Occupational Exposure to Antineoplastic Agents
Environmental sampling is a relatively new approach used to determine
the level of workplace contamination by antineoplastic agents. The procedure
has been used extensively in other situations, especially for monitoring
contamination by radioactive materials. Typically, work surfaces are sampled
with a moistened wipe and the material is extracted and analyzed for specific
antineoplastic agents. Currently, it is possible to identify and quantitate
six to eight agents with this technique.
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Connor TH Anderson RW, Sessink PJM, Broadfield L and Power LA. Surface contamination with antineoplastic agents in six cancer treatment centers in the United Sates and Canada. Am J Health-Syst Pharm. 1999; 56: 1427-1432.
Connor TH, Van Balen P and Sessink PJ. Monitoring for hazardous drugs in the operating room. Ann Surg Oncol. 2002;10:821-822 (comment).
Connor TH, Anderson RW, Sessink PJ, Spivey SM. Effectiveness of a closed-system device in containing surface contamination with cyclophosphamide and ifosfamide in an i.v. admixture area. Am J Health-Syst Pharm. 2002; 59: 68-72.
Connor TH, Sessink PJM, Harrison BR, Pretty JR, Peters BG, Alfaro RM, Bilos A, Beckmann G, Bing MR, Anderson LM, DeChristoforo R. Surface contamination of chemotherapy drug vials and evaluation of new vial-cleaning techniques: Results of three studies. Am J Health-Syst Pharm. 2005; 62:475-484.
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Delporte JP, Chenoix P and Hubert P. Chemical contamination of the primary packaging of 5-fluorouracil RTU solutions commercially available on the Belgian market. Eur Hosp Pharm. 1999; 5:119-121.
deWerk Neal A, Wadden RA and Chiou WL. Exposure of hospital workers to airborne antineoplastic agents. Am J Hosp Pharm. 1983;40:597-601.
Dorr RT and Alberts DS. Topical absorption and inactivaon of cytotoxic anticancer agents in vitro. Cancer. 1992; 70 (supp 4): 983-987.
Favier B, Rull FM, Bertucat H, Pivot C, LeBoucher G, Charlety D, Dubois V, Veyre MC, Ardiet C and Latour JF. Surface and human contamination with 5-fluorouracil in six hospital pharmacies. J Pharmacie Clinique. 2001; 20; 157-162.
Favier B, Gilles L, Ardiet C and Latour JF. External contamination of vials containing cytotoxic agents supplied by pharmaceutical manufacturers. J Oncol Pharm Practice. 2003; 9:15-20.
Favier B, Gilles L, Latour JF, Desage M, Giammarile F. Contamination of syringe plungers during the sampling of cyclophosphamide solutions. J Oncol Pharm Practice. 2005; 11:1-5.
Fransman W, Vermeulen R, Kromhout H. Occupational dermal exposure to cyclophosphamide in Dutch hospitals: A pilot study. Ann Occup Hyg. 2004; 48:237-244.Fransman W, Vermeulen R, Kromhout H. Dermal exposure to cyclophosphamide in hospitals during preparation, nursing and cleaning activities. Int Arch Occup Health. 2005; 78:403-412.
Fransman W, Huizer D, Tuerk J. Inhalation and dermal exposure t eight antineoplastic drugs in an industrial laundry facility. Int Arch Occup Environ Health. 2007; 80:396-403.
Gilbar PJ. External contamination of cytotoxic drug vials. J Pharm Pract Res. 2005; 35:264-265
Guerbet M, Goullé JP, Lubrano J. Evaluation of the risk of contamination of surgical personnel by vaporization of oxaliplatin during the intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC). Eur J Surg Oncol. 2007; 33:623-629.Harrison BR, Peters BG, Bing MR. Comparison of surface contamination with cyclophosphamide and fluorouracil using a closed-system drug transfer device versus standard preparation techniques. Am J Health-Syst Pharm. 2006; 63:1736-1744.
Hedmer M, Georgiadi A, Rämme Bremberg E, Jönsson BAG, Eksborg S. Surface contamination of cyclophosphamide packaging and surface contamination with antineoplastic drugs in a hospital pharmacy in Sweden. Ann Occup Hyg. 2005; 49:629-637.
Hedmer M, Tinnerberg H, Axmon A, Joensson BAG. Environmental and biologocal monitoring of antineoplastic drugs in four workplaces in a Swedish hospital. Int Arch Occup Environ Health. 2008; 81:899-911Hepp R and Gentschew G. Untersuchung zur außenkontamination der primärverpackungen von zytostatika. Krankenhauspharmazie. 1988;1:22-27.
