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Although a higher lung cancer risk has been already associated with arsenic exposure, the contribution of arsenic and its compounds to the carcinogenic effects of other agents, such as tobacco smoke, is not well characterized. This systematic review examined the relationship between occupational and non-occupational arsenic exposure and tobacco smoking on lung cancer risk using papers published from 2010 to 2022. Two databases, PUBMED and Scifinder, were used for the searches. Among the sixteen human studies included, four were about occupational exposure, and the others were about arsenic in drinking water. Furthermore, only three case-control studies and two cohort studies evaluated an additive or multiplicative interaction. The interaction between arsenic exposure and tobacco smoke seems to be negligible at low arsenic concentrations (<100 μg/L), while there is a synergistic effect at higher concentrations. Finally, it is not yet possible to assess whether a linear no-threshold (LNT) model for lung cancer risk can be applied to the co-exposure to arsenic and tobacco smoke. Although the methodological quality of the included studies is good, these findings suggest that rigorous and accurate prospective studies on this topic are highly needed.

Sex-related biological differences might lead to different effects in women and men when they are exposed to risk factors. A scoping review was carried out to understand if sex could be a discriminant in health outcomes due to benzene. Studies on both animals and humans were collected. In vivo surveys, focusing on genotoxicity, hematotoxicity and effects on metabolism suggested a higher involvement of male animals (mice or rats) in adverse health effects. Conversely, the studies on humans, focused on the alteration of blood parameters, myeloid leukemia incidence and biomarker rates, highlighted that, overall, women had significantly higher risk for blood system effects and a metabolization of benzene 23-26% higher than men, considering a similar exposure situation. This opposite trend highlights that the extrapolation of in vivo findings to human risk assessment should be taken with caution. However, it is clear that sex is a physiological parameter to consider in benzene exposure and its health effects. The topic of sex difference linked to benzene in human exposure needs further research, with more numerous samples, to obtain a higher strength of data and more indicative findings. Sex factor, and gender, could have significant impacts on occupational exposures and their health effects, even if there are still uncertainties and gaps that need to be filled.

Although Radon (Rn) is a known agent for lung cancer, the link between Rn exposure and other non-pulmonary neoplasms remains unclear. The aim of this review is to investigate the role of Rn in the development of tumors other than lung cancer in both occupational and environmental exposure. Particularly, our attention has been focused on leukemia and tumors related to brain and central nervous system (CNS), skin, stomach, kidney, and breast. The epidemiologic literature has been systematically reviewed focusing on workers, general population, and pediatric population. A weak increase in leukemia risk due to Rn exposure was found, but bias and confounding factors cannot be ruled out. The results of studies conducted on stomach cancer are mixed, although with some prevalence for a positive association with Rn exposure. In the case of brain and CNS cancer and skin cancer, results are inconclusive, while no association was found for breast and kidney cancers. Overall, the available evidence does not support a conclusion that a causal association has been established between Rn exposure and the risk of other non-pulmonary neoplasms mainly due to the limited number and heterogeneity of existing studies. To confirm this result, a statistical analysis should be necessary, even if it is now not applicable for the few studies available.

Idiopathic pulmonary fibrosis (IPF) is a rare lung disease of unknown origin that rapidly leads to death. However, the rate of disease progression varies from one individual to another and is still difficult to predict. The prognosis of IPF is poor, with a median survival of three to five years after diagnosis, without curative therapies other than lung transplantation. The factors leading to disease onset and progression are not yet completely known. The current disease paradigm is that sustained alveolar epithelial micro-injury caused by environmental triggers (e.g., cigarette smoke, microaspiration of gastric content, particulate dust, viral infections or lung microbial composition) leads to alveolar damage resulting in fibrosis in genetically susceptible individuals. Numerous epidemiological studies and case reports have shown that occupational factors contribute to the risk of developing IPF. In this perspective, we briefly review the current understanding of the pathophysiology of IPF and the importance of occupational factors in the pathogenesis and prognosis of the disease. Prompt identification and elimination of occult exposure may represent a novel treatment approach in patients with IPF.

