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      Screening of preservatives and evaluation of sterilized cellulose nanofibers for toxicity studies

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          Abstract

          Objectives

          The aim of this study is to establish a sterilization method for cellulose nanofibers (CNFs) dispersions that uses multiple preservatives with different hydrophilicities without affecting the physical and chemical properties of CNFs, and to provide useful information for sample preparation in future toxicity study of CNFs.

          Methods

          Various preservatives were added to the phosphorylated CNF dispersions, endotoxin level and the numbers of bacteria and fungi in the CNF dispersion were analyzed. The pH values and viscosity of sterilized CNF dispersions were compared with those of control and autoclaved CNF dispersions.

          Results

          Phosphorylated CNF dispersions at a concentration of 2.0 mg/mL or lower and the addition of 10 µg/mL benzalkonium chloride alone or 250 µg/mL methyl parahydroxybenzoate and 250 µg/mL propyl parahydroxybenzoate in combination can sterilize CNF dispersions without changing the physical and chemical properties of CNFs.

          Conclusions

          We developed sterilization method for CNF dispersions that uses multiple preservatives with different hydrophilicities without affecting the physical and chemical properties of CNFs. This sterilization method for CNFs dispersions can be applied to the safety assessment of CNF with different physicochemical properties in the future.

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          Most cited references37

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          TEMPO-oxidized cellulose nanofibers.

          Native wood celluloses can be converted to individual nanofibers 3-4 nm wide that are at least several microns in length, i.e. with aspect ratios>100, by TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical)-mediated oxidation and successive mild disintegration in water. Preparation methods and fundamental characteristics of TEMPO-oxidized cellulose nanofibers (TOCN) are reviewed in this paper. Significant amounts of C6 carboxylate groups are selectively formed on each cellulose microfibril surface by TEMPO-mediated oxidation without any changes to the original crystallinity (∼74%) or crystal width of wood celluloses. Electrostatic repulsion and/or osmotic effects working between anionically-charged cellulose microfibrils, the ζ-potentials of which are approximately -75 mV in water, cause the formation of completely individualized TOCN dispersed in water by gentle mechanical disintegration treatment of TEMPO-oxidized wood cellulose fibers. Self-standing TOCN films are transparent and flexible, with high tensile strengths of 200-300 MPa and elastic moduli of 6-7 GPa. Moreover, TOCN-coated poly(lactic acid) films have extremely low oxygen permeability. The new cellulose-based nanofibers formed by size reduction process of native cellulose fibers by TEMPO-mediated oxidation have potential application as environmentally friendly and new bio-based nanomaterials in high-tech fields.
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            Obtaining cellulose nanofibers with a uniform width of 15 nm from wood.

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              Endotoxin removal from protein solutions.

              Endotoxins liberated by gram-negative bacteria are frequent contaminations of protein solutions derived from bioprocesses. Because of their high toxicity in vivo and in vitro, their removal is essential for a safe parenteral administration. A general method for the removal of endotoxins from protein solutions is not available. Methods used for decontamination of water, such as ultrafiltration, have little effect on endotoxin levels in protein solutions. Various techniques described in the patent literature are not broadly applicable, as they are tailored to meet specific product requirements. Besides ion-exchangers and two-phase extraction, affinity techniques are applied with varying success. Also, taylor-made endotoxin-selective adsorber matrices for the prevention of endotoxin contamination and endotoxin removal are discussed for this purpose. After giving an overview of the properties of endotoxins and the significance of endotoxin contamination, this review intends to provide an overall picture of the various methods employed for their removal. Avenues are pointed out how to optimise a method with regard to the specific properties of endotoxins in aqueous solution.
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                Author and article information

                Contributors
                ka-fujita@aist.go.jp
                Journal
                J Occup Health
                J Occup Health
                10.1002/(ISSN)1348-9585
                JOH2
                Journal of Occupational Health
                John Wiley and Sons Inc. (Hoboken )
                1341-9145
                1348-9585
                07 November 2020
                Jan-Dec 2020
                : 62
                : 1 ( doiID: 10.1002/joh2.v62.1 )
                : e12176
                Affiliations
                [ 1 ] Innovation Promotion Division Oji Holdings Corporation Tokyo Japan
                [ 2 ] Research Institute of Science and Sustainability (RISS) National Institute of Advanced Industrial Science and Technology (AIST) Tsukuba Japan
                Author notes
                [*] [* ] Correspondence

                Katsuhide Fujita, RISS, AIST, 16‐1 Onogawa, Tsukuba, Ibaraki 305‐8569, Japan.

                Email: ka-fujita@ 123456aist.go.jp

                Author information
                https://orcid.org/0000-0001-9392-5210
                https://orcid.org/0000-0002-2838-569X
                Article
                JOH212176
                10.1002/1348-9585.12176
                7648261
                33159502
                96afb275-f26f-4263-bc30-afdb177bc23f
                © 2020 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 December 2019
                : 22 June 2020
                : 08 October 2020
                Page count
                Figures: 2, Tables: 4, Pages: 8, Words: 5639
                Funding
                Funded by: New Energy and Industrial Technology Development Organization , open-funder-registry 10.13039/501100001863;
                Award ID: P13006
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                January/December 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.3 mode:remove_FC converted:07.11.2020

                cellulose nanofibers,preservatives,sterilization,toxicity study,viscosity

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