Environmental Sampling
for 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.
Acampora A, Castiglia L, Miraglia N, Pieri M, Soave C, Liotti F, Sannolo
N. A case study: Surface contamination of cyclophosphamide due to working
practices and cleaning procedures in two Italian hospitals. Ann Occup
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Burton LC and James CA. Rapid method for the determination of ifosfamide
and cyclophosphamide in plasma by high-performance liquid chromatography
with solid-phase extraction. J Chromatog. 1988; 431:450-454.
Cavallo D, Ursini CL, Perniconi B, Francesco AD, Giglio M, Rubino FM, Marinaccio A, Iavicoli S. Evaluation of gentotoxic effects induced by exposure to antineoplastic drugs in lymphocytes and exfoliated buccal cells of oncology nurses and pharmacy employees. Mutat Res. 2005; 587:45-51.
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.
Connor, TH. External contamination of antineoplastic drug vials. Hosp
Pharm Eur. 2005; Nov/Dec: 52-54.
Crauste-Manciet S, Sessink PJM, Ferrari S, Jomier J-Y, Brossard D. Environmental
contamination with cytotoxic drugs in healthcare using positive air pressure
isolators. Ann Occup Hyg. 2005; 49:619-628.
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.
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. Ann Occup Hyg. 2005; 49:629-637.
Hepp R and Gentschew G. Untersuchung zur außenkontamination der
primärverpackungen von zytostatika. Krankenhauspharmazie. 1988;1:22-27.
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.
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.
2003; 47:681-685.
McDevitt JJ, Lees PSJ and McDiarmid MA. Exposure of hospital pharmacists
and nurses to antineoplastic agents. J Occup Med. 1993;35:57-60.
McDiarmid MA, Egan T, Furio M, Bonacci M and Watts SR. Sampling for airborne
fluorouracil in a hospital drug preparation area. Am J Hosp Pharm. 1986;
43:1942-1945.
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.
Nygren O, Gustavsson B, Eriksson R. A test method for assessment of spill and leakage from drug preparation systems. Ann Occup Hyg. 2005; 49:711-718.
Pethran A, Hauff K and Hessel H . Biological, cytogenetic and ambient
monitoring of exposure to antineoplastic drugs. J Oncol Pharm Practice.
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manufacturing and hospitals. Am Ind Hyg Assoc J. 1988; 49: 314-317.
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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.
Rubino FM, Floridia L, Pietropaolo AM, Tavazzani M and Colombi A. Measurement
of surface contamination by certain antineoplastic drugs using high-performance
liquid chromatography: Applications in occupational hygiene investigations
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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
exposure to tablet trituration dust. ASHP Midyear Clinical Meeting. 1993;
P-59(E) abs.
Sorsa M, Pyy L, Salomaa S, Nyland L and Yager JW. Biological and environmental
monitoring of occupational exposure to cyclophosphamide in industry and
hospitals. Mutat Res. 1988;204:465-479.
Sottani C, Turci R, Micoli G, Fiorention ML and Minoia C. Rapid and sensitive
determination of paclitaxel (Taxol) in environmental samples by high-performance
liquid chromatography tandem mass spectrometry. Rapid Comm Mass Spectrom.
2000; 14:930-935.
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.
Stuart A, Stephens AD, Welch L and Sugarbaker PH. Safety monitoring of
the coliseum technique for heated intraoperative intraperitoneal chemotherapy
with mitomycin C. Ann Surg Oncol. 2002; 9:186-191.
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.
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 Chromatog B. 2003; 789:169-209.
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Wilken A. Beobachtungen zur Außenkotamination der primärverpackungen
von zytostatika. Krakenhauspharmazie. 1997;1:37-39.
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.
Zeedijk M, Greijdanus B, Steenstra FB, Uges DRA. Monitoring exposure
of cytotoxics on the hospital ward: measuring surface contamination of
four different cytotoxic drugs from one wipe sample. Eur J Hosp Pharm.
2005; 1:18-22.
Decontamination and Deactivation of
Antineoplastic Agents
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.
Benvenuto JA, Connor TH, Monteith DK, Laidlaw JA, Adams SC, Matney TS
and Theiss JC. Degradation and inactivation of antitumor drugs. J Pharm
Sci. 1993;82:988-991.
Castegnaro M, De Meo M, Laget M, Michelon J, Garren L, Sportouch MH and
Hansel S. Chemical degradation of wastes of antineoplastic agents 2: Six
anthracyclines: idarubicin,doxorubicin, epirubicin, pirarubicin, aclarubicin,
and daunorubicin. Int Arch Occup Environ Health. 1997;70:378-384.
Hansel S, Castegnaro M, Sportouch MH, De Meo M, Milhavet JC, Laget M and
Dumenil G. Chemical degradation of wastes of antineoplastic agents: cyclophosphamide,
ifosfamide and melphalan. Int Arch Occup Environ Health. 1997;69:109-114.
Lunn G and Sansone EB. Reductive destruction of dacarbazine, procarbazine
hydrochloride, isoniazid, and iproniazid. Am J Hosp Pharm. 1987;44:2519-2524.
Lunn G, Sansone EB, Andrews AW and Hellwig LC. Degradation and disposal
of some antineoplastic drugs. J Pharm Sci. 1989;78:652-659.
Roberts S, Khammo N, McDonnell, Sewell GJ. Studies on the decontamination of surfaces exposed to cytotoxic drugs in chemotherapy workstations. J Oncol Pharm Practice. 2006; 12:95-104.
