Exposure Assessment and Monitoring of Antiblastic Drugs Preparation in Health Care Settings: A Systematic Review
Main Article Content
Keywords
Antineoplastic drugs, Cytotoxic drugs, Healthcare workers, Risk assessment, Risk management
Abstract
Several antiblastic drugs (ADs) are classified as carcinogenic, mutagenic, and/or toxic for reproduction. Despite established guidelines and safe handling technologies, ADs contamination of the work environments could occur in healthcare settings, leading to potential exposure of healthcare staff. This systematic review aims to investigate the main techniques and practices for assessing ADs occupational exposure in healthcare settings. The reviewed studies unveil that workplace contamination by ADs appears to be a still-topical problem in healthcare settings. These issues are linked to difficulties in guaranteeing: (i) the adherence to standardized protocols when dealing with ADs, (ii) the effective use of personal protective equipment by operators involved in the administration or management of ADs, (iii) a comprehensive training of the healthcare personnel, and (iv) a thorough health surveillance of exposed workers. A "multi-parametric" approach emerges as a desirable strategy for exposure assessment. In parallel, exposure assessment should coincide with the introduction of novel technologies aimed at minimizing exposure (i.e., risk management). Assessment must consider various departments and health operators susceptible to ADs contamination, with a focus extended beyond worst-case scenarios, also considering activities like surface cleaning and logistical tasks related to ADs management. A comprehensive approach in ADs risk assessment enables the evaluation of distinct substance behaviors and subsequent exposure routes, affording a more holistic understanding of potential risks.
References
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30. Koller M, Böhlandt A, Haberl C, Nowak D, Schierl R. Environmental and biological monitoring on an oncology ward during a complete working week. Toxicol Lett. 2018;298:158–63.
31. Lalande L, Galy G, Dussossoy E, Noyel J-E, Pivot C. Evaluation of Safe Infusion Devices for Antineoplastic Administration. J Infus Nurs. 2015;38 Suppl 6:S29-35.
32. Larroque M, Arnaudguilhem C, Bouyssiere B, Quenet F, Bouazza N, Jarlier M, et al. Evaluation of the environmental contamination and exposure risk in medical/non-medical staff after oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy. Toxicol Appl Pharmacol. 2021;429:115694.
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35. Rossignol E, Amiand MB, Sorrieul J, Bard JM, Bobin-Dubigeon C. A fully validated simple new method for environmental monitoring by surface sampling for cytotoxics. J Pharmacol Toxicol Methods. 2020;101:106652.
36. Sadeghipour F, Lorenzini KI, Ziewitz C, Dobrinas M, Fleury M, Bonnabry P. Chemical contamination during the preparation of cytotoxics: validation protocol for operators in hospital pharmacies. J Oncol Pharm Pract. 2013;19:57–64.
37. Sessink PJM, Connor TH, Jorgenson JA, Tyler TG. Reduction in surface contamination with antineoplastic drugs in 22 hospital pharmacies in the US following implementation of a closed-system drug transfer device. J Oncol Pharm Pract. 2011;17:39–48.
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43. Viegas S, Oliveira de AC, Carolino E, Pádua M. Occupational exposure to cytotoxic drugs: the importance of surface cleaning to prevent or minimise exposure. Arh Hig Rada Toksikol. 2018;69:238–49.
44. Viegas S, Pádua M, Veiga AC, Carolino E, Gomes M. Antineoplastic drugs contamination of workplace surfaces in two Portuguese hospitals. Environ Monit Assess. 2014;186:7807–18.
45. Benoist H, Eveno C, Wilson S, Vigneron N, Guilloit J-M, Morello R, et al. Perception, knowledge and protective practices for surgical staff handling antineoplastic drugs during HIPEC and PIPAC. Pleura Peritoneum. 2022;7:77–86.
46. Boiano JM, Steege AL, Sweeney MH. Adherence to Precautionary Guidelines for Compounding Antineoplastic Drugs: A Survey of Nurses and Pharmacy Practitioners. J Occup Environ Hyg. 2015;12:588–602.
