Chemical risk in hospital settings: Overview on monitoring strategies and international regulatory aspects
Chemical risk in hospital settings is a growing concern that health professionals and supervisory authorities must deal with daily. Exposure to chemical risk is quite different depending on the hospital department involved and might origin from multiple sources, such as the use of sterilizing agents, disinfectants, detergents, solvents, heavy metals, dangerous drugs, and anesthetic gases. Improving prevention procedures and constantly monitoring the presence and level of potentially toxic substances, both in workers (biological monitoring) and in working environments (environmental monitoring), might significantly reduce the risk of exposure and contaminations. The purpose of this article is to present an overview on this subject, which includes the current international regulations, the chemical pollutants to which medical and paramedical personnel are mainly exposed, and the strategies developed to improve safety conditions for all healthcare workers.
McDiarmid MA. Chemical hazards in health care: high hazard, high risk, but low protection. Ann N Y Acad Sci 2006;1076:601-6. DOI: https://doi.org/10.1196/annals.1371.032
Vecchio D, Sasco AJ, Cann CI. Occupational risk in health care and research. Am J Ind Med 2003;43:369-97. DOI: https://doi.org/10.1002/ajim.10191
Stewart-Evans JL, Sharman A, Isaac J. A narrative review of secondary hazards in hospitals from cases of chemical self-poisoning and chemical exposure. Eur J Emerg Med 2013;20:304-9. DOI: https://doi.org/10.1097/MEJ.0b013e32835d002c
Leso V, Ercolano ML, Cioffi DL, Iavicoli I. Occupational exposure and breast cancer risk according to hormone receptor status: a systematic review. Cancers (Basel) 2019;11:1882. DOI: https://doi.org/10.3390/cancers11121882
European Agency for Safety and Health at work. Available from: https://osha.europa.eu/en/about-eu-osha
European Commission. EC regulation N 1907/2006 (2006) of the European Parliament and of the Council concerning the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH), establishing a European Chemicals Agency.
Ha S, Seidle T, Lim KM. Act on the Registration and Evaluation of Chemicals (K-REACH) and replacement, reduction or refinement best practices. Environ Health Toxicol 2016;31:e2016026. DOI: https://doi.org/10.5620/eht.e2016026
European Commission Health and Consumers Directorate-General. Guidelines for Good Manufacturing Practice (GMP). Public Health and Risk Assessment Medicinal Product – quality, safety and efficacy. 2013.
European Commission. EC directive 2004/10/EC (2004). Council Directive 2004/10/EC on the harmonisation of laws, regulations and administrative provisions relating to the application of the principles of good laboratory practice and the verification of their applications for tests on chemical substances.
European Commission. EC regulation N° 605/2014 (2014) of the European Parliament and of the Council amending, for the purposes of introducing hazard and precautionary statements in the Croatian language and its adaptation to technical and scientific progress, Regulation (EC) No 1272/2008 of the European Parliament and of the Council on classification, labelling and packaging of substances and mixtures.
Italian Government. Legislative Decree 1994 n.626, G.U. n265 (November 12,1994).
European Commission. EC directive 89/391/EEC (1989). Council Directive 89/391/EEC on the introduction of measures to encourage improvements in the safety and health of workers at work. (89/391/EEC).
European Commission. EC regulation N° 1272/2008 (2008) of the European Parliament and of the Council on classification, labelling and packaging of substances and mixtures.
Occupational Safety and Health Administration. OSH Act of 1970. Available from: https://www.osha.gov/laws-regs/oshact/toc
National Institute for Occupational Safety and Health (NIOSH). Occupational Exposure Sampling Strategy Manual. Cincinnati: NIOSH. 1977.
Environmental Protection Agency (EPA). Regulatory Reform - Laws & Regulations. 2017. Available from: https://www.epa.gov/laws-regulations/regulatory-reform
Environmental Protection Agency. Summary of the toxic substances control act. TSCA; 1976.
