Worse pulmonary function in association with cumulative exposure to nanomaterials. Hints of a mediation effect via pulmonary inflammation.

BACKGROUND: Today, nanomaterials are broadly used in a wide range of industrial applications. Such large utilization and the limited knowledge on to the possible health effects have raised concerns about potential consequences on human health and safety, beyond the environmental burden. Given that inhalation is the main exposure route, workers exposed to nanomaterials might be at risk of occurrence of respiratory morbidity and/or reduced pulmonary function. However, epidemiological evidence regarding the association between cumulative exposure to nanomaterials and respiratory health is still scarce. This study focused on the association between cumulative exposure to nanomaterials and pulmonary function among 136 workers enrolled in the framework of the European multicentric NanoExplore project. RESULTS: Our findings suggest that, independently of lifelong tobacco smoking, ethnicity, age, sex, body mass index and physical activity habits, 10-year cumulative exposure to nanomaterials is associated to worse FEV1 and FEF25 - 75%, which might be consistent with the involvement of both large and small airway components and early signs of airflow obstruction. We further explored the hypothesis of a mediating effect via airway inflammation, assessed by interleukin (IL-)10, IL-1ß and Tumor Necrosis Factor alpha (TNF-α), all quantified in the Exhaled Breath Condensate of workers. The mediation analysis results suggest that IL-10, TNF-α and their ratio (i.e., anti-pro inflammatory ratio) may fully mediate the negative association between cumulative exposure to nanomaterials and the FEV1/FVC ratio. This pattern was not observed for other pulmonary function parameters. CONCLUSIONS: Safeguarding the respiratory health of workers exposed to nanomaterials should be of primary importance. The observed association between cumulative exposure to nanomaterials and worse pulmonary function parameters underscores the importance of implementing adequate protective measures in the nanocomposite sector. The mitigation of harmful exposures may ensure that workers can continue to contribute productively to their workplaces while preserving their respiratory health over time.

Occupational Exposure to Metal-Based Nanomaterials: A Possible Relationship between Chemical Composition and Oxidative Stress Biomarkers.

Nanomaterials (NMs) are in high demand for a wide range of practical applications; however, comprehensively understanding the toxicity of these materials is a complex challenge, due to the limited availability of epidemiological evidence on the human health effects arising from workplace exposures. The aim of this work is to assess whether and how urinary metal concentrations could be reliable and useful in NM biomonitoring. In the framework of "NanoExplore Project" [EU LIFE17 Grant ENV/GR/000285], 43 not-exposed subjects and 40 exposed workers were recruited to measure exposure to NMs (PCN and LDSA) in the proximity of the workstations and biological biomarkers (urinary metal concentrations-Aluminum (Al), Silica (Si), Titanium (Ti), and Chromium (Cr); urinary OS biomarkers-TAP, Isop, and MDA). The results showed that Si and Ti were directly associated with NM exposure (both PCN and LDSA), as well as with OS biomarkers, especially in exposed workers. Moreover, the mediation analyses showed that Si could account for about 2.8% in the relationship between LDSA and OS biomarkers, possibly by decreasing OS antioxidant defenses in exposed people. In conclusion, our study provides evidence that occupational exposure to mixtures containing NMs can represent an underestimated hazard for exposed people, increasing the body burden and the oxidative balance.

Assessing the inhaled dose of nanomaterials by nanoparticle tracking analysis (NTA) of exhaled breath condensate (EBC) and its relationship with lung inflammatory biomarkers.

