Evaluation of Systemic Genotoxic/Oxidative and Proinflammatory Effects in Workers of a Titanium Dioxide Production Plant.

This study is aimed at evaluating whether the occupational exposure to TiO2 during the industrial production process is able to induce genotoxic, oxidative, and inflammatory effects on blood, biomonitoring the same workers that showed micronucleus induction in the exfoliated buccal cells, as previous published. The final aim was to find sensitive and suitable biomarkers to evaluate potential early toxicity of occupational exposure to TiO2. On the same 40 workers involved in the manufacture of TiO2 pigment, 5 office workers, and 18 controls previously studied, we used formamidopyrimidine glycosylase- (Fpg-) comet assay on lymphocytes to evaluate genotoxic/oxidative effects and detected cytokine (IL-6, IL-8, and TNFα) release by ELISA to evaluate proinflammation. Moreover, we studied the possible influence of single nucleotide polymorphisms of XRCC1 and hOGG1 DNA repair genes and of GST metabolism-related genes (GSTT1 and GSTM1) on the evaluated effects. We did not find statistically significant differences in the mean values of the analysed Fpg-comet assay parameters; only the percentage of DNA damaged cells appearing in the test as comets (% comets) resulted higher in the exposed workers compared to controls. Also, the data analysed taking into account the specific task (bagging, industrial cleaning, mobile operations, maintaining, and production) showed differences only for % comets which resulted higher in industrial cleaners compared to controls. We found variations of IL-6 and IL-8 levels in the exposed workers with concentrations that were lower for IL-6 and higher for IL-8 compared to the control group. XRCC1, hOGG1, and GSTT1 polymorphisms did not influence neither comet parameters nor cytokine release. These findings demonstrate that TiO2 production process is able to induce slight proinflammatory effects in terms of IL-8 increased release but not significant genotoxic/oxidative effects on lymphocytes, which do not seem to be a target of TiO2, prevalently inhalable particles, generated in the studied production site.

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.

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.

Urinary Oxidative Stress Biomarkers in Workers of a Titanium Dioxide Based Pigment Production Plant.

Titanium dioxide is produced or imported into the EU for over one million tons/year. The International Agency for Research on Cancer (IARC) classification is 2B, a possible inhalation carcinogen for humans. This study evaluates urinary biomarkers of oxidative stress in workers of a plant producing TiO2 pigment powder, having 0.25 µm average particle size and an ultrafine fraction, compared to unexposed subjects. Urine samples were collected from forty workers before and after the shift, from six employees of the same company and eighteen volunteers from the same geographical area. Titanium and other metals concentrations were measured by ICP-MS, while DNA, RNA, and protein oxidation products by HPLC/MS-MS. A statistically significant increase was found for the urinary concentration of Al, Cd, Cr, Cu, Fe, Mn, Pb, Ti, and Zr, and for all biomarkers of oxidative stress in post-shift workers' urine samples. Urinary concentrations after the working shift were higher than for employees and volunteers pooled together for Cd, Mn, and Zr, and for the oxidative stress biomarkers 8-oxoGuo, 8-oxodGuo, and 3NO2Tyr. Biomonitoring studies on dose and effect biomarkers for TiO2 occupational exposure provide information useful for protecting workers' health even in conditions that comply with health and safety standards, highlighting reversible effects of chronic exposure at very low doses.

Characterization and distribution of petroleum hydrocarbons and heavy metals in groundwater from three Italian tank farms.

The present paper highlights the utility of petroleum chemical fingerprinting in investigating known or suspected tank farm releases. A detailed characterization of groundwater was carried out in three tank farms located in north, central and south Italy. Eighteen parent polycyclic aromatic hydrocarbons (naphthalene through coronene), n-alkanes (n-C(10) through n-C(36)), isoprenoids pristane and phytane, vanadium, nickel and lead were determined. Distribution profiles and diagnostic ratios of specific fuel constituents were studied in order to identify contamination sources. Data analysis shows that in the study sites multiple pollutant sources affecting the tank farms and the surrounding industrial areas are present. Both high concentrations of contaminants coming from fuel releases and noticeable concentrations of biogenic compounds were found. A detailed data analysis suggests the origin and the level of pollution of the three sites. The results demonstrate that threshold concentration approach is not always sufficient and it is necessary to carry out studies of contaminant distribution and their diagnostic ratios in order to perform a successful forensic investigation.