Occupational exposure to cytotoxic drugs: the importance of surface cleaning to prevent or minimise exposure

Open access

Abstract

Healthcare workers who prepare or administer cytotoxic agents run the risk of exposure, and the risks for health are real even at doses lower than those applied in cancer patients, because, in theory, no dose is safe. The most common and problematic route of exposure is through the skin, especially as work surfaces can remain contaminated even after cleaning. This pilot study aimed to demonstrate the importance of having an effective surface decontamination protocol by determining surface contamination with cyclophosphamide, 5-fluorouracil, and paclitaxel as the most common cytotoxic drugs in an oncology day service. Samples were collected before and after drug handling and analysed with high performance liquid chromatography with diode array detection (HPLC-DAD). Of the 29 samples collected before drug handling 23 were contaminated, five of which with more than one drug. Of the 30 samples collected after drug handling 25 were contaminated, eight of which with more than one drug. The two time points did not significantly differ, which evidences a widespread contamination and ineffective cleaning. This calls for revising the cleaning protocol and handling procedure to place contamination under control as much as possible.

1. Falck K, Gröhn P, Sorsa M, Vainio H, Heinonen E, Holsti LR. Mutagenicity in urine in nurses handling cytotoxic drugs. Lancet 1979;8128:1250-1. PMID: 87722

2. European Agency for Health and Safety at Work (EU-OSHA). Current and emerging occupational safety and health (OSH) issues in the healthcare sector, including home and community care, 2014 [displayed 16 August 2018]. Available at https://osha.europa.eu/en/publications/reports/current-andemerging-occupational-safety-and-health-osh-issues-in-thehealthcare-sector-including-home-and-community-care/view

3. European Commission Directorate-General for Employment, Social Affairs (EC). Occupational health and safety risks in the healthcare sector - Guide to prevention and good practice, 2011 [displayed 16 August 2018]. Available at http://ec.europa.eu/social/BlobServlet?docId=7167&langId=en

4. European Parliament (EP). Preventing occupational exposure to cytotoxic and other hazardous drugs: European policy recommendations, 2016 [displayed 16 August 2018]. Available at http://www.europeanbiosafetynetwork.eu/wpcontent/uploads/2016/05/Exposure-to-Cytotoxic-Drugs_Recommendation_DINA4_10-03-16.pdf

5. Besse JP, Latour JF, Garric J. Anticancer drugs in surface waters. What can we say about the occurrence and environmental significance of cytotoxic, cytostatic and endocrine therapy drugs? Environ Int 2012;39:73-86. doi:

6. Deblonde T, Hartemann P. Environmental impact of medical prescriptions: assessing the risks and hazards of persistence, bioaccumulation and toxicity of pharmaceuticals. Public Health 2013;127:312-7. doi:

7. Gajski G, Gerić M, Domijan A-M, Garaj-Vrhovac V. Combined cyto/genotoxic activity of a selected antineoplastic drug mixture in human circulating blood cells. Chemosphere 2016;165:529-38. doi:

8. Kosjek T, Heath E. Occurrence, fate and determination of cytostatic pharmaceuticals in the environment. TrAC Trends Anal Chem 2011;30:1065-87. doi:

9. Toolaram AP, Kümmerer K, Schneider M. Environmental risk assessment of anti-cancer drugs and their transformation products: a focus on their genotoxicity characterization-state of knowledge and short comings. Mutat Res-Rev Mutat 2014;760:18-35. doi:

10. Zhang J, Chang VWC, Giannis A, Wang JY. Removal of cytostatic drugs from aquatic environment: a review. Sci Total Environ 2013;445-446:281-98. doi:

11. Zounkova R, Kovalova L, Blaha L, Dott W. Ecotoxicity and genotoxicity assessment of cytotoxic antineoplastic drugs and their metabolites. Chemosphere 2010;81:253-60. doi:

12. Kopjar N, Milas I, Garaj-Vrhovac V, Gamulin M. Alkaline comet assay study with breast cancer patients: evaluation of baseline and chemotherapy-induced DNA damage in nontarget cells. Clin Exp Med 2006;6:177-90. doi:

13. Moretti M, Grollino MG, Pavanello S, Bonfiglioli R, Villarini M, Appolloni M, Carrieri M, Sabatini L, Dominici L, Stronati L, Mastrangelo G, Barbieri A, Fatigoni C, Bartolucci GB, Ceretti E, Mussi F, Monarca S. Micronuclei and chromosome aberrations in subjects occupationally exposed to antineoplastic drugs: a multicentric approach. Int Arch Occ Env Hea 2015;88:683-95. doi:

