OBJECTIVE: Antineoplastic drugs (ADs) pose risks to healthcare staff. Surface disinfectants are used in hospitals to prevent microbial contamination but the efficiency of disinfectants to degrade ADs is not known. We studied nine disinfectants on ten ADs in the standardized laboratory and realistic in situ hospital conditions. METHODS: A survey in 43 hospitals prioritized nine most commonly used disinfections based on different ingredients. These were tested on inert stainless steel and in situ on contaminated hospital flooring. The effects against ten ADs were studied by LC-MS/MS (Cyclophosphamide CP; Ifosfamide IF; Capecitabine CAP; Sunitinib SUN; Methotrexate MET; Doxorubicin DOX; Irinotecan IRI; Paclitaxel PX; 5-Fluorouracil FU) and ICP-MS (Pt as a marker of platinum-based ADs). RESULTS: Monitoring of the floor contamination in 26 hospitals showed that the most contaminated are the outpatient clinics that suffer from a large turnover of staff and patients and have limited preventive measures. The most frequent ADs were Pt, PX, FU and CP with maxima exceeding the recommended 1 ng/cm2 limit by up to 140 times. IRI, FU, MET, DOX and SUN were efficiently removed by hydrolysis in clean water and present thus lower occupational risk. Disinfectants based on hydrogen peroxide were efficient against PX and FU (> 70% degradation) but less against other ADs, such as carcinogenic CP or IF, IRI and CAP. The most efficient were the active chlorine and peracetic acid-based products, which however release irritating toxic vapors. The innovative in situ testing of ADs previously accumulated in hospital flooring showed highly problematic removal of carcinogenic CP and showed that alcohol-based disinfectants may mobilize persistent ADs contamination from deeper floor layers. CONCLUSION: Agents based on hydrogen peroxide, peracetic acid, quaternary ammonium salts, glutaraldehyde, glucoprotamine or detergents can be recommended for daily use for both disinfection and AD decontamination. However, they have variable efficiencies and should be supplemented by periodic use of strong chlorine-based disinfectants efficient also against the carcinogenic and persistent CP.

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

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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

Adé A, Chauchat L, Frève JFO, Gagné S, Caron N, Bussières JF (2017) Comparison of decontamination efficacy of cleaning solutions on a biological safety cabinet workbench contaminated by cyclophosphamide. Can J Hosp Pharm 70:407–414. https://doi.org/10.4212/cjhp.v70i6.1708 DOI

ASHP Guidelines on Handling Hazardous Drugs (2006) American J Health-System Pharmacy 63(12):1172–1191. https://doi.org/10.2146/ajhp050529 DOI

Benvenuto JA, Connor TH, Monteith DK, Laidlaw J, Adams SC, Matney TS, Theiss JC (1993) Degradation and inactivation of antitumor drugs. J Pharm Sci 82(10):988–991 DOI

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://doi.org/ https://doi.org/10.1007/978-3-030-21048-9

Bobin-Dubigeon C, Amiand M, Percheron C, Audeval C, Rochard S, Leynia P, Bard JM (2013) A new, validated wipe-sampling procedure coupled to lc-ms analysis for the simultaneous determination of 5-fluorouracil, doxorubicin and cyclophosphamide in surface contamination. J Anal Toxicol 37:433–439. https://doi.org/10.1093/jat/bkt045 DOI

Böhlandt A, Sverdel Y, Schierl R (2017) Antineoplastic drug residues inside homes of chemotherapy patients. Int J Hyg Environ Health 220:757–765. https://doi.org/10.1016/j.ijheh.2017.03.005 DOI

Castiglia L, Miraglia N, Pieri M, Simonelli A, Basilicata P, Genovese G, Guadagni R, Acampora A, Sannolo N, Scafarto MV (2008) Evaluation of occupational exposure to antiblastic drugs in an Italian Hospital Oncological Department. J Occup Health 50:48–56. https://doi.org/10.1539/joh.50.48 DOI

Chauchat L, Tanguay C, Caron N, Gagné S, Labrèche F, Bussières J (2019) Surface contamination with ten antineoplastic drugs in 83 Canadian centers. J Oncol Pharm Pract 25:1089–1098. https://doi.org/10.1177/1078155218773862 DOI

Cherrie JW, Hutchings S, Gorman Ng M, Mistry R, Corden C, Lamb J, Sánchez Jiménez A, Shafrir A, Sobey M, Van Tongeren M, Rushton L (2017) Prioritising action on occupational carcinogens in Europe: A socioeconomic and health impact assessment. Br J Cancer 117:274–281. https://doi.org/10.1038/bjc.2017.161 DOI

Connor TH, Anderson RW, Sessink PJ, Spivey SM (2002) Effectiveness of a closed-system device in containing surface contamination with cyclophosphamide and ifosfamide in an i.v. admixture area. Am J Heal Pharm 59:68–72. https://doi.org/10.1093/ajhp/59.1.68 DOI

Connor TH, McDiarmid MA (2006) Preventing occupational exposures to antineoplastic drugs in health care settings. CA Cancer J Clin 56:354–365. https://doi.org/10.3322/canjclin.56.6.354 DOI

Cox J, Speed V, O’Neal S, Hasselwander T, Sherwood C, Eckel SF, Zamboni WC (2017) Development and evaluation of a novel product to remove surface contamination of hazardous drugs. J Oncol Pharm Pract 23:103–115. https://doi.org/10.1177/1078155215621151 DOI

Crul M, Simons-Sanders K (2018) Carry-over of antineoplastic drug contamination in Dutch hospital pharmacies. J Oncol Pharm Pract 24:483–489. https://doi.org/10.1177/1078155217704990 DOI

