JOURNAL OF THE CZECH PHARMACEUTICAL SOCIETY AND THE SLOVAK PHARMACEUTICAL SOCIETY

Čes. slov. farm. 2011, 60(1):25-31

Determination of airborne and surface contamination with cyclophosphamide at the Masaryk Memorial Cancer Institute, Brno, Czech Republic

Lucie Gorná1, Pavel Odráška1,2,*, Lenka Doležalová1, Pavel Piler2, Michal Oravec2, Luděk Bláha1,2
1 Masarykův onkologický ústav, Brno
2 Masarykova univerzita v Brně, Přírodovědecká fakulta, RECETOX (Výzkumné centrum pro toxické látky v prostředí)

Manipulation with cytotoxic drugs (CDs) during the preparation and administration of chemotherapy to cancer patients can potentially lead to contamination of working areas and consequently to occupational exposure of hospital staff. This study aimed to assess the potential of inhalation and dermal contact with CDs. For this purpose, distribution of the marker drug (cyclophosphamide, CP) in the working environment of the Masaryk Memorial Cancer Institute (Czech Republic) was studied. The study determined airborne and surface contamination of the hospital pharmacy and the outpatient clinic. Determination of airborne contamination was based on active stationary sampling of air using a PTFE filter, an impinger filled with distilled water and two solid sorbent tubes (Anasorb 708 and Strata-X) as sampling devices. Surface contamination was determined by the wipe sampling method. The airborne contamination was rare and the concentrations were many times lower than the maximal value calculated from the vapour pressure (0.36 mg/m3 at 20 °C). Detectable airborne CP was found in Strata-X samples collected at the outpatient clinic (n = 5, all samples positive at concentrations from 0.3 to 4.3 ng/m3). Surface contamination was determined at 75% of wipe samples (n = 65) with a median concentration of 750 ng/m2. In conclusion, inhalation of CDs seems to be of low importance at our hospital, which is up to the standard specified by current legislation (drug preparation performed in a clean room equipped with negative pressure isolators). The main proportion of contamination was present on the surfaces at all workplaces studied. Consequently, attention should be given to the elimination of the sources of surface contamination and to the prevention of dermal contact with contaminated material.

Keywords: cytotoxic drugs; cyclophosphamide; occupational exposure; surface contamination; airborne contamination
Grants and funding:

Studie vznikla v rámci řešení projektu CYTO podporovaného MŠMT ČR (NPVII, 2B06171). Infrastruktura Centra pro výzkum toxických látek v prostředí je podporována projektem CETOCOEN financovaným ze strukturálních fondů EU (CZ.1.05/2.1.00/01.0001). Infrastruktura Masarykova onkologického ústavu je podporována projektem RECAMO (CZ 1.05/2.1.00/03.0101).

Received: December 3, 2010; Accepted: December 15, 2010; Published: January 1, 2011  Show citation

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Gorná L, Odráška P, Doležalová L, Piler P, Oravec M, Bláha L. Determination of airborne and surface contamination with cyclophosphamide at the Masaryk Memorial Cancer Institute, Brno, Czech Republic. Čes. slov. farm. 2011;60(1):25-31.
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References