14. Turci R, Minoia C, Sottani C, Coghi R, Severi P, Castriotta C, Del Bianco M, Imbriani M. Occupational exposure to antineoplastic drugs in seven Italian hospitals: The effect of quality assurance and adherence to guidelines. J Oncol Pharm Pract 2011;17:320-32. doi:

15. Yoshida J, Koda S, Nishida S, Yoshida T, Miyajima K, Kumagai S. Association between occupational exposure levels of antineoplastic drugs and work environment in five hospitals in Japan. J Oncol Pharm Pract 2011;17:29-38. doi:

16. Zhang X, Zheng Q, Lv L, An M, Zhang Y, Wei Y, Feng W. Evaluation of adverse health risks associated with antineoplastic drug exposure in nurses at two Chinese hospitals: the effects of implementing a pharmacy intravenous admixture service. Am J Ind Med 2016;59:264-73. doi:

17. 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:

18. Fransman W, Roeleveld N, Peelen S, de Kort W, Kromhout H, Heederik D. Nurses with dermal exposure to antineoplastic drugs: Reproductive outcomes. Epidemiology 2007;18:112-9. doi:

19. Fransman W, Peelen S, Hilhorst S, Roeleveld N, Heederik D, Kromhout H. A pooled analysis to study trends in exposure to antineoplastic drugs among nurses. Ann Occup Hyg 2007;51:231-9. doi:

20. McDiarmid MA, Oliver MS, Rogers B, Escalante C. Chromosome 5 and 7 abnormalities in oncology personnel handling anticancer drugs. J Occup Environ Med 2010;52:1028-34. doi:

21. Rombaldi F, Cassini C, Salvador M, Saffi J, Erdtmann B. Occupational risk assessment of genotoxicity and oxidative stress in workers handling anti-neoplasic drugs during a working week. Mutagenesis 2009;24:143-8. doi:

22. Mahboob M, Rahman MF, Rekhadevi PV, Sailaja N, Balasubramanyam A, Prabhakar PV, Singh SP, Reddy UA, Rao GS, Grover P. Monitoring of oxidative stress in nurses occupationally exposed to antineoplastic drugs. Toxicol Int 2012;19:20-4. doi:

23. Connor TH. Hazardous anticancer drugs in health care: environmental exposure assessment. Ann NY Acad Sci 2006;1076:615-23. doi:

24. Kiffmeyer TK, Tuerk J, Hahn M, Stuetzer H, Hadtstein C, Heinemann A, Eickmann U. Application and assessment of a regular environmental monitoring of the antineoplastic drug contamination level in pharmacies - the MEWIP project. Ann Occup Hyg 2013;57:444-55. doi:

25. Meijster T, Fransman W, Veldhof R, Kromhout H. Exposure to antineoplastic drugs outside the hospital environment. Ann Occup Hyg 2006;50:657-64. doi:

26. Sessink PJ, Bos RP. Drugs hazardous to healthcare workers. Evaluation of methods for monitoring occupational exposure to cytostatic drugs. Drug Safety 1999;20:347-59. PMID: 10230582

27. 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 Chromatogr B 2003;789:169-209. doi:

28. Minoia C, Turci R, Sottani C, Schiavi A, Perbellini L, Angeleri S, Draicchio F, Apostoli P. Application of high performance liquid chromatography/tandem mass spectrometry in the environmental and biological monitoring of health care personnel occupationally exposed to cyclophosphamide and ifosfamide. Rapid Commun Mass Spectrom 1998;12:1485-93. doi:

29. Connor TH, Anderson RW, Sessink PJ, Broadfield L, Power LA. Surface contamination with antineoplastic agents in six cancer treatment centers in Canada and the United States. Am J Health-Syst Ph 1999;56:1427-32. PMID: 10428450

30. Fleury-Souverain S, Mattiuzzo M, Mehl F, Nussbaumer S, Bouchoud L, Falaschi L, Gex-Fabry M, Rudaz S, Sadeghipour F, Bonnabry P. Evaluation of chemical contamination of surfaces during the preparation of chemotherapies in 24 hospital pharmacies. Eur J Hosp Pharm 2015;22:333-41. doi:

31. Hedmer M, Georgiadi A, Bremberg ER, Jönsson BA, Eksborg S. Surface contamination of cyclophosphamide packaging and surface contamination with antineoplastic drugs in a hospital pharmacy in Sweden. Ann Occup Hyg 2005;49:629-37. doi:

32. Schmaus G, Schierl R, Funck S. Monitoring surface contamination by antineoplastic drugs using gas chromatography-mass spectrometry and voltammetry. Am J Health Syst Pharm 2002;59:956-61. PMID: 12040735

33. Viegas S, Pádua M, Veiga A, Carolino E, Gomes M. Antineoplastic drugs contamination of workplace surfaces in two Portuguese hospitals. Environ Monit Assess 2014;186:7807-18. doi:

34. Hon CY, 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. doi:

35. Sessink PJ, Cerná M, Rössner P, Pastorková A, Bavarová H, Franková K, Anzion RB, Bos RP. Urinary cyclophosphamide excretion and chromosomal aberrations in peripheral blood lymphocytes after occupational exposure to antineoplastic agents. Mutat Res 1994;309:193-9. doi:

36. Sottani C, Rinaldi P, Leoni E, Poggi G, Teragni C, Delmonte A, Minoia C. Simultaneous determination of cyclophosphamide, ifosfamide, doxorubicin, epirubicin and daunorubicin in human urine using high-performance liquid chromatography/electrospray ionization tandem mass spectrometry: bioanalytical method validation. Rapid Commun Mass Spectrom 2008;22:2645-59. doi:

37. Sottani C, Porro B, Imbriani M, Minoia C. Occupational exposure to antineoplastic drugs in four Italian health care settings. Toxicol Lett 2011;213:107-15. doi:

38. Schierl R, Böhlandt A, Nowak D. Guidance values for surface monitoring of antineoplastic drugs in German pharmacies. Ann Occup Hyg 2009;53:703-11. doi:

39. 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. doi:

40. Touzin K, Bussières JF, Langlois E, Lefebvre M. Evaluation of surface contamination in a hospital hematology-oncology pharmacy. J Oncol Pharm Pract 2009;15:53-61. doi:

41. Castiglia L, Miraglia N, Pieri M, Simonelli A, Basilicata P, Genovese G, Guadagni R, Acampora A, Sannolo N, Scafarto MV. Evaluation of occupational exposure to antiblastic drugs in an Italian hospital oncological department. J Occup Health 2008;50:48-56. PMID: 18285644

42. 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. doi:

43. Larson RR, Khazaeli MB, Dillon HK. Monitoring method for surface contamination caused by selected antineoplastic agents. Am J Health Syst Pharm 2002;59:270-7. PMID: 11862639

44. 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:

45. Vyas N, Turner A, Clark JM, Sewell GJ. Evaluation of a closed-system cytotoxic transfer device in a pharmaceutical isolator. J Oncol Pharm Pract 2014;22:10-9. doi:

46. 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:

47. Simon N, Vasseur M, Pinturaud M, Soichot M, Richeval C, Humbert L, Lebecque M, Sidikou O, Barthelemy C, Bonnabry P, Allorge D, Décaudin B, Odou P. Effectiveness of a closed-system transfer device in reducing surface contamination in a new antineoplastic drug - compounding unit: a prospective, controlled, parallel study. PLoS One 2016;11:e0159052. doi:

48. Barek J, Cvacka J, de Méo M, Laget M, Michelon J, Castegnaro M. Chemical degradation of wastes of antineoplastic agents amsacrine, azathioprine, asparaginase and thiotepa. Ann Occup Hyg 1998;42:259-66. doi:

49. Benvenuto JA, Connor TH, Monteith DK, Laidlaw JL, Adams SC, Matney TS, Theiss JC. Degradation and inactivation of antitumor drugs. J Pharm Sci 1993;82:988-91. doi:

50. Castegnaro M, De Méo M, Laget M, Michelon J, Garren L, Sportouch MH, Hansel S. Chemical degradation of wastes of antineoplastic agents. 2: six anthra-cyclines: darubicin, doxorubicin, epirubicin, pirarubicin, aclarubicin, and daunorubicin. Int Arch Occup Environ Health 1997;70:378-84. doi:

51. Hansel S, Castegnaro M, Sportouch MH, De Méo M, Milhavet JC, Laget M, Duménil G. Chemical degradation of wastes of antineoplastic agents: cyclophosphamide, ifosfamide and melphalan. Int Arch Occup Env He 1997;69:109-14. doi:

52. Lamerie TQ, Nussbaumer S, Décaudin B, Fleury-Souverain S, Goossens JF, Bonnabry P, Odou P. Evaluation of decontamination efficacy of cleaning solutions on stainless steel and glass surfaces contaminated by 10 antineoplasic agents. Ann Occup Hyg 2013;57:456-69. doi:

