Phd in ADVANCES IN INFECTIOUS DISEASES, MICROBIOLOGY, LEGAL
MEDICINE AND PUBLIC HEALTH SCIENCES

Thesis title: Occupational exposure to Antineoplastic Drugs and Formaldehyde in healthcare settings: sensitive biomarkers to assess health risks.

Introduction. In healthcare settings, several professional groups are potentially exposed to hazardous compounds used for therapeutic and preservation purposes, such as antineoplastic drugs (ADs) and formaldehyde (FA), recognized for their carcinogenic, mutagenic, and cyto-genotoxic properties. This research aimed to investigate early biological effects associated with: a) exposure to ADs among workers handling them during preparation, administration, and disposal; b) exposure to FA among anatomical pathology laboratory workers. The research adopts a combined approach that integrates environmental and personal contamination assessment with biomonitoring of exposed workers with the final aim to identify suitable early biomarkers on large size worker populations useful to assess effects of carcinogenic chemicals exposure in healthcare settings. Methods. Biological monitoring was performed using the non-invasive Buccal Micronucleus Cytome (BMCyt) assay to evaluate cyto-genotoxic effects in exfoliated cells of oral mucosa, and the very sensitive Fpg-Comet assay to estimate direct/oxidative DNA damage in whole blood samples. We enrolled: a) 214 exposed workers and 164 controls from seven oncological Units; b) 55 exposed workers from anatomical pathology laboratory of four hospitals and 54 controls. Environmental and personal monitoring for ADs was conducted using wipe and pad sampling techniques on a panel of five drugs analysed by UHPLC-MS/MS and ICP-MS. To evaluate airborne FA concentrations in different work areas, both active and passive sampling techniques were performed, and FA was analysed by LC-MS/MS (active sampling) and HPLC-UV (passive sampling). Results. We found drugs contamination in all the tested workplaces. Workers exposed to ADs showed higher frequency of cells with Micronuclei and increased levels of direct and oxidative DNA damage compared with controls. A weak but statistically significant correlation was found between the two biomarkers, supporting their combined use in the assessment of effects induced by AD exposure. Airborne FA concentrations showed variability among hospitals and job tasks, suggesting heterogeneous exposure scenarios, although most measurement were below European occupational exposure limit (0.37 mg/m3). The BMCyt assay did not show significant differences between workers exposed to FA and controls; however, the Fpg-comet assay results demonstrated induction of single and double DNA strand breaks, indicating direct slight DNA damage in workers exposed to FA. Discussion. This study demonstrates that both early biomarkers of effect used are suitable for the biomonitoring of workers handling ADs, due to their high sensitivity. In contrast, for FA exposure and related effects, the results highlight the need for further studies on a larger population and the use of different biological matrices to confirm the obtained results. This research also provides valuable information for the validation of BMCyt assay and fpg-comet assay as biomarkers of effect. Overall, this study contributes to the growing body of evidence highlighting that continuous exposure assessment, refinement of safety procedures, and extension of biomonitoring protocols are key steps in ensuring the protection of healthcare workers regularly exposed to hazardous substances.