The consumption of hazardous antineoplastic drugs (ADs) used in anticancer chemotherapies is steadily increasing representing thus risks to both human health and the environment. Hospitals may serve as a contamination source, and pharmacists preparing the antineoplastic drugs (ADs) as well as nurses administering chemotherapy and caring for oncology patients are among the healthcare professionals being highly exposed. Here, we present the results of systematic monitoring (2018-2020) of surface contamination by 13 ADs in the pharmacies and hospitals in the Czech Republic (CZ; large-scale monitoring, 20 workplaces) and Slovak Republic (SK; pilot study at 4 workplaces). The study evaluated contamination by three commonly monitored ADs, i.e., 5-fluorouracil (FU), cyclophosphamide (CP), and platinum (total Pt representing cis-, carbo-, and oxaliplatin) together with ten less explored ADs, i.e., gemcitabine (GEM), ifosfamide (IF), paclitaxel (PX), irinotecan (IRI), docetaxel (DOC), methotrexate (MET), etoposide (ETOP), capecitabine (CAP), imatinib (IMAT), and doxorubicin (DOX). Floors and desktop surfaces in hospitals (chemotherapy application rooms, nurse working areas) were found to be more contaminated, namely with CP and Pt, in both countries when compared to pharmacies. Comparison between the countries showed that hospital surfaces in SK are generally more contaminated (e.g., CP median was 20 times higher in SK), while some pharmacy areas in the CZ were more contamined in comparison with SK. The newly studied ADs were detected at lower concentrations in comparison to FU, CP, and Pt, but some markers (GEM, IF, PX, and IRI) were frequently observed, and adding these compounds to routine monitoring is recommended.

Faculty of Pharmacy Masaryk University Palackeho 1946 1 61200 Brno Czech Republic

Faculty of Science Masaryk University RECETOX Kamenice 753 5 Building D29 62500 Brno Czech Republic

Masaryk Memorial Cancer Institute Žlutý kopec 7 65653 Brno Czech Republic

University Hospital Brno Jihlavská 20 62500 Brno Czech Republic

Environ Sci Pollut Res Int. 2022 Apr;29(18):26820. doi: 10.1007/s11356-022-19548-6. PubMed

Zobrazit více v PubMed

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. https://doi.org/10.1093/annhyg/mei029 DOI

Adade CA, Diop BB, Attjioui H, Cheikh A, Mefetah H, Bouatia M (2021) Anticancer drug waste minimization and cost-saving study by using a closed-system transfer device for chemotherapy compounding. J Oncol Pharm Pract: 107815522110085. https://doi.org/10.1177/10781552211008527

Blahova L, Dolezalova L, Kuta J, Kozáková Š, Bláha L (2020) Hospitals and pharmacies as sources of contamination by cytostatic pharmaceuticals: long-term monitoring in the Czech Republic. In: Heath E, Isidori M, Kosjek T, Filipič M (eds) Fate and Effects of Anticancer Drugs in the Environment. Springer Nature Switzerland AG, pp 57–70. https://link.springer.com/chapter/10.1007/978-3-030-21048-9_3

Chabut C, Tanguay C, Gagné S, Caron N, Bussières JF (2021) Surface contamination with nine antineoplastic drugs in 109 canadian centers; 10 years of a monitoring program. J Oncol Pharm Pract. https://doi.org/10.1177/1078155221992103 DOI

Connor TH, Zock MD, Snow AH (2016) Surface wipe sampling for antineoplastic (chemotherapy) and other hazardous drug residue in healthcare settings: methodology and recommendations. J Occup Environ Hyg 13:658–667. https://doi.org/10.1080/15459624.2016.1165912 DOI

Colombo M, Jeronimo M, Astrakianakis G, Apte C, Hon CY (2017) Wipe sampling method and evaluation of environmental variables for assessing surface contamination of 10 antineoplastic drugs by liquid chromatography/tandem mass spectrometry. Ann Work Expo Heal 61:1003–1014. https://doi.org/10.1093/annweh/ DOI

Decree 84/2008 Coll (2008) Vyhlaska o spravne lekarenske praxi, blizsích podminkach zachazeni s lecivy v lekarnach, zdravotnickych zarizenich a u dalsich provozovatelu a zarizeni vydavajicich lecive pripravky. Vyhlaska c. 84/2008 Sb. [in Czech] [Good pharmaceutical practice and drugs handling conditions for pharmacies, healthcare facilities and other entities emitting pharmaceutical products to final consumers; Decree 84/2008 Coll.]

Decree 129/2012 Coll (2012) Vyhlaska Ministerstva zdravotnictva Slovenskej republiky o poziadavkach na spravnu lekarensku prax. Vyhlaska c. 129/2012 Z. z. [in Slovak] [Requirements on good pharmaceutical practice; Decree 129/2012 Coll.]