The widespread and increasing use of nanomaterials has resulted in a higher likelihood of exposure by inhalation for nanotechnology workers. However, tracking the internal dose of nanoparticles deposited at the airways level, is still challenging. To assess the suitability of particle number concentration determination as biomarker of internal dose, we carried out a cross sectional investigation involving 80 workers handling nanomaterials. External exposure was characterized by portable counters of particles DISCminiTM (Testo, DE), allowing to categorize 51 workers as exposed and 29 as non-exposed (NE) to nanoparticles. Each subject filled in a questionnaire reporting working practices and health status. Exhaled breath condensate was collected and analysed for the number of particles/ml as well as for inflammatory biomarkers. A clear-cut relationship between the number of airborne particles in the nano-size range determined by the particle counters and the particle concentration in exhaled breath condensate (EBC) was apparent. Moreover, inflammatory cytokines (IL-1ß, IL-10, and TNF-α) measured in EBC, were significantly higher in the exposed subjects as compared to not exposed. Finally, significant correlations were found between external exposure, the number concentration of particles measured by the nanoparticle tracking analysis (NTA) and inflammatory cytokines. As a whole, the present study, suggests that NTA can be regarded as a reliable tool to assess the inhaled dose of particles and that this dose can effectively elicit inflammatory effects.

Different greenness exposure in Europe and respiratory outcomes in youths. A systematic review and meta-analysis.

The existing evidence on the association between greenness and respiratory outcomes remains inconclusive. We aimed at systematically summarizing existing literature on greenness exposure and respiratory outcomes in European children and adolescents, with a preliminary attempt to qualify the distribution of dominant tree species across different geographical areas and bioclimatic regions. Overall, 4049 studies were firstly identified by searching PubMed/MEDLINE, EMBASE, Scopus, Web of Science, GreenFile and CAB direct, up to 29 August 2023. Eighteen primary studies were included in the systematic review and six were meta-analyzed. No overall significant association was observed between the Normalized Difference Vegetation Index, assessed within 500-m buffers (i.e. NDVI-500), and the odds of asthma for 0.3-increase in the exposure (OR: 0.97, 95% CI from 0.53 to 1.78). Similarly, an overall exposure to the NDVI-300 highest tertile, as compared to the lowest tertile, was not significantly associated with asthma (OR: 0.65, 95% CI from 0.22 to 1.91): heterogeneity among studies was significant (p = 0.021). We delineated some key elements that might have mostly contributed to the lack of scientific consensus on this topic, starting from the urgent need of harmonized approaches for the operational definition of greenness. Additionally, the complex interplay between greenness and respiratory health may vary across different geographical regions and climatic conditions. At last, the inconsistent findings may reflect the heterogeneity and complexity of this relationship, rather than a lack of scientific consensus itself. Future research should compare geographical areas with similar bioclimatic parameters and dominant or potentially present vegetation species, in order to achieve a higher inter-study comparability.

Working from home during the COVID-19 pandemic. The role of physical activity to counteract the workers' oxidative stress. A pilot study.

Objective: Office workers spend typically more than two-thirds of their working time sitting and this negative behaviour could have been increased during the pandemic. Low levels of Physical Activity (PA) can have detrimental effects on health, well-being, and Quality of Life (QoL), as well as on the oxidative stress burden. Our aim was to evaluate the role of moderate PA remotely administered in modulating the bio-molecular profile and the QoL of a group of workers during the COVID-19 pandemic. Methods: The 26 subjects recruited were sampled at the beginning of the study (T0), after 3 months of remotely administered training (T1), and 3 months after the suspension of the online workouts (T2). Each of the three times, subjects filled out a questionnaire and provided a spot urine sample for the quantification of oxidative stress (15-F2t-Isoprostane, Thiobarbituric Acid Reactive Substances (TBARS), and Total Antioxidant Power (TAP)) and inflammatory biomarkers (Interleukin (IL)-6 and IL-10). Results: The PA administration resulted in a significant decrease in 15-F2t-Isoprostane (p = 0.02) and TAP (p = 0.019). A significant increase in TAP was observed between T1 and T2 (p = 0.044). Conclusion: A PA-based health promotion strategy could be a valuable intervention in the working environment to promote the well-being of an ageing workforce, especially for white collars.

Biomarkers of oxidative stress, inflammation, and genotoxicity to assess exposure to micro- and nanoplastics. A literature review.