47. 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.
48. Kieffer C, Verhaeghe P, Lagrassa S, Grégoire R, Moussaoui Z, Casteras-Ducros C, et al. Preventing the contamination of hospital personnel by cytotoxic agents: evaluation and training of the para-professional healthcare workers in oncology units. Eur J Cancer Care (Engl). 2015;24:404–10.
49. Constantinidis TC, Vagka E, Dallidou P, Basta P, Drakopoulos V, Kakolyris S, et al. Occupational health and safety of personnel handling chemotherapeutic agents in Greek hospitals. Eur J Cancer Care (Engl). 2011;20:123–31.
50. Altini M, Bernabini M, Marchetti P, Orlando L, Rebesco B, Sirna V. Risk management of onco-hematological drugs: how and how fast can we improve? Tumori. 2016;102:15–29.
51. Kim O, Lee H, Jung H, Jang HJ, Pang Y, Cheong H. Korean nurses’ adherence to safety guidelines for chemotherapy administration. Eur J Oncol Nurs. 2019;40:98–103.
52. Liu N, Lu H, Yi X-Q, Yang Y, Huang X-H. Nurses’ knowledge, perceptions, and behaviors regarding antineoplastic drugs: the mediating role of protective knowledge. Frontiers of Nursing. 3922;9:155–63.
53. Connor TH, DeBord DG, Pretty JR, Oliver MS, Roth TS, Lees PSJ, et al. Evaluation of antineoplastic drug exposure of health care workers at three university-based US cancer centers. J Occup Environ Med. 2010;52:1019–27.
54. Kopp B, Schierl R, Nowak D. Evaluation of working practices and surface contamination with antineoplastic drugs in outpatient oncology health care settings. Int Arch Occup Environ Health. 2013;86:47–55.
55. Ladeira C, Viegas S, Pádua M, Gomes M, Carolino E, Gomes MC, et al. Assessment of genotoxic effects in nurses handling cytostatic drugs. J Toxicol Environ Health A. 2014;77:879–87.
56. Moretti M, Grollino MG, Pavanello S, Bonfiglioli R, Villarini M, Appolloni M, et al. Micronuclei and chromosome aberrations in subjects occupationally exposed to antineoplastic drugs: a multicentric approach. Int Arch Occup Environ Health. 2015;88:683–95.
57. Crickman R, Finnell DS. Chemotherapy Safe Handling: Limiting nursing exposure with a hazardous drug control program. Clin J Oncol Nurs. 2017;21:73–78.
58. Ursini CL, Omodeo Salè E, Fresegna AM, Ciervo A, Jemos C, Maiello R, et al. Antineoplastic drug occupational exposure: a new integrated approach to evaluate exposure and early genotoxic and cytotoxic effects by no-invasive Buccal Micronucleus Cytome Assay biomarker. Toxicol Lett. 2019;316:20–6.
59. Villarini M, Dominici L, Piccinini R, Fatigoni C, Ambrogi M, Curti G, et al. Assessment of primary, oxidative and excision repaired DNA damage in hospital personnel handling antineoplastic drugs. Mutagenesis. 2011;26:359–69.
60. Leduc-Souville B, Bertrand E, Schlatter J. Risk management of excreta in a cancer unit. Clin J Oncol Nurs. 2013;17:248–52.
61. Fernandes NM, Pelissari IG, Cogo LA, Santos Filha VAV Dos. Workplace Activity in Health Professionals Exposed to Chemotherapy Drugs: An Otoneurological Perspective. Int Arch Otorhinolaryngol. 2016;20:331–8.
62. Vermette ML, Hicks MR, Khoroush K, Teo MY, Gates BD. Wipe sampling of antineoplastic drugs from workplace surfaces: A review of analytical methods and recommendations. Hygiene and Environmental Health Advances. 2024;9:100089.
