ARCHIVES

Abstract: Chemical risk in hospital settings is an increasing worry that health professionals and regulatory bodies must address on a daily basis. Chemical risk exposure varies depending on the hospital department and can result from a variety of causes, including the use of sterilizing agents, disinfectants, detergents, solvents, heavy metals, toxic medications, and anesthetic gases. Strengthening preventative methods and continuously monitoring the presence and level of potentially harmful compounds in employees (biological monitoring) and working surroundings (environmental monitoring) may minimize the risk of exposure and contamination dramatically. The goal of this article is to provide an overview of the current international legislation, the chemical pollutants to which medical and paramedical staff are mostly exposed, and the techniques devised to combat them. Key Word: Risk assessment; Occupational medicine; Environmental monitoring; Biological monitoring; Sampling techniques References 1. McDiarmid MA. Chemical hazards in health care: high hazard, high risk, but low protection. Ann N Y AcadSci 2006;1076:601-6. [PubMed] [Google Scholar] 2. Vecchio D, Sasco AJ, Cann CI. Occupational risk in health care and research. Am J Ind Med 2003;43:369-97. [PubMed] [Google Scholar] 3. Stewart-Evans JL, Sharman A, Isaac J. A narrative review of secondary hazards in hospitals from cases of chemical selfpoisoning and chemical exposure. Eur J Emerg Med 2013;20:304-9. [PubMed] [Google Scholar] 4. 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. [PMC free article] [PubMed] [Google Scholar] 5. European Agency for Safety and Health at work. Available from: https://osha.europa.eu/en/about-eu-osha [Google Scholar] 6. 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. [Google Scholar] 7. 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. [PMC free article] [PubMed] [Google Scholar] 8. 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. [Google Scholar] 9. 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. [Google Scholar] 10. 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. [Google Scholar] 11. Italian Government. Legislative Decree 1994 n.626, G.U. n265 (November 12,1994). [Google Scholar] 12. 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). [Google Scholar] 13. 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. [Google Scholar] 14. Occupational Safety and Health Administration. OSH Act of 1970. Available from: https://www.osha.gov/lawsregs/oshact/toc [Google Scholar] 15. National Institute for Occupational Safety and Health (NIOSH). Occupational Exposure Sampling Strategy Manual. Cincinnati: NIOSH. 1977. [Google Scholar] 16. Environmental Protection Agency (EPA). Regulatory Reform - Laws & Regulations. 2017. Available from: https://www.epa.gov/laws-regulations/regulatory-reform [Google Scholar] 17. Environmental Protection Agency. Summary of the toxic substances control act. TSCA; 1976. [Google Scholar] 18. Jakubowski M. Biological monitoring versus air monitoring strategies in assessing environmental-occupational exposure. J Environ Monit 2012;14:348-52. [PubMed] [Google Scholar] 19. Marć M, Tobiszewski M, Zabiegała B, et al.. Current air quality analytics and monitoring: a review. Anal ChimActa 2015;853:116-26. [PubMed] [Google Scholar] 20. Roberts SM, Rohr AC, Mikheev VB, et al.. Influence of airborne particulates on respiratory tract deposition of inhaled toluene and naphthalene in the rat. InhalToxicol 2018;30:19-28. [PubMed] [Google Scholar] 21. 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 OccupHyg 2015;59:401-15. [PubMed] [Google Scholar] 22. 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: MartinusNijhoff Publishers; 1984. p. 84-94. [Google Scholar] 23. Manno M. Viau C in collaboration with Cocker J et al. Biomonitoring for occupational health risk assessment (BOHRA). Toxicol Lett 2010;192:3-16. [PubMed] [Google Scholar] 24. World Health Organization. Technical guides. Elemental speciation in human health risk assessment / authors: Postoli P., et al.. Geneva: World Health Organization; 2006. [Google Scholar] 25. Mutti A, De Palma G, Manini P, et al.. Lineeguida per ilmonitoraggiobiologico. Pavia: PIME; 2006. [Google Scholar] 26. American Conference of Governmental Industrial Hygienists (ACGIH). Documentation of the threshold limit values and biological exposure indices, 7th Ed. Cincinnati: ACGIH Signature Publications; 2001. [Google Scholar] 27. Dascalaki E, Gaglia AG, Balaras C, Lagoudi A. Indoor environmental quality in Hellenic hospital operating rooms. Energ Build 2009;41:51-60. [Google Scholar] 28. LeBouf RF, Virji MA, Saito R, et al.. Exposure to volatile organic compounds in healthcare settings. Occup Environ Med 2014;71:642-50. [PMC free article] [PubMed] [Google Scholar] 29. 