Occupational exposure to cytotoxic drugs: the importance of surface cleaning to prevent or minimise exposure

Abstract Healthcare workers who prepare or administer cytotoxic agents run the risk of exposure, and the risks for health are real even at doses lower than those applied in cancer patients, because, in theory, no dose is safe. The most common and problematic route of exposure is through the skin, especially as work surfaces can remain contaminated even after cleaning. This pilot study aimed to demonstrate the importance of having an effective surface decontamination protocol by determining surface contamination with cyclophosphamide, 5-fluorouracil, and paclitaxel as the most common cytotoxic drugs in an oncology day service. Samples were collected before and after drug handling and analysed with high performance liquid chromatography with diode array detection (HPLC-DAD). Of the 29 samples collected before drug handling 23 were contaminated, five of which with more than one drug. Of the 30 samples collected after drug handling 25 were contaminated, eight of which with more than one drug. The two time points did not significantly differ, which evidences a widespread contamination and ineffective cleaning. This calls for revising the cleaning protocol and handling procedure to place contamination under control as much as possible.

[1]  S. Viegas,et al.  Genotoxicity assessment of a selected cytostatic drug mixture in human lymphocytes: A study based on concentrations relevant for occupational exposure , 2018, Environmental research.

[2]  S. Viegas,et al.  Forgotten public health impacts of cancer – an overview , 2017, Arhiv za higijenu rada i toksikologiju.

[3]  G. Gajski,et al.  Combined cyto/genotoxic activity of a selected antineoplastic drug mixture in human circulating blood cells. , 2016, Chemosphere.

[4]  P. Bonnabry,et al.  Effectiveness of a Closed-System Transfer Device in Reducing Surface Contamination in a New Antineoplastic Drug-Compounding Unit: A Prospective, Controlled, Parallel Study , 2016, PloS one.

[5]  E. Davoli,et al.  Antineoplastic drugs determination by HPLC-HRMS(n) to monitor occupational exposure. , 2016, Drug testing and analysis.

[6]  S. Viegas,et al.  How to deal with uncertainties regarding the occupational exposure to antineoplastic mixtures: additive effect should always be considered? , 2016 .

[7]  W. Feng,et al.  Evaluation of adverse health risks associated with antineoplastic drug exposure in nurses at two Chinese hospitals: The effects of implementing a pharmacy intravenous admixture service. , 2016, American journal of industrial medicine.

[8]  A. Turner,et al.  Evaluation of a closed-system cytotoxic transfer device in a pharmaceutical isolator , 2016, Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners.

[9]  J. Bussières,et al.  Surface Contamination in a Teaching Hospital: A 6 Year Perspective , 2016 .

[10]  S. Rudaz,et al.  Evaluation of chemical contamination of surfaces during the preparation of chemotherapies in 24 hospital pharmacies , 2015 .

[11]  E. Ceretti,et al.  Micronuclei and chromosome aberrations in subjects occupationally exposed to antineoplastic drugs: a multicentric approach , 2015, International Archives of Occupational and Environmental Health.

[12]  M. McDiarmid,et al.  Reproductive Health Risks Associated With Occupational Exposures to Antineoplastic Drugs in Health Care Settings: A Review of the Evidence , 2014, Journal of occupational and environmental medicine.

[13]  S. Viegas,et al.  Antineoplastic drugs contamination of workplace surfaces in two Portuguese hospitals , 2014, Environmental Monitoring and Assessment.

[14]  M. Sweeney,et al.  Adherence to Safe Handling Guidelines by Health Care Workers Who Administer Antineoplastic Drugs , 2014, Journal of occupational and environmental hygiene.

[15]  K. Kümmerer,et al.  Environmental risk assessment of anti-cancer drugs and their transformation products: A focus on their genotoxicity characterization-state of knowledge and short comings. , 2014, Mutation research. Reviews in mutation research.

[16]  T. de Jong,et al.  Current and emerging occupational safety and health (OSH) issues in the healthcare sector, including home and community care , 2014 .

[17]  J. Tuerk,et al.  Application and assessment of a regular environmental monitoring of the antineoplastic drug contamination level in pharmacies - the MEWIP project. , 2013, The Annals of occupational hygiene.

[18]  P. Bonnabry,et al.  Evaluation of decontamination efficacy of cleaning solutions on stainless steel and glass surfaces contaminated by 10 antineoplastic agents. , 2013, The Annals of occupational hygiene.

[19]  P. Hartemann,et al.  Environmental impact of medical prescriptions: assessing the risks and hazards of persistence, bioaccumulation and toxicity of pharmaceuticals. , 2013, Public health.