  1. Baker, G. L., Kahl, L. E., Zee, B. C., Stolzer, B. L., Agarwal, A. K., Medsger, T. A.: Malignancy following treatment of rheumatoid-arthritis with cyclophospha-mide - long-term case-control follow-up study. Am. J. Med. 1987; 83, 1-9. Go to original source... Go to PubMed...
  2. Fuchs, J., Hengstler, J. G., Jung, D., Hiltl, G., Konietzko, J., Oesch, F.: DNA damage in nurses handling antineoplastic agents. Mutation Research/ Genetic Toxicology 1995; 342, 17-23. Go to original source... Go to PubMed...
  3. Krstev, S., Perunicic, B. and Vidakovic, A.: Work practice and some adverse health effects in nurses handling antineoplastic drugs. Med. Lav. 2003; 94, 432-439.
  4. Hemminki, K., Kyyronen, P., Lindbohm, M. L.: Spontaneous-abortions and malformations in the offspring of nurses exposed to anesthetic-gases, cytostatic drugs, and other potential hazards in hospitals, based on registered information of outcome. J. Epidemiol. Community Health 1985; 39, 141-147. Go to original source... Go to PubMed...
  5. Greene, M. H., Harris, E. L., Gershenson, D. M., Malkasian, G. D., Melton, L. J., Dembo, A. J., Bennett, J. M., Moloney, W. C., Boice, J. D.: Melphalan may be a more potent leukemogen than cyclophosphamide. Ann. Intern. Med. 1986; 105, 360-367. Go to original source... Go to PubMed...
  6. Haas, J. F., Kittelmann, B., Mehnert, W. H., Staneczek, W., Mohner, M., Kaldor, J. M., Day, N. E.: Risk of leukemia in ovarian tumor and breast-cancer patients following treatment by cyclophosphamide. Br. J. Cancer 1987; 55, 213-218. Go to original source... Go to PubMed...
  7. Kaldor, J. M., Day, N. E., Pettersson, F., Clarke, E. A., Pedersen, D., Mehnert, W., Bell, J., Host, H., Prior, P., Karjalainen, S., Neal, F., Koch, M., Band, P., Choi, W., Kirn, V. P., Arslan, A., Zaren, B., Belch, A. R., Storm, H., Kittelmann, B., Fraser, P., Stovall, M.: Leukemia following chemotherapy for ovarian-cancer. N. Engl. J. Med. 1990; 322, 1-6. Go to original source... Go to PubMed...
  8. Sessink, P. J. M., Vandekerkhof, M. C. A., Anzion, R. B. M., Noordhoek, J., Bos, R. P.: Environmental contamination and assessment of exposure to antineoplastic agents by determination of cyclo-pho-sphamide in urine of exposed pharmacy technicians - is skin absorption an important exposure route. Arch. Environ. Health 1994; 49, 165-169. Go to original source... Go to PubMed...
  9. Micoli, G., Turci, R., Arpellini, M., Minoia, C.: Determination of 5-fluorouracil in environmental samples by solid-phase extraction and high-performance liquid chromatography with ultraviolet detection. Journal of Chromatography B 2001; 750, 25-32. Go to original source... Go to PubMed...
  10. Mason, H. J., Blair, S., Sams, C., Jones, K., Garfitt, S. J., Cuschieri, M. J., Baxter, P. J.: Exposure to antineoplastic drugs in two uk hospital pharmacy units. Ann. Occup. Hyg. 2005; 49, 603-610.
  11. Kiffmeyer, T., Kube, C., Opiolka, S., Schmidt, K. G., Schoppe, G., Sessink, P. J. M.: Vapour pressures, evaporation behaviour and airborne concentrations of hazardous drugs: Implications for occupational safety. The Pharmaceutical Journal 2002; 268, 331-337.
  12. Kromhout, H., Hoek, F., Uitterhoeve, R., Huijbers, R., Overmars, R. F., Anzion, R., Vermeulen, R.: Postulating a dermal pathway for exposure to anti-neoplastic drugs among hospital workers. Ann Occup Hyg 2000; 44, 551-560. Go to original source... Go to PubMed...
  13. Fransman, W., Vermeulen, R., Kromhout, H.: Dermal exposure to cyclophosphamide in hospitals during preparation, nursing and cleaning activities. Int. Arch. Occup. Environ. Health 2005; 78, 403-412. Go to original source... Go to PubMed...
  14. Sessink, P. J. M., Boer, K. A., Scheefhals, A. P. H., Anzion, R. B. M., Bos, R. P.: Occupational exposure to antineoplastic agents at several departments in a hospital - environmental contamination and excretion of cyclophosphamide and ifosfamide in urine of exposed workers. Int. Arch. Occup. Environ. Health 1992; 64, 105-112. Go to original source... Go to PubMed...
  15. Sessink, P. J. M., Timmersmans, J. L., Anzion, R. B. M., Bos, R. P.: Assessment of occupational exposure of pharmaceutical plant workers to 5-fluo-rouracil - determination of alpha-fluoro-beta-alanine in urine. J. Occup. Environ. Med. 1994; 36, 79-83.
