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

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: 8772210.1016/S0140-6736(79)91939-1Search in Google Scholar

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/viewSearch in Google Scholar

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=enSearch in Google Scholar

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.pdfSearch in Google Scholar

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: 10.1016/j.envint.2011.10.002Search in Google Scholar

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: 10.1016/j.puhe.2013.01.026Search in Google Scholar

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: 10.1016/j.chemosphere.2016.09.058Search in Google Scholar

8. Kosjek T, Heath E. Occurrence, fate and determination of cytostatic pharmaceuticals in the environment. TrAC Trends Anal Chem 2011;30:1065-87. doi: 10.1016/j.trac.2011.04.007Search in Google Scholar

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: 10.1016/j.mrrev.2014.02.001Search in Google Scholar

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: 10.1016/j. scitotenv.2012.12.061Search in Google Scholar

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: 10.1016/j.chemosphere.2010.06.029Search in Google Scholar

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: 10.1007/s10238-006-0113-8Search in Google Scholar

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: 10.1007/s00420-014-0993-ySearch in Google Scholar

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: 10.1177/1078155210381931Search in Google Scholar

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: 10.1177/1078155210380485Search in Google Scholar

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: 10.1002/ajim.22553Search in Google Scholar

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: 10.1097/JOM.0000000000000249Search in Google Scholar

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: 10.1097/01.ede.0000246827.44093.c1Search in Google Scholar

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: 10.1093/annhyg/mel081Search in Google Scholar

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: 10.1097/JOM.0b013e3181f73ae6Search in Google Scholar

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: 10.1093/mutage/gen060Search in Google Scholar

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: 10.4103/0971-6580.94510Search in Google Scholar

23. Connor TH. Hazardous anticancer drugs in health care: environmental exposure assessment. Ann NY Acad Sci 2006;1076:615-23. doi: 10.1196/annals.1371.021Search in Google Scholar

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: 10.1093/annhyg/mes081Search in Google Scholar

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: 10.1093/annhyg/mel023Search in Google Scholar

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: 1023058210.2165/00002018-199920040-0000410230582Search in Google Scholar

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: 10.1016/S1570-0232(03)00100-4Search in Google Scholar

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: 10.1002/(SICI)1097-0231(19981030)12:20<1485::AID-RCM333>3.0.CO;2-NSearch in Google Scholar

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: 1042845010.1093/ajhp/56.14.142710428450Search in Google Scholar

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: 10.1136/ejhpharm-2014-000549Search in Google Scholar

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: 10.1093/annhyg/mei042Search in Google Scholar

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: 1204073510.1093/ajhp/59.10.95612040735Search in Google Scholar

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: 10.1007/s10661-014-3969-1Search in Google Scholar

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: 10.5491/SHAW.2011.2.3.273Search in Google Scholar

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: 10.1016/0027-5107(94)90092-2Search in Google Scholar

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: 10.1002/rcm.3657Search in Google Scholar

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: 10.1016/j.toxlet.2011.03.028Search in Google Scholar

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: 10.1093/annhyg/mep050Search in Google Scholar

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: 10.1177/1078155210361431Search in Google Scholar

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: 10.1177/1078155208096904Search in Google Scholar

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: 1828564410.1539/joh.50.4818285644Search in Google Scholar

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: 10.1007/s00420-012-0742-zSearch in Google Scholar

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: 1186263910.1093/ajhp/59.3.27011862639Search in Google Scholar

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: 10.1080/15459624.2014.916809Search in Google Scholar

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: 10.1177/1078155214544993Search in Google Scholar

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: 10.1310/hpj4803-204Search in Google Scholar

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: 10.1371/journal.pone.0159052Search in Google Scholar

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: 10.1016/S0003-4878(98)00023-4Search in Google Scholar

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: 10.1002/jps.2600821003Search in Google Scholar

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: 10.1007/s004200050232Search in Google Scholar

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: 10.1007/s004200050124Search in Google Scholar

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: 10.1093/annhyg/mes087Search in Google Scholar

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: 331565610.1002/em.28501004043315656Search in Google Scholar

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: 10.3109/10837459609031420Search in Google Scholar

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: 10.1093/annhyg/meq004Search in Google Scholar

56. Lunn G, Sansone EB, Andrew AW, Hellwig LC. Degradation and disposal of some antineoplastic drugs. J Pharm Sci 1989;78:652-9. doi: 10.1002/jps.2600780811Search in Google Scholar

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: 10.1081/DDC-100101250Search in Google Scholar

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.pdfSearch in Google Scholar

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: 10.1016/j.mrgentox.2005.07.008Search in Google Scholar

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: 10.1016/S1383-5718(98)00084-9Search in Google Scholar

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: 10.1515/pthp-2016-0016Search in Google Scholar

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: 10.1515/aiht-2017-68-3005Search in Google Scholar

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: 10.1016/j.mrgentox.2006.10.014Search in Google Scholar

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: 10.1016/j.envres.2017.10.044Search in Google Scholar

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: 10.1002/jms.840Search in Google Scholar

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: 10.1177/1078155210376846Search in Google Scholar

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: 10.1002/dta.1827.Search in Google Scholar