Dekyndt B, Décaudin B, Lannoy D, Odou P (2014) Economic assessment of aseptic compounding rooms in hospital pharmacies in five European countries. J Oncol Pharm Pract 21:102–110. https://doi.org/10.1177/1078155214520820 DOI

Dranitsaris G, Johnston M, Poirier S, Schueller TT, Savage T, Milliken DD, Green E, Evans W, 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 Clin Oncol Off J Am Soc Clin Oncol 23:548S-548S DOI

European Commission (2019) Proposal for a DIRECTIVE OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL amending Directive 2004/37/EC on the protection of workers from the risks related to exposure to carcinogens or mutagens at work [COM (2018)171]

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

Gabay M (2014) USP General Chapter <800>: handling hazardous drugs. Hosp Pharm 49:811–812 DOI

Gohma H, Inoue Y, Asano M, Sugiura SI (2015) Testing the degradation effects of three reagents on various antineoplastic compounds. J Oncol Pharm Pract 21:268–273. https://doi.org/10.1177/1078155214530175 DOI

Hansel S, Castegnaro M, Sportouch MH, De Meo M, Milhavet JC, Laget M, Dumenil G (1997) Chemical degradation of wastes of antineoplastic agents: cyclophosphamide, ifosphamide and mel- phalan. Int Arch Occup Environ Health 69:109–114 DOI

Hon C-Y, Barzan C, Astrakianakis G (2014a) Identification of knowledge gaps regarding healthcare workers exposure to antineoplastic drug: review of literature, North America versus Europe. Saf Heal Work 5:169–174 DOI

Hon C-Y, Chua PPS, Danyluk Q, Astrakianakis G (2014b) Examining factors that influence the effectiveness of cleaning antineoplastic drugs from drug preparation surfaces: A pilot study. J Oncol Pharm Pract 20:210–216. https://doi.org/10.1177/1078155213497070 DOI

IARC: International Agency for Research on Cancer. IARC Monographs on the evaluation of carcinogenic risks to humans – Volume 100A Pharmaceuticals, https://mono-graphs.iarc.fr/wp-content/uploads/2018/06/mono100A.pdf (accessed 2 February 2019).

ISOP: International Society of Oncology Pharmacy Practicioners Standards Committee. ISOPP standards of practice. Safe handling of cytotoxics. J Oncol Pharm Pract. 2007;13 Suppl:1‐81. doi: https://doi.org/10.1177/1078155207082350

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, 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) 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

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 40:604–621. https://doi.org/10.7399/fh.2016.40.6.9103 DOI

Lê LMM, Jolivot PA, Yaye HS, Rieutord A, Bellanger A, Pradeau D, Barbault-Foucher S, Caudron E (2013) Effectiveness of cleaning of workplace cytotoxic surface. Int Arch Occup Environ Health 86:333–341. https://doi.org/10.1007/s00420-012-0769-1 DOI

Lee SG, Ambados F, Tkaczuk M, Jankewicz G (2009) Paclitaxel exposure and its effective decontamination. J Pharm Pract Res 39:181–185. https://doi.org/10.1002/j.2055-2335.2009.tb00449.x DOI

Maeda S, Miwa Y (2013) Multicomponent high-performance liquid chromatography/tandem mass spectrometry analysis of ten chemotherapeutic drugs in wipe samples. J. Chromatogr B Anal Technol Biomed Life Sci 921–922:43–48. https://doi.org/10.1016/j.jchromb.2013.01.014 DOI

NIOSH, n.d. Preventing Occupational Exposure to Antineoplastic and Other Hazardous Drugs in Health Care Settings [citado 15–04- 2015]. Disponible en: 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

Power LA, Coyne JW, Hawkins B (2018) ASHP guidelines on handling hazardous drugs. Am J Heal Pharm 75:1996–2031. https://doi.org/10.2146/ajhp050529 DOI

Queruau Lamerie T, Nussbaumer S, Décaudin B, Fleury-Souverain S, Goossens JF, Bonnabry P, Odou P (2013) Evaluation of decontamination efficacy of cleaning solutions on stainless steel and glass surfaces contaminated by 10 antineoplastic agents. Ann Occup Hyg 57:456–469. https://doi.org/10.1093/annhyg/mes087 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

Simon N, Odou P, Decaudin B, Bonnabry P, Fleury-Souverain S (2019) Efficiency of degradation or desorption methods in antineoplastic drug decontamination: A critical review. J Oncol Pharm Pract 25:929–946. https://doi.org/10.1177/1078155219831427 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

Soubieux A, Palamini M, Tanguay C, Bussières JF (2020) Evaluation of decontamination strategies for cyclophosphamide. J Oncol Pharm Pract 26:413–422. https://doi.org/10.1177/1078155219865931 DOI

Touzin K, Bussières JF, Langlois É, Lefebvre M, Métra A (2010) Pilot study comparing the efficacy of two cleaning techniques in reducing environmental contamination with cyclophosphamide. Ann Occup Hyg 54:351–359. https://doi.org/10.1093/annhyg/meq004 DOI

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 789:169–209 DOI

US Pharmacopeia, 2017. US Pharmacopeia USP 800. Hazardous drugs— Handling in healthcare settings.

Viegas S, De Oliveira AC, Carolino E, Pádua M (2018) Occupational exposure to cytotoxic drugs: The importance of surface cleaning to prevent or minimise exposure. Arh Hig Rada Toksikol 69:238–249. https://doi.org/10.2478/aiht-2018-69-3137 DOI

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