  16. Sessink, P. J. M., Cerna, M., Rossner, P., Pastorkova, A., Bavarova, H., Frankova, K., Anzion, R. B. M., Bos, R. P.: Urinary cyclophosphamide excretion and chromo-somal aberrations in peripheral blood lymphocytes after occupational exposure to antineo-plastic agents. Mutation Research/Fundamental and Mole-cular Mechanisms of Mutagenesis 1994; 309, 193-199. Go to original source... Go to PubMed...
  17. Mader, R. M., Rizovski, B., Steger, G. G., Wachter, A., Kotz, R., Rainer, H.: Exposure of oncologic nurses to methotrexate in the treatment of osteosarcoma. Arch. Environ. Health 1996; 51, 310-314. Go to original source... Go to PubMed...
  18. 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. Occup. Environ. Health 1997; 70, 209-214. Go to original source... Go to PubMed...
  19. 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. Go to original source...
  20. NIOSH: Preventing occupational exposures to antineoplastic and other hazardous drugs in health care settings. NIOSH Alert. Cincinnati, OH: NIOSH. 2004; 1-61.
  21. ASHP: Guidelines on handling hazardous drugs. Am. J. Health. Syst. Pharm. 2006; 63, 1172-1193. Go to original source...
  22. ISOPP: Isopp standards of practice: Safe handling of cytotoxics. Journal of Oncology Pharmacy Practice 2007; 13(Suppl.), 1-81.
  23. Doležalová, L., Odráška, P., Gorná, L., Kuta, J., Oravec, M., Prudilová, M., Vejpustková, R., Bláha, L.: Studium kontaminace pracovišť a profesio-nální expozice zdravotnických pracovníků zajišťujících přípravu a aplikaci protinádorových léčiv. Pracovní lékařství 2009; 61, 117-122.
  24. Odráška, P., Gorná, L., Doležalová, L., Oravec, M., Kuta, J., Bláha, L.: Monitoring povrchové kontaminace cytotoxickými léčivy v nemocničních lékárnách české republiky. Čes. slov Farm. 2009; 58, 225-229.
  25. Opiolka, S., Molter, W., Kiffmeyer, T., Goldschmidt, R., Schoppe, G., Schmidt, K. G.: Dampfdrucke von zytostatika. Gefahrstoffe Reinhaltung Der Luft 1999; 59, 443-444.
  26. Connor, T. H., Shults, M., Fraser, M. P.: Determination of the vaporization of solutions of mutagenic antineo-plastic agents at 23 and 37 ľC using a desiccator technique. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 2000; 470, 85-92. Go to original source... Go to PubMed...
  27. Larson, R. R., Khazaeli, M. B., Dillon, H. K.: A new monitoring method using solid sorbent media for evaluation of airborne cyclophosphamide and other antineoplastic agents. Appl. Occup. Environ. Hyg. 2003; 18, 120-131. Go to original source... Go to PubMed...
  28. Chafer-Pericas, C., Herraez-Hernandez, R., Cam-pins-Falco, P.: Selective determination of trimethyl-amine in air by liquid chromatography using solid phase extraction cartridges for sampling. Journal of Chromato-graphy A 2004; 1042, 219-223. Go to original source... Go to PubMed...
  29. Tollback, J., Tamburro, D., Crescenzi, C., Carlsson, H.: Air sampling with empore solid phase extraction membranes and online single-channel desorption/liquid chromatography/mass spectrometry analysis: Deter-mination of volatile and semi-volatile organopho-sphate esters. Journal of Chromatography A 2006; 1129, 1-8. Go to original source... Go to PubMed...
  30. deWerk Neal, A., Wadden, R., Chiou, W.: Exposure of hospital workers to airborne antineoplastic agents. Am. J. Health Syst. Pharm. 1983; 40, 597-601. Go to original source...
  31. Sessink, P. J. M., Wittenhorst, B. C. J., Anzion, R. B. M., Bos, R. P.: Exposure of pharmacy technicians to antineoplastic agents: Reevaluation after additional protective measures. Arch. Environ. Health 1997; 52, 240-244. Go to original source... Go to PubMed...
  32. McDevitt, J. J., Lees, P. S. J., McDiarmid, M. A.: Exposure of hospital pharmacists and nurses to anti-neo-plastic agents. J. Occup. Environ. Med. 1993; 35, 57-60.
  33. Doležalová, L., Odráška, P., Gorná, L., Prudi-lová, M., Vejpustková, R., Bláha, L.: Studie evaporace vybraných cytostatik a propustnosti ochranných rukavic v rámci výzkumu profesní zátěže zdravotnických pracov-níků exponovaných cytotoxickým protinádorovým léči-vům (projekt cyto). Klinická onkologie 2009; 22, 218-222.




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