Summary: Laboratory animal allergy (LAA) is caused by an immunological hypersensitivity reaction to highmolecular- weight antigens that are present in laboratory animals' urine, dander and saliva. All laboratory animal facility personnel who regularly come in contact with laboratory animals, such as technicians, researchers, cleaning staff, veterinarians and even administrative staff, are at risk of developing LAA. Generally, most epidemiological studies indicate a LAA prevalence ranging from 6% to 44% and an incidence ranging from 9% to 30%. Prevalence and incidence data vary widely because the diagnosis is not uniformly defined: some diagnoses are made solely on the basis of symptoms, whereas others also require a positive skin test or confirmation of the presence of laboratory animal allergen-specific IgE antibodies., Competing Interests: The authors of this article have no conflict of interests to disclose., (Copyright© by Aracne Editrice, Roma, Italy.)

The respiratory tract is the main target organ of the inhaled hexavalent chromium (Cr-VI) and nickel (Ni) contained in stainless steel (SS) welding fumes (WFs). The aim of this study was to investigate the Cr and Ni content of the exhaled breath condensate (EBC) of SS tungsten inert gas (TIG) welders, and relate their concentrations with oxidative stress and inflammatory biomarkers. EBC and urine from 100 SS TIG welders were collected pre-(T 0 ) and post-shift (T 1 ) on a Friday, and pre-shift (T 2 ) on the following Monday morning. Both EBC and urinary Cr concentrations were higher at T 1 (0.08 μg/L and 0.71 μg/g creatinine) and T 0 (0.06 μg/L and 0.74 μg/g creatinine) than at T 2 (below the limit of detection [LOD] and 0.59 μg/g creatinine), and EBC Ni concentrations generally remained 2 O 2 ) concentration increased from 0.18 μM at T 0 to 0.25 μM at T 1 , but had decreased to 0.16 μM by T 2 . EBC malondialdehyde (MDA) concentrations were higher at T 0 (2.79 nM) and T 1 (2.98 nM) than at T 2 (2.43 nM), and EBC 4-hydroxy-nonenal (HNE) concentrations were higher at T 0 (0.53 nM) than at T 2 (0.51 nM). These findings confirm that, unlike Ni-EBC, Cr-EBC is a reliable biomarker of exposure even at very low environmental concentrations. However, given the weak relationship between the biomarkers and effects of exposure, we speculate that other substances generated during SS TIG welding also play a role in generating lung oxidative stress., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: Laboratory animal allergy is a highly prevalent occupational disease among exposed workers. The aim of the study was to validate the biomarkers of airway inflammation in laboratory animal (LA) care workers., Methods: All of the participants in this observational study (63 LA care workers and 64 controls) were administered a clinical questionnaire, underwent spirometry and a skin prick or radioallergosorbent test for common and occupational aeroallergens, and the fraction of exhaled nitric oxide (FeNO 50 ), exhaled breath condensate hydrogen peroxide (EBC H 2 O 2 ) and serum pneumoprotein levels were measured. Multivariate analysis (ANCOVA) was used to assess the interactions of the variables., Results: FeNO 50 levels correlated with exposure (p = 0.002), sensitisation (p = 0.000) and age (p = 0.001), but there was no interaction between exposure and sensitisation when age was considered in the model (p = 0.146). EBC-H 2 O 2 levels were higher in the sensitised workers than in the sensitised controls [0.14 (0.08-0.29) µM vs 0.07 (0.05-0.12) µM; p < 0.05]. Serum surfactant protein A (SP-A) levels were unaffected by exposure, sensitisation or age, although higher levels were observed in symptomatic workers; however, SP-D levels were influenced by exposure (p = 0.024) and age (p = 0.022), and club cell 16 levels were influenced by sensitisation (p = 0.027) and age (p = 0.019)., Conclusions: The presence of the clinical symptoms associated with LA exposure and high FeNO levels should prompt further medical assessments in LA workers. Although EBC-H 2 O 2 levels do not seem to reflect eosinophilic inflammation, serum SP-A levels could be used to monitor progression from rhinitis to asthma.

Current occupational exposure levels to benzene are reduced by three orders of magnitudo (from ppm to ppb) as compared to the past. As benzene toxicity is related to its biotransformation and bioactivation pathways seem to be more active at lower exposure levels, observed effects could be higher than expected. Although the genetic polymorphisms of relevant and functional metabolic enzymes are implied in the modulation of either the risk of adverse effects [myeloperoxidase and NAD(P)H:quinone oxidoreductase] or of the biomarkers of internal dose (glutathione S-transferases M1-1, T1-1, A1-1), they are not appliable as biomarkers of susceptibility. Among biomarkers of early effect, only the longitudinal monitoring of blood cell count seems suitable to be applied in health surveillance protocols, whereas the use of biomarkers of genotoxic effect at current exposure levels is at the present not supported by literature data.