Jakubowski M. Biological monitoring versus air monitoring strategies in assessing environmental-occupational exposure. J Environ Monit 2012;14:348-52. DOI: https://doi.org/10.1039/C1EM10706B
Marć M, Tobiszewski M, Zabiegała B, et al. Current air quality analytics and monitoring: a review. Anal Chim Acta 2015;853:116-26. DOI: https://doi.org/10.1016/j.aca.2014.10.018
Roberts SM, Rohr AC, Mikheev VB, et al. Influence of airborne particulates on respiratory tract deposition of inhaled toluene and naphthalene in the rat. Inhal Toxicol 2018;30:19-28. DOI: https://doi.org/10.1080/08958378.2018.1438539
Tynkkynen S, Santonen T, Stockmann-Juvala H. A comparison of REACH-derived no-effect levels for workers with EU indicative occupational exposure limit values and national limit values in Finland. Ann Occup Hyg 2015;59:401-15.
Zielhuis RL. Recent and potential advances applicable to the protection of workers’ health - Biological Monitoring. II. Assessment of toxic agents at the workplace - Roles of ambient and biological monitoring. Boston: Martinus Nijhoff Publishers; 1984. p. 84-94. DOI: https://doi.org/10.1007/978-94-009-6762-5_10
Manno M, Viau C, in collaboration with Cocker J, et al. Biomonitoring for occupational health risk assessment (BOHRA). Toxicol Lett 2010;192:3-16. DOI: https://doi.org/10.1016/j.toxlet.2009.05.001
World Health Organization. Technical guides. Elemental speciation in human health risk assessment / authors: P. Postoli et al. Geneva: World Health Organization; 2006.
Mutti A, De Palma G, Manini P, et al. Linee guida per il monitoraggio biologico. Pavia: PIME; 2006.
American Conference of Governmental Industrial Hygienists (ACGIH). Documentation of the threshold limit values and biological exposure indices, 7th Ed. Cincinnati: ACGIH Signature Publications; 2001.
Dascalaki E, Gaglia AG, Balaras C, Lagoudi A. Indoor environmental quality in Hellenic hospital operating rooms. Energ Build 2009;41:51-60. DOI: https://doi.org/10.1016/j.enbuild.2008.11.023
LeBouf RF, Virji MA, Saito R, et al. Exposure to volatile organic compounds in healthcare settings. Occup Environ Med 2014;71:642-50. DOI: https://doi.org/10.1136/oemed-2014-102080
Cipolla M, Izzotti A, Ansaldi F, et al. Volatile organic compounds in anatomical pathology wards: Comparative and qualitative assessment of indoor airborne pollution. Int J Environ Res Public Health 2017;14:609. DOI: https://doi.org/10.3390/ijerph14060609
Fritzsche FR, Ramach C, Soldini D, et al. Occupational health risks of pathologists--results from a nationwide online questionnaire in Switzerland. BMC Public Health 2012;12:1054. DOI: https://doi.org/10.1186/1471-2458-12-1054
Hall A, Harrington JM, Aw TC. Mortality study of British pathologists. Am J Ind Med 1991;20:83-9. DOI: https://doi.org/10.1002/ajim.4700200108
Costa S, Pina C, Coelho P, et al. Occupational exposure to formaldehyde: Genotoxic risk evaluation by comet assay and micronucleus test using human peripheral lymphocytes. J Toxicol Environ Health A 2011;74:1040-51. DOI: https://doi.org/10.1080/15287394.2011.582293
Maison A, Pasquier E. [Institut National de Recherche et de Sécurité – Technical guides. Le point des connaissances sur le formaldehyde].[in French]. ED 5032. 1-4. 3ème Edition. Paris: Institut National de Recherche et de Sécurité; 2008.
D'Ettorre G, Criscuolo M, Mazzotta M. Managing formaldehyde indoor pollution in anatomy pathology departments. Work 2017;56:397-402. DOI: https://doi.org/10.3233/WOR-172505
Azari MR, Asadi P, Jafari MJ, et al. Occupational exposure of a medical school staff to formaldehyde in Tehran. Tanaffos 2012;11:36-41.
Bono R, Romanazzi V, Munnia A, et al. Malondialdehyde-deoxyguanosine adduct formation in workers of pathology wards: the role of air formaldehyde exposure. Chem Res Toxicol 2010;23:1342-8. DOI: https://doi.org/10.1021/tx100083x
Costa S, Carvalho S, Costa C, et al. Increased levels of chromosomal aberrations and DNA damage in a group of workers exposed to formaldehyde. Mutagenesis 2015;30:463-73. DOI: https://doi.org/10.1093/mutage/gev002
Sancini A, Rosati MV, De Sio S, et al. Exposure to formaldehyde in health care: an evaluation of the white blood count differential. G Ital Med Lav Ergon 2014;36:153-9.