[20]  Jason S. Trahan,et al.  Reduction in Surface Contamination with Cyclophosphamide in 30 US Hospital Pharmacies following Implementation of a Closed-System Drug Transfer Device , 2013, Hospital pharmacy.

[21]  Jing-Yuan Wang,et al.  Removal of cytostatic drugs from aquatic environment: a review. , 2013, The Science of the total environment.

[22]  M. Imbriani,et al.  Occupational exposure to antineoplastic drugs in four Italian health care settings. , 2012, Toxicology letters.

[23]  J. Garric,et al.  Anticancer drugs in surface waters: what can we say about the occurrence and environmental significance of cytotoxic, cytostatic and endocrine therapy drugs? , 2012, Environment international.

[24]  S. Singh,et al.  Monitoring of Oxidative Stress in Nurses Occupationally Exposed to Antineoplastic Drugs , 2012, Toxicology international.

[25]  D. Nowak,et al.  Evaluation of working practices and surface contamination with antineoplastic drugs in outpatient oncology health care settings , 2012, International Archives of Occupational and Environmental Health.

[26]  M. Imbriani,et al.  Occupational exposure to antineoplastic drugs in seven Italian hospitals: The effect of quality assurance and adherence to guidelines , 2011, Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners.

[27]  V. Castagné,et al.  Cytotoxics compounded sterile preparation control by HPLC during a 16-month assessment in a French university hospital: importance of the mixing bags step , 2011, Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners.

[28]  K. Teschke,et al.  Occupational Exposure to Antineoplastic Drugs: Identification of Job Categories Potentially Exposed throughout the Hospital Medication System , 2011, Safety and health at work.

[29]  E. Heath,et al.  Occurrence, fate and determination of cytostatic pharmaceuticals in the environment , 2011 .

[30]  S. Kumagai,et al.  Association between occupational exposure levels of antineoplastic drugs and work environment in five hospitals in Japan , 2011, Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners.

[31]  P. Sessink,et al.  Reduction in surface contamination with antineoplastic drugs in 22 hospital pharmacies in the US following implementation of a closed-system drug transfer device , 2011, Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners.

[32]  B. Rogers,et al.  Chromosome 5 and 7 Abnormalities in Oncology Personnel Handling Anticancer Drugs , 2010, Journal of occupational and environmental medicine.

[33]  Ludek Blaha,et al.  Ecotoxicity and genotoxicity assessment of cytotoxic antineoplastic drugs and their metabolites. , 2010, Chemosphere.

[34]  É. Langlois,et al.  Pilot study comparing the efficacy of two cleaning techniques in reducing environmental contamination with cyclophosphamide. , 2010, The Annals of occupational hygiene.

[35]  D. Nowak,et al.  Guidance values for surface monitoring of antineoplastic drugs in German pharmacies. , 2009, The Annals of occupational hygiene.

[36]  É. Langlois,et al.  Evaluation of surface contamination in a hospital hematology—oncology pharmacy , 2009, Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners.

[37]  J. Saffi,et al.  Occupational risk assessment of genotoxicity and oxidative stress in workers handling anti-neoplastic drugs during a working week. , 2008, Mutagenesis.

[38]  G. Poggi,et al.  Simultaneous determination of cyclophosphamide, ifosfamide, doxorubicin, epirubicin and daunorubicin in human urine using high-performance liquid chromatography/electrospray ionization tandem mass spectrometry: bioanalytical method validation. , 2008, Rapid communications in mass spectrometry : RCM.

[39]  N. Miraglia,et al.  Evaluation of Occupational Exposure to Antiblastic Drugs in an Italian Hospital Oncological Department , 2008, Journal of occupational health.

[40]  H. Kromhout,et al.  A pooled analysis to study trends in exposure to antineoplastic drugs among nurses. , 2007, The Annals of occupational hygiene.

[41]  S. Iavicoli,et al.  Micronucleus induction and FISH analysis in buccal cells and lymphocytes of nurses administering antineoplastic drugs. , 2007, Mutation research.

[42]  H. Kromhout,et al.  Nurses With Dermal Exposure to Antineoplastic Drugs: Reproductive Outcomes , 2007, Epidemiology.

[43]  V. Garaj-Vrhovac,et al.  Alkaline comet assay study with breast cancer patients: evaluation of baseline and chemotherapy-induced DNA damage in non-target cells , 2006, Clinical and Experimental Medicine.

[44]  H. Kromhout,et al.  Exposure to antineoplastic drugs outside the hospital environment. , 2006, The Annals of occupational hygiene.

