YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Assessment of Occupational Exposure to Antineoplastic Agents in a Healthcare Setting

무균조제 항암제 취급의 안전관리

  • Lee, Su-Mi (Department of Pharmaceutical Services, Samsung Medical Center) ;
  • Chung, Seon-Young (Department of Pharmaceutical Services, Samsung Medical Center) ;
  • Im, Hyun-Jeong (Department of Pharmaceutical Services, Samsung Medical Center) ;
  • Park, Hyo-Jung (Department of Pharmaceutical Services, Samsung Medical Center) ;
  • Lee, Su-Yun (Department of Pharmaceutical Services, Samsung Medical Center) ;
  • Jeon, Eun-Yong (Department of Pharmaceutical Services, Samsung Medical Center) ;
  • Sohn, Kie-Ho (Department of Pharmaceutical Services, Samsung Medical Center)
  • Received : 2010.05.05
  • Accepted : 2010.12.03
  • Published : 2011.04.30
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Abstract

Most antineoplastic agents are nonselective in their mechanism of action, affecting noncancerous as well as cancerous cells, and resulting in acute effects such as irritation of mucous membranes and chronic effects such as genotoxicity, teratogenicity, and carcinogenicity. Healthcare workers occupationally exposed to antineoplastic agents are at risk. The present study aimed to develop and apply methods to monitor occupational exposure to antineoplastic agents, using cyclophosphamide (CP) as the model compound. To monitor environmental and biological exposure, potentially contaminated surfaces were wiped and 24 hour urine samples were collected from workers. Liquid chromatography combined with tandem mass spectrometry was performed, with a limit of detection of 0.05 ng/ml. Measurable amounts of CP were detected on 92% of the sampled surfaces, with a geometric mean of 175.22 $ng/m^2$. Despite the environmental contamination of the model compound, CP was below the detection limit in all urine samples. If workplace contamination cannot be completely avoided, it is importance to reduce exposure to the lowest possible levels. To this aim, efforts to minimize occupational exposure along with biological and environmental monitoring are required. The standardized sampling techniques, and specific and sensitive analytical methods reported in this study may be helpful in assessing occupational exposure and devising strategies to reduce exposure.

