Bisphenol-A inhibits mitochondrial biogenesis via impairment of GFER mediated mitochondrial protein import in the rat brain hippocampus.

Mitochondrial biogenesis relies on different protein import machinery, as mitochondrial proteins are imported from the cytosol. The mitochondrial intermembrane space assembly (MIA) pathway consists of GFER/ALR and CHCHD4/Mia40, responsible for importing proteins and their oxidative folding inside the mitochondria. The MIA pathway plays an essential role in complex IV (COX IV) biogenesis via importing copper chaperone COX17, associated with the respiratory chain. BPA, an environmental toxicant, found in consumable plastics, causes neurotoxicity via impairment in mitochondrial dynamics, neurogenesis, and cognitive functions. We studied the levels of key regulatory proteins of mitochondrial import pathways and mitochondrial biogenesis after BPA exposure in the rat hippocampus. BPA caused a significant reduction in the levels of mitochondrial biogenesis proteins (PGC1α, and TFAM) and mitochondrial import protein (GFER). Immunohistochemical analysis showed reduced co-localization of NeuN with GFER, PGC-1α, and TFAM suggesting impaired mitochondrial biogenesis and protein import. BPA exposure resulted in damaged mitochondria with distorted cristae in neurons and caused a significant reduction in GFER localization inside IMS as depicted by immunogold electron microscopy. The reduced levels of GFER resulted in defective COX17 import. The translocation of cytochrome c into the cytosol and increased cleaved caspase-3 levels triggered apoptosis due to BPA toxicity. Overall, our study implicates GFER as a potential target for impaired mitochondrial protein machinery, biogenesis, and apoptosis against BPA neurotoxicity in the rat hippocampus.

Association between benzene exposure, serum levels of cytokines and hematological measures in Chinese workers: A cross-sectional study.

BACKGROUND: Low benzene exposure leads to hematotoxicity, but we still lack sensitive early monitoring and early warning markers. Benzene is associated with inflammation, which is mainly mediated by cytokines network. However, until now few studies have conducted high-throughput detection of multi-cytokines to get a global view of cytokine changes and screen for markers of benzene-induced toxicity. We hypothesized that cytokine profiles mediate benzene-induced hematotoxicity. METHODS: 228 subjects consisting of 114 low benzene exposed workers and 114 healthy controls were recruited at Research Center of Occupational Medicine, Peking University Third Hospital, Beijing. The serum concentrations of 27 cytokines were detected by cytokinomics array, urinary benzene series metabolites were measured by UPLC-MS/MS, and peripheral blood cell counts were observed by basic blood test. RESULTS: Among 27 cytokines, IL-9 and MIP1-α were significantly lower, but IL-4, IL-10, IL-15, MCP-1, TNF-α and VEGF were significantly higher in benzene exposure group than controls. Urinary benzene metabolite S-phenylmercapturic acid (S-PMA) was significantly higher in benzene exposure group and had a negative linear relationship with WBC count. S-PMA was only significantly associated with IL-9, meanwhile IL-9, IL-15 and VEGF had a positive linear relationship with WBC count. The bootstrapping mediation models showed that the effect of S-PMA on WBC count was partially explained by IL-9 for 10.11%. CONCLUSION: This study suggests that exposure to benzene was associated with alternation of blood cell count and cytokine profiles in workers exposed to low levels of benzene, especially decreases of WBC count and IL-9. We also found IL-9 partially mediated the effect of low benzene exposure on WBC count, which may be a potential and promising early monitoring and early warning marker of benzene hematotoxicity.

Whole-brain R1 predicts manganese exposure and biological effects in welders.