Lin D, Guo Y, Yi J, et al. Occupational exposure to formaldehyde and genetic damage in the peripheral blood lymphocytes of plywood workers. J Occup Health 2013;55:284-91. DOI: https://doi.org/10.1539/joh.12-0288-OA
Peteffi GP, Antunes MV, Carrer C, et al. Environmental and biological monitoring of occupational formaldehyde exposure resulting from the use of products for hair straightening. Environ Sci Pollut Res Int 2016;23:908-17. DOI: https://doi.org/10.1007/s11356-015-5343-4
Nielsen GD, Larsen ST, Wolkoff P. Recent trend in risk assessment of formaldehyde exposures from indoor air. Arch Toxicol 2013;87:73-98. DOI: https://doi.org/10.1007/s00204-012-0975-3
Kalantari N, Bayani M, Ghaffari T. Deparaffinization of formalin-fixed paraffin-embedded tissue blocks using hot water instead of xylene. Anal Biochem 2016;15:507:71-3. DOI: https://doi.org/10.1016/j.ab.2016.05.015
McKenzie LM, Witter RZ, Newman LS, Adgate JL. Human health risk assessment of air emissions from development of unconventional natural gas resources. Sci Total Environ 2012;424:79-87. DOI: https://doi.org/10.1016/j.scitotenv.2012.02.018
Xiao Y, Sheng ZM, Taubenberger JK. Isolating viral and host RNA sequences from archival material and production of cDNA libraries for high-throughput DNA sequencing. Curr Protoc Microbiol 2015;37:1E.8.1-16. DOI: https://doi.org/10.1002/9780471729259.mc01e08s37
Inoue O, Seiji K, Kawai T, et al. Excretion of methylhippuric acids in urine of workers exposed to a xylene mixture: comparison among three xylene isomers and toluene. Int Arch Occup Environ Health 1993;64:533-9. DOI: https://doi.org/10.1007/BF00381104
Yılmaz S, Çalbayram NÇ. Exposure to anesthetic gases among operating room personnel and risk of genotoxicity: A systematic review of the human biomonitoring studies. J Clin Anesth 2016;35:326-31. DOI: https://doi.org/10.1016/j.jclinane.2016.08.029
Tankò B, Molnàe L, Fülesdi B, Molnàr C. Occupational hazards of halogenated volatile anesthetics and their prevention: review of the literature. J Anesth Clin Res 2014;5:1-7.
Guirguis SS, Pelmear PL, Roy ML, Wong L. Health effects associated with exposure to anaesthetic gases in Ontario hospital personnel. Br J Ind Med 1990;47:490-7. DOI: https://doi.org/10.1136/oem.47.7.490
Cohen EN, Bellville JW, Brown BW Jr. Anesthesia, pregnancy and miscarriage. A study of operating room nurses and anesthetists. Anesthesiology 1971;35:343-7. DOI: https://doi.org/10.1097/00000542-197110000-00005
Wrońska-Nofer T, Nofer JR, Jajte J, et al. Oxidative DNA damage and oxidative stress in subjects occupationally exposed to nitrous oxide (N(2)O). Mutat Res 2012;731:58-63. DOI: https://doi.org/10.1016/j.mrfmmm.2011.10.010
Ferguson LR. Chronic inflammation and mutagenesis. Mutat Res 2010;690:3-11. DOI: https://doi.org/10.1016/j.mrfmmm.2010.03.007
Brodsky JB, Cohen EN. Adverse effects of nitrous oxide. Med Toxicol 1986;1:362-74. DOI: https://doi.org/10.1007/BF03259849
Byhahn C, Wilke HJ, Westpphal K. Occupational exposure to volatile anaesthetics: epidemiology and approaches to reducing the problem. CNS Drugs 2001;15:197-215. DOI: https://doi.org/10.2165/00023210-200115030-00004
Scapellato ML, Mastrangelo G, Fedeli U, et al. A longitudinal study for investigating the exposure level of anesthetics that impairs neurobehavioral performance. Neurotoxicology 2008;29:116–23. DOI: https://doi.org/10.1016/j.neuro.2007.10.001
Smith FD. Management of exposure to waste anesthetic gases. AORN J 2010;91:482–94. DOI: https://doi.org/10.1016/j.aorn.2009.10.022
Basford AB, Fink BR. The teratogenicity of halothane in the rat. Anesthesiology 1968;29:1167-73. DOI: https://doi.org/10.1097/00000542-196811000-00014