2. European Commission. Guidance for the safe management of hazardous medicinal products at work. Second Edition. Luxembourg: Publications Office of the European Union, 2023.
3. Bernabeu-Martínez MÁ, Sánchez-Tormo J, García-Salom P, Sanz-Valero J, Wanden-Berghe C. Perception of risk of exposure in the management of hazardous drugs in home hospitalization and hospital units. PLoS One. 2021;16:e0253909.
4. Mahboob M, Rahman MF, Rekhadevi P V., Sailaja N, Balasubramanyam A, Prabhakar P V., et al. Monitoring of oxidative stress in nurses occupationally exposed to antineoplastic drugs. Toxicol Int. 2012;19:20–4.
5. Asefa S, Aga F, Dinegde NG, Demie TG. Knowledge and Practices on the Safe Handling of Cytotoxic Drugs Among Oncology Nurses Working at Tertiary Teaching Hospitals in Addis Ababa, Ethiopia. Drug Healthc Patient Saf. 2021;13:71–80.
6. Korczowska E, Crul M, Tuerk J, Meier K. Environmental contamination with cytotoxic drugs in 15 hospitals from 11 European countries—results of the MASHA project. European Journal of Oncology Pharmacy. 2020;3.
7. European Parliament and Counci. Directive (EU) 2022/431 of the European Parliament and of the Council of 9 March 2022 amending Directive 2004/37/EC on the protection of workers from the risks related to exposure to carcinogens or mutagens at work. 2022.
8. Kumari S, Lobo DJ, Sequira L. Potential Health Risks among Oncology Staff Nurses of Selected Hospitals due to Antineoplastic Drug Exposure. Indian J Public Health Res Dev. 2017;8:358–61.
9. Forges F, Blanc E, Raymond B, Menguy S, Macé A, Hugues M, et al. Evaluation of a safe infusion device on reducing occupational exposure of nurses to antineoplastic drugs: a comparative prospective study. Contamoins-1. Int Arch Occup Environ Health. 2021;94:1317–25.
10. NIOSH. N ational Institute Occupational Safety and Health (2017). Hazardous drug exposures in healthcare. Available online at: https://www.cdc.gov/niosh/topics/hazdrug/antineoplastic.html (last accessed 29-03-202)
11. IARC. International Agency for Research on Cancer (2024). Agents classified by the IARC monographs. Available online at: https://monographs.iarc.who.int/agents-classified-by-the-iarc/ (last accessed 29-03-2024)
12. OSHA. Occupational Safety and Health Administration (2024). Controlling Occupational Exposure to Hazardous Drugs. Available online at: https://www.osha.gov/hazardous-drugs/controlling-occex (last accessed 29-03-2024).
13. Sottani C, Porro B, Imbriani M, Minoia C. Occupational exposure to antineoplastic drugs in four Italian health care settings. Toxicol Lett. 2012;213:107–15.
14. Schierl R, Böhlandt A, Nowak D. Guidance values for surface monitoring of antineoplastic drugs in German pharmacies. Ann Occup Hyg. 2009;53:703–11.
15. Crul M, Simons-Sanders K. Carry-over of antineoplastic drug contamination in Dutch hospital pharmacies. J Oncol Pharm Pract. 2018;24:483–9.
16. Gabay M. Handling Hazardous Drugs. Hosp Pharm. 2014;49:811–2.
17. Ministero della Sanità. Linee-Guida per la sicurezza e la salute dei lavoratori esposti a chemioterapici antiblastici in ambiente sanitario (Repertorio Atti No. 736). Official Gazette of the Italian Republic, 07 October 1999, No 236. Rome; 1999.
18. Leso V, Sottani C, Santocono C, Russo F, Grignani E, Iavicoli I. Exposure to Antineoplastic Drugs in Occupational Settings: A Systematic Review of Biological Monitoring Data. Int J Environ Res Public Health. 2022;19.