Ikeda K, Yagi Y, Tkegami M, Lu Y, Morimoto K, Kurokawa N. Efforts to ensure safety of hospital pharmacy personnel occupationally exposed to antineoplastic drugs during a preparation task. Hosp Pharm. 2007; 42:209-218.Kleinberg ML and Quinn MJ. Airborne drug levels in a laminar flow hood. Am J Hosp Pharm. 1981; 38:1301-1303.
Kiffmeyer T, Götze H-J, Jursch M and Lüders U. Trace enrichment, chromatographic separtation and biodegradation of cytostatic compounds in surface water. Fresenius J Anal Chem. 1998;361:185-191.
Kiffmeyer ThK, Ing, KG and Schoppe G. External contamination of cytotoxic drug packing: Safe handling and cleaning procedures. J Onc Pharm Practice. 2000;6:13.
Kiffmeyer TK, Kube C, Opiolka S, Schmidt KG, Schoppe G, Sessink PJM. Vapour pressures, evaporation behaviour and airborne concentrations of hazardous drugs: implications for occupational safety. Pharaceutical J. 2002; 268:331-337.
Kromhout H, Hoek F, Uitterhoeve R, Huijbers R, Overmars RF, Anzion R, Vermeulen R. Postulating a dermal pathway for exposure to antineoplastic drugs among hospital workers. Applying a conceptual model to the results of three workplace surveys. Ann occup Hyg. 2000; 44:551-560.
Larson RR, Khazaeli MB, Dillon HK. A new monitoring method using solid sorbent media for evaluation of airborne cyclophosphamide and other antineoplastic agents. Appl Occ Env Hyg. 2003;18:120-131.
Larson RR, Khazaeli MB, Dillon HK. Development of an HPLC Method for simultaneous analysis of five antineoplastic agents Appl Occ Env Hyg. 2003; 18:109-119.Labuhn K, Valanis B, Schoeny R, Loveday K and Vollmer WM. Nurses' and pharmacists exposure to antineoplastic drugs:Findings from industrial hygiene scans and urine mutagenicity tests. Cancer Nursing. 1998;21:79-89.
Larson RR, Khazaeli MB, Dillon HK. Monitoring method for surface contamination caused by selected antineoplastic agents. Am J Health-Syst Pharm. 2002; 59:270-277.
Leboucher G, Serratrice F, Bertholle V Thore L and Bost M. Evaluation of platinum contamination of a hazardous drug preparation area in a hospital pharmacy. Bull Cancer. 2002; 89:949-955.
Mader RM, Rizovski B and Steger GG. On-line solid-phase extraction and determination of paclitaxel in human plasma. J Chromatog B. 2002; 769:357-361.
Mason HJ, Morton J, Garfitt SJ, Iqbal S and Jones K. Cytotoxic drug contamination
on the outside of vails delivered to a hospital pharmacy. Ann occup Hyg.
Meijster T, Veldhof R, Kromhout H. Inventariserend onderzoek naar gebruik van en blootstelling aan cytostatica buiten het ziekenhuis. 2003 (English abstarct)Micoli G, Turci R, Arpellini M and Minoia C. Determination of 5-fluorouracil in environmental samples by solid-phase extraction and high-performance liquid chromatography with ultraviolet detection. J Chromatog B. 2001; 750:25-32.
Minoia C, Turci R, Sottani C, Schiavi A, Perbellini L, Angeleri S, Draicchio F and 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: 1485-1493.
Minoia C, Turci R, Sottani C, Schiavi A, Perbellini L, Angeleri S, Frigerio F, Draicchio F and Apostoli P. Risk assessment concerning hospital personnel participating in the preparation and administration of antineoplastic drugs. [Italian] Giornale Italiano di Medicina del Lavoro ed Ergonomia. 1999; 21:93-107.
Nygren O and Lundgren C. Determination of platinum in workroom air and in blood and urine from nursing staff attending patients receiving cisplatin chemotherapy. Int Arch Occ Environ Health. 1997;70:209-214.
Nygren O, Gustavsson B, Strom L and Friberg A. Cisplatin contamination on the outside of drug vials. Ann occup Hyg. 2002; 46: 555-557.