The increased awareness about possible health effects arising from micro- and nanoplastics (MNPs) pollution is driving a huge amount of studies. Many international efforts are in place to better understand and characterize the hazard of MNPs present in the environment. The literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology in two different databases (PubMed and Embase). The selection of articles was carried out blind, screening titles and abstracts according to inclusion and exclusion criteria. In general, these studies rely on the methodology already in use for assessing hazard from nanomaterials and particles of concern. However, only a limited number of studies have so far directly measured human exposure to MNPs and examined the relationship between such exposure and its impact on human health. This review aims to provide an overview of the current state of research on biomarkers of oxidative stress, inflammation, and genotoxicity that have been explored in relation to MNPs exposure, using human, cellular, animal, and plant models. Both in-vitro and in-vivo models suggest an increased level of oxidative stress and inflammation as the main mechanism of action (MOA) leading to adverse effects such as chronic inflammation, immunotoxicity and genotoxicity. With the identification of such biological endpoints, representing critical key initiating events (KIEs) towards adaptive or adverse outcomes, it is possible to identify a panel of surrogate biomarkers to be applied and validated especially in occupational settings, where higher levels of exposure may occur.

Occupational exposure to nanomaterials and biomarkers in exhaled air and urine: Insights from the NanoExplore international cohort.

The current evidence on nanomaterial toxicity is mostly derived from experimental studies making it challenging to translate it into human health risks. We established an international cohort (N = 141 workers) within the EU-LIFE project "NanoExplore" to address possible health effects from occupational exposures to nanomaterials. We used a handheld direct-reading optical particle counter to measure airborne nanoparticle number concentrations (PNC) and lung-deposited surface areas (LDSAs). Airborne particles were characterized by TEM and SEM-EDAX. We assessed oxidative/nitrosative stress with a panel of biomarkers in exhaled breath condensate (EBC) (8-isoprostane, malondialdehyde, nitrotyrosine), inflammation (high-sensitivity C reactive protein (hs-CRP), IL-1ß, TNF-α, IL-10) and KL-6 (considered as biomarker of interstitial lung fibrosis) and urine (total antioxidant power (TAP), 8-isoprostane, and malondialdehyde). Exhaled breath sampled in gas-sampling bags were assessed for oxidative potential. These biomarkers were quantified pre-shift at the beginning of the workweek and post-shift the 4th day. Relationships between airborne nanoparticle concentration and biomarkers were assessed by multiple linear regression with log-transformed exposure and biomarker concentrations adjusted for potential confounders. We found a positive dose-response relationship for three inflammation biomarkers (IL-10, IL-1ß and TNF-α) in EBC with both PNC and LDSA. A negative dose-response relationship was observed between PNC and TAP. This study suggests that occupational exposures to nanoparticles can affect the oxidative balance and the innate immunity in occupationally exposed workers. However, owing to the intrinsic variability of biomarkers, the observed changes along with their health significance should be assessed in a long-term perspective study.

The Effect of Dietary Patterns and Nutrient Intake on Oxidative Stress Levels in Pregnant Women: A Systematic Review.

During pregnancy, reactive oxygen species (ROS) may physiologically increase due to changes and growth of mother and fetal tissues. Consequently, oxidative stress (OS) may occur and be involved in the onset of pregnancy and newborn complications. Among exogenous antioxidant sources, diet is a cost-effective prevention strategy supporting the health of mothers and newborns; however, there is still a lack of nutritional education during pregnancy interviews. This review aims to systematically summarize the knowledge on the association between OS and diet during pregnancy. Four electronic databases (PubMed Central, EMBASE, Web of Science, and Food Science and Technology Abstracts) were searched on 22 December 2022. Among 4162 records, 13 original articles were finally included. Overall, 80% of the studies considered dietary patterns as exposure and 60% of them assessed the association with malondialdehyde levels in blood and urine. Three studies analyzed the influence of daily intakes of fruit and vegetables on different OS biomarkers (malondialdehyde, nitric oxide and 8-hydroxy-2'-deoxyguanosine). Among studies exploring dietary fat intakes (39%), 80% focused on polyunsaturated fatty acids, finding a positive association with glutathione peroxidase, biopirryn and isoprostane levels, respectively. Four studies analyzed vitamin intakes and 50% of them in association with 8-hydroxy-2'-deoxyguanosine.