Manganese (Mn) is a neurotoxicant that, due to its paramagnetic property, also functions as a magnetic resonance imaging (MRI) T1 contrast agent. Previous studies in Mn toxicity have shown that Mn accumulates in the brain, which may lead to parkinsonian symptoms. In this article, we trained support vector machines (SVM) using whole-brain R1 (R1 = 1/T1) maps from 57 welders and 32 controls to classify subjects based on their air Mn concentration ([Mn]Air), Mn brain accumulation (ExMnBrain), gross motor dysfunction (UPDRS), thalamic GABA concentration (GABAThal), and total years welding. R1 was highly predictive of [Mn]Air above a threshold of 0.20 mg/m3 with an accuracy of 88.8% and recall of 88.9%. R1 was also predictive of subjects with GABAThal having less than or equal to 2.6 mM with an accuracy of 82% and recall of 78.9%. Finally, we used an SVM to predict age as a method of verifying that the results could be attributed to Mn exposure. We found that R1 was predictive of age below 48 years of age with accuracies ranging between 75 and 82% with recall between 94.7% and 76.9% but was not predictive above 48 years of age. Together, this suggests that lower levels of exposure (< 0.20 mg/m3 and < 18 years of welding on the job) do not produce discernable signatures, whereas higher air exposures and subjects with more total years welding produce signatures in the brain that are readily identifiable using SVM.

Carbon content in airway macrophages and genomic instability in Chinese carbon black packers.

Carbon black (CB) particulates as virtually pure elemental carbon can deposit deep in the lungs of humans. International Agency for Research on Cancer classified CB as a Group 2B carcinogen due to inconclusive human evidence. A molecular epidemiological study was conducted in an established cohort of CB packers (CBP) to assess associations between CB exposure and genomic instability in peripheral lymphocytes using cytokinesis-block micronucleus assay (CBMN). Carbon content in airway macrophages (CCAM) was quantified as a bio-effective dosimeter for chronic CB exposure. Dose-response observed in CBPs was compared to that seen in workers exposed to diesel exhaust. The association between CB exposure status and CBMN endpoints was identified in 85 CBPs and 106 non-CBPs from a 2012 visit and replicated in 127 CBPs and 105 non-CBPs from a 2018 visit. The proportion of cytoplasm area occupied by carbon particles in airway macrophages was over fivefold higher in current CBPs compared to non-CBPs and was associated with CBMN endpoints in a dose-dependent manner. CB aerosol and diesel exhaust shared the same potency of inducing genomic instability in workers. Circulatory pro-inflammatory factors especially TNF-α was found to mediate associations between CB exposure and CBMN endpoints. In vitro functional validation supported the role of TNF-α in inducing genomic instability. An estimated range of lower limits of benchmark dose of 4.19-7.28% of CCAM was recommended for risk assessment. Chronic CB exposure increased genomic instability in human circulation and this provided novel evidence supporting its reclassification as a human carcinogen.

Quantification of eight bisphenol analogues in blood and urine samples of workers in a hazardous waste incinerator.

Bisphenol A (BPA) has been widely used in the manufacture of polycarbonate plastic and epoxy resins. In recent years, producers have started replacing BPA by other chemical analogues, such as bisphenol -S (BPS) and -F (BPF), all of them under the label "BPA-free". However, despite bisphenol (BP) analogues have a very similar structure, their endocrine-disrupting properties could differ from those of BPA. Unfortunately, information regarding human exposure to BP analogues is very limited, not only as single substances, but also as chemical mixtures. The aim of this study was to determine the levels of 8 BP analogues (A, S, F, B, AF, Z, E, and AP) in biological samples from a controlled cohort of workers in a hazardous waste incinerator (HWI) located in Constantí (Catalonia, Spain). Firstly, a chemical method to analyze a mixture of those 8 analogues in total blood and urine was optimized, being samples quantified by means of gas chromatography coupled to mass spectrometry (GC-MS). Furthermore, a biomonitoring study was performed by collecting samples of total blood and urine of 29 people working in the HWI. Among the 8 BP analogues assessed, BPA presented the highest levels in both biological samples, with mean total (free + conjugated) BPA concentrations of 0.58 and 0.86 µg/L in blood and urine, respectively. Free vs. total BPA levels presented a mean percentage of 79% in blood and 19% in urine. Beyond BPA, traces of BPB were also found in a single sample of blood. Furthermore, none of the remaining BP analogues was detected in blood or urine. Despite BPA has been regulated, it is still very present in the environment, being human exposure to this chemical still an issue of concern for the public health.