[45]  T. Connor Hazardous Anticancer Drugs in Health Care , 2006, Annals of the New York Academy of Sciences.

[46]  Q. M. Khan,et al.  Cytogenetic analysis of Pakistani individuals occupationally exposed to pesticides in a pesticide production industry. , 2006, Mutagenesis.

[47]  Sergio Iavicoli,et al.  Evaluation of genotoxic effects induced by exposure to antineoplastic drugs in lymphocytes and exfoliated buccal cells of oncology nurses and pharmacy employees. , 2005, Mutation research.

[48]  S. Eksborg,et al.  Surface contamination of cyclophosphamide packaging and surface contamination with antineoplastic drugs in a hospital pharmacy in Sweden. , 2005, The Annals of occupational hygiene.

[49]  F. Violante,et al.  A new high-performance liquid chromatographic/electrospray ionization tandem mass spectrometric method for the simultaneous determination of cyclophosphamide, methotrexate and 5-fluorouracil as markers of surface contamination for occupational exposure monitoring. , 2005, Journal of mass spectrometry : JMS.

[50]  C. Minoia,et al.  Biological and environmental monitoring of hospital personnel exposed to antineoplastic agents: a review of analytical methods. , 2003, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[51]  R. Schierl,et al.  Monitoring surface contamination by antineoplastic drugs using gas chromatography-mass spectrometry and voltammetry. , 2002, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[52]  R. Larson,et al.  Monitoring method for surface contamination caused by selected antineoplastic agents. , 2002, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[53]  D. Loffredo,et al.  Low-Level (PPB)Determination of Cisplatin in Cleaning Validation (Rinse Water) Samples. II. A High-Performance Liquid Chromatogrphic Method , 2000, Drug development and industrial pharmacy.

[54]  P. Sessink,et al.  Surface contamination with antineoplastic agents in six cancer treatment centers in Canada and the United States. , 1999, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[55]  P. Sessink,et al.  Drugs Hazardous to Healthcare Workers , 1999, Drug safety.

[56]  P. Apostoli,et al.  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. , 1998, Rapid communications in mass spectrometry : RCM.

[57]  A. Fucic,et al.  Cytogenetic consequences after occupational exposure to antineoplastic drugs. , 1998, Mutation research.

[58]  J. Cvačka,et al.  Chemical degradation of wastes of antineoplastic agents amsacrine, azathioprine, asparaginase and thiotepa. , 1998, The Annals of occupational hygiene.

[59]  J T Walker,et al.  Validation of cleaning procedures for highly potent drugs. II. Bisnafide. , 1998, Pharmaceutical development and technology.

[60]  G. Duménil,et al.  Chemical degradation of wastes of antineoplastic agents: cyclophosphamide, ifosfamide and melphalan , 1996, International archives of occupational and environmental health.

[61]  M. Castegnaro,et al.  Chemical degradation of wastes of antineoplastic agents , 1997 .

[62]  M. Castegnaro,et al.  Chemical degradation of wastes of antineoplastic agents. 2: Six anthracyclines: idarubicin, doxorubicin, epirubicin, pirarubicin, aclarubicin, and daunorubicin. , 1997, International archives of occupational and environmental health.

[63]  J T Rubino,et al.  Validation of cleaning procedures for highly potent drugs. I. Losoxantrone. , 1996, Pharmaceutical development and technology.

[64]  P. Sessink,et al.  Urinary cyclophosphamide excretion and chromosomal aberrations in peripheral blood lymphocytes after occupational exposure to antineoplastic agents. , 1994, Mutation research.

[65]  M. Caira,et al.  X-ray structural characterization of anhydrous metronidazole benzoate and metronidazole benzoate monohydrate. , 1993, Journal of pharmaceutical sciences.

[66]  J. Benvenuto,et al.  Degradation and inactivation of antitumor drugs. , 1993, Journal of pharmaceutical sciences.

[67]  Eric B. Sansone,et al.  Degradation and disposal of some antineoplastic drugs. , 1989, Journal of pharmaceutical sciences.

[68]  J. Benvenuto,et al.  Stability and inactivation of mutagenic drugs and their metabolites in the urine of patients administered antineoplastic therapy , 1987, Environmental and molecular mutagenesis.

[69]  D. Gompertz,et al.  MUTAGENICITY OF URINE FROM NURSES HANDLING CYTOTOXIC DRUGS , 1984, The Lancet.

[70]  Pham-Huu-Chanh,et al.  Some biological effects of thyronamine. , 1966, Medicina et pharmacologia experimentalis. International journal of experimental medicine.