Inflammatory Biomarkers in Exhaled Breath Condensate: A Systematic Review.

Inflammation is a comprehensive set of physiological processes that an organism undertakes in response to a wide variety of foreign stimuli, such as viruses, bacteria, and inorganic particles. A key role is played by cytokines, protein-based chemical mediators produced by a broad range of cells, including the immune cells recruited in the inflammation site. The aim of this systematic review is to compare baseline values of pro/anti-inflammatory biomarkers measured in Exhaled Breath Condensate (EBC) in healthy, non-smoking adults to provide a summary of the concentrations reported in the literature. We focused on: interleukin (IL)-1ß, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor-alpha (TNF-α), and C reactive protein (CRP). Eligible articles were identified in PubMed, Embase, and Cochrane CENTRAL. Due to the wide differences in methodologies employed in the included articles concerning EBC sampling, storage, and analyses, research protocols were assessed specifically to test their adherence to the ATS/ERS Task Force guidelines on EBC. The development of reference intervals for these biomarkers can result in their introduction and use in both research and clinical settings, not only for monitoring purposes but also, in the perspective of future longitudinal studies, as predictive parameters for the onset and development of chronic diseases with inflammatory aetiology.

A Biomonitoring Pilot Study in Workers from a Paints Production Plant Exposed to Pigment-Grade Titanium Dioxide (TiO2).

Among particulate matter composing paints, titanium dioxide (TiO2) forms about 20% of the final suspension. Although TiO2 is broadly used in many applications, TiO2 powders represent an established respiratory hazard for workers with long-term exposure. In 35 workers of a paints production plant (15 exposed and 20 not exposed), we assessed pro-inflammatory cytokines (IL-1ß, TNF-α, IL-10, IL-17), surfactant protein D (SP-D) and Krebs von den Lungen-6 glycoprotein (KL-6) in exhaled breath condensate (EBC). In urine samples, we measured 8-isoprostane (Isop) and Malondialdehyde (MDA) as biomarkers of oxidative stress, and Titanium (Ti-U) as a biomarker of exposure. Health status, habits and occupational history were recorded. Airborne respirable dusts and Ti were quantified. Particle number concentration and average diameter (nm) were detected by a NanoTracer™ monitoring device. Ti was measurable in filters collected at the respiratory breathing zone (0.11−0.44 µg/m3 8-h TWA). IL-1ß and IL-10 values were significantly higher in exposed workers, whereas SP-D was significantly lower (p < 0.001). KL-6 was significantly higher in workers than in controls (p < 0.01). MDA levels were significantly increased in exposed workers and were positively correlated with Ti-U. Exposure to TiO2 in paint production is associated with the subtle alterations of lung pathobiology. These findings suggest the need for an integrated approach relying on both personal exposure and biomarker assessment to improve the hazard characterisation in occupational settings.

The formation of SCEs as an effect of occupational exposure to formaldehyde.

Formaldehyde (FA) is a ubiquitous toxic chemical employed worldwide due to its disinfectant and preservative properties. Despite being classified as a human carcinogen, FA is still employed as formalin in pathology wards as standard fixative. We evaluated its relationship with the formation of sister-chromatid exchanges (SCEs) in cultured peripheral blood lymphocytes on 57 pathologists and 48 controls and the risk/protective role played by several genetic polymorphisms. All subjects were assessed for SCEs and genotyped for the most common cancer-associated gene polymorphisms: CYP1A1 exon 7 (A > G), CYP1A1*2A (T > C), CYP2C19*2 (G > A), GSTT1 (presence/absence), GSTM1 (presence/absence), GSTP1 (A > G), XRCC1 (G399A), XRCC1 (C194T), XRCC1 (A280G), XPC exon 15 (A939C), XPC exon 9 (C499T), TNFα - 308 G > A), IL10 - 1082 (G > A), and IL6 - 174 (G > C). Air-FA concentration was assessed through passive personal samplers. Pathologists, exposed to 55.2 µg/m3 of air-FA, showed a significantly higher SCEs frequency than controls, exposed, respectively, to 18.4 µg/m3. Air-FA was directly correlated with SCEs frequency and inversely with the replication index (RI). Regression models showed FA exposure as a significant predictor in developing SCEs, while did not highlight any role of the selected polymorphisms. Our study confirms the role of low air-FA levels as genotoxicity inductor, highlighting the importance to define exposure limits that could be safer for exposed workers.