Effect of bisphenol-A (BPA) on placental biomarkers for inflammation, neurodevelopment and oxidative stress.

Background Bisphenol-A (BPA) is a widespread pollutant whose effects on pregnant women are poorly understood. Therefore, we investigated the effects of BPA on basal and bacteria-stimulated production of proinflammatory cytokines [interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α) and IL-6], anti-inflammatory mediators [soluble glycoprotein 130 (sgp) 130, heme oxidase-1 (HO-1) and IL-10] and biomarkers for neurodevelopment [brain-derived neurotrophic factor (BDNF)], and oxidative stress [8-isoprostane (8-IsoP)] by the placenta. Methods Placental explant cultures were treated with BPA (0-10,000 nM) in the presence or absence of 107 colony-forming unit (CFU)/mL heat-killed Escherichia coli for 24 h. Biomarker concentrations in conditioned medium were quantified by the enzyme-linked immunosorbent assay (ELISA). Results Under basal conditions, IL-1ß and IL-6 production was enhanced by BPA in a dose-dependent manner. Sgp130, a soluble receptor that reduces IL-6 bioactivity, was suppressed by BPA at 1000-10,000 nM. BPA also enhanced BDNF production at 1000 and 10,000 nM, and 8-IsoP expression at 10 and 100 nM. For bacteria-treated cultures, BPA increased IL-6 production at 100 nM and reduced sgp130 at 1000 nM but had no effect on IL-1ß, TNF-α, BDNF, HO-1, 8-IsoP or IL-10 production. Conclusion BPA may increase placental inflammation by promoting IL-1ß and IL-6 but inhibiting sgp130. It may also disrupt oxidative balance and neurodevelopment by increasing 8-IsoP and BDNF production.

Exposure to lead and its effect on sleep quality and digestive problems in soldering workers.

Some studies show that exposure to lead affects sleep quality and causes digestive disorders. The aim of this study was to evaluate the quality of sleep and digestive disorders in solderers exposed to lead. In a cross-sectional study, the occupational exposure of 40 soldering workers to lead fume and their blood lead levels were measured in the electronics industry of Neyshabur city, according to standard methods. The sleep quality of workers was measured by the Pittsburgh Sleep Quality Index (PSQI) questionnaire and their digestive disorders were recorded in a checklist. This study showed that 67.5% of subjects had poor sleep quality. There was a significant relation between sleep quality, air lead (p = 0.02), and blood lead (p = 0.03). Bad sleep quality was 2.4 times higher in subjects exposed to lead above the threshold (p = 0.03). 92.5% of the population under study suffered from at least one digestive disorder. Digestive disorders such as hiccupping (85%) and nausea (67%) were more common among the workers, and their odds was 3.09 and 2.00 times higher in workers exposed to lead above the threshold, compared with others. Bad sleep quality and gastrointestinal disorders were prevalent among workers exposed to lead. The results of this study confirm the need for further research about the side effects of lead on humans. It also clarifies the need for a revision in the recommended occupational exposure level for lead.

Higher Hippocampal Mean Diffusivity Values in Asymptomatic Welders.

Chronic high-level manganese (Mn)-induced neurotoxicity has been associated with Mn accumulation in the basal ganglia and higher risk for developing parkinsonism. Recent studies in Mn-exposed animals revealed Mn accumulation in the hippocampus, the presence of Aß diffuse plaques, and deficits in associative learning, the latter being hallmarks of Alzheimer's disease (AD) or related disorders. This and recent evidence of hippocampal Mn accumulation in welders prompted us to test the hypothesis that welders with chronic Mn exposure would display changes in the hippocampus. Subjects with (welders; n = 42) or without (controls; n = 31) welding history were studied. Mn exposure was estimated by occupational questionnaires, whole blood Mn, and R1 imaging (estimate of short-term brain Mn accumulation). Hippocampal diffusion tensor imaging (DTI; estimate of microstructural brain changes) and volume were determined. Compared with controls, welders displayed no significant difference in hippocampal volume (p = .165). Welders, however, exhibited higher DTI hippocampal mean diffusivity (MD) values compared with controls (p = .035) that was evident particularly in older welders (>50 years, p = .002). Hippocampal MD was associated significantly with age in welders (R = 0.59; p < .001) but not in controls (p = .16). Moreover, higher hippocampal MD values (age adjusted) were associated with long-term cumulative Mn exposure (R = 0.36, p = .021). Welders with chronic exposure have higher MD values in the hippocampus that become greater with increasing age, a brain change that is similar to that observed in those at risk for AD. The current results suggest that Mn exposure, coupled with aging, may make welders more vulnerable to AD or AD-like changes.