Keywords

References

  1. ASHP (American Society of Hospital Pharmacists) : ASHP technical assistance bulletin on handling cytotoxic and hazardous drugs. Am. J. Hosp. Pharm. 47, 1033 (1990).
  2. NIOSH (National Institute for Occupational Safety and Health) : NIOSH alert: Preventing occupational exposure to antineoplastic and other hazardous drugs in health care settings. www.cdc.gov/niosh/docs/ 2004-165/.
  3. Sessink, P. J. M. and Bos, R. P. : Drugs hazardous to healthcare workers: evaluation of methods for monitoring occupational exposure to cytostatic drugs. Drug. Saf. 20, 347 (1999). https://doi.org/10.2165/00002018-199920040-00004
  4. ASHP (American Society of Hospital Pharmacists) : ASHP guidelines on handling hazardous drug. Am. J. Health-Syst. Pharm. 63, 1172 (2006). https://doi.org/10.2146/ajhp050529
  5. IARC (International Agency for Research on Cancer) : IARC monographs: chemicals and industrial processes associated with cancer in humans. Lyons, France (1979).
  6. Falck, K., Grohn, P., Sorsa, M., Vainio, H., Heinonen, E. and Holsti, L. R. : Mutagenicity in urine of nurses handling cytostatic drugs. Lancet. 1, 1250 (1979).
  7. Sessink, P. J. M., Anzion, R. B. M., Van der Broek, P. H. H. and Bos, R. P. : Detection of contamination with antineoplastic agents in a hospital pharmacy department. Pharm. Week. Sci. 14, 16 (1992). https://doi.org/10.1007/BF01989220
  8. Connor, T. H., Anderson, R. W., Sessink, P. J., Broadfield, L. and Power, L. A. : Surface contamination with antineoplastic agents in six cancer treatment centers in Canada and the United States. Am. J. Health Syst. Pharm. 56, 1427 (1999).
  9. Schmaus, G., Schierl, R. and Funck, S. : Monitoring surface contamination by antineoplastic drugs using gas chromatography mass spectrometry and voltammetry. Am. J. Health Syst. Pharm. 59, 956 (2002).
  10. Soave, C., Giuliari, C., Bartolucci, G. B., Carrieri, M., Festa, D., Sannolo, N., Miraglia, N., Acampora, A. and Viotti, P. L. : Cyclophosphamide environmental contamination in drug reconstitution units in twenty one Italian hospitals. EJHP 6, 15 (2003).
  11. Wick, C., Slawson, M. H., Jorgenson, J. A. and Tyler, L. S. : Using a closed-system protective device to reduce personnel exposure to antineoplastic agents. Am. J. Health Syst. Pharm. 60, 2314 (2003).
  12. Mason, H. J., Blair, S., Sams, C., Jones, K., Garfitt, S. J., Cuschieri, M. J. and Baxter, P. J. : Exposure to Antineoplastic drugs in two UK hospital pharmacy units. Ann. Occup. Hyg. 49, 603 (2005). https://doi.org/10.1093/annhyg/mei023
  13. Acampora, A., Castiglia, L., Miraglia, N., Pieri, M., Soave, C., Liotti, F. and Sannolo, N. : A case study: surface contamination of cyclophosphamide due to working practices and cleaning procedures in two Italian hospitals. Ann. Occup. Hyg. 49, 611 (2005). https://doi.org/10.1093/annhyg/mei029
  14. Hedmer, M., Georgiadi, A., Bremberg, E. R., Jonsson, B. A. and Eksborg, S. : Surface contamination of cyclophosphamide packaging and surface contamination with antineoplastic drugs in a hospital pharmacy in Sweden. Ann. Occup. Hyg. 49, 629 (2005). https://doi.org/10.1093/annhyg/mei042
  15. Fransman, W., Peelen, S., Hilhorst, S., Roeleveld, N., Heederik, D. and Kromhout, H. : A pooled analysis to study trends in exposure to antineoplastic drugs among nurses. Ann. Occup. Hyg. 51, 231 (2007).
  16. Hedmer, M., Tinnerberg, H., Axmon, A. and Jonsson, B. A. : Environmental and biological monitoring of antineoplastic drugs in four workplaces in a Swedish hospital. Int. Arch. Occup. Environ. Health 81, 899 (2008). https://doi.org/10.1007/s00420-007-0284-y
  17. Castiglia, L., Miraglia, N., Pieri, M., Simonelli, A., Basilicata, P., Genovese, G., Guadagni, R., Acampora, A., Sannolo, N. and Scafarto, M. V. : Evaluation of occupational exposure to antiblastic drugs in an Italian hospital oncological department. J. Occup. Health 50, 48 (2008). https://doi.org/10.1539/joh.50.48
  18. Martins, I., Apostoli, P. and Della Rosa, H. V. : Cyclophosphamide levels in sites of preparation and administration of antineoplastic drugs. Lat. Am. J. Pharm. 27, 217 (2008).
  19. Yoshida, J., Tei, G., Mochizuki, C., Masu, Y., Koda, S. and Kumagai, S. : Use of a closed system device to reduce occupational contamination and exposure to antineoplastic drugs in the hospital work environment. Ann. Occup. Hyg. 53, 153 (2009). https://doi.org/10.1093/annhyg/men081
  20. Sessink, P. J. M., Boer, K. A., Scheefhals, A. P. H., Anzion, R. B. M. and Bos, R. P. : Occupational exposure to antineoplastic agents at several departments in a hospital: environmental contamination and excretion of cyclophosphamide and ifosfamide in urine of exposed workers. Int. Arch. Occup. Environ. Health 64, 105 (1992). https://doi.org/10.1007/BF00381477
  21. McDevitt, J., Lees, P. and McDiarmid, M. : Exposure of hospital pharmacists and nurses to antineoplastic drugs. J. Occup. Med. 35, 57 (1993).
  22. Sessink, P. J. M., Van der Kerkhof, M. C. A., Anzion, R. B. M., Noordhoek, J. and Bos, R. P. : Environmental contamination and assessment of exposure to antineoplastic agents by determination of cyclophosphamide in urine of exposed pharmacy technicians: is skin absorption an important exposure route? Arch. Environ. Health 49, 165 (1994). https://doi.org/10.1080/00039896.1994.9940377