Smith CA. Managing pharmaceutical Waste-What pharmacists should know.
J Phram Soc Wisconsin. 2002; Nov/Dec:17-22.
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.
Evaluation of Protective Equipment
for Handling Antineoplastic Agents
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.
Cazin J-L and Gosselin P. Implementing a multple-isolator unit for centralized
preparation of cytotoxic drugs in a cancer center pharmacy. Pharm World
Sci. 1999;21:177-183.
Colligan SA and Horstman SW. Permeation of cancer chemotherapeutic drugs
through glove materials under static and flexed conditions. Appl Occ Environ
Hyg. 1990;5:848-852.
Connor TH, Laidlaw JL, Theiss JC Anderson RW and Matney TS. Permeability
of latex and polyvinyl chloride gloves to carmustine. Am J Hosp Pharm.
1984;41:676-679.
Connor TH. An evaluation of the permeability of disposable poylpropylene-based
protective gowns to a battery of cancer chemotherapy drugs. Appl Occup
Environ Hyg. 1993;8:785-789.
Connor TH. Permeability testing of glove materials for use with cancer
chemotherapy drugs. Oncology. 1995;52:256-259.
Connor TH. Permeability of nitrile rubber, latex, polyurethane, and neoprene
gloves to 18 antineoplastic drugs. Am J Health-Syst Pharm. 1999; 56: 2450-53.
Connor TH and Xiang Q. The effect of isopropyl alcohol on the permeation
of gloves exposed to antineoplastic agents. J Oncol Pharm Practice. 2000;
6: 109-114.
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. Using PPE to prevent occupational exposure to antineoplastic and other hazardous drugs. Pharm Purchasing & Products. 2006, 2; 4-6.
Connor TH. Personal protective equipment for use in handling hazardous drugs. Pharm Purchasing & Products. 2006; 3:2-6.
Dinter-Heidorn H and Carstens G. Comparative study on protective gloves
for handling cytotoxic medications: A model study with carmustine. Pharmaceutisch
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Donner AL. Possible risk of working with antineoplastic drugs in horizontal
laminar flow hoods (letter). Am J Hosp Pharm. 1978;35:900.
Gross ER and Groce DF. An evaluation of nitrile gloves as an alternative
to natural rubber latex for handling chemotherapeutic agents. J Oncol
Pharm Practice. 1998;4:165-168.
Harrison BR and Kloos MD. Penetration and splash protection of six disposable
gown materials against fifteen antineoplastic drugs. J Oncol Pharm Practice.
1999; 5: 61-66.
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.
Klein M, Rau S, Samev N and Carstens G. Protection offered by selected
medical gloves made of either latex or a synthetic elastomer against exposure
to nine cytotoxic agents. European Hosp Pharm. 1999;5:152-158.
Klein M, Lambov N, Samev N, Carstens G. Permeation of cytotoxic formulations
through swatches from selected medical gloves. Am J Health-Syst Pharm.
2003; 1006-1011.
Laidlaw JL, Connor TH, Theiss JC Anderson RW and Matney TS . Permeability
of latex and polyvinyl gloves to 20 antineoplastic drugs. Am J Hosp Pharm.
1984;41:2618-2623.
Laidlaw JL, Connor TH, Theiss JC anderson RW and Matney TS. Permeability
of four disposable protective-clothing materials to seven antineoplastic
drugs. Am J Hosp Pharm. 1985;42:2449-2454.
Mader RM, Rizovski B, Steger GG Moser K, Rainer H and Dittrich C. Permeability
of latex membranes to anti-cancer drugs. Int J Pharmaceut. 1991;68:151-156.
Mellström GA, Wrangsjö K, Wahlberg JE and Fryklund B. The value
and limitations of protective gloves in medical health service:Part I.
Dermatol Nurs. 1996;8:160-164.
Mellström GA, Wrangsjö K, Wahlberg JE and Fryklund B. The value
and limitations of protective gloves in medical health service:Part II.
Dermatol Nurs. 1996;8:287-295.
Mellström GA, Wrangsjö K, Wahlberg JE and Fryklund B. The value
and limitations of protective gloves in medical health service:Part III.
Dermatol Nurs. 1996;8:345-355.
Nygren O, Gustavsson B, Strom L, Eriksson R, Jarneborn L and Friberg A.
Exposure to anti-cancer drugs during preparation and administration. Investigations
of an open and a closed system. J Environ Monit. 2002; 4:739-732.
Nygren O. Wipe samples as a tool for monitoring aerosol deposition in workplaces. J Environ Monit. 2006; 8;49-52.
Nygren O, Gustavsson B, Eriksson R. A test method for assessment of spill and leakage from drug preparation systems. Ann Occup Hyg. 2005; 49:711-718.
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.
Stajich GV, Barnett CW, Turner SV and Henderson CA. Protective measures
used by oncologic office nurses handling parenteral antineoplastic agents.
Oncol Nurs Forum. 1986;13:47-49.
Stoikes ME, Carlson JD, Farris FF and Walker PR. Permeability of latex
and polyvinyl chloride gloves to fluorouracil and methotrexate. Am J Hosp
Pharm. 1987;44:1341-1346.
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.
Thomas PH and Fenton-May V. Protection offered by various gloves to carmustine
exposure. The Pharm J. 1987;238:775-777.
Thomsen K and Mikklesen HI. Protective capacity of gloves used for handling
nitrogen mustard. Contact Derm. 1975;1:268-269.
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.
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