A case study of the translocation, bioprocessing and tissue interactions of EMP following inhalation exposure.

Human autopsied lung sections from a resident in the Quebec asbestos region were examined. The study utilized high resolution transmission electron microscopy, scanning transmission electron microscopy (HRTEM/STEM) with the analytical capabilities of electron energy loss spectroscopy (EELS) and energy dispersive spectroscopy (EDS) detectors. We report the first analytical ultrastructural characteristics of EMPs, detailing chemical concentration gradients inside the iron-protein coatings and lateral elemental gradients in the local tissue regions. It is shown that the EMPs are subjected to bioprocessing which involves physicochemical transformations and also an elemental transport mechanism that alters the inhaled EMP as well as the surrounding cellular matrix. At high resolution imaging the iron-rich coating around the EMP was observed to have a distinct channel-like nanostructure with some parallel aligned nanofibrils that are reminiscent of tooth enamel which consists of biomineralized nanocomposites with alternating organic/inorganic matrices.

Characterization of lung burden E.M.P.S.

The physical characterisation of retained EMPS is extremely important in providing information regarding the aetiology of the disease they may produce. It is now accepted that the biological effects fibres may produce in lung tissue once deposited are closely related to their concentration but more critically to their variation in length and diameter. To assess the disease risk of exposure to EMPs it is necessary to accurately describe their lengths and diameter distribution. Microscopic examination of lung burden and respirable airborne dust samples of EMPs are therefore among the most important investigations necessary to assess the risks of exposure to EMPs and provide an understanding of the manner in which they can produce a disease response. While optical microscopy and electron (SEM and TEM) microscopy are techniques that might be applied in the study of lung burden, in practice the TEM is the only viable procedure suitable for such a purpose as the optical method, for example, cannot resolve the smaller fibres and the SEM may in some instances have similar limitations. It is also necessary to ensure that meaningful samples of EMPs are prepared in order to produce results that can be critically interpreted. Data collection relating to the physical size of fibres is very important and should be collected in a bi-variate form for comparative purposes. Airborne dust samples should relate to respirable sizes and be collected for direct examination. Tissue preparation techniques should be designed to ensure no alteration in the chemical or physical properties of fibre or other particle characteristics. Collection of numerical data by detailed sample analysis enables a better understanding of the most important factors which influence the disease potential of EMP dust clouds.

Micronucleus frequency is correlated with antioxidant enzyme levels in workers occupationally exposed to pesticides.

Oxidative stress can cause DNA damage leading to nuclear anomalies such as micronuclei (MN). Antioxidant enzymes involved in protection against intracellular oxidative stress include glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT). Pesticide exposure induces oxidative stress and alters antioxidant defense mechanisms, including detoxification and scavenger enzymes. The aim of this study was to evaluate MN frequency in workers occupationally exposed to pesticides and their relationship with antioxidant enzyme activities. A cross-sectional study was conducted in 201 individuals, some of whom were dedicated to the spraying of pesticides. The cytokinesis-block micronucleus (CBMN) assay was conducted, and the activities of GPx, GR, SOD, and CAT were determined. The geometric mean (GM) of MN was 5.4 (1-26 MN). The GM for the antioxidant enzymes was 198.68 U/mL for GPx, 38.96 U/g Hb for GR, 94.78 U/mL for SOD, and 69.77 U/g Hb for CAT. There was a lower MN frequency in males than that in females, and a higher nuclear index. In addition, age affected MN frequency. There was a negative correlation between MN frequency and GPx activity, but a positive one between MN frequency and GR activity. These findings suggest the involvement of GPx in MN frequency.