This cross-sectional study was aimed at reconstructing the exposure to gasoline in 102 petrol station attendants by environmental and biological monitoring of benzene, toluene, ethylbenzene and xylene (BTEX) and biomonitoring of methyl tert-butyl ether (MTBE). Airborne BTEX were higher for manual refuelers than self-service assistants and were highly correlated with each other. Significant relationships were found between airborne BTX and the corresponding urinary solvents (U-BTX) and beween airborne B and urinary MTBE (U-MTBE). Smokers eliminated higher values of U-B, trans,trans-muconic (t,t-MA) and S-phenylmercapturic (S-PMA) acids but not U-MTBE. All these biomarkers were, however, significantly raised during the shift, independently from smoking. Linear regression confirmed that occupational exposure was a main predictor of U-MTBE, U-B and S-PMA values, both the latter confounded by smoking habits. The study supports the usefulness of biomonitoring even at low exposure levels.

This study investigated nucleic acid oxidation associated with exposure to benzene at low levels in 239 workers recruited among traffic policemen, taxi drivers and gasoline pump attendants of the city of Parma (Italy). Biomarkers of exposure, namely urinary t,t-muconic acid (t,t-MA) and S-phenylmercapturic acid (S-PMA), urinary cotinine, and urinary biomarkers of nucleic acid oxidation, namely 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydroguanine (8-oxoGua) were determined by liquid chromatography-tandem mass spectrometry. Relevant polymorphisms of NAD(P)H:quinone oxidoreductase (NQO1), glutathione S-transferases M1-1 (GSTM1), T1-1 (GSTT1), and A1 (GSTA1) were characterized by polymerase chain reaction-based methods in a subgroup of subjects. Biomarkers of nucleic acid oxidation were correlated with each other (r> or =0.32, p<0.0001) and with exposure biomarkers (r> or =0.28, p<0.0001). Multiple linear regression models including age, sex and smoking habits as independent variables demonstrated that benzene exposure is associated with oxidation damage to nucleic acid, particularly to RNA (p<0.0001) and is modulated by the NQO1 polymorphism. The study confirmed a significant modulating effect of GSTM1 (p=0.010), GSTT1 (p=0.023) and GSTA1 (p=0.048) polymorphisms on S-PMA excretion, with a significant interaction between GSTM1 and both GSTT1 and GSTA1 (p=0.006 and p=0.037, respectively)., (2010 Elsevier Ireland Ltd. All rights reserved.)

This study investigated nucleic acid oxidation associated with styrene exposure, mRNA expression levels of hOGG1 gene and the role of the genetic polymorphism Ser326Cys of human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) in 60 styrene-exposed workers and 50 unexposed clerks. Biomarkers of exposure (styrene in blood, mandelic and phenylglyoxylic acids and 4-vinylphenol in urine) and urinary biomarkers of nucleic acid oxidation, namely 8-oxo-7,8-dihydro-2'-deoxyguanosine (U-8-oxodGuo), 8-oxo-7,8-dihydroguanosine (U-8-oxoGuo) and 8-oxo-7,8-dihydroguanine (U-8-oxoGua) were determined by liquid chromatography-tandem mass spectrometry. The levels of 8-oxodGuo adduct and 2'-deoxyguanosine (dGuo) were measured by HPLC in DNA from white blood cells (WBC). Genomic DNA and RNA from blood samples were used to characterize the Ser326Cys polymorphism and the mRNA expression levels of the hOGG1 gene, respectively, by PCR-based methods. Exposed workers showed lower values of 8-oxodGuo/10(5) dGuo ratio in WBC-DNA but higher concentrations of U-8-oxoGuo compared to controls (p=0.002 and p=0.008, respectively, t-test for independent samples). In the whole group, all urinary biomarkers of nucleic acid oxidation correlated with both the sum of mandelic and phenylglyoxylic acids (rho>0.33, p<0.0001) and 4-vinylphenol (rho>0.29, p<0.001), whereas 8-oxodGuo/10(5) dGuo in WBC showed a negative correlation with exposure parameters (rho<-0.24, p<0.02). Subjects bearing the hOGG1 Ser/Ser genotype showed lower values of 8-oxodGuo/10(5) dGuo in WBC than those with at least one variant Cys allele (0.34+/-0.16 vs 0.45+/-0.21, p=0.008). In the subgroup of hOGG1 Ser/Ser subjects, laminators showed lower levels of WBC 8-oxodGuo/10(5) dGuo ratio and significantly higher concentrations of U-8-oxoGua than controls (p=0.07 and p=0.01, respectively, t-test for independent samples). Interestingly, workers showed higher levels of hOGG1 expression compared to controls (p<0.0005). Styrene exposure seems to be associated with oxidation damage to nucleic acids, particularly to RNA and with an induction of the BER system.

