Objectives: To determine cyclophosphamide exposure to preparers during tablet crushing and subsequent handling by analyzing indoor air collected using a high-performance volatile organic compounds-solvent desorption (VOC-SD) passive air sampler.
Methods: The passive sampler was taped to the mask over the mouth of the preparer and indoor air was collected during crushing and preparation of cyclophosphamide tablets (Endoxan®). After collection, the carbon molecular sieve adsorbent of the passive sampler was placed in a centrifuge tube, and 1 mL of carbon disulfide was used to elute cyclophosphamide from the adsorbent. Liquid–liquid extraction with 1 mL of water was performed, and the aqueous phase was used as the test solution. Cyclophosphamide concentration was determined by liquid chromatography with ultraviolet and tandem mass spectrometry detection.
Results: Cyclophosphamide concentration was detected in the range of 7.6–157.7 ng/sampler. Our results showed that low-level exposure occurred near the mouth of the preparer, which could present risks for long-term exposure, especially if combined with multiple toxic drug exposures.
Conclusion: The anticancer drug monitoring methodology described here is a simple exposure assessment that can be used to ensure the safety of hospital pharmacy tablet preparers. Furthermore, since the anticancer drug exposure risk is very high for preparers, preparation should be in hood or with face mask.
ConnorTHMcDiarmidMA. Preventing occupational exposures to antineoplastic drugs in health care settings. CA Cancer J Clin2006; 56: 354–365.
2.
StellmanJMZolothSR. Cancer chemotherapeutic agents as occupational hazards. Cancer Invest1986; 4: 127–135.
3.
SorsaMHemminkiKVainioH. Occupational exposure to anticancer drugs-potential and real hazards. Mutation Res1985; 154: 135–149.
4.
IARC. IARC monographs on the evaluation of carcinogenic risks to humans. Some antineoplastic and immunosuppressive agents. Lyon: International Agency for Research on Cancer, vol. 26, 1981, p.411.
5.
IARC. IARC monographs on the evaluation of carcinogenic risks to humans. Pharmaceutical drugs. Lyon: International Agency for Research on Cancer, vol. 50, 1990.
6.
ShiratoS. Problems of cytotoxicity drug mainly based on antineoplastic tumor medicine. J Jpn Med Waste Res1992; 5: 1–32.
7.
KrstevSPerunicicBVidakovicA. Work practice and some adverse health effects in nurses handling antineoplastic drugs. Med Lav2003; 94: 432–439.
8.
The Society of Hospital Pharmacists of Australia. Guidelines for safe handling of cytotoxic drugs in pharmacy departments and hospital wards. Hospital Pharm1981; 16: 17–17.
9.
Canadian Society of Hospital Pharmacists. Guidelines for the handling of hazardous pharmaceuticals. Can J Hosp Pharm1981; 34: 126–128.
10.
Working Party Report: Guidelines for handling of cytotoxic drugs. Pharm J 1983; 230.
11.
ASHP technical assistance bulletin on handling cytotoxic drugs in hospitals. Am J Hosp Pharm 1985; 42: 131–137.
12.
Directorate of Labour Inspection. Guidelines concerning the handling of cytostatic agents , Oslo, Norway: Directorate of Labour Inspection, 1980.
13.
HakanssonLLandersjoL. Instructions for handling and administering of cytostatics , Stockholm, Sweden: National Social Welfare Board, 1978.
14.
Health and Safety Executive (U.K.). Precautions for the safe handling of cytotoxic drugs. Guidance Note MS 1984; 21.
15.
NIOSH Alert. Preventing occupational exposures to antineoplastic and other hazardous drugs in health caresettings 2004. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No 2004–2165.
16.
KitadaKMorikawaAKatoY. Kouganzai tyousei manyuaru (in Japanese) , Tokyo: Jiho, 2005.
17.
Japanese Society of Hospital Pharmacists. Kou akusei syuyou yakuzai no innai toriatukai sisin (in Japanese) , Tokyo: Japanese Society of Hospital Pharmacists, 1991.
18.
KiffmeyerTKKubeCOpiolkaS. Vapour pressures, evaporation behaviour and airborne concentrations of hazardous drugs: implications for occupational safety. Pharm J2002; 268: 331–337.
19.
YoshidaJKosakaHTomiokaK. Genotoxic risks to nurses from contamination of the work environment with antineoplastic drugs in Japan. J Occup Health2006; 48: 517–522.
20.
YoshidaJKodaSNishidaS. Association between occupational exposure levels of antineoplastic drugs and work environment in five hospitals in Japan. J Oncol Pharm Pract2010; 17: 29–38.
21.
ConnorTHAndersonRWSessinkPJM. Surface contamination with antineoplastic agents in six cancer treatment centers in Canada and the United States. Am J Health-Syst Pharm1999; 56: 1427–1432.
22.
YoshidaJTeiGMochizukiC. Use of a closed system device to reduce occupational contamination and exposure to antineoplastic drugs in the hospital work environment. Ann Occup Hyg2009; 53: 153–160.
23.
HarrisonBRPetersBGBingMR. Comparison of surface contamination with cyclophosphamide and fluorouracil using a closed-system drug transfer device versus standard preparation techniques. Am J Health Syst Pharm2006; 63: 1736–1744.
24.
MuraokaYYaharaIItoH. Ifosphamide (Z4942) no rat ni okeru a mansei narabini mansei dokusei siken (in Japanese). Kiso To Rinsyo1982; 16(2): 439–461.
25.
WickCSlawsonMHJorgensonJA. Using a closed-system protective device to reduce personnel exposure to antineoplastic agents. Am J Health Syst Pharm2003; 22: 2314–2320.
26.
ConnorTHAndersonRWSessinkPJ. Effectiveness of a closed-system device in containing surface contamination with cyclophosphamide and ifosfamide in an i.v. admixture area. Am J Health Syst Pharm2002; 59: 68–72.