Effects of Genetic Polymorphism on Susceptibility to Nephrotoxic Properties of BTEXs Compounds.

OBJECTIVE: The aim of this study was to ascertain whether genetic polymorphism affects susceptibility of individuals to nephrotoxic potentials of benzene, toluene, ethyl-benzene, and xylenes (BTEXs). METHODS: Fifty BTEXs exposed workers with one or more abnormal parameter of kidney function and 232 referent subjects, with similar exposure history, free from any abnormal kidney parameters were investigated. Atmospheric concentrations of BTEXs were measured. In addition, genetic polymorphisms were determined by multiplex polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP). RESULTS: The frequencies of GSTP1 Ile-Val/Val-Val, null GSTT1, and null GSTT1/GSTM1 genotypes and mean values of blood urea nitrogen and plasma creatinine were significantly higher, while average glomerular filtration rate was significantly lower in cases than in referent subjects. CONCLUSION: These findings indicate that individuals carrying null GSTT1 or null GSTT1/GSTM1 are more susceptible to nephrotoxic properties of BTEXs compounds.

Disposition and metabolism of the bisphenol analogue, bisphenol S, in Harlan Sprague Dawley rats and B6C3F1/N mice and in vitro in hepatocytes from rats, mice, and humans.

With the removal of bisphenol A (BPA) from many consumer products, the potential use of alternatives such as bisphenol S (BPS) and its derivatives is causing some concerns. These studies investigated the comparative in vitro hepatic clearance and metabolism of BPS and derivatives and the disposition and metabolism of BPS in rats and mice following gavage and intravenous administration. The clearance of BPS and its derivatives was slower in human hepatocytes than in rodents. In male rats following gavage administration of 50, 150, and 500 mg/kg [14C]BPS the main route of excretion was via urine; the urinary excretion decreased (72 to 48%) and the fecal excretion increased (16 to 30%) with increasing dose. The disposition was similar in female rats and male and female mice following gavage administration. Radioactivity remaining in tissues at 72 h in both species and sexes was ≤2.4%. In bile duct cannulated rats 53% of a gavage dose was secreted in bile suggesting extensive enterohepatic recirculation of [14C]BPS. Following an intravenous dose in rats and mice, the pattern of excretion was similar to gavage. These data suggest that the dose excreted in feces folowing gavage administration is likely the absorbed dose. Urinary metabolites included the glucuronide and sulfate conjugates with a moderate amount of parent. The pattern of in vitro hepatic metabolsim was similar to in vivo with some difference among derivatives. These data suggest that similar to other bisphenol analogues, BPS was well absorbed following oral expsosure and extensively excreted with minimal tissue retention.

Association of exposure to manganese and iron with striatal and thalamic GABA and other neurometabolites - Neuroimaging results from the WELDOX II study.

