Skip to main content

Advertisement

SpringerLink
Log in

Environmental and biological monitoring of antineoplastic drugs in four workplaces in a Swedish hospital

  • Original Article
  • Published:
International Archives of Occupational and Environmental Health Aims and scope Submit manuscript

Abstract

Objectives

Exposure to antineoplastic drugs should be avoided due to the risk of getting adverse health effects. Antineoplastic drugs such as cyclophosphamide (CP) and ifosfamide (IF) are commonly used in medical attendance. In this study the variability of surface contamination of CP and IF was investigated by repeated wipe sampling over time in four workplaces in a university hospital. The surface contamination levels were also evaluated and health care workers were biologically monitored.

Methods

A hospital pharmacy, two oncology wards and one oncology outpatient department were selected. Between 10 and 13 different surface areas such as work areas, floors and handles were selected in each workplace and wiped between 7 and 8 times during 9 months. Pre- and post-shift urine samples were collected from the workers in the investigated workplaces. Analysis was performed by liquid chromatography combined with tandem mass spectrometry.

Results

Measurable amounts of CP and IF were detected on the majority of the sampled surfaces. The highest concentrations were found on the floors in the patient lavatories and utility rooms (up to 95 ng cm−2). In general, the surface contamination of CP and IF on floors did not vary much over time. Work areas and handles had larger variability. Neither CP nor IF were detected in any of the collected urine samples.

Conclusions

The variability in surface contamination of CP and IF was rather low especially on floors. Higher concentrations of CP and IF were found on the floors compared with the work areas. The highest surface loads were found on floors (in patient lavatories and utility rooms) that were related to patient activities such as handling of patients’ urine. Although high contaminations were found, the biological monitoring showed no uptake. Wipe sampling is a good method to improve the work practices.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Acampora A, Castiglia L, Miraglia N, Pieri M, Soave C, Liotti F, Sannolo N (2005) A case study: surface contamination of cyclophosphamide due to working practices and cleaning procedures in two Italian hospitals. Ann Occup Hyg 49:611–618

    Article  PubMed  CAS  Google Scholar 

  • Boddy AV, Yule SM (2000) Metabolism and pharmacokinetics of oxazaphosphorines. Clin Pharmacokinet 38:291–304

    Article  PubMed  CAS  Google Scholar 

  • Burgaz S, Karahalil B, Canhi Z, Terzioglu F, Ancel G, Anzion RB, Bos RP, Huttner E (2002) Assessment of genotoxic damage in nurses occupationally exposed to antineoplastics by the analysis of chromosomal aberrations. Hum Exp Toxicol 21:129–135

    Article  PubMed  CAS  Google Scholar 

  • Buringh E, Lanting R (1991) Exposure variability in the workplace: its implications for the assessment of compliance. Am Ind Hyg Assoc J 52:6–13

    PubMed  CAS  Google Scholar 

  • Cavallo D, Ursini CL, Perniconi B, Francesco AD, Giglio M, Rubino FM, Marinaccio A, Iavicoli S (2005) Evaluation of genotoxic effects induced by exposure to antineoplastic drugs in lymphocytes and exfoliated buccal cells of oncology nurses and pharmacy employees. Mutat Res 587:45–51

    PubMed  CAS  Google Scholar 

  • Connor TH, Anderson RW, Sessink PJ, Broadfield L, Power LA (1999a) Surface contamination with antineoplastic agents in six cancer treatment centers in Canada and the United States. Am J Health Syst Pharm 56:1427–1432

    PubMed  CAS  Google Scholar 

  • Connor TH (1999b) Permeability of nitrile rubber, latex, polyurethane, and neoprene gloves to 18 antineoplastic drugs. Am J Health Syst Pharm 56:2450–2453

    PubMed  CAS  Google Scholar 

  • Crauste-Manciet S, Sessink PJ, Ferrari S, Jomier JY, Brossard D (2005) Environmental contamination with cytotoxic drugs in healthcare using positive air pressure isolators. Ann Occup Hyg 49:619–628

    Article  PubMed  CAS  Google Scholar 

  • Dranitsaris G, Johnston M, Poirier S, Schueller T, Milliken D, Green E, Zanke B (2005) 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 Pract 11:69–78

    Article  PubMed  Google Scholar 

  • Ensslin AS, Stoll Y, Pethran A, Pfaller A, Römmelt H, Fruhmann G (1994) Biological monitoring of cyclophosphamide and ifosfamide in urine of hospital personnel occupationally exposed to cytostatic drugs. Occup Environ Med 51:229–233