19. Moher D, Liberati A, Tetzlaff J, Altman DG, Altman D, Antes G, et al. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 200; 6(7):e1000097.
20. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.
21. Ndaw S, Hanser O, Kenepekian V, Vidal M, Melczer M, Remy A, et al. Occupational exposure to platinum drugs during intraperitoneal chemotherapy. Biomonitoring and surface contamination. Toxicol Lett. 2018;298:171–6.
22. Ferron G, Simon L, Guyon F, Glehen O, Goere D, Elias D, et al. Professional risks when carrying out cytoreductive surgery for peritoneal malignancy with hyperthermic intraperitoneal chemotherapy (HIPEC): A French multicentric survey. Eur J Surg Oncol. 2015;41:1361–7.
23. Acramel A, Fouque J, Blondeel-Gomes S, Huguet S, Rezai K, Madar O, et al. Application of an Environmental Monitoring to Assess the Practices and Control the Risk of Occupational Exposure to Cyclophosphamide in Two Sites of a French Comprehensive Cancer Center. Ann Work Expo Health. 2022;66:1215–23.
24. Bobin-Dubigeon C, Amiand M, Percheron C, Audeval C, Rochard S, Leynia P, et al. A new, validated wipe-sampling procedure coupled to LC-MS analysis for the simultaneous determination of 5-fluorouracil, doxorubicin and cyclophosphamide in surface contamination. J Anal Toxicol. 2013;37:433–9.
25. Claraz P, Riff I, Vert C, Wolff E, Perriat S, Grand A, et al. Assessment of efficacy of postinfusion tubing flushing in reducing risk of cytotoxic contamination. Am J Health Syst Pharm. 2020;77:1866–73.
26. Cotteret C, Secretan P-H, Gilles-Afchain L, Rousseau J, Vidal F, Salguero-Hernandez G, et al. External contamination of antineoplastic drug vials: an occupational risk to consider. Eur J Hosp Pharm. 2022;29:284–6.
27. Fransman W, Kager H, Meijster T, Heederik D, Kromhout H, Portengen L, et al. Leukemia from dermal exposure to cyclophosphamide among nurses in The Netherlands: quantitative assessment of the risk. Ann Occup Hyg. 2014;58:271–82.
28. Hon C-Y, Astrakianakis G, Danyluk Q, Chu W. Pilot Evaluation of Dermal Contamination by Antineoplastic Drugs among Hospital Pharmacy Personnel. Can J Hosp Pharm. 2011;64:327–32.
29. Hon C-Y, Teschke K, Chua P, Venners S, Nakashima L. Occupational Exposure to Antineoplastic Drugs: Identification of Job Categories Potentially Exposed throughout the Hospital Medication System. Saf Health Work. 2011;2:273–81.
30. Koller M, Böhlandt A, Haberl C, Nowak D, Schierl R. Environmental and biological monitoring on an oncology ward during a complete working week. Toxicol Lett. 2018;298:158–63.
31. Lalande L, Galy G, Dussossoy E, Noyel J-E, Pivot C. Evaluation of Safe Infusion Devices for Antineoplastic Administration. J Infus Nurs. 2015;38 Suppl 6:S29-35.
32. Larroque M, Arnaudguilhem C, Bouyssiere B, Quenet F, Bouazza N, Jarlier M, et al. Evaluation of the environmental contamination and exposure risk in medical/non-medical staff after oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy. Toxicol Appl Pharmacol. 2021;429:115694.
33. Azari M, Panahi D, Akbari ME, Mirzaei HR, Rezvani HR, Zendehdel R, et al. Environmental Monitoring of Occupational Exposure to Cyclophosphamide Drug in Two Iranian Hospitals. Iran J Cancer Prev. 2017;10:e7229.
34. Mucci N, Dugheri S, Farioli A, Garzaro G, Rapisarda V, Campagna M, et al. Occupational exposure to antineoplastic drugs in hospital environments: potential risk associated with contact with cyclophosphamide- and ifosfamide-contaminated surfaces. Med Pr. 2020;71:519–29.
