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

Introduction: The exposures to hazardous antineoplastic drugs (AD) represent serious risks for health care personnel but the exposure limits are not commonly established because of the no-threshold effects (genotoxic action, carcinogenicity) of many ADs. In this study, we discussed and derived practically applicable technical guidance values (TGV) suitable for management of AD risks. Methods: The long-term monitoring of surface contamination by eight ADs was performed in pharmacies and hospitals in the Czech Republic and Slovak Republic in 2008-2021; in total 2,223 unique samples were collected repeatedly in 48 facilities. AD contamination was studied by LC-MS/MS for cyclophosphamide, ifosfamide, methotrexate, irinotecan, paclitaxel, 5-fluorouracil and gemcitabine and by ICP-MS for total Pt as a marker of platinum-based ADs. Results: The study highlighted importance of exposure biomarkers like 5-fluorouracil and especially carcinogenic and persistent cyclophosphamide, which should be by default included in monitoring along with other ADs. Highly contaminated spots like interiors of laminar biological safety cabinets represent a specific issue, where monitoring of contamination does not bring much added value, and prevention of staff and separated cleaning procedures should be priority. Rooms and surfaces in health care facilities that should be virtually free of ADs (e.g., offices, kitchenettes, daily rooms) were contaminated with lower frequency and concentrations but any contamination in these areas should be carefully examined. Discussion and conclusions: For all other working places, i.e., majority of areas in pharmacies and hospitals, where ADs are being prepared, packaged, stored, transported, or administered to patients, the study proposes a generic TGV of 100 pg/cm2. The analysis of long-term monitoring data of multiple ADs showed that the exceedance of one TGV can serve as an indicator and trigger for improvement of working practices contributing thus to minimizing of unintended exposures and creating a safe work environment.

Levels and risks of surface contamination by thirteen antineoplastic drugs in the Czech and Slovak hospitals and pharmacies.

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.