Nygren O. Wipe samples as a tool for monitoring aerosol deposition in workplaces. J Environ Monit. 2006; 8;49-52.
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Nyman H, Jorgenson J, Slawson MH. Workplace Contamination with Antineoplastic Agents in a new cancer hospital using a closed-system drug transfer device. Hosp Pharm. 2007; 42:219-225Pethran A, Hauff K and Hessel H . Biological, cytogenetic and ambient monitoring of exposure to antineoplastic drugs. J Oncol Pharm Practice. 1998;4:57.
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Ros JJW, Simons KA, Verzijl JM, de Bijl GA and Pelders MG. Practical applications of a validated method of analysis for the detection of traces of cyclophosphamide on injection bottles and at oncological outpatient center. Ziekenhuisfarmacie. 1997; 13:168-171.
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Sabatini L, Barbieri A, Tosi M, Violante FS. A new high-performance 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;40:669-674.
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; 59:956-961.
Sessink PJM, Anzion RB, Van den Broek PHH and Bos RP. Detection of contamination with antineoplastic agents in a hospital pharmacy department. Pharm Weekbl (Sci). 1992;14:16-22.
Sessink PJM, Friemèl NSS, Anzion RBM and Bos RP. Biological and environmental monitoring of occupational exposure of pharmaceutical plant workers to methotrexate. Int Arch Occup Environ Health. 1994;65:401-403.
Sessink PJM, Joost HC, Pierik FH, Anzion RBM and Bos RP. Occupational exposure of animal caretakers to cyclophosphamide. J Occup Med. 1993;35:47-52.
Sessink PJM, Rolf M-AE and Ryden NS. Evaluation of the PhaSeal hazardous drug containment system. Hosp Pharm. 1999; 34: 1311-1317.
Sessink PJM, Wittenhorst BCJ, Anzion RBM and Rob RP. Exposure of pharmacy technicians to antineoplastic agents: Reevaluation after additional protective measures. Arch Environ Health. 1997;52:240-244.
Sessink PJM, Rolf M-AE, Rydèn NS. Evaluation of the PhaSeal hazardous drug containment system. Hosp Pharm. 1999; 34:1311-1317.
Shahsavarani S, Godefroid RJ and Harrison BR. Evaluation of occupational
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Sottani C, Truci R, Schierl R, Gaggeri R, Barbieri A, Violante FS, Minoia C. Simultaneous determinatin of gemcitabine, taxol, cyclophosphamid and ifosphamid in wipe sampels by high-performance liquid chromatography/tandem mass spectrometry: protocol of validation and uncertainty of measurment. Rapid Commun Mass Spectrom. 2007; 21:1289:1296.
Spivey S, Connor TH. Determining sources of workplace contamination with
antineoplastic drugs and comparing conventional IV drug preparation with
a closed system. Hosp Pharm. 2003; 38:135-139.
Touzin K, Bussières JF, Langlois É, Lefebvre M, Gallant C. Cyclophosphamide contamination observed on the surface of drug vials and the efficacy of cleaning on vial contamination. Ann Occup Hyg. 2008; 1-7.
Tuerk J, Reinders M, Dryer M, Kiffmeyer TK, Schmidt KG, Kuss HM. Analysis of antibiotics in urine and wipe samples from environmental and biological monitoring- comparison of HPLC with UV-, single MS- and tandem MS-detection. J Chromatog. 2006; 831:72-80.Turci R, Micoli G and Minoia C. Determination of methotrexate in environmental samples by solid phase extraction and high performance liquid chromatorgraphy: ultraviolet or tandem mass spectrometry detection. Rapid Comm Mass Spectrom. 2000; 14:685-691.
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of analytical methods. J Chromatog B. 2003; 789:169-209.
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Wick C, Slawson MH, Jorgenson JA and Tyler LS. Using a closed-system protective device to reduce personnel exposure to antineoplastic agents. Am J Health-Syst Pharm. 2003; 60:2314-2320.
Yoshida J, Kosaka H, Tomika K, Kumagai S. Genotoxic Risks to nurses from contamination of the work enviroment with antineoplastic drugs in Japan. J Occup Health; 2006; 48:517-522.
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Ziegler E, Mason HJ, Baxter PJ. Occupational exposure to cytotoxic drugs in two UK onkology wards. Occup Environ Med. 2002; 59:608-612.
