Monitoring surface contamination for thirty antineoplastic drugs: a new proposal for surface exposure levels (SELs)

Abstract

Background: Chemotherapy drugs are widely used to treat cancer, but their active compounds represent a danger for workers who could be exposed to them. However, they aren't yet included in directive CE No. 1272/2008 and the European Biosafety Network has only recommended a limit value of 100 pg/cm 2 for surface contamination. Thus, it is crucial to assess surface contaminations in healthcare environments. Currently, the technique of choice is surface wipe test combined with liquid chromatography tandem mass spectrometry to achieve high sensibility. Material and Methods: A campaign involving Careggi University Hospital (Florence, Italy) was performed from January 2020 to December 2021, collecting 1449 wipe samples between administration units, preparation unit, and personnel gloves. From the obtained data, the 90th percentile was calculated for 30 antiblastic drugs and proposed as surface exposure levels (SELs); while from data concerning personnel glove contamination, weekly contamination was estimated. Results: In the 2-year period only 417 wipe samples were found positive (28.8%), the majority of which regard samples coming from administration unit bathrooms. The proposed SELs are almost all <100 pg/cm 2 , except for few drugs which produce higher contamination on bathroom surfaces. Also, the estimation of pharmacy personnel's glove contamination highlighted very low results (ng/week). Conclusions: Deeply established protocols and procedures for safe handling of ADs allow for obtaining excellent cleaning results and thus a safer work environment, however, the risk of cytostatic contaminations cannot be avoided in healthcare workplaces, and thus a harmonization of classification and labeling of chemotherapy drugs throughout the European Union should be done. Med Pr. 2022;73(5)

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

“…Similar observations of higher floor contamination with 75th percentiles exceeding the 100 pg/cm 2 threshold were also reported by other authors such as Hedmer et al ( 37 ) for CP and IF contamination in Sweden or Labrèche et al ( 38 ) for FU in Canada. Similar conclusions were recently published by Dugheri et al ( 45 ) who observed higher floor contamination (compared to desktops), and suggested the new surface exposure level of 100 pg/cm 2 (with the exception of bathrooms).…”

Evaluation of the risk of occupational exposure to antineoplastic drugs in healthcare sector: part I – medical gloves

“…In this respect, we would also like to point out another important factor which contributes to glove permeation. Literature data show that 5-fluorouracil, cyclophosphamide, iphosphamide, and gemcitabine, which are used in greater quantities ( 56 , 57 ), have low molecular weight (MW) (130, 261, 261, and 263 Da, respectively), and which, according to Oriyama et al ( 39 ), increases the glove permeation rate. Besides low molecular weight, these and other authors point to a possible influence of other chemico-physical properties, such as high drug lipophilia (high logarithm of octanol-water partition coefficient, Log P) ( 39 ), which is still controversial ( 58 ), topological polar surface area, and hydrogen bond donor capacity( 59 ).…”

“…5-FU -5-fluorouracil; BSF -busulfan; CP -cyclophosphamide; CarboPt -carboplatin; CisPt -cisplatin; OxaliPt -oxaliplatin; CTB -cytarabine; DC -dacarbazine; DNR -daunorubicin; DTX -docetaxel; DXR -doxorubicin; EPIepirubicin; ETP -etoposide; GEM -gemcitabine; FTM -fotemustine; IDC -idarubicine; IP -iphosfamide; IRT -irinotecan; MP -melphalan; MT -methotrexate; MITC -mitomycin C; PTX -paclitaxel; PMX -pemetrexed; TMX -tamoxifen; RTX -raltitrexed; TPT -topotecan; VNB -vinblastine; VNC -vincristine; VND -vindesine; VNR -vinorelbine In this respect, we would also like to point out another important factor which contributes to glove permeation. Literature data show that 5-fluorouracil, cyclophosphamide, iphosphamide, and gemcitabine, which are used in greater quantities (56,57), have low molecular weight (MW) (130, 261, 261, and 263 Da, respectively), and which, according to Oriyama et al (39), increases the glove permeation rate. Besides low molecular weight, these and other authors point to a possible influence of other chemico-physical properties, such as high drug lipophilia (high logarithm of octanolwater partition coefficient, Log P) (39), which is still controversial (58), topological polar surface area, and hydrogen bond donor capacity (59).…”

An Automated Micro Solid-Phase Extraction (μSPE) Liquid Chromatography-Mass Spectrometry Method for Cyclophosphamide and Iphosphamide: Biological Monitoring in Antineoplastic Drug (AD) Occupational Exposure

“…Both Directive 2022/431/EU and the resulting guidelines, "Guidance for the safe management of hazardous medicinal products at work" [9], published in 2023, encourage the development of monitoring methods and biological surveillance for exposed health professionals. While surface contamination sampling remains an important tool to detect incorrect working procedures and increase the awareness of hospital workers [10][11][12][13][14], biological monitoring is still the only way to truly assess occupational exposure and identify possible pathological correlations. Nowadays, ADs can still often be found in the biological fluids of exposed healthcare personnel [15].…”