Non-Invasive Measurement of Exercise-Induced Oxidative Stress in Response to Physical Activity. A Systematic Review and Meta-Analysis.

Physical activity may benefit health by modulating oxidative stress and inflammation. However, the selection of suitable exercise-induced oxidative stress biomarkers is still challenging. This study aimed at systematically summarizing the available evidence on exercise-induced oxidative stress measured in urine and/or saliva. Two meta-analyses including the most frequently quantified biomarkers of oxidative stress, namely, urinary isoprostane and DNA oxidation products, were performed. Three electronic databases (PubMed, EMBASE and Cochrane CENTRAL) were interrogated. Among 4479 records, 43 original articles were included in the systematic review and 11 articles were included in meta-analysis I and II, respectively. We observed a pooled trend of increase of urinary isoprostanes in response to physical activity (+0.95, 95% CI: -0.18; 2.09). In comparison with aerobic exercise, anaerobic training determined a greater induction of isoprostanes (+5.21, 95% CI: 2.76; 7.66, p < 0.0001), which were markedly increased after vigorous physical activity (+6.01, 95% CI: 1.18; 10.84, p < 0.001) and slightly decreased in response to exercise interventions protracted over time (e.g., months) (-1.19, 95% CI: -2.25; -0.12, p < 0.001). We recommend the most integrative approach of oxidative stress multi-marker panels in response to physical activity instead of selecting one preferential biomarker to quantify physical activity-induced oxidative stress in humans.

Formaldehyde in Hospitals Induces Oxidative Stress: The Role of GSTT1 and GSTM1 Polymorphisms.

Despite the toxicity and health risk characteristics of formaldehyde (FA), it is currently used as a cytological fixative and the definition of safe exposure levels is still a matter of debate. Our aim was to investigate the alterations in both oxidative and inflammatory status in a hospital working population. The 68 workers recruited wore a personal air-FA passive sampler, provided a urine sample to measure 15-F2t-Isoprostane (15-F2t-IsoP) and malondialdehyde (MDA) and a blood specimen to measure tumour necrosis factor α (TNFα). Subjects were also genotyped for GSTT1 (Presence/Absence), GSTM1 (Presence/Absence), CYP1A1 exon 7 (A > G), and IL6 (-174, G > C). Workers were ex post split into formalin-employers (57.3 µg/m3) and non-employers (13.5 µg/m3). In the formalin-employers group we assessed significantly higher levels of 15-F2t-IsoP, MDA and TNFα (<0.001) in comparison to the non-employers group. The air-FA levels turned out to be positively correlated with 15-F2t-IsoP (p = 0.027) and MDA (p < 0.001). In the formalin-employers group the MDA level was significantly higher in GSTT1 Null (p = 0.038), GSTM1 Null (p = 0.031), and CYP1A1 exon 7 mutation carrier (p = 0.008) workers, compared to the wild type subjects. This study confirms the role of FA in biomolecular profiles alterations, highlighting how low occupational exposure can also result in measurable biological outcomes.

The role of phase I, phase II, and DNA-repair gene polymorphisms in the damage induced by formaldehyde in pathologists.