Wharton RS, Wilson AI, Mazze RI, et al. Fetal morphology in mice exposed to halothane. Anesthesiology 1979;51:532-7. DOI: https://doi.org/10.1097/00000542-197912000-00010
Cassiano da Rosa A, Beier SL, Oleskovicz N, et al. Effects of exposure to halothane, isoflurane, and sevoflurane on embryo viability and gestation in female mice. Semin-Cienc Agrar 2015;36:871-81. DOI: https://doi.org/10.5433/1679-0359.2015v36n2p871
Baeder C, Albrecht M. Embryotoxic/teratogenic potential of halothane. Int Arch Occup Environ Health 1990;62:263-71. DOI: https://doi.org/10.1007/BF00640832
Popova S, Virgieva T, Atanasova J, et al. Embryotoxicity and fertility study with halothane subanesthetic concentration in rats. Acta Anaesthesiol Scand 1979;23:505-12. DOI: https://doi.org/10.1111/j.1399-6576.1979.tb01480.x
Krajewski W, Kucharska M, Pilacik B, et al. Impaired vitamin B12 metabolic status in healthcare workers occupationally exposed to nitrous oxide. Br J Anaesth 2007;99:812-8. DOI: https://doi.org/10.1093/bja/aem280
Sardas S, Izdes S, Ozcagli E, et al. The role of antioxidant supplementation in occupational exposure to waste anaesthetic gases. Int Arch Occup Environ Health 2006;80:154-9. DOI: https://doi.org/10.1007/s00420-006-0115-6
Fujinaga M, Baden JM, Yhap EO, Mazze RI. Reproductive and teratogenic effects of nitrous oxide, isoflurane, and their combination in Sprague-Dawley rats. Anesthesiology 1987;67:960-4. DOI: https://doi.org/10.1097/00000542-198712000-00014
Olfert SM. Reproductive outcomes among dental personnel: a review of selected exposures. J Can Dent Assoc 2006;72:821-5.
Jafari A, Bargeshadi R, Jafari F, et al. Environmental and biological measurements of isoflurane and sevoflurane in operating room personnel. Int Arch Occup Environ Health 2018;91:349-59. DOI: https://doi.org/10.1007/s00420-017-1287-y
Accorsi A, Valenti S, Barbieri A, et al. Proposal for single and mixture biological exposure limits for sevoflurane and nitrous oxide at low occupational exposure levels. Int Arch Occup Environ Health 2003;76:129-36. DOI: https://doi.org/10.1007/s00420-002-0379-4
Sackey PV, Martling CR, Nise G, Radell PJ. Ambient isoflurane pollution and isoflurane consumption during intensive care unit sedation with the Anesthetic Conserving Device. Crit Care Med 2005;33:585-90. DOI: https://doi.org/10.1097/01.CCM.0000156294.92415.E2
Accorsi A, Morrone B, Domenichini I, et al. Urinary sevoflurane and hexafluoro-isopropanol as biomarkers of low-level occupational exposure to sevoflurane. Int Arch Occup Environ Health 2005;78:369-78. DOI: https://doi.org/10.1007/s00420-004-0580-8
Imbriani M, Ghittori S, Pezzagno G, Capodaglio E. Anesthetic in urine as biological index of exposure in operating-room personnel. J Toxicol Environ Health 1995;46:249-60. DOI: https://doi.org/10.1080/15287399509532032
Kovatsi L, Giannakis D, Arzoglou V, Samanidou V. Development and validation of a direct headspace GC-FID method for the determination of sevoflurane, desflurane and other volatile compounds of forensic interest in biological fluids: application on clinical and post-mortem samples. J Sep Sci 2011;34:1004-10. DOI: https://doi.org/10.1002/jssc.201000921
Scapellato ML, Carrieri M, Maccà I, et al. Biomonitoring occupational sevoflurane exposure at low levels by urinary sevoflurane and hexafluoroisopropanol. Toxicol Lett 2014;231:154-60. DOI: https://doi.org/10.1016/j.toxlet.2014.10.018
Haufroid V, Gardinal S, Licot C, et al. Biological monitoring of exposure to sevoflurane in operating room personnel by the measurement of hexafluoroisopropanol and fluoride in urine. Biomarkers 2000;5:141-51. DOI: https://doi.org/10.1080/135475000230451
Italian Department of Health. Circular n. 5, March 14, 1989.