35. Rossignol E, Amiand MB, Sorrieul J, Bard JM, Bobin-Dubigeon C. A fully validated simple new method for environmental monitoring by surface sampling for cytotoxics. J Pharmacol Toxicol Methods. 2020;101:106652.
36. Sadeghipour F, Lorenzini KI, Ziewitz C, Dobrinas M, Fleury M, Bonnabry P. Chemical contamination during the preparation of cytotoxics: validation protocol for operators in hospital pharmacies. J Oncol Pharm Pract. 2013;19:57–64.
37. Sessink PJM, Connor TH, Jorgenson JA, Tyler TG. Reduction in surface contamination with antineoplastic drugs in 22 hospital pharmacies in the US following implementation of a closed-system drug transfer device. J Oncol Pharm Pract. 2011;17:39–48.
38. Siderov J, Kirsa S, McLauchlan R. Reducing workplace cytotoxic surface contamination using a closed-system drug transfer device. J Oncol Pharm Pract. 2010;16:19–25.
39. Sottani C, Porro B, Comelli M, Imbriani M, Minoia C. An analysis to study trends in occupational exposure to antineoplastic drugs among health care workers. J Chromatogr B Analyt Technol Biomed Life Sci. 2010;878:2593–605.
40. Dugheri S, Bonari A, Pompilio I, Boccalon P, Mucci N, Arcangeli G. A new approach to assessing occupational exposure to antineoplastic drugs in hospital environments. Arh Hig Rada Toksikol. 2018;69:226–37.
41. Sugiura S, Nakanishi H, Asano M, Hashida T, Tanimura M, Hama T, et al. Multicenter study for environmental and biological monitoring of occupational exposure to cyclophosphamide in Japan. J Oncol Pharm Pract. 2011;17:20–8.
42. Sugiura S, Asano M, Kinoshita K, Tanimura M, Nabeshima T. Risks to health professionals from hazardous drugs in Japan: a pilot study of environmental and biological monitoring of occupational exposure to cyclophosphamide. J Oncol Pharm Pract. 2011;17:14–9.
43. Viegas S, Oliveira de AC, Carolino E, Pádua M. Occupational exposure to cytotoxic drugs: the importance of surface cleaning to prevent or minimise exposure. Arh Hig Rada Toksikol. 2018;69:238–49.
44. Viegas S, Pádua M, Veiga AC, Carolino E, Gomes M. Antineoplastic drugs contamination of workplace surfaces in two Portuguese hospitals. Environ Monit Assess. 2014;186:7807–18.
45. Benoist H, Eveno C, Wilson S, Vigneron N, Guilloit J-M, Morello R, et al. Perception, knowledge and protective practices for surgical staff handling antineoplastic drugs during HIPEC and PIPAC. Pleura Peritoneum. 2022;7:77–86.
46. Boiano JM, Steege AL, Sweeney MH. Adherence to Precautionary Guidelines for Compounding Antineoplastic Drugs: A Survey of Nurses and Pharmacy Practitioners. J Occup Environ Hyg. 2015;12:588–602.
47. 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.
48. Kieffer C, Verhaeghe P, Lagrassa S, Grégoire R, Moussaoui Z, Casteras-Ducros C, et al. Preventing the contamination of hospital personnel by cytotoxic agents: evaluation and training of the para-professional healthcare workers in oncology units. Eur J Cancer Care (Engl). 2015;24:404–10.
49. Constantinidis TC, Vagka E, Dallidou P, Basta P, Drakopoulos V, Kakolyris S, et al. Occupational health and safety of personnel handling chemotherapeutic agents in Greek hospitals. Eur J Cancer Care (Engl). 2011;20:123–31.
50. Altini M, Bernabini M, Marchetti P, Orlando L, Rebesco B, Sirna V. Risk management of onco-hematological drugs: how and how fast can we improve? Tumori. 2016;102:15–29.
