Occupational exposure to antineoplastic agents in hospital pharmacy

Occupational exposure to antineoplastic agents in hospital pharmacy in comparison with other departments of Masaryk Memorial Cancer Institute (Brno, Czech Republic) 1 Dolezalova L. , 1, 2 Odraska P. , 1 Prudilova M. , 1 Vejpustkova R. , 1 Gorna L. , 1, 2 Blaha L. 1 Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic (email: dolezalova@mou. cz); 2 RECETOX (Research Center for Environmental Chemistry and Ecotoxicology), Masaryk University, Kamenice 3, Brno, Czech Republic Introduction Handling of antineoplastic drugs (ADs) during the drug preparation, administration, disposal of unintentional release or nursing the oncological patients pose a potential health risk for the health care personnel. Many ADs were shown to be mutagenic, carcinogenic, embryotoxic and teratogenic 1. Furthermore, they can induce hypersensitive reactions or toxicities to endocrine or immune systems 2. Table 1: Results of the surface contamination of preparation and administration working areas (ng/sample) Objectives Our study focused on monitoring of surface contamination of preparation and administration working areas at Masaryk Memorial Cancer Institute, Brno. For this purpose, the most exposed working places were wiped analyzed for the presence of cyclophosphamide, 5 -fluorouracil and platinum containing drugs. Preparation room Outpatients clinic Storage area Nursing clinic Methods Sampling procedure utilized wiping of selected surfaces by nonwoven swabs moistened with acetate buffer (20 m. M, p. H = 4). Contamination was monitored mainly on the working tables, floor and objects with often hand contact (telephone, computer mouse, door handles etc. ). Used wipers were extracted in acetate buffer and analyzed for cyclophosphamide and 5 -fluorouracil by high performance liquid chromatography (Agilent HP 1200 HPLC System equipped with ZORBAX SB-18 column, 2, 1 x 30 mm, 3, 5 µm) with mass spectrometry detection (Agilent 6410 Triple. Guad detector). Platinum containing drugs were analysed as a sum of platinum by inductively coupled plasma mass spectrometry (Agilent ICP-MS 7500 ce). Results In general, we collected 159 samples during the study and more than 70% (118 samples) were positive for at least one of the drugs. The results for cyclophosphamide and platinum are presented in Table 1. Unfortunately, analytical methods for 5 -fluorouracil showed low selectivity and sensitivity, and results of these analyses were not considered as valid. References 1. Cardonick, E. , & Iacobucci, A. (2004). Use of chemotherapy during human pregnancy. Lancet Oncology, 5(5), 283 -291. 2. Dubeau, H. , Zazi, W. , Baron, C. , & Messing, K. (1994). Effects of lymphocyte subpopulations on the clonal assay of HPRT mutants: occupational exposure to cytostatic drugs. Mutation Research/Genetic Toxicology, 321(3), 147 -157. * Number of positive samples/total number of samples Discussion and Conclusion Regarding the results of both areas in the hospital pharmacy (preparation room and storage area), higher contamination was found in the preparation room, where intensive manipulations with ADs (dissolution, dilution, mixing) are centralised. It was shown, that concentrations on the working bench of the negative pressure cabinet can reach up to several micrograms per sample (area 900 cm 2). These concentrations are approximately 100 -times higher than those found in other areas outside of the negative pressure cabinet. Storage area was contaminated less frequently and detected levels of contamination were also lower. Only the concentrations of cyclophosphamide on the reception table were within the same order of magnitude like concentrations in the preparation room. The source of the contamination of this table is not clear, but presumably it might be related to handling ADs during the unpacking and labeling the drugs delivered to pharmacy by external suppliers. Interestingly, contamination of outpatient clinic was of the same level as the preparation room. Micrograms of cyclophosphamide and platinum per sample were found on the floor under the application post (IV tripod). This contamination results from the manipulation during the chemotherapy administration (infusion switching off, connecting of bolus doses, the finalization of administration), when ADs can be spread into the surrouding environment. Micrograms of cyclophosphamide and platinum were detected also on the floor of the patient toilets (WC). GENERAL RECOMMENDATIONS for personnel administering ADs 1. Protect yourselves! Wear working clothes with long sleeves, change this clothes after each workshift, use disposable gloves thoroughly. 2. Eliminate workplace contamination! Connect the infusion line into infusion bag during the AD preparation in the controlled environment inside the biological safety cabinet. 3. Don´t use one infusion line for more administrations (replacing of the infusion line represents a hazardous manipulation). 4. Instruct patients using toilets that the urine is a significant source of contamination (sitting during the emiction is a good practice). Acknowledgement The research is supported by the Ministry of Education, Czech Republic, project "CYTO", No. 2 B 06171. www. cytostatika. cz