A Study on Environmental Monitoring of Fluorouracil and Decontamination Reagents

Fluorouracil의 환경감시 및 제거약제에 관한 연구

  • Lee, Su-Gil (Discipline of Public Health, School of Population Health & Clinical Practice, University of Adelaide) ;
  • Lee, Nae-Woo (Division of Safety Engineering, Pukyong National University)
  • 이수길 (아델라이드 대학교, 공중보건학과) ;
  • 이내우 (부경대학교 안전공학부)
  • Published : 2009.08.30

Abstract

This study has been to examine the occupational exposure levels of Fluorouracil (5-FU) in a hospital and to investigate the most effective cleaning reagent for control. Fluorouracil is one of the cytotoxic drugs which are therapeutic agents used to treat cancer. The health practitioners working in the cytotoxic work room and oncology ward areas are exposed to adverse health risks like cytogenetic and DNA damage from cytotoxic drugs exposure by frequent skin contact from contaminated surfaces. Four kinds of cleaning reagents has been examined to degrade the 5-FU. It was found that 5-FU was only degraded soon after the reaction in 0.5%(w/v) NaClO solution. Therefore, 0.5%(w/v) NaClO solution has been chosen to decompose any residues on the contamination surfaces. A substantial level of contamination was found on the surfaces of cytotoxic work room and oncology ward areas. The contamination ranges of the surfaces in cytotoxic work room and oncology ward areas were from 2.0 to $13.8{\mu}g/m^2$ and 5.39 to $11.53{\mu}g/m^2$ respectively. Consequently, regulation of the occupational exposure limit, procedure of special cleaning, and the use of personal protective equipment are recommended during the manipulation and administration of the drugs to avoid skin contamination from cytotoxic drugs like 5-FU.

이 연구는 Fluorouracil(5-FU)가 병원에서 암치료제로 쓰이는 세포독성약제의 한 종류이기 때문에 병원내부에 5-FU의 폭로 정도와 그 관리를 위한 가장 효율적인 세척약제를 조사하기 위한 것이다. 이러한 세포독성 약제실이나 종약학 병동에서 근무하는 실무자들은 세포독성약제로 오염된 표면에 빈번하게 접촉하게 되면 세포유전성이나 DNA손상에 대한 위험이 높게 된다. 따라서 이러한 약제의 세척제실험을 위하여 4가지 약제로서 시행한분해시험에서 0.5%(w/v) NaClO 용액만이 5-FU를 즉시 분해시켰으므로 이 용액은 오염표면의 잔유물을 분해시키는데 사용될 수 있다. 세포독성 약제실의 오염표면에서 확인된 농도범위는 2.0에서 $13.8{\mu}g/m^2$까지이고, 종약학 병동의 오염표면에서 측정한 농도범위는 5.39에서 $11.53{\mu}g/m^2$이었다. 5-FU와 같은 세포독성약제로부터 피부오염을 피하기 위하여 작업장의 노출허용기준과 같은 법적인 조치, 완벽한 표면세척제 및 보호구사용과 같은 엄격한 관리기준이 마련되어야 할 것이다.