Heath E, Filipič M, Kosjek T, Isidori M (2016) Fate and effects of the residues of anticancer drugs in the environment. Environ Sci Pollut Res 23:14687–14691. https://doi.org/10.1007/s11356-016-7069-3 DOI

Ensslin A S, Pethran A, Schierl R, Fruhmann G (1994) Urinary platinum in hospital personnel occupationally exposed to platinum-containing antineoplastic drugs. Int Arch Occup Environ Health 65(5): 339–42. https://doi.org/10.1007/BF00405699

Fabrizi G, Fioretti M, Mainero Rocca L (2016) Dispersive solid-phase extraction procedure coupled to UPLC-ESI-MS/MS analysis for the simultaneous determination of thirteen cytotoxic drugs in human urine. Biomed Chromatogr 30:1297–1308. https://doi.org/10.1002/bmc.3684 DOI

Fleury-Souverain S, Mattiuzzo M, Mehl F, Nussbaumer S, Bouchoud L, Falaschi L, Gex-Fabry M, Rudaz S, Sadeghipour F, Bonnabry P (2015) Evaluation of chemical contamination of surfaces during the preparation of chemotherapies in 24 hospital pharmacies. Eur J Hosp Pharm 22:333–341. https://doi.org/10.1136/ejhpharm-2014-000549 DOI

Fransman W, Huizer D, Tuerk J, Kromhout H (2007a) Inhalation and dermal exposure to eight antineoplastic drugs in an industrial laundry facility. Int Arch Occup Environ Health 80:396–403. https://doi.org/10.1007/s00420-006-0148-x DOI

Fransman W, Roeleveld N, Peelen S, De Kort W, Kromhout H, Heederik D (2007b) Nurses with dermal exposure to antineoplastic drugs: reproductive outcomes. Epidemiology 18:112–119. https://doi.org/10.1097/01.ede.0000246827.44093.c1 DOI

Hedmer M, Wohlfart G (2012) Hygienic guidance values for wipe sampling of antineoplastic drugs in Swedish hospitals. J Environ Monit 14:1968–1975. https://doi.org/10.1039/c2em10704j DOI

Hon CY, Abusitta D (2016) Causes of health care workers’ exposure to antineoplastic drugs: an exploratory study. Can J Hosp Pharm 69:216–223. https://doi.org/10.4212/cjhp.v69i3.1558 DOI

Jeronimo M, Colombo M, Astrakianakis G, Hon CY (2015) A surface wipe sampling and LC-MS/MS method for the simultaneous detection of six antineoplastic drugs commonly handled by healthcare workers. Anal Bioanal Chem 407:7083–7092. https://doi.org/10.1007/s00216-015-8868-y DOI

Kiffmeyer TK, Tuerk J, Hahn M, Stuetzer H, Hadtstein C, Heinemann A, Eickmann U (2013) Application and assessment of a regular environmental monitoring of the antineoplastic drug contamination level in pharmacies-the MEWIP project. Ann Occup Hyg 57:444–455. https://doi.org/10.1093/annhyg/mes081 DOI

Kopp B (2012) Untersuchung der Arbeitsweise, Sicherheitsstandards und mgebungskontaminationen bei der Verabreichung von Zytostatika in onkologischen Praxen und Tageskliniken. Dissertationsschrift (Institut und Poliklinik für Arbeits-, Sozial- und Umweltmedizin der Ludwig-Maximilians-Universität). München 2012

Kopp B, Schierl R, Nowak D (2013) Evaluation of working practices and surface contamination with antineoplastic drugs in outpatient oncology health care settings. Int Arch Occup Environ Health 86:47–55. https://doi.org/10.1007/s00420-012-0742-z DOI

Kromhout H, Hoek F, Uitterhoeve R, Huijbers R, Overmars RF, Anzion R, Vermeulen R (2000) Erratum: postulating a dermal pathway for exposure to anti-neoplastic drugs among hospital workers. Applying a conceptual model to the results of three workplace surveys (Annals of Occupational Hygiene (2000) 44 (551–560) PII: S003487800000508). Ann Occup Hyg 44:551–560 DOI

Kümmerer K, Haiß A, Schuster A, Hein A, Ebert I (2016) Antineoplastic compounds in the environment—substances of special concern. Environ Sci Pollut Res 23:14791–14804. https://doi.org/10.1007/s11356-014-3902-8 DOI

Lancharro PM, De Castro-Acuna Iglesias N, Gonzalez-Barcala FJ, Gonzalez JDM (2016) Evidence of exposure to cytostatic drugs in healthcare staff: a review of recent literature. Farm Hosp 40(6):604–621. https://doi.org/10.7399/fh.2016.40.6.9103 DOI

Meijster T, Fransman W, Veldhof R, Kromhout H (2006) Exposure to antineoplastic drugs outside the hospital environment. Ann Occup Hyg 50:657–664. https://doi.org/10.1093/annhyg/mel023 DOI

Nassour C, Barton SJ, Nabhani-Gebara S, Saab Y, Barker J (2020) Occurrence of anticancer drugs in the aquatic environment: a systematic review. Environ Sci Pollut Res 27:1339–1347. https://doi.org/10.1007/s11356-019-07045-2 DOI

