무균조제 항암제 취급의 안전관리 = Assessment of Occupational Exposure to Antineoplastic Agents in a Healthcare Setting

다국어 초록 (Multilingual 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/m2. 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.

참고문헌 (Reference)

1 김소정, "항암제에 폭로된 간호사들의 염색체 이상과 자매염색체 교환빈도" 서울대학교 1995

2 김봉임, "항암제 취급간호사의 항암제 체내흡수에 관한 조사" 27 : 520-, 1997

3 김봉임, "항암제 취급 간호사의 소변중 돌연변이 유발능과 자각 증상 및 스트레스" 경북대학교 1996

4 최봉규, "종합병원 근무 간호사와 약사의 항암제 노출에 관한 연구" 서울대학교 1999

5 신혜숙, "간호사에서 항암제 취급양상과 건강증상" 8 : 228-, 1996

6 Connor, T. H., "etermination of the vaporization of solutions of mutagenic antineoplastic agents at 23 and 37 degrees using a desiccator technique" 470 : 85-, 2000

7 Product Information: Cytoxan(R), "cyclophosphamide. Bristol- Myers Squibb" Princeton, NJ, USA

8 Hedmer, M, "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" 81 : 285-, 2008

9 Wick, C., "Using a closed-system protective device to reduce personnel exposure to antineoplastic agents" 60 : 2314-, 2003

10 Yoshida, J, "Use of a closed system device to reduce occupational contamination and exposure to antineoplastic drugs in the hospital work environment" 53 : 153-, 2009

11 Pethran, A, "Uptake of antineoplastic agents in pharmacy and hospital personnel. Part I: monitoring of urinary concentrations" 76 : 5-, 2003

12 Connor, T. H, "Surface contamination with antineoplastic agents in six cancer treatment centers in Canada and the United States" 56 : 1427-, 1999

13 Hedmer, M, "Surface contamination of cyclophosphamide packaging and surface contamination with antineoplastic drugs in a hospital pharmacy in Sweden" 49 : 629-, 2005

14 Connor, T. H, "Surface contamination of chemotherapy drug vials and evaluation of new vial-cleaning techniques: results of three studies" 62 : 475-, 2005

15 Harrison, B. R, "Safety handling cytotoxic drugs. The chemotherapy source book. 2nd ed" Williams & Wilkins 905-945, 1996

16 Turci, R, "Residual hazard assessment related to handling of antineoplastic drugs: safety system evolution and quality assurance of analytical measurement" 1076 : 649-, 2006

17 Connor, T. H, "Preventing occupational exposures to antineoplastic drugs in health care settings" 56 : 354-, 2006

18 Sessink, P. J. M, "Occupational exposure to antineoplastic agents at several departments in a hospital: environmental contamination and excretion of cyclophosphamide and ifosfamide in urine of exposed workers" 64 : 105-, 1992

19 NIOSH (National Institute for Occupational Safety and Health), "NIOSH alert: Preventing occupational exposure to antineoplastic and other hazardous drugs in health care settings"

20 Falck, K, "Mutagenicity in urine of nurses handling cytostatic drugs" 1 : 1250-, 1979

21 Schmaus, G, "Monitoring surface contamination by antineoplastic drugs using gas chromatography mass spectrometry and voltammetry" 59 : 956-, 2002

22 Larson, R. R, "Monitoring method for surface contamination caused by selected antineoplastic agents" 59 : 270-, 2002

23 Sottani, C, "Liquidliquid extraction procedure for trace determination of cyclophosphamide in human urine by high-performance liquid chromatography tandem mass spectrometry" 12 : 1063-, 1998

24 IARC (International Agency for Research on Cancer), "IARC monographs: chemicals and industrial processes associated with cancer in humans"

25 IARC (International Agency for Research on Cancer), "IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans"

26 Mason, H. J, "Exposure to Antineoplastic drugs in two UK hospital pharmacy units" 49 : 603-, 2005

27 Sessink, P. J. M, "Exposure of pharmacy technicians to antineoplastic agents - reevaluation after additional protective measures" 52 : 240-, 1997

28 McDevitt, J, "Exposure of hospital pharmacists and nurses to antineoplastic drugs" 35 : 57-, 1993

29 Castiglia, L, "Evaluation of occupational exposure to antiblastic drugs in an Italian hospital oncological department" 50 : 48-, 2008

30 Sessink, P. J. M, "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" 49 : 165-, 1994

31 Hedmer, M, "Environmental and biological monitoring of antineoplastic drugs in four workplaces in a Swedish hospital" 81 : 899-, 2008

32 Sessink, P. J. M, "Drugs hazardous to healthcare workers: evaluation of methods for monitoring occupational exposure to cytostatic drugs" 20 : 347-, 1999

33 Hedmer, M, "Development and validation of methods for environmental monitoring of cyclophosphamide in workplaces" 6 : 979-, 2004

34 Sessink, P. J. M, "Detection of contamination with antineoplastic agents in a hospital pharmacy department" 14 : 16-, 1992

35 Mason, H. J, "Cytotoxic drug contamination on the outside of vials delivered to a hospital pharmacy" 47 : 681-, 2003

36 Martins, I., "Cyclophosphamide levels in sites of preparation and administration of antineoplastic drugs" 27 : 217-, 2008

37 Soave, C, "Cyclophosphamide environmental contamination in drug reconstitution units in twenty one Italian hospitals" 6 : 15-, 2003

38 Touzin, K, "Cyclophosphamide contamination observed on the external surfaces of drug vials and the efficacy of cleaning on vial contamination" 52 : 765-, 2008

39 Hansel, S, "Chemical degradation of wastes of antineoplastic agents: cyclophosphamide, ifosfamide, and melphalan" 69 : 109-, 1997

40 Sessink, P. J., "Cancer risk assessment for health care workers occupationally exposed to cyclophosphamide" 67 : 317-, 1995

41 Turci, R, "Biological and environmental monitoring of hospital personnel exposed to antineoplastic agents: a review of analytical methods" 789 : 169-, 2003

42 Dranitsaris, G., "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" 11 : 69-, 2005

43 ASHP (American Society of Hospital Pharmacists), "ASHP technical assistance bulletin on handling cytotoxic and hazardous drugs" 47 : 1033-, 1990

44 ASHP (American Society of Hospital Pharmacists), "ASHP guidelines on handling hazardous drug" 63 : 1172-, 2006

45 Fransman, W, "A pooled analysis to study trends in exposure to antineoplastic drugs among nurses" 51 : 231-, 2007

46 Acampora, A, "A case study: surface contamination of cyclophosphamide due to working practices and cleaning procedures in two Italian hospitals" 49 : 611-, 2005