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. [PMC free article] [PubMed] [Google Scholar] 30. 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. [PMC free article] [PubMed] [Google Scholar] 31. Hall A, Harrington JM, Aw TC. Mortality study of British pathologists. Am J Ind Med 1991;20:83-9. [PubMed] [Google Scholar] 32. 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. [PubMed] [Google Scholar] 33. 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. [Google Scholar] 34. D'Ettorre G, Criscuolo M, Mazzotta M. Managing formaldehyde indoor pollution in anatomy pathology departments. Work 2017;56:397-402. [PubMed] [Google Scholar] 35. Azari MR, Asadi P, Jafari MJ, et al.. Occupational exposure of a medical school staff to formaldehyde in Tehran. Tanaffos 2012;11:36-41. [PMC free article] [PubMed] [Google Scholar] 36. Bono R, Romanazzi V, Munnia A, et al.. Malondialdehydedeoxyguanosine adduct formation in workers of pathology wards: the role of air formaldehyde exposure. Chem Res Toxicol 2010;23:1342-8. [PMC free article] [PubMed] [Google Scholar] 37. 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. [PubMed] [Google Scholar] 38. 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. [PubMed] [Google Scholar] 39. 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. [PubMed] [Google Scholar] 40. 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 SciPollut Res Int 2016;23:908-17. [PubMed] [Google Scholar] 41. Nielsen GD, Larsen ST, Wolkoff P. Recent trend in risk assessment of formaldehyde exposures from indoor air. Arch Toxicol 2013;87:73-98. [PMC free article] [PubMed] [Google Scholar] 42. 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. [PubMed] [Google Scholar] 43. 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. [PubMed] [Google Scholar] 44. Niaz K, Bahadar H, Maqbool F, Abdollahi M. A review of environmental and occupational exposure to xylene and its health concerns. EXCLI J 2015;14:1167-86. [PMC free article] [PubMed] [Google Scholar] 45. 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. [PubMed] [Google Scholar] 46. 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 ClinAnesth 2016;35:326-31. [PubMed] [Google Scholar] 47. Tankò B, Molnàe L, Fülesdi B, Molnàr C. Occupational hazards of halogenated volatile anesthetics and their prevention: review of the literature. J AnesthClin Res 2014;5:1-7. [Google Scholar] 48. 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. [PMC free article] [PubMed] [Google Scholar] 49. Cohen EN, Bellville JW, Brown BW. Anesthesia, pregnancy and miscarriage. A study of operating room nurses and anesthetists. Anesthesiology 1971;35:343-7. [PubMed] [Google Scholar] 50. 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. [PubMed] [Google Scholar] 51. Ferguson LR. Chronic inflammation and mutagenesis. Mutat Res 2010;690:3-11. [PubMed] [Google Scholar] 52. Brodsky JB, Cohen EN. Adverse effects of nitrous oxide. Med Toxicol 1986;1:362-74. [PubMed] [Google Scholar] 53. Byhahn C, Wilke HJ, Westpphal K. Occupational exposure to volatile anaesthetics: epidemiology and approaches to reducing the problem. CNS Drugs 2001;15:197-215. [PubMed] [Google Scholar] 54. 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. [PubMed] [Google Scholar] 55. Smith FD. Management of exposure to waste anesthetic gases. AORN J 2010;91:482–94. [PubMed] [Google Scholar] 56. Basford AB, Fink BR. The teratogenicity of halothane in the rat. Anesthesiology 1968;29:1167-73. [PubMed] [Google Scholar] 57. Wharton RS, Wilson AI, Mazze RI, et al.. Fetal morphology in mice exposed to halothane. Anesthesiology 1979;51:532-7. [PubMed] [Google Scholar] 58. 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-CiencAgrar 2015;36:871-81. [Google Scholar] 59. Baeder C, Albrecht M. Embryotoxic/teratogenic potential of halothane. Int Arch Occup Environ Health 1990;62:263-71. [PubMed] [Google Scholar] 60. Popova S, Virgieva T, Atanasova J, et al.. Embryotoxicity and fertility study with halothane subanesthetic concentration in rats. ActaAnaesthesiolScand 1979;23:505-12. [PubMed] [Google Scholar] 61. 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. [PubMed] [Google Scholar] 62. 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. [PubMed] [Google Scholar] 63. 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. [PubMed] [Google Scholar] 64. Olfert SM. Reproductive outcomes among dental personnel: a review of selected exposures. J Can Dent Assoc 2006;72:821-5. [PubMed] [Google Scholar] 65. 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. [PubMed] [Google Scholar] 66. 