Characterization of the internal working-life exposome using minimally and non-invasive sampling methods - a narrative review.

During recent years, we are moving away from the 'one exposure, one disease'-approach in occupational settings and towards a more comprehensive approach, taking into account the totality of exposures during a life course by using an exposome approach. Taking an exposome approach however is accompanied by many challenges, one of which, for example, relates to the collection of biological samples. Methods used for sample collection in occupational exposome studies should ideally be minimally invasive, while at the same time sensitive, and enable meaningful repeated sampling in a large population and over a longer time period. This might be hampered in specific situations e.g., people working in remote areas, during pandemics or with flexible work hours. In these situations, using self-sampling techniques might offer a solution. Therefore, our aim was to identify existing self-sampling techniques and to evaluate the applicability of these techniques in an occupational exposome context by conducting a literature review. We here present an overview of current self-sampling methodologies used to characterize the internal exposome. In addition, the use of different biological matrices was evaluated and subdivided based on their level of invasiveness and applicability in an occupational exposome context. In conclusion, this review and the overview of self-sampling techniques presented herein can serve as a guide in the design of future (occupational) exposome studies while circumventing sample collection challenges associated with exposome studies.

Systematic review of genotoxicity induced by occupational exposure to antineoplastic drugs.

With increasing numbers of cancer cases, the use of antineoplastic agents is expected to rise. This will be accompanied by an increase in occupational exposure, which can cause unwanted health effects in workers. Our aim was to give an overview of genotoxic and epigenetic effects after occupational exposure to antineoplastic agents and to assess the concentration-effect relation. Four databases were searched for papers investigating genotoxic and/or epigenetic effects of occupational exposure to antineoplastic agents. Out of the 245 retrieved papers, 62 were included in this review. In this systematic literature review, we confirmed that exposure of healthcare workers to antineoplastic agents can lead to genotoxic damage. However, we observed a lack of data on exposure as well as genotoxic and epigenetic effects in workers other than healthcare workers. Furthermore, gaps in the current knowledge regarding the potential epigenetic effects caused by antineoplastic drug exposure and regarding the link between internal antineoplastic drug concentration and genotoxic and epigenetic effects after occupational exposure to antineoplastic agents were identified, offering a first step for future research.

Characterization of the genotoxic profile of antineoplastic drugs using the cytokinesis-block micronucleus cytome assay.

Since antineoplastic agents are frequently used in cancer therapy and able to affect the patient's DNA, it is important to know the genotoxic consequences on non-cancerous tissue. Therefore, we aimed to characterize the genotoxic profile of antineoplastic drugs belonging to different classes, using the cytokinesis-block micronucleus cytome assay in a human monocytic cell line (THP-1). All tested antineoplastic agents resulted in increased micronucleus formation. Exposure to anthracyclines led to an increased number of vacuolated cells and cell death, while for mitotic spindle inhibitors, (different stages of) cell death and an increased nuclear bud formation was observed. Alkylating agents induce a high proportion of vacuolated cells and increased nuclear bud formation. No striking differences of nuclear division index or nucleoplasmic bridge formation were observed between exposed and non-exposed cells. The here presented class-specific aberrations may facilitate interpretation of genotoxic aberrations when evaluating clinical samples from patients treated with these antineoplastic agents.

Quantification of three antineoplastic agents in urine using the UniSpray ionisation source.

BACKGROUND: Many guidelines and safety measures led to a decrease in exposure to antineoplastic agents. Since healthcare workers are often exposed to lower concentrations than patients, a sensitive method is needed to quantify occupational exposure. OBJECTIVE: The aim of this study was to develop and validate a sensitive method for simultaneous detection and quantification of cyclophosphamide, ifosfamide and paclitaxel in urine by use of UPLC-MS/MS with a UniSpray ionisation source. METHODS: Compounds were extracted from urine using Novum simplified liquid extraction cartridges, separated on a C18 column, ionised by a UniSpray ionisation source and detected with MS/MS. In the second part of the study, a field study was performed to assess occupational exposure to antineoplastic agents. RESULTS: Eighty-three samples from healthcare workers were analysed and resulted in seventeen samples containing quantifiable concentrations of at least one compound. In conclusion, a sensitive method for simultaneous detection and quantification of cyclophosphamide (LLOQ 0.05 ng/mL), ifosfamide (LLOQ 0.3 ng/mL) and paclitaxel (LLOQ 0.7 ng/mL) was developed and validated.

Environmental Contamination and Occupational Exposure of Algerian Hospital Workers.

Guidelines are in place to assure limited occupational exposure to cytostatic drugs. Even though this has led to a reduction in exposure, several studies reported quantifiable concentrations of these compounds in healthcare workers. In this study, we evaluated occupational exposure to cytostatic drugs in hospital workers from the University Hospital in Tlemcen, Algeria. Monitoring was performed by collecting wipe samples from surfaces, objects, personal protective equipment (gloves and masks) and from the skin of employees at an Algerian university hospital. Wipe samples were analyzed with ultra-performance liquid chromatography coupled to a mass spectrometer. Concentrations ranged from below the limit of quantification up to 208.85, 23.45, 10.49, and 22.22 ng/cm2 for cyclophosphamide, ifosfamide, methotrexate and 5-fluorouracil, respectively. The highest values were observed in the oncology department. Nowadays, there are still no safe threshold limit values for occupational exposure to cytostatic agents. Therefore, contamination levels should be kept as low as reasonably achievable. Yet, healthcare workers in this hospital are still exposed to cytostatic agents, despite the numerous guidelines, and recommendations. Consequently, actions should be taken to reduce the presence of harmful agents in the work environment.