    Article  PubMed  CAS  Google Scholar 

  • Evelo CT, Bos RP, Peters JG, Henderson PT (1986) Urinary cyclophosphamide assay as a method for biological monitoring of occupational exposure to cyclophosphamide. Int Arch Occup Environ Health 58:151–155

    Article  PubMed  CAS  Google Scholar 

  • Fenske RA, Curry PB, Wandelmaier F, Ritter L (1991) Development of dermal and respiratory sampling procedures for human exposure to pesticides in indoor environments. J Expo Anal Environ Epidemiol 1:11–30

    PubMed  CAS  Google Scholar 

  • Floridia L, Pietropaolo AM, Tavazzani M, Rubino FM, Colombi A (1999) High-performance liquid chromatography of methotrexate for environmental monitoring of surface contamination in hospital departments and assessment of occupational exposure. J Chromatogr B Biomed Sci Appl 726:95–103

    Article  PubMed  CAS  Google Scholar 

  • Fransman W, Vermeulen R, Kromhout H (2005) Dermal exposure to cyclophosphamide in hospitals during preparation, nursing and cleaning activities. Int Arch Occup Environ Health 78:403–412

    Article  PubMed  CAS  Google Scholar 

  • Fransman W, Roeleveld N, Peelen S, de Kort W, Kromhout H, Heederik D (2007a) Nurses with dermal exposure to antineoplastic drugs: reproductive outcomes. Epidemiology 18:112–119

    Article  PubMed  Google Scholar 

  • Fransman W, Peelen S, Hilhorst S, Roeleveld N, Heederik D, Kromhout H (2007b) A pooled analysis to study trends in exposure to antineoplastic drugs among nurses. Ann Occup Hyg 51:231–239

    Article  PubMed  CAS  Google Scholar 

  • Fuchs J, Hengstler JG, Jung D, Hiltl G, Konietzko J, Oesch F (1995) DNA damage in nurses handling antineoplastic agents. Mutat Res 342:17–23

    Article  PubMed  CAS  Google Scholar 

  • Hedmer M, Jönsson BAG, Nygren O (2004) Development and validation of methods for environmental monitoring of cyclophosphamide in workplaces. J Environ Monit 6:979–984

    Article  PubMed  CAS  Google Scholar 

  • Hedmer M, Georgiadi A, Rämme Bremberg E, Jönsson BAG, Eksborg S (2005) Surface contamination of cyclophosphamide packaging and surface contamination with antineoplastic drugs in a hospital pharmacy in Sweden. Ann Occup Hyg 49:629–637

    Article  PubMed  CAS  Google Scholar 

  • Hedmer M, Höglund P, Cavallin-Ståhl E, Albin M, Jönsson BAG (2008) Validation of urinary excretion of cyclophosphamide as a biomarker of exposure by studying its renal clearance at high and low plasma concentrations in cancer patients. Int Arch Occup Environ Health 81:285–293

    Google Scholar 

  • IARC (1981) monographs on the evaluation of the carcinogenic risk of chemicals to humans, vol 26. Some antineoplastic and immunosuppressive agents. International Agency for Research on Cancer, Lyon

    Google Scholar 

  • IARC (1987) monographs on the evaluation of the carcinogenic risk to humans, suppl 7. Overall evaluation of carcinogenicity: An updating of IARC monographs volumes 1–42. International Agency for Research on Cancer, Lyon

    Google Scholar 

  • IARC (1990) monographs on the evaluation of the carcinogenic risk to humans, vol 50. Pharmaceutical drugs. International Agency for Research on Cancer, Lyon

    Google Scholar 

  • Kiffmeyer TK, Kube C, Opiolka S, Schmidt KG, Schöppe G, Sessink PJM (2002) Vapour pressures, evaporation behaviour and airborne concentrations of hazardous drugs; implications for occupational safety. Pharm J 268:331–337

    Google Scholar 

  • Kromhout H, Hoek F, Uitterhoeve R, Huijbers R, Overmars RF, Anzion R, Vermeulen R (2000) Postulating a dermal pathway for exposure to anti-neoplastic drugs among hospital workers. Applying a conceptual model to the results of three workplace surveys. Ann Occup Hyg 44:551–560

    PubMed  CAS  Google Scholar 

  • Krstev S, Perunicic B, Vidakovic A (2003) Work practice and some adverse health effects in nurses handling antineoplastic drugs. Med Lav 94:432–439

    PubMed  CAS  Google Scholar 

  • Laidlaw JL, Connor TH, Theiss JC, Anderson RW, Matney TS (1984) Permeability of latex and polyvinyl chloride gloves to 20 antineoplastic drugs. Am J Hosp Pharm 41:2618–2623