Castiglia L, Miraglia N, Pieri M, et al. Evaluation of occupational exposure to antiblastic drugs in an Italian hospital oncological department. J Occup Health 2008;50:48-56. DOI: https://doi.org/10.1539/joh.50.48
Lancharro PM, De Castro-Acuña Iglesias N, González-Barcala FJ, Moure González JD. Evidence of exposure to cytostatic drugs in healthcare staff: a review of recent literature. Farm Hosp 2016;40:604-21.
Wahlang JB, Laishram PD, Brahma DK, et al. Adverse drug reactions due to cancer chemotherapy in a tertiary care teaching hospital. Ther Adv Drug Saf 2017;8:61-6. DOI: https://doi.org/10.1177/2042098616672572
Skarin AT. Atlas of diagnostic oncology: Systemic and mucocutaneous reactions to chemotherapy. Philadelphia: Mosby Elsevier; 2010. p. 721-36. DOI: https://doi.org/10.1016/B978-0-323-05905-3.00021-2
Moretti M, Bonfiglioli R, Feretti D, et al. A study protocol for the evaluation of occupational mutagenic/carcinogenic risks in subjects exposed to antineoplastic drugs: a multicentric project. BMC Public Health 2011;11:195. DOI: https://doi.org/10.1186/1471-2458-11-195
Italian Department of Health. Action August 5,1999. Official Journal n. 236, 1999.
Topçu S, Beşer A. Oncology nurses' perspectives on safe handling precautions: a qualitative study. Contemp Nurse 2017;53:271-83. DOI: https://doi.org/10.1080/10376178.2017.1315828
Petit M, Curti C, Roche M, et al. Environmental monitoring by surface sampling for cytotoxics: a review. Environ Monit Assess 2017;189:52. DOI: https://doi.org/10.1007/s10661-016-5762-9
Falck K, Gröhn P, Sorsa M, et al. Mutagenicity in urine of nurses handling cytostatic drugs. Lancet 1979;1:1250-1. DOI: https://doi.org/10.1016/S0140-6736(79)91939-1
Boiano JM, Steege AL, Sweeney MH. Adherence to safe handling guidelines by health care workers who administer antineoplastic drugs. J Occup Environ Hyg 2014;11:728-40. DOI: https://doi.org/10.1080/15459624.2014.916809
McDiarmid MA, Oliver MS, Roth TS, et al. Chromosome 5 and 7 abnormalities in oncology personnel handling anticancer drugs. J Occup Environ Med 2010;52:1028-34. DOI: https://doi.org/10.1097/JOM.0b013e3181f73ae6
Connor TH, Lawson CC, Polovich M, McDiarmid MA. Reproductive health risks associated with occupational exposures to antineoplastic drugs in health care settings: a review of the evidence. J Occup Environ Med 2014;56:901-10. DOI: https://doi.org/10.1097/JOM.0000000000000249
Warembourg C, Cordier S, Garlantézec R. An update systematic review of fetal death, congenital anomalies and fertility disordes among health care workers. Am J Ind Med 2017;60:578-90. DOI: https://doi.org/10.1002/ajim.22711
Sessink PJ, Trahan J, Coyne JW. Reduction in surface contamination with cyclophosphamide in 30 US hospital pharmacies following implementation of a closed-system drug transfer device. Hosp Pharm 2013;48:204-12. DOI: https://doi.org/10.1310/hpj4803-204
Connor TH, Zock MD, Snow AH. Surface wipe sampling for antineoplastic (chemotherapy) and other hazardous drug residue in healthcare settings: Methodology and recommendations. J Occup Environ Hyg 2016;13:658-67. DOI: https://doi.org/10.1080/15459624.2016.1165912
National Institute for Occupational Safety and Health (NIOSH). Application of biological monitoring methods - Manual of analytical methods. 4th ed. Cincinnati: NIOSH; 1994.