Keywords

References

  1. NIOSH, "Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Healthcare Settings", National Institute for Occupational Safety and Health: U.S. Department of Health and Human Services, Public Health Service, Centres for Disease Control and Prevention, 2004-165, 2004
  2. W. Fransman, R. Vermeulen and H, Kromhout, 'Occupationnal dermal exposure to cyclophosphamide in dutch hospital: a pilot study', Ann Occup Hyg., Vol. 48, pp. 237 -244,2004 https://doi.org/10.1093/annhyg/meh017
  3. W. Fransman, R. Vermeulen and H. Kromhout, 'Dermal exposure to cyclophosphamide in hospitals during preparation, nursing and cleaning activities', Int Arch Occup Environ Health, Vol. 78, pp. 403-412, 2005 https://doi.org/10.1007/s00420-004-0595-1
  4. M. Hedmer, A. Georgiadi, R. Bremberg, BAG. Jonsson and S. Eksborg, 'Surface contamination of cyclophosphamide packaging and surface contamination with antineoplastic drugs in a hospital pharmacy in Sweden', Ann Occup Hyg, Vol. 49, pp. 629-637, 2005 https://doi.org/10.1093/annhyg/mei042
  5. P. Gilbar, 'External contamination of antineoplastic agent vials( editorial)', J Pharm PractRes, Vol. 35, pp. 264-265, 2005 https://doi.org/10.1002/j.2055-2335.2005.tb00359.x
  6. MG. Jakab, J. Major, A. Tompa, 'Follow-up genotoxicological monitoring of nurses handling antineoplastic drugs', J Toxicol Environ Health A, Vol. 62, pp. 307-318, 2001 https://doi.org/10.1080/152873901300018011
  7. TH. Connor, PJ. Sessink, BR. Harrison, JR. Pretty, BG. Peters, RM. Alfaro, et al. 'Surface contamination of chemotheraphy drug vials and evaluation of new vial-cleaning techniques: results of three studies', Am J Syst Pharm, Vol. 62, pp. 475-484, 2005
  8. TH. Connor, MA. McDiarmid, 'Preventing occupational exposures to antineoplastic drugs in health care settings, CA Cancer', J Clin, Vol. 56, pp. 354- 365, 2006 https://doi.org/10.3322/canjclin.56.6.354
  9. CA. Jackson, DA. Wilson, 'World at work: Hospital pharmacy clean-rooms', Occup Environ Med, Vol. 63, pp. 68-70, 2006 https://doi.org/10.1136/oem.2005.020719
  10. CL. Ursini, D. Cavallo, A. Colombi, M. Giglio, A. Marinaccio, S. lavicoli, 'Evaluation of early DNA damage in healthcare workers handling antineoplastic drugs', Int Arch Occup Environ Health, Vol. 80, pp.134-140, 2006 https://doi.org/10.1007/s00420-006-0111-x
  11. Authority; 2003, 'Handling Cytotoxic Drugs in the Workplace; Managing Health & Safety Risks Associated with Handling Cytotoxic Drugs in the Healthcare Industry', WorkCover Advisory Service. Worksafe Victoria: Division of the Victorian WorkCover Authority; 2003
  12. Queensland Workplace Health and Safety Strategy,'Guide for handling Cytotoxic Drugs and Related Waste', Department of Industrial Relations, Workplace Health and safety Queensland. Queensland Government; 2005
  13. SHPA Committee of Specialty Practice in Oncology, 'SHPA standards of practice for the safe handling of cytotoxic drugs in pharmacy departments', J Pharm Pract Res, Vol. 35, pp. 44-52, 2005
  14. A. Acapora, L. Castigia, N. Miraglia, M.Pieri, C. Soave, F. Liotti, et aI, 'A case study: Surface contamination of cyclophosphamide due to working practices and cleaning procedures in two Italian hospitals', Ann Occup Hyg. Vol 49, pp. 611-618, 2005 https://doi.org/10.1093/annhyg/mei029
  15. K. Touzin, JF. Bussieres, E. Langlois, M. Lefebvre, C. Gallant, 'Cyclophosphamide contamination observed on the external surfaces of drug vials and the efficiency of cleaning on vial contamination', Ann. Occup. Hyg,. Vol. 52, No.8, pp. 765-771,2008 https://doi.org/10.1093/annhyg/men050
  16. J. Siderov, 'Is the death knell for cytotoxic manufacturing in hospitals ringing?', J Pharm Prac Res, Vol. 36, p. 78, 2006
  17. K. Labuhn, B. Valanis, R. Schoeny, K. Loveday, WM. Vollmer, 'Nurses' and pharmacists' exposure to antineoplastic drugs: findings from industrial hygiene and urine mutagenicity tests', Cancer Bursing, Vol. 21, pp. 79-89, 1998 https://doi.org/10.1097/00002820-199804000-00001
  18. PJ. Sessink, Be. Wittenhorst, RB. Anzion, RP. Bos, 'Exposure to pharmacy to antineoplastic agents: reevaluation after additional protective measures', Arch Environ Health, Vol. 52, pp. 240-244, 1997 https://doi.org/10.1080/00039899709602893
  19. E. Ziegler, HJ. Mason, PJ. Baxter, 'Occupational exposure to cytotoxic drugs in the two UKoncology wards', Occup Environ Med, Vol. 59, pp. 608-612, 2002 https://doi.org/10.1136/oem.59.9.608
  20. S. Crauste-Manciet, PJM. Sessink, S. Ferrari, JY. Jomier, D. Brossard, 'Environmental contamination with cytotoxic drugs in healthcare using positive air pressure isolators', Ann Occup Hyg, Vol. 49, pp. 619-628,2005 https://doi.org/10.1093/annhyg/mei045
  21. G. Dranitsaris, M. Johnston, S. Poirier, T. Schueller, D. Milliken, E. Green, B. Zanke, 'Are health care providers who work with cancer drugs at an increased risk for toxic events? A systematic review and meta-analysis of the literature', J Oncol Pharm Prac, Vol. II, pp. 69-78,2005 https://doi.org/10.1191/1078155205jp155oa
  22. HJ. Mason, S. Blair, e. Sams, K. Jones, SJ. Garfitt, MJ. Cuschieri, et al. 'Exposure to antineoplastic drugs in two UK hospital pharmacy units', Ann Occup Hyg, Vol. 49, pp. 603-610, 2005 https://doi.org/10.1093/annhyg/mei023
  23. OSHA, "Controlling Occupational Exposure to Hazardous Drugs. OSHA Technical Manual(TED 01-00-015). Section VI: Chapter 2", U.S Department of Labor, Occupational Safety & Health Administration. Washington, DC. URL : http://www.osha.gov/dts/ostai/otm/otm vi/otm vi 2.html. 1999