Several reports have dealt with methods for the decontamination and/or deactivation of antineoplastic agents. Although bleach (hypochlorite) is often recommended for the decontamination purposes, it is not effective with all classes of agents. Therefore, it cannot be assumed that cleaning with bleach solutions will destroy all types of antineoplastic agents. Some antineoplastic drugs are listed by the US Environmental Protection Agency as Hazardous waste and must be disposed of accordingly (see 40 CFR 261.33) available: http://www.erefdn.org/educationact2/40cfr261driverrecordact.pdf
Barek J, Cvaccka J, Zima J, De Meo M, Laget M, Michelon J and Castegnaro
M. Chemical degradation of wastes of antineoplastic agents amsacrine,
azathioprine, asparaginase and thiotepa. Ann Occup Hyg. 1998;42:259-266.
Smith CA. Managing pharmaceutical Waste-What pharmacists should know.
J Phram Soc Wisconsin. 2002; Nov/Dec:17-22.
Touzin K, Bussières JF, Langlois É, Lefebvre M, Gallant C. Cyclophosphamide contamination observed on the surface of drug vials and the efficacy of cleaning on vial contamination. Ann Occup Hyg. 2008; 1-7.Wren AE, Melia CD, Garner ST and Denyer SP. Decontamination methods for cytotoxic drugs. 1. Use of a bioluminescent technique to monitor the inactivation of methotrexate with chlorine-based agents. J Clin Pharm and Therap. 1993;18:133-137.
The most often used type of protective equipment for handling antineoplastic
agents is gloves. Typically latex and other materials have been employed
for this use. However, with the growing concern over latex allergies,
newer materials are being marketed and evaluated for use with these agents.
Protective gowns are another piece of equipment that is commonly used
in the handling of antineoplastic agents. This section also deals with
biological safety cabinets and closed system devices used in the preparation
of antineoplastic drugs.
Korinth G, Schmidt K., Midasch O, Boettcher M I, Angerer J, Drexler H. Investigations on permeation of mitomycin C through double layers of natural rubber gloves. Ann Occup Hyg. 2007; 51:593-600.
Labella CJ, Does your pharmacy have a compounding isolator? Am J Health-Syst Pharm. 2007; 64:855-858.
Klein M, Lambov N, Samev N, Carstens G. Permeation of cytotoxic formulations
through swatches from selected medical gloves. Am J Health-Syst Pharm.
Nygren O, Olofsson E, Johansson L. Spill leakage using a drug preparing system based on double-filter technology. Ann Occup Hyg. 2008; 1-4.
Nyman H, Jorgenson J, Slawson MH. Workplace Contamination with Antineoplastic Agents in a new cancer hospital using a closed-system drug transfer device. Hosp Pharm. 2007; 42:219-225
Peters GF, McKeon, Weiss WT. Potential for airborne contamination in turbulent- and unidirectional-airflow compounding aseptic isolators. Am J Health-Syst Pharm. 2007; 64:622-631.Sessink PJM, Rolf M-AE and Ryden NS. Evaluation of the PhaSeal hazardous drug containment system. Hosp Pharm. 1999: 34: 1311-17.
Singleton L and Connor, TH. An evaluation of the permeability of chemotherapy gloves to three cancer chemotherapy drugs. Onc Nurs Forum. 1999; 26:1491-1496.
Slevin ML, Ang LM, Johnston A and Turner P. The efficiency of protective gloves used in the handling of cytotoxic drugs. Cancer Chemother Pharmacol,. 1984;12:151-53.
Spivey S and Connor TH. Determining sources of workplace contamination
with antineoplastic drugs and comparing conventional IV drug preparation
with a closed system. Hosp Pharm. 2003; 38:135-139.
Tans B, Willems L. Comparative contamination study with cyclophosphamide,
fluorouracil and ifosfamide: standard versus a proprietary closed-handling
system. J Oncol Pharm Practice. 2004; 10:217-223.
Wagner JT, Considerations for Choosing a Primary engeneering control for compounding sterile products. Int J Pharm Comp. 2005 9:284-290.Wallemacq PE, Capron A, Vanbinst R, Boeckmans E, Gillard J, Favier B. Permeability of 13 different gloves to 13 cytotoxic agents under controlled dynamic conditions. Am J Health-Syst Pharm. 2006; 63:547-556.
Wick C, Slawson MH, Jorgenson JA and Tyler LS. Using a closed-system
protective device to reduce personnel exposure to antineoplastic agents.
Am J Health-Syst Pharm. 2003; 60:2314-2320.