51. Kim O, Lee H, Jung H, Jang HJ, Pang Y, Cheong H. Korean nurses’ adherence to safety guidelines for chemotherapy administration. Eur J Oncol Nurs. 2019;40:98–103.
52. Liu N, Lu H, Yi X-Q, Yang Y, Huang X-H. Nurses’ knowledge, perceptions, and behaviors regarding antineoplastic drugs: the mediating role of protective knowledge. Frontiers of Nursing. 3922;9:155–63.
53. Connor TH, DeBord DG, Pretty JR, Oliver MS, Roth TS, Lees PSJ, et al. Evaluation of antineoplastic drug exposure of health care workers at three university-based US cancer centers. J Occup Environ Med. 2010;52:1019–27.
54. Kopp B, Schierl R, Nowak D. Evaluation of working practices and surface contamination with antineoplastic drugs in outpatient oncology health care settings. Int Arch Occup Environ Health. 2013;86:47–55.
55. Ladeira C, Viegas S, Pádua M, Gomes M, Carolino E, Gomes MC, et al. Assessment of genotoxic effects in nurses handling cytostatic drugs. J Toxicol Environ Health A. 2014;77:879–87.
56. Moretti M, Grollino MG, Pavanello S, Bonfiglioli R, Villarini M, Appolloni M, et al. Micronuclei and chromosome aberrations in subjects occupationally exposed to antineoplastic drugs: a multicentric approach. Int Arch Occup Environ Health. 2015;88:683–95.
57. Crickman R, Finnell DS. Chemotherapy Safe Handling: Limiting nursing exposure with a hazardous drug control program. Clin J Oncol Nurs. 2017;21:73–78.
58. Ursini CL, Omodeo Salè E, Fresegna AM, Ciervo A, Jemos C, Maiello R, et al. Antineoplastic drug occupational exposure: a new integrated approach to evaluate exposure and early genotoxic and cytotoxic effects by no-invasive Buccal Micronucleus Cytome Assay biomarker. Toxicol Lett. 2019;316:20–6.
59. Villarini M, Dominici L, Piccinini R, Fatigoni C, Ambrogi M, Curti G, et al. Assessment of primary, oxidative and excision repaired DNA damage in hospital personnel handling antineoplastic drugs. Mutagenesis. 2011;26:359–69.
60. Leduc-Souville B, Bertrand E, Schlatter J. Risk management of excreta in a cancer unit. Clin J Oncol Nurs. 2013;17:248–52.
61. Fernandes NM, Pelissari IG, Cogo LA, Santos Filha VAV Dos. Workplace Activity in Health Professionals Exposed to Chemotherapy Drugs: An Otoneurological Perspective. Int Arch Otorhinolaryngol. 2016;20:331–8.
62. Vermette ML, Hicks MR, Khoroush K, Teo MY, Gates BD. Wipe sampling of antineoplastic drugs from workplace surfaces: A review of analytical methods and recommendations. Hygiene and Environmental Health Advances. 2024;9:100089.
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Apr 24, 2024
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Borghi F, Zellino C, Zago A, De Vito G, Del Vecchio RL, Cattaneo A, et al. Exposure Assessment and Monitoring of Antiblastic Drugs Preparation in Health Care Settings: A Systematic Review. Med Lav [Internet]. 2024 Apr. 24 [cited 2024 Jul. 26];115(2):e2024012. Available from: https://mattioli1885journals.com/index.php/lamedicinadellavoro/article/view/15609
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How to Cite
1.
Borghi F, Zellino C, Zago A, De Vito G, Del Vecchio RL, Cattaneo A, et al. Exposure Assessment and Monitoring of Antiblastic Drugs Preparation in Health Care Settings: A Systematic Review. Med Lav [Internet]. 2024 Apr. 24 [cited 2024 Jul. 26];115(2):e2024012. Available from: https://mattioli1885journals.com/index.php/lamedicinadellavoro/article/view/15609