  23. Sessink, P. J. M., Wittenhorst, B. C., Anzion, R. B. and Bos, R. P. : Exposure of pharmacy technicians to antineoplastic agents - reevaluation after additional protective measures. Arch. Environ. Health 52, 240 (1997). https://doi.org/10.1080/00039899709602893
  24. Larson, R. R., Khazaeli, M. B. and Dillon, H. K. : Monitoring method for surface contamination caused by selected antineoplastic agents. Am. J. Health Syst. Pharm. 59, 270 (2002).
  25. Pethran, A., Schierl, R., Hauff, K., Grimm, C. H., Boos, K. S. and Nowak, D. : Uptake of antineoplastic agents in pharmacy and hospital personnel. Part I: monitoring of urinary concentrations. Int. Arch. Occup. Environ. Health 76, 5 (2003).
  26. 김소정 : 항암제에 폭로된 간호사들의 염색체 이상과 자매염색체 교환빈도. 석사학위논문, 서울대학교 (1995).
  27. 김봉임 : 항암제 취급 간호사의 소변중 돌연변이 유발능과 자각증상 및 스트레스. 박사학위논문, 경북대학교 (1996).
  28. 신혜숙, 이세훈 : 간호사에서 항암제 취급양상과 건강증상. 대한산업의학지 8, 228 (1996).
  29. 김봉임 : 항암제 취급간호사의 항암제 체내흡수에 관한 조사. 간호학회지 27, 520 (1997).
  30. 최봉규 : 종합병원 근무 간호사와 약사의 항암제 노출에 관한 연구. 석사학위논문, 서울대학교 (1999).
  31. Turci, R., Sottani, C., Spagnoli, G. and Minoia, C. : Biological and environmental monitoring of hospital personnel exposed to antineoplastic agents: a review of analytical methods. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 789, 169 (2003). https://doi.org/10.1016/S1570-0232(03)00100-4
  32. IARC (International Agency for Research on Cancer) : IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans. Lyons, France (2004).
  33. Product Information: Cytoxan(R), cyclophosphamide. Bristol-Myers Squibb, Princeton, NJ, USA.
  34. Hedmer, M., Hoglund, P., Cavallin-Stahl, E., Albin, M. and Jonsson, B. A. : Validation of urinary excretion of cyclophosphamide as a biomarker of exposure by studying its renal clearance at high and low plasma concentrations in cancer patients. Int. Arch. Occup. Environ. Health 81, 285 (2008).
  35. Connor, T. H., Shults, M. and Fraser, M. P. : Determination of the vaporization of solutions of mutagenic antineoplastic agents at 23 and 37 degrees using a desiccator technique. Mutat. Res. 470, 85 (2000). https://doi.org/10.1016/S1383-5718(00)00105-4
  36. Hedmer, M., Jonsson, B. A. and Nygren, O. : Development and validation of methods for environmental monitoring of cyclophosphamide in workplaces. J. Environ. Monit. 6, 979 (2004). https://doi.org/10.1039/b409277e
  37. Harrison, B. R. : Safety handling cytotoxic drugs. The chemotherapy source book. 2nd ed. Williams & Wilkins, 905-945 (1996).
  38. Sottani, C., Turci, R., Perbellini, L. and Minoia, C. : Liquidliquid extraction procedure for trace determination of cyclophosphamide in human urine by high-performance liquid chromatography tandem mass spectrometry. Rapid Commun. Mass. Spectrom. 12, 1063 (1998). https://doi.org/10.1002/(SICI)1097-0231(19980831)12:16<1063::AID-RCM287>3.0.CO;2-K
  39. Turci, R. and Minoia, C. : Residual hazard assessment related to handling of antineoplastic drugs: safety system evolution and quality assurance of analytical measurement. Ann. N Y Acad. Sci. 1076, 649 (2006). https://doi.org/10.1196/annals.1371.047
  40. Mason, H. J., Morton, J., Garfitt, S. J., Iqbal, S. and Jones, K. : Cytotoxic drug contamination on the outside of vials delivered to a hospital pharmacy. Ann. Occup. Hyg. 47, 681 (2003). https://doi.org/10.1093/annhyg/meg078
  41. Connor, T. H., Sessink, P. J., Harrison, B. R., Pretty, J. R., Peters, B. G., Alfaro, R. M., Bilos, A., Beckmann, G., Bing, M. R., Anderson, L. M. and Dechristoforo, R. : Surface contamination of chemotherapy drug vials and evaluation of new vial-cleaning techniques: results of three studies. Am. J. Health Syst. Pharm. 62, 475 (2005).
  42. Touzin, K., Bussieres, J. F., Langlois, E., Lefebvre, M. and Gallant, C. : Cyclophosphamide contamination observed on the external surfaces of drug vials and the efficacy of cleaning on vial contamination. Ann. Occup. Hyg. 52, 765 (2008). https://doi.org/10.1093/annhyg/men050
  43. Connor, T. H. and McDiarmid, M. A. : Preventing occupational exposures to antineoplastic drugs in health care settings. CA Cancer. J. Clin. 56, 354 (2006). https://doi.org/10.3322/canjclin.56.6.354
  44. Hansel, S., Castegnaro, M., Sportouch, M. H. et al. : Chemical degradation of wastes of antineoplastic agents: cyclophosphamide, ifosfamide, and melphalan. Int. Arch. Occup. Environ. Health 69, 109 (1997).
  45. Dranitsaris, G., Johnston, M., Poirier, S., Schueller, T., Milliken, D., Green, E. and Zanke, B. : Are health care providers who work with cancer drugs at an increased risk for toxic events? A systematic review and meta-analysis of the literature. J. Oncol. Pharm. Pract. 11, 69 (2005). https://doi.org/10.1191/1078155205jp155oa
  46. Sessink, P. J., Kroese, E. D., van Kranen, H. J. and Bos, R. P. : Cancer risk assessment for health care workers occupationally exposed to cyclophosphamide. Int. Arch. Occup. Environ. Health 67, 317 (1995). https://doi.org/10.1007/BF00385647