NIOSH (n.d) Preventing occupational exposure to antineoplastic and other hazardous drugs in health care settings [citado 15–04- 2015]. http://www.cdc.gov/niosh/docs/2004-165/ . NIOSH Alert, Cincinnati

Nussbaumer S, Geiser L, Sadeghipour F, Hochstrasser D, Bonnabry P, Veuthey JL, Fleury-Souverain S (2012) Wipe sampling procedure coupled to LC-MS/MS analysis for the simultaneous determination of 10 cytotoxic drugs on different surfaces. Anal Bioanal Chem 402:2499–2509. https://doi.org/10.1007/s00216-011-5157-2 DOI

Odraska P, Dolezalova L, Kuta J, Oravec M, Piler P, Blaha L (2013) Evaluation of the efficacy of additional measures introduced for the protection of healthcare personnel handling antineoplastic drugs. Ann Occup Hyg 57:240–250. https://doi.org/10.1093/annhyg/mes057 DOI

Odraska P, Dolezalova L, Piler P, Oravec M, Blaha L (2011) Utilization of the solid sorbent media in monitoring of airborne cyclophosphamide concentrations and the implications for occupational hygiene. J Environ Monit 13:1480–1487. https://doi.org/10.1039/c0em00660b DOI

Odraska P, Dolezalova L, Kuta J, Oravec M, Piler P, Synek S, Blaha L (2014) Association of surface contamination by antineoplastic drugs with different working conditions in hospital pharmacies association of surface contamination by antineoplastic drugs with different working conditions in hospital pharmacies. Arch Environ Occup Health 693:148–158. https://doi.org/10.1080/19338244.2013.763757 DOI

Ozakin GY, Ciftci AH, Sanci K (2019) Evaluation of a safe handling and cytotoxic drug preparation training program for oncology pharmacy practitioners. J Oncol Pharm Pract 25:1979–1986. https://doi.org/10.1177/1078155219853612 DOI

Palamini M, Gagné S, Caron N, Bussières JF (2020) Cross-sectional evaluation of surface contamination with 9 antineoplastic drugs in 93 Canadian healthcare centers: 2019 results. J Oncol Pharm Pract 26:1921–1930. https://doi.org/10.1177/1078155220907125 DOI

Roland C, Caron N, Bussières JF (2017) Multicenter study of environmental contamination with cyclophosphamide, ifosfamide, and methotrexate in 66 canadian hospitals: a 2016 follow-up study. J Occup Environ Hyg 14:650–658. https://doi.org/10.1080/15459624.2017.1316389 DOI

Schierl R, Böhlandt A, Nowak D (2009) Guidance values for surface monitoring of antineoplastic drugs in German pharmacies. Ann Occup Hyg 53:703–711. https://doi.org/10.1093/annhyg/mep050 DOI

Schierl R, Fries HG, Van De Weyer C, Fruhmann G (1998) Urinary excretion of platinum from platinum industry workers. Occup Environ Med 55:138–140. https://doi.org/10.1136/oem.55.2.138 DOI

Segner V, Kimbel R, Jochems P, Heinemann A, Letzel S, Wollschläger D, Roßbach B (2017) Liquid release as a source of potential drug exposure during the handling of intravenous infusions in nursing. Int Arch Occup Environ Health 90:275–284. https://doi.org/10.1007/s00420-017-1196-0 DOI

Sessink PJ, Van de Kerkhof MC, Anzion RB, Noordhoek J, Bos RP (1994) Environmental contamination and assessment of exposure to antineoplastic agents by determination of cyclophosphamide in urine of exposed pharmacy technicians: is skin absorption an important exposure route? Arch Environ Health 49:165–169. https://doi.org/10.1080/00039896.1994.9940377 DOI

Sessink PJM, Connor TH, Jorgenson J, Tyler TG (2011) Reduction in surface contamination with antineoplastic drugs in 22 hospital pharmacies in the US following implementation of a closed-system drug transfer device. J Oncol Pharm Pract 17:39–48. https://doi.org/10.1177/1078155210361431 DOI

Siderov J, Kirsa S, McKauchlan R (2010) Reducing workplace cytotoxic surface contamination using a closed-system drug transfer device. J Oncol Pharm Pract 16:19–25. https://doi.org/10.1177/1078155209352543 DOI

Sottani C, Grignani E, Oddone E, Dezza B, Negri S, Villani S, Cottica D (2017) Monitoring surface contamination by antineoplastic drugs in Italian hospitals: performance-based hygienic guidance values (HGVs) Project. Ann Work Expo Heal 61:1–9. https://doi.org/10.1093/annweh/wxx065 DOI

Yoshida J, Koda S, Nishida S, Nakano H, Tei G, Kumagai S (2013) Association between occupational exposure and control measures for antineoplastic drugs in a pharmacy of a hospital. Ann Occup Hyg 57:251–260. https://doi.org/10.1093/annhyg/mes061 DOI

Proposals of guidance values for surface contamination by antineoplastic drugs based on long term monitoring in Czech and Slovak hospitals and pharmacies