Australian Government Department of Consumer and Employment Protection. Risk-based health surveillance and biological monitoring — guideline: Resources Safety. Department of Consumer and Employment Protection; Western Australia; 2008.
Health and Safety Executive. Biological monitoring in the workplace: a guide to its practical application to chemical exposure. Richmond: Health and Safety Executive; 1997. Available from: https://www.hse.gov.uk/pubns/books/hsg167.htm
Singh KD, Tancev G, Decrue F, et al. Standardization procedures for real-time breath analysis by secondary electrospray ionization high-resolution mass spectrometry. Anal Bioanal Chem 2019;19:4883-98. DOI: https://doi.org/10.1007/s00216-019-01764-8
McClenny WA, Holdren MW. Compendium method TO-15, determination of volatile organic compounds (VOCs) in air collected in specially-prepared canisters and analyzed by gas chromatography-mass spectrometry (GC-MS). Environmental Protection Agency, technical guides 1999. Available from: https://www3.epa.gov/ttnamti1/files/ambient/airtox/to-15r.pdf
Cucciniello R, Proto A, La Femina R, et al. A new sorbent tube for atmospheric NOX determination by active sampling. Talanta 2017;164:403-6. DOI: https://doi.org/10.1016/j.talanta.2016.12.006
Motta O, Cucciniello R, La Femina R, et al. Development of a new radial passive sampling device for atmospheric NOx determination. Talanta 2018;190:199-203. DOI: https://doi.org/10.1016/j.talanta.2018.07.088
Cucciniello R, Proto A, Rossi F, et al. An improved method for BTEX extraction from charcoal. Anal Meth 2015;7:4811-5. DOI: https://doi.org/10.1039/C5AY00828J
International Organization for Standardization. ISO 16000-2004. Indoor air - Part 1. General aspects of a sampling strategy. Geneva: International Organization for Standardization; 2004.
Sassine M, Picquet-Varrault B, Perraudin E, Chiappini L, et al. A new device for formaldehyde and total aldehydes real-time monitoring. Environ Sci Pollut Res Int 2014;21:1258-69. DOI: https://doi.org/10.1007/s11356-013-2010-5
Olmos V, Lenzken SC, López CM, Villaamil EC. High-performance liquid chromatography method for urinary trans, trans-Muconic acid. Application to environmental exposure to benzene. J Anal Toxicol 2006;30:258-61. DOI: https://doi.org/10.1093/jat/30.4.258
Inoue O, Seiji K, Suzuki T, et al. Simultaneous determination of hippuric acid, o-, m-, and p-methylhippuric acid, phenylglyoxylic acid, and mandelic acid by HPLC. Bull Environ Contam Toxicol 1991;47:204-10. DOI: https://doi.org/10.1007/BF01688641
Ashfaq M, Noor N, Saif Ur Rehman M, et al. Determination of commonly used pharmaceuticals in hospital waste of Pakistan and evaluation of their ecological risk assessment. Clean Soil Air Water 2017;45:1500392. DOI: https://doi.org/10.1002/clen.201500392
Viegas S, Pádua M, Veiga AC, et al.. Antineoplastic drugs contamination of workplace surfaces in two Portuguese hospitals. Environ Monit Assess 2014;186:7807-18. DOI: https://doi.org/10.1007/s10661-014-3969-1
Gómez MJ, Petrović M, Fernández-Alba AR, Barceló D. Determination of pharmaceuticals of various therapeutic classes by solid-phase extraction and liquid chromatography-tandem mass spectrometry analysis in hospital effluent wastewaters. J Chromatogr A 2006;1114:224-33. DOI: https://doi.org/10.1016/j.chroma.2006.02.038
Izzo V, Charlier B, Bloise E, et al. A UHPLC-MS/MS-based method for the simultaneous monitoring of eight antiblastic drugs in plasma and urine of exposed healthcare workers. J Pharm Biomed Anal 2018;154:245-51. DOI: https://doi.org/10.1016/j.jpba.2018.03.024
Turci R, Sottani C, Spagnoli G, Minoia C. Biological and environmental monitoring of hospital personnel exposed to antineoplastic agents: a review of analytical methods. J Chrom B 2003;789:169–209. DOI: https://doi.org/10.1016/S1570-0232(03)00100-4
- Abstract views: 96
- PDF: 57
- HTML: 0
Copyright (c) 2021 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.