Workplace Safety and Health Topics

NIOSH

OCCUPATIONAL EXPOSURE TO ANTINEOPLASTIC AGENTS

Environmental Sampling, Decontamination, and Protective Equipment

Muti-channel infusion pump for delivery of chemotherapy and needle and syringe

Environmental Sampling

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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Pethran A, Schierl R and Schmaus G. Wipe samples of workplaces with cytotoxic drug exposition. Krankenhauspharmazie. 2001; 1:11-15. (English abstract).

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Sottani C, Truci R, Schierl R, Gaggeri R, Barbieri A, Violante FS and Minoia C. Simultaneous determination of gemcitabine, taxol, cyclophosphamide and ifosphamide 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.

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Tanimura M, Yamada K, Sugiura S, Mori K, Nagata H, Tadokoro K, Miyake T, Hamaguchi Y, Sessink P, Nabeshima T. An environmental and biological study of occupational exposure to cyclophosphamide in the pharmacy of a Japanese community hospital designated for the treatment of cancer. J Health Sci. 2009; 55: 750-756.

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Touzin K, Bussières JF and Langlois É. Evaluation of surface contamination in a hospital hematology-oncology pharmacy. J Oncol Pharm Practice. 2009; 15: 53-61.

Tuerk J, Reinders M, Dryer M, Kiffmeyer TK, Schmidt KG and 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.

Tuerk J, Kiffmeyer TK, Hadtstein C, Heinemann A, Hahn M, Stuetzer H, Kuss HM and Eickmann U. Development and validation of an LC-MS/MS procedure for environmental monitoring of eight cytostatic drugs in pharmacies. Intern J Environ Anal Chem. 2011; 91:1178-1190.

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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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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Yabunaka H, Sakaguchi F, Kobayashi Y and Nakanishi H. Investigation on vaporization of solution of Endoxan^®. Jpn J Pharm Health Care Sci. 2010; 36:343- 346.

Yoshida J, Kosaka H, Tomika K and Kumagai S. Genotoxic Risks to nurses from contamination of the work enviroment with antineoplastic drugs in Japan. J Occup Health; 2006; 48:517-522.

Yoshida J, Koda S, Nishida S, Yoshida T, Miyajima K and Kumagai S. Association between occupational exposure levels of antineoplastic drugs and work environment in five hospitals in Japan. J Oncol Pharm Practice. 2010; 17:29-38.

Yoshida J, Kosaka H, Tomioka K and Kumagai S. Genotoxic risks to nurses from contamination of the work environment with antineoplastic drugs in Japan. J Occup Health. 2006; 48:517-522.

Zeedijk M, Greijdanus B, Steenstra FB and 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.

Ziegler E, Mason HJ and Baxter PJ. Occupational exposure to cytotoxic drugs in two UK oncology wards. Occup Environ Med. 2002; 59:608-612.

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).

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 and 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.

Touzin K, Bussières JF, Langlois É, Lefebvre M and Métra A. Pilot study comparing the efficacy of two cleaning techniques in reducing environmental contamination with cyclophosphamide. Ann Occup Hyg. 2010; 54:351-359.

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.

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Boccellino M, Pedata P, Castiglia L, La Porta R, Pieri M, Quagliuolo L, Acampora A, Sannolo N and Miraglia N. Doxorubicin can penetrate nitrile gloves and induces apoptosis in keratinocytes cell lines. Toxicol Lett. 2010; 197:61-68.

Cazin J-L and Gosselin P. Implementing a multiple-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. Using PPE to prevent occupational exposure to antineoplastic and other hazardous drugs. Pharm Purchasing & Products. 2006; 2:4-6.

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Work Practice Evaluation

Several approaches have been developed for evaluating work practice techniques for drug preparation and drug administration. These approaches typically rely on a non-toxic substitute for the drug that can be easily visualized by ultra violet light or other means. Some test kits are available for various manufacturers.

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