    PubMed  CAS  Google Scholar 

  • Leidel NA, Busch KA, Crouse WE (1975) Exposure measurement action level and occupational environmental variability. DHEW (NIOSH) Pub. No. 76–131; NTIS Pub. No. PB-267–509. US National Technical Information Service, Springfield, VA, USA

  • Mason H, Sams C, Jones K, Cairns W (2001) Cytotoxic drug exposure in two pharmacies using positive and negative pressure enclosures for the formulation of cytotoxic drugs, Report no. HEF01/01: 1–42. Sheffield: Health and Safety Laboratory

  • Mason HJ, Morton J, Garfitt SJ, Iqbal S, Jones K (2003) Cytotoxic drug contamination on the outside of vials delivered to a hospital pharmacy. Ann Occup Hyg 47:681–685

    Article  PubMed  CAS  Google Scholar 

  • Mason HJ, Blair S, Sams C, Jones K, Garfitt SJ, Cuschieri MJ, Baxter PJ (2005) Exposure to antineoplastic drugs in two UK hospital pharmacy units. Ann Occup Hyg 49:603–610

    Article  PubMed  CAS  Google Scholar 

  • McDevitt JJ, Lees PS, McDiarmid MA (1993) Exposure of hospital pharmacists and nurses to antineoplastic agents. J Occup Med 35:57–60

    PubMed  CAS  Google Scholar 

  • Meijster T, Fransman W, Veldhof R, Kromhout H (2006) Exposure to antineoplastic drugs outside the hospital environment. Ann Occup Hyg 50:657–664

    Article  PubMed  CAS  Google Scholar 

  • Minoia C, Turci R, Sottani C, Schiavi A, Perbellini L, Angeleri S, Draicchio F, Apostoli P (1998) 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 12:1485–1493

    Article  PubMed  CAS  Google Scholar 

  • Peretz C, Goldberg P, Kahan E, Grady S, Goren A (1997) The variability of exposure over time: a prospective longitudinal study. Ann Occup Hyg 41:485–500

    PubMed  CAS  Google Scholar 

  • Pethran A, Schierl R, Hauff K, Grimm CH, Boos KS, Nowak D (2003) Uptake of antineoplastic agents in pharmacy and hospital personnel. Part I: monitoring of urinary concentrations. Int Arch Occup Environ Health 76:5–10

    PubMed  CAS  Google Scholar 

  • Rappaport SM (1991) Assessment of long-term exposures to toxic substances in air. Ann Occup Hyg 35:61–121

    Article  PubMed  CAS  Google Scholar 

  • Ringborg U, Henriksson R, Friberg S (1998) Onkologi [Oncology]. Liber, Stockholm

    Google Scholar 

  • Roberts S, Khammo N, McDonnell G, Sewell GJ (2006) Studies on the decontamination of surfaces exposed to cytotoxic drugs in chemotherapy workstations. J Oncol Pharm Pract 12:95–104

    Article  PubMed  CAS  Google Scholar 

  • Rubino FM, Floridia L, Pietropaolo AM, Tavazzani M, Colombi A (1999) Measurement of surface contamination by certain antineoplastic drugs using high-performance liquid chromatography: applications in occupational hygiene investigations in hospital environments. Med Lav 90:572–583

    PubMed  CAS  Google Scholar 

  • Schmaus G, Schierl R, Funck S (2002) Monitoring surface contamination by antineoplastic drugs using gas chromatography-mass spectrometry and voltammetry. Am J Health Syst Pharm 59:956–961

    PubMed  CAS  Google Scholar 

  • Schulz H, Bigelow S, Dobish R, Chambers CR (2005) Antineoplastic agent workplace contamination study: the Alberta cancer board pharmacy perspective. J Oncol Pharm Pract 11:101–109

    Article  PubMed  CAS  Google Scholar 

  • Selevan SG, Lindbohm ML, Horung RW, Hemminki K (1985) A study of occupational exposure to antineoplastic drugs and fetal loss in nurses. N Engl J Med 313:1173–1178

    Article  PubMed  CAS  Google Scholar 

  • Sessink PJ, Boer KA, Scheefhals AP, Anzion RB, Bos RP (1992a) 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 64:105–112

    Article  PubMed  CAS  Google Scholar 

  • Sessink PJ, Anzion RB, Van den Broek PH, Bos RP (1992b) Detection of contamination with antineoplastic agents in a hospital pharmacy department. Pharm Weekbl Sci 14:16–22

