Mutagenicity assessment of environmental contaminations in a hospital centralized reconstitution unit

Source avec lien : Ecotoxicology and Environmental Safety, 165(15), 12/15/2018. 10.1016/j.ecoenv.2018.09.002

L’exposition aux médicaments cytotoxiques du personnel hospitalier préparant une chimiothérapie par voie intraveineuse est un problème majeur et les risques mutagènes associés devraient être davantage explorés. Le but de cette étude était d’évaluer la mutagénicité de plusieurs mélanges cytotoxiques préparés à des concentrations fixes, ainsi que la mutagénicité d’échantillons environnementaux prélevés dans une unité de reconstitution centralisée hospitalière. Parallèlement, l’exposition cytotoxique dans des échantillons environnementaux a été quantifiée.

Abstract

Introduction

Cytotoxic drug exposure of hospital staff preparing intravenous chemotherapy is a major issue and related mutagenic risks should be more explored. The aim of this study was to assess the mutagenicity of several cytotoxic mixtures prepared at fixed concentrations, and the mutagenicity of environmental samples collected in a hospital centralized reconstitution unit. In parallel cytotoxic exposure in environmental samples was quantified.

Methods

Environmental samples were performed by wiping method using swabs in five critical production unit areas. Mutagenicity was assessed with a liquid microplate AMES test using two salmonella typhimurium strains (TA98 and TA100), in prepared cytotoxic mixtures containing 14 cytotoxic drugs (cyclophosphamide, cytarabine, dacarbazine, docetaxel, doxorubicin, epirubicin, etoposide, 5-fluorouracil, gemcitabine, ifosfamide, irinotecan, methotrexate, paclitaxel and pemetrexed) according a dichotomous strategy and in environmental samples. Cytotoxic drugs were quantified in samples using liquid chromatography coupled to mass tandem spectrometry.

Results

Mutagenesis was observed for the mix of 14 cytotoxic drugs with TA98 strain ± S9 fraction but not TA100 strain. After dichotomous approach, only doxorubicin and epirubicin exposure were associated to mutagenesis. The mutagenesis observed was expressed at lower concentrations with the mix of the 14 drugs than with anthracyclins alone, assuming a synergistic effect. Despite measurable level of cytotoxic contamination in environmental samples, no mutagenesis was highlighted in Ames tests performed on these environmental samples.

Conclusions

The analyses carried out show the conservation of the mutagenicity of cytotoxic drugs found in very low quantities in the environment. The traces of cytotoxic drugs found in our unit regularly exceed the limits given by some authors. This approach may be considered as a new tool to monitor environmental contamination by cytotoxic drugs.

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