Formaldehyde (FA) is a human carcinogen used as formalin in hospital laboratories. We evaluated its association with human chromosomal aberrations (CAs) and the risk/protective role played by several genetic polymorphisms in this relationship, on a cohort of 57 exposed pathologists vs 48 controls. All subjects were assessed for CAs on peripheral blood lymphocytes and genotyped for the most common cancer-associated gene polymorphisms which could be related with the genotoxic outcome: CYP1A1 exon 7 (A>G), CYP1A1*2A (T>C), CYP2C19*2 (G>A), GSTT1 (Positive/Null), GSTM1 (Positive/null), GSTP1 (A>G), XRCC1 (G399A), XRCC1 (C194T), XRCC1 (A280G), XPD (A751C), XPC exon 15 (A939C), XPC exon 9 (C499T), TNFα - 308 (G>A), IL10 - 1082 (G>A), IL10 - 819 (C>T) and IL6 - 174 (G>C). Air-FA concentration was assessed through personal samplers. The comparison between pathologists and controls showed a significantly higher CAs frequency in pathologists. Significant positive correlations were found between CAs frequency and air-FA concentration while significant associations were found between variation in CAs frequency and the mutated allele for CYP1A1 exon 7 (A>G), CYP2C19*2 (G>A), GSTT1-positive, GSTM1-positive and XRCC1 (G399A). Our study confirms the role of FA as genotoxicity inductor, even in workers chronically exposed to low air-FA levels and reveals the role played by some genetic polymorphisms in this association, highlighting the importance of individual susceptibility biomarkers assessment in occupational health studies.

Oxidative stress induction in woodworkers occupationally exposed to wood dust and formaldehyde.

BACKGROUND: Many workers are exposed to wood dust (WD) and formaldehyde (FA), whose carcinogenic activity is supposed to be oxidative stress-mediated. This study aims to assess to what extent the occupational exposure to WD and FA, albeit within regulatory limits, could result in OS induction in a woodworkers' population. METHODS: The sample population consisted of 127 woodworkers from 4 factories and 111 unexposed controls. Individual exposure was assessed by personal air-samplers. Each participant enrolled in the study filled out a questionnaire and provided a urinary sample to quantify OS biomarkers, namely 15-F2t-IsoProstane (15-F2t-IsoP) and 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dGuo). The main confounding factor for OS, i.e. tobacco smoking exposure, was assessed by measuring cotinine in urine samples. RESULTS: Woodworkers were exposed to significantly higher amounts of WD and FA as compared to controls (p < 0.001). Among OS biomarkers, 15-F2t-IsoP showed statistically significant higher values in woodworkers compared to controls (p = 0.004). A significant, positive correlation was observed between 15-F2t-IsoP and 8-oxo-dGuo (p = 0.005), cotinine (p = 0.05), FA (p < 0.001) and WD (p = 0.01); 8-oxo-dGuo was significantly correlated with cotinine (p = 0.001) and WD (p = 0.004). In addition, WD and FA were significantly correlated each other (p < 0.001). CONCLUSIONS: The study confirms that WD and FA may induce OS in woodworkers, and highlights that even the compliance with occupational exposure limits can result in measurable biological outcomes.

Formaldehyde, Oxidative Stress, and FeNO in Traffic Police Officers Working in Two Cities of Northern Italy.

Personal air formaldehyde (air-FA) was measured as risk factor of airways inflammation and oxidative stress (SO) induction. Overall, 154 police officers were enrolled from two differently urbanised Italian cities, Turin and Pavia. Urinary F2t-isoprostane (15-F2t-IsoP), a prostaglandin-like compound, was quantified as a biomarker of general OS in vivo and fractional exhaled nitric oxide (FeNO) was measured for monitoring local inflammatory processes. Urinary cotinine was quantified as a biomarker of tobacco smoking exposure. Traffic police officers living in Turin showed an increased level of log air-FA (p < 0.001), equal to +53.6% (p < 0.001). Log air-(FA) mean values were 3.38 (C.I. 95% 3.33-3.43) and 2.84 (C.I. 95% 2.77-2.92) in Turin and Pavia, respectively. Log (air-FA) was higher in "outdoor workers" (3.18, C.I. 95% 3.13-3.24, p = 0.035) compared to "indoor workers", showing an increase of +9.3%, even controlling for sex and city. The analyses on 15-F2t-IsoP and FeNO, both adjusted for log air-FA, highlighted that OS and inflammation were higher (+66.8%, p < 0.001 and +75%, p < 0.001, respectively) in Turin traffic police officers compared to those from Pavia. Our findings suggest that even low exposures to traffic-related emissions and urbanisation may influence both general oxidative stress levels and local inflammation.