LDH. Materials include untreated cells (UT); simulated gastrointestinal fluid (VC: vehicle control); 1% (v/v) Triton X-100 (PC: positive control); unmodified cellulose material (MFC: unmodified cellulose fiber); periodate-chlorite surface-functionalized CNs (PCCNF); sulfonate surface-functionalized CNs (SCNF); and TEMPO surface-functionalized CNs (TCNF). Values corresponding to statistically adverse effects compared to vehicle control are denoted (* p < 0.05).
Figure 6
Figure 6
Inflammation induced by CN exposure for (A) 15 min and (B) 4 h to SbD dermal co-culture model as measured by IL-1β. Materials include untreated cells (UT); simulated gastrointestinal fluid (VC: vehicle control); 1 mM phorbol myristate acetate (PMA, PC: positive control); unmodified cellulose material (MFC: unmodified cellulose fiber); periodate-chlorite surface-functionalized CNs (PCCNF); sulfonate surface-functionalized CNs (SCNF); and TEMPO surface-functionalized CNs (TCNF). Values corresponding to statistically adverse effects compared to vehicle control are denoted (* p < 0.05).
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