    PubMed  CAS  Google Scholar 

  • Sladek NE (1994) Metabolism and pharmacokinetic behavior of cyclophosphamide and related oxazaphosphorines. In: Powis G (ed) Anticancer drugs:reactive metabolism and drug interactions. Pergamon Press, Oxford

    Google Scholar 

  • Soule RD (1991) Industrial hygiene sampling and analysis. In: Clayton GD, Clayton FE (eds) Patty´s industrial hygiene and toxicology, vol I, Part B, 4th edn. Wiley, NY

  • Stucker I, Caillard JF, Collin R, Gout M, Poyen D, Hemon D (1990) Risk of spontaneous abortion among nurses handling antineoplastic drugs. Scand J Work Environ Health 16:102–107

    PubMed  CAS  Google Scholar 

  • Swedish Work Environment Authority (2005) Cytostatika och andra läkemedel med bestående toxisk effekt [Cytostatics and other drugs with permanent toxic effects]. AFS 2005:5, Solna, Sweden

  • Turci R, Sottani C, Ronchi A, Minoia C (2002) Biological monitoring of hospital personnel occupationally exposed to antineoplastic agents. Toxicol Lett 134:57–64

    Article  PubMed  CAS  Google Scholar 

  • Turci R, Sottani C, Spagnoli G, Minoia C (2003) Biological and environmental monitoring of hospital personnel exposed to antineoplastic agents: a review of analytical methods. J Chromatogr B Analyt Technol Biomed Life Sci 789:169–209

    Article  PubMed  CAS  Google Scholar 

  • Turci R, Minoia C (2006) Residual hazard assessment related to handling of antineoplastic drugs: safety system evolution and quality assurance of analytical measurement. Ann N Y Acad Sci 1076:649–656

    Article  PubMed  CAS  Google Scholar 

  • Undeger U, Basaran N, Kars A, Guc D (1999) Assessment of DNA damage in nurses handling antineoplastic drugs by the alkaline COMET assay. Mutat Res 439:277–285

    PubMed  CAS  Google Scholar 

  • Valanis BG, Vollmer WM, Labuhn KT, Glass AG (1993a) Association of antineoplastic drug handling with acute adverse effects in pharmacy personnel. Am J Hosp Pharm 50:455–462

    PubMed  CAS  Google Scholar 

  • Valanis BG, Vollmer WM, Labuhn KT, Glass AG (1993b) Acute symptoms associated with antineoplastic drug handling among nurses. Cancer Nurs 16:288–295

    Article  PubMed  CAS  Google Scholar 

  • Valanis B, Vollmer W, Labuhn K, Glass A (1997) Occupational exposure to antineoplastic agents and self-reported infertility among nurses and pharmacists. J Occup Environ Med 39:574–580

    Article  PubMed  CAS  Google Scholar 

  • Valanis B, Vollmer WM, Steele P (1999) Occupational exposure to antineoplastic agents: self-reported miscarriages and stillbirths among nurses and pharmacists. J Occup Environ Med 41:632–638

    Article  PubMed  CAS  Google Scholar 

  • Vermeulen R, Bos RP, Kromhout H (2001) Mutagenic exposure in the rubber manufacturing industry: an industry wide survey. Mutat Res 490:27–34

    PubMed  CAS  Google Scholar 

  • Wick C, Slawson MH, Jorgenson JA, Tyler LS (2003) Using a closed-system protective device to reduce personnel exposure to antineoplastic agents. Am J Health Syst Pharm 60:2314–2320

    PubMed  CAS  Google Scholar 

  • Ziegler E, Mason HJ, Baxter PJ (2002) Occupational exposure to cytotoxic drugs in two UK oncology wards. Occup Environ Med 59:608–612

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Gertrud Wohlfart for skillful technical and laboratory assistance and Lena Jernström at the Hospital pharmacy (Lund University Hospital) for all of the help provided during the samplings. The authors also thank AFA Foundation (Sweden), the Swedish Council for Work Life and Social Research, the Swedish Research Council, the County Councils of Southern Sweden and the Medical Faculty at Lund University in Lund (Sweden) for financial support of this work.

Author information

Authors and Affiliations

  1. Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University Hospital, 221 85, Lund, Sweden

    M. Hedmer, H. Tinnerberg, A. Axmon & B. A. G. Jönsson

Authors
  1. M. Hedmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Tinnerberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Axmon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B. A. G. Jönsson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Hedmer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hedmer, M., Tinnerberg, H., Axmon, A. et al. Environmental and biological monitoring of antineoplastic drugs in four workplaces in a Swedish hospital. Int Arch Occup Environ Health 81, 899–911 (2008). https://doi.org/10.1007/s00420-007-0284-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00420-007-0284-y

Keywords

Search

Navigation