53. Monteith DK, Connor TH, Benvenuto JA, Fairchild EJ, Theiss JC. Stability and inactivation of mutagenic drugs and their metabolites in the rine of patients administered antineoplastic therapy. Environ Mol Mutagen 1987;10:341-56. PMID: 3315656

54. Shea JA, Shamrock WF, Abboud CA, Woodeshick RW, Nguyen LQ, Rubino JT, Segretario J. Validation of cleaning procedures for highly potent drugs. I. Losoxantrone. Pharm Dev Technol 1966;1:69-75. doi:

55. Touzin K, Bussières JF, Langlois E, Lefebvre M, Métra A. Pilot study comparing the efficacy of two cleaning techniques in reducing environmental contamination with cyclophosphamide. Ann Occup Hyg 2010;54:351-9. doi:

56. Lunn G, Sansone EB, Andrew AW, Hellwig LC. Degradation and disposal of some antineoplastic drugs. J Pharm Sci 1989;78:652-9. doi:

57. Raghavan R, Burchett M, Loffredo D, Mulligan JA. Lowlevel (PPB) determination of cisplatin in cleaning validation (rinse water) samples. II. A high-performance liquid chromatographic method. Drug Dev Ind Pharm 2000;26:429-40. doi:

58. Ladeira C, Viegas S, Costa-Veiga A. How to deal with uncertainties regarding the occupational exposure to antineoplastic mixtures: additive effect should always be considered? In: Topical Scientific Workshop - New Approach Methodologies in Regulatory Science, Proceedings of a Scientific Workshop Helsinki, 19-20 April 2016 [displayed 17 August 2018]. Available at https://echa.europa.eu/documents/10162/22816069/scientific_ws_proceedings_en.pdf

59. Cavallo D, Ursini CL, Perniconi B, Francesco AD, Giglio M, Rubino FM, Marinaccio A, Iavicoli S. Evaluation of genotoxic effects induced by exposure to antineoplasic drugs in lynphocytes and exfoliated buccal cells of oncologu nurses and pharmacy employees. Mutat Res 2005;587:45-51. doi:

60. Fučić A, Jazbec A, Mijić A, Šešo-Šimić D, Tomek R. Cytogenetic consequences after occupational expo-sure to antineoplastic drugs. Mutat Res 1998;416:59-66. doi:

61. Roland C, Ouellette-Frève JF, Plante C, Bussières J-F. Surface contamination in a teaching hospital: a 6 year perspective. Pharm Technol Hosp Pharm 2016;1:187-93. doi:

62. Viegas S, Ladeira C, Costa-Veiga A, Perelman J, Gajski G. Forgotten public health impacts of cancer - an overview. Arh Hig Rada Toksikol 2017;68:287-97. doi:

63. Cavallo D, Ursini CL, Omodeo-Salè E, Iavicoli S. Micronucleus induction and FISH analysis in buccal cells and lymphocytes of nurses administering antineoplastic drugs. Mutat Res 2007;628:11-8. doi:

64. Gajski G, Ladeira C, Gerić M, Garaj-Vrhovac V, Viegas S. Genotoxicity assessment of a selected cytostatic drug mixture in human lymphocytes: a study based on concentrations relevant for occupational exposure. Environ Res 2018;161:26-34. doi:

65. Sabatini L, Barbieri A, Tosi M, Violante FS. A new highperformance liquid chromatographic/electrospray ionization tandem mass spectrometric method for the simultaneous determination of cyclophosphamide, methotrexate and 5-fluorouracil as markers of surface contamination for occupational exposure monitoring. J Mass Spectrom 2005;40:669-74. doi:

66. Castagne V, Habert H, Abbara C, Rudant E, Bonhomme- Faivre L. Cytotoxics compounded sterile preparation control by HPLC during a 16-month assessment in a French university hospital: importance of the mixing bags step. J OncolPharm Pract 2011;17:191-6.doi:

67. Dal Bello F, Santoro V, Scarpino V, Martano C, Aigotti R, Chiappa A, Davoli E, Medana C. Antineoplastic drugs determination by HPLC-HRMS(n) to monitor occupational exposure. Drug Test Anal 2016;8:730-7. doi:

Archives of Industrial Hygiene and Toxicology

The Journal of Institute for Medical Research and Occupational Health

Journal Information


IMPACT FACTOR 2017: 1.117
5-year IMPACT FACTOR: 1.335



CiteScore 2017: 1.24

SCImago Journal Rank (SJR) 2017: 0.341
Source Normalized Impact per Paper (SNIP) 2017: 0.494

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 426 426 67
PDF Downloads 299 299 54