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. [PubMed] [Google Scholar] 67. 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. [PubMed] [Google Scholar] 68. 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. [PubMed] [Google Scholar] 69. 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. [PubMed] [Google Scholar] 70. 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. [PubMed] [Google Scholar] 71. 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. [PubMed] [Google Scholar] 72. 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. [PubMed] [Google Scholar] 73. Italian Department of Health. Circular n. 5, March 14, 1989. [Google Scholar] 74. 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. [PubMed] [Google Scholar] 75. 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. [PubMed] [Google Scholar] 76. Wahlang JB, Laishram PD, Brahma DK, et al.. Adverse drug reactions due to cancer chemotherapy in a tertiary care teaching hospital. TherAdv Drug Saf 2017;8:61-6. [PMC free article] [PubMed] [Google Scholar] 77. SkarinAT. Atlas of diagnostic oncology: Systemic and mucocutaneous reactions to chemotherapy. Philadelphia: Mosby Elsevier; 2010. p. 721-36. [Google Scholar] 78. 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. [PMC free article] [PubMed] [Google Scholar] 79. Italian Department of Health. Action August 5,1999. Official Journal n. 236, 1999. [Google Scholar] 80. Topçu S, Beşer A. Oncology nurses' perspectives on safe handling precautions: a qualitative study. Contemp Nurse 2017;53:271-83. [PubMed] [Google Scholar] 81. Petit M, Curti C, Roche M, et al.. Environmental monitoring by surface sampling for cytotoxics: a review. Environ Monit Assess 2017;189:52. [PubMed] [Google Scholar] 82. Falck K, Gröhn P, Sorsa M, et al.. Mutagenicity in urine of nurses handling cytostatic drugs. Lancet 1979;1:1250-1. [PubMed] [Google Scholar] 83. 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. [PMC free article] [PubMed] [Google Scholar] 84. 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. [PubMed] [Google Scholar] 85. 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. [PMC free article] [PubMed] [Google Scholar] 86. 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. [PubMed] [Google Scholar] 87. 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. [PMC free article] [PubMed] [Google Scholar] 88. 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. [PMC free article] [PubMed] [Google Scholar] 89. National Institute for Occupational Safety and Health (NIOSH). Application of biological monitoring methods - Manual of analytical methods. 4th ed. Cincinnati: NIOSH; 1994. [Google Scholar] 90. 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. [Google Scholar] 91. 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 [Google Scholar] 92. Singh KD, Tancev G, Decrue F, et al.. Standardization procedures for real-time breath analysis by secondary electrospray ionization high-resolution mass spectrometry. Anal BioanalChem 2019;19:4883-98. [PMC free article] [PubMed] [Google Scholar] 93. 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 [Google Scholar] 94. 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. [PubMed] [Google Scholar] 95. 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. [PubMed] [Google Scholar] 96. Cucciniello R, Proto A, Rossi F, et al.. An improved method for BTEX extraction from charcoal. Anal Meth 2015;7:4811-5. [Google Scholar] 97. International Organization for Standardization. ISO 16000-2004. Indoor air - Part 1. General aspects of a sampling strategy. Geneva: International Organization for Standardization; 2004. [Google Scholar] 98. Sassine M, Picquet-Varrault B, Perraudin E, Chiappini L, et al.. A new device for formaldehyde and total aldehydes realtime monitoring. Environ SciPollut Res Int 2014;21:1258-69. [PubMed] [Google Scholar] 99. 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. [PubMed] [Google Scholar] 100. 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 ContamToxicol 1991;47:204-10. [PubMed] [Google Scholar] 101. 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. [Google Scholar] 102. 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. [PubMed] [Google Scholar] 103. Gómez MJ, Petrović M, Fernández-Alba AR, Barceló D. Determination of pharmaceuticals of various therapeutic classes by solid-phase extraction and liquid chromatographytandem mass spectrometry analysis in hospital effluent wastewaters. J Chromatogr A 2006;1114:224-33. [PubMed] [Google Scholar] 104. 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. [PubMed] [Google Scholar] 105. 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. [PubMed] [Google Scholar]