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

Front Public Health. 2023 Sep 14:11:1235496. doi: 10.3389/fpubh.2023.1235496. eCollection 2023.

Abstract

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.

Keywords: antineoplastic drugs; hazardous drugs; monitoring; surface contamination; technical guidance values.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents*
  • Chromatography, Liquid
  • Cyclophosphamide / analysis
  • Czech Republic
  • Fluorouracil / analysis
  • Hospitals
  • Humans
  • Occupational Exposure* / analysis
  • Pharmacies*
  • Slovakia
  • Tandem Mass Spectrometry

Substances

  • Antineoplastic Agents
  • Cyclophosphamide
  • Fluorouracil

Grants and funding

The results of the project were created with the financial support of the provider Ministry of Health of the Czech Republic, within the project no. NV18–09–00188. Authors thank the RECETOX Research Infrastructure (No. LM2018121) financed by the Ministry of Education, Youth and Sports, and the Operational Programme Research, Development and Education (the CETOCOEN EXCELLENCE project no. CZ.02.1.01/0.0/0.0/17_043/0009632) for supportive background. This work was also supported from the European Union's Horizon 2020 research and innovation program under grant agreement no. 857560.