An integrated approach based on ambient and biological monitoring, the latter including both biomarkers of exposure and susceptibility, was applied to characterize benzene exposure in a group of 37 taxi drivers of the city of Parma (Italy). Airborne benzene concentrations were assessed by 24 h personal sampling and work-shift sampling inside the taxicab using passive samplers (Radiello). Benzene metabolites, trans,trans-muconic acid (t,t-MA) and S-phenylmercapturic acid (S-PMA), and urinary cotinine as biomarker of smoking habits were measured by isotopic dilution liquid chromatography tandem mass spectrometry in both pre-shift (PS) and end-of-shift (EOS) samples. Urinary benzene (U-B) levels were determined by solid-phase microextraction gas chromatography-mass spectrometry in EOS samples. Relevant polymorphisms of microsomal epoxide hydrolase, NAD(P)H:quinone oxidoreductase, glutathione S-transferases M1-1 (GSTM1), T1-1, and A1 were characterized by PCR-based methods. Mean airborne benzene concentration was 5.85 +/- 1.65 microg/m3, as assessed by 24 h personal sampling integrating for work-shift, indoor or general environment activities. Significantly, higher benzene concentrations were detected in the taxicab during the work-shift (7.71 +/- 1.95 microg/m3, p < 0.005). Smokers eliminated significantly higher concentrations of U-B and S-PMA than non-smokers in EOS samples [geometric mean (geometric S.D.): 2.58 (4.23) versus 0.44 (1.79) microg/l for U-B; 3.79 (1.50) versus 2.14 (1.87) microg/gcreat. for S-PMA, p < 0.002]. Within smokers, S-PMA concentrations significantly increased at the end of the work-shift compared to pre-shift values (p < 0.05). t,t-MA showed a similar behaviour, although differences were not significant. In the narrow range examined, no correlation was observed between air benzene concentration and urinary biomarkers. All benzene biomarkers but EOS t,t-MA were correlated with U-cotinine (p < 0.05). GSTM1 polymorphism significantly modulated S-PMA excretion, as subjects bearing the GSTM1pos genotype [3.61 (1.15) microg/gcreat.] excreted significantly higher S-PMA concentrations than GSTM1null subjects [2.19 (1.18) microg/gcreat., p < 0.05].

Two workers were accidentally exposed to unusually high styrene concentrations (>1000 ppm) for about 30 min. In addition to the main styrene metabolites, mandelic acid (MA) and phenylglyoxylic acid (PGA), other minor metabolites, including specific mercapturic acids, (R,R)- and (S,R)-N-acetyl-S-(1-phenyl-2-hydroxyethyl)-L-cysteine [(R,R)-M1 and (S,R)-M1] and (R,R)- and (S,R)-N-acetyl-S-(2-phenyl-2-hydroxyethyl)-L-cysteine [(R,R)-M2 and (S,R)-M2], 4-vinylphenol-glucuronide and -sulfate, and phenylglycine, were determined by Liquid Chromatography Electrospray Tandem Mass Spectrometry (LC-ESI-MS/MS) in urine samples collected 12, 24, 36, 48, 75 and 99 h after the episode. The genotypes of microsomal epoxide hydrolase, glutathione-S-transferases M1-1 (GSTM1), T1-1 (GSTT1) and P1-1 (GSTP1) were characterized by PCR-based methods. The two subjects showed similar peak levels of MA and PGA, as well as 4-vinylphenol conjugates, whereas mercapturic acids were five times higher in the subject bearing the GSTM1pos than in the GSTM1null subject. Also, relative proportions of diasteroisomers of mercapturic acids were influenced by the GSTM1 polymorphism.

Biochar is currently garnering interest as an alternative to commercial fertilizer and as a tool to counteract global warming. However, its use is increasingly drawing attention, particularly concerning the fine dust that can be developed during its manufacture, transport, and use. This work aimed to assess the toxicity of fine particulate Biochar (