Biomonitoring of workers employed in a titanium dioxide production plant: Use of buccal micronucleus cytome assay as noninvasive biomarker to evaluate genotoxic and cytotoxic effects.

Abstract

We aimed to evaluate whether TiO2 production process induces genotoxic and cytotoxic effects on the first target organ of inhalable particles by a sensitive and noninvasive biomarker of effect. Final aim was to find a useful and suitable tool to assess and manage the risk of TiO2 occupational exposure. We enrolled 40 workers employed in TiO2 production, 5 office workers, and 18 external controls. Buccal micronucleus cytome assay (BMCyt assay) was applied because it allows to evaluate micronucleus (MN), nuclear buds (NB), and broken eggs (BE) indicating the presence of chromosomal instability and gene amplification and binucleated cells (BIN), karyolytic cells (KL), and condensed chromatin (CC) indicating cytokinesis defect or arrest, cell death and apoptosis respectively. We characterized the exposure measuring inhalable and respirable particles by personal monitoring. BMCyt-assay showed in exposed workers compared with external controls a higher value of MN frequency (2.57 vs. 0.05‰, p < .001) and MN positivity, evaluated as percentage of subjects with MN frequency higher than a 1.5‰ cut-off value (52.5 vs. 0%). We also found in exposed workers higher frequency of BE + NB (2.41 vs. 0.22‰, p = .002), BIN (9.45 vs. 8.44‰, p = .047) and CC (1.80 vs. 0.21, p = .001) than in controls. Moreover, we found a relationship between personal monitoring results and presence of MN and other cellular anomalies. This study demonstrates induction of genotoxic and cytotoxic effects on buccal cells of workers involved in TiO2 production, suggesting the suitability of BMCyt assay as tool for risk assessment and management of TiO2 exposure.