OBJECTIVE: Magnetic resonance spectroscopy (MRS) is a non-invasive method to quantify neurometabolite concentrations in the brain. Within the framework of the WELDOX II study, we investigated the association of exposure to manganese (Mn) and iron (Fe) with γ-aminobutyric acid (GABA) and other neurometabolites in the striatum and thalamus of 154 men. MATERIAL AND METHODS: GABA-edited and short echo-time MRS at 3T was used to assess brain levels of GABA, glutamate, total creatine (tCr) and other neurometabolites. Volumes of interest (VOIs) were placed into the striatum and thalamus of both hemispheres of 47 active welders, 20 former welders, 36 men with Parkinson's disease (PD), 12 men with hemochromatosis (HC), and 39 male controls. Linear mixed models were used to estimate the influence of Mn and Fe exposure on neurometabolites while simultaneously adjusting for cerebrospinal fluid (CSF) content, age and other factors. Exposure to Mn and Fe was assessed by study group, blood concentrations, relaxation rates R1 and R2* in the globus pallidus (GP), and airborne exposure (active welders only). RESULTS: The median shift exposure to respirable Mn and Fe in active welders was 23µg/m3 and 110µg/m3, respectively. Airborne exposure was not associated with any other neurometabolite concentration. Mn in blood and serum ferritin were highest in active and former welders. GABA concentrations were not associated with any measure of exposure to Mn or Fe. In comparison to controls, tCr in these VOIs was lower in welders and patients with PD or HC. Serum concentrations of ferritin and Fe were associated with N-acetylaspartate, but in opposed directions. Higher R1 values in the GP correlated with lower neurometabolite concentrations, in particular tCr (exp(ß)=0.87, p<0.01) and choline (exp(ß)=0.84, p=0.04). R2* was positively associated with glutamate-glutamine and negatively with myo-inositol. CONCLUSIONS: Our results do not provide evidence that striatal and thalamic GABA differ between Mn-exposed workers, PD or HC patients, and controls. This may be due to the low exposure levels of the Mn-exposed workers and the challenges to detect small changes in GABA. Whereas Mn in blood was not associated with any neurometabolite content in these VOIs, a higher metal accumulation in the GP assessed with R1 correlated with generally lower neurometabolite concentrations.

Association of exposure to manganese and iron with relaxation rates R1 and R2*- magnetic resonance imaging results from the WELDOX II study.

OBJECTIVE: Magnetic resonance imaging is a non-invasive method that allows the indirect quantification of manganese (Mn) and iron (Fe) accumulation in the brain due to their paramagnetic features. The WELDOX II study aimed to explore the influence of airborne and systemic exposure to Mn and Fe on the brain deposition using the relaxation rates R1 and R2* as biomarkers of metal accumulation in regions of interest in 161 men, including active and former welders. MATERIAL AND METHODS: We obtained data on the relaxation rates R1 and R2* in regions that included structures within the globus pallidus (GP), substantia nigra (SN), and white matter of the frontal lobe (FL) of both hemispheres, as well as Mn in whole blood (MnB), and serum ferritin (SF). The study subjects, all male, included 48 active and 20 former welders, 41 patients with Parkinson's disease (PD), 13 patients with hemochromatosis (HC), and 39 controls. Respirable Mn and Fe were measured during a working shift for welders. Mixed regression models were applied to estimate the effects of MnB and SF on R1 and R2*. Furthermore, we estimated the influence of airborne Mn and Fe on the relaxation rates in active welders. RESULTS: MnB and SF were significant predictors of R1 but not of R2* in the GP, and were marginally associated with R1 in the SN (SF) and FL (MnB). Being a welder or suffering from PD or HC elicited no additional group effect on R1 or R2* beyond the effects of MnB and SF. In active welders, shift concentrations of respirable Mn>100µg/m3 were associated with stronger R1 signals in the GP. In addition to the effects of MnB and SF, the welding technique had no further influence on R1. CONCLUSIONS: MnB and SF were significant predictors of R1 but not of R2*, indicative of metal accumulation, especially in the GP. Also, high airborne Mn concentration was associated with higher R1 signals in this brain region. The negative results obtained for being a welder or for the techniques with higher exposure to ultrafine particles when the blood-borne concentration was included into the models indicate that airborne exposure to Mn may act mainly through MnB.

Association between polymorphism of GSTP1, GSTT1, GSTM1 and CYP2E1 genes and susceptibility to benzene-induced hematotoxicity.

Occupational exposure to benzene has been associated with leukemia, anemia, leukopenia, and thrombocytopenia. Genetic susceptibility to benzene toxicity in humans may be related to variations in benzene metabolizing genes. The main objective of this study was to ascertain whether polymorphism of GSTP1, GSTM1, GSTT1 and CYP2E1 genes might influence susceptibility to the adverse effects of benzene among employees of a petrochemical plant. In this cross-sectional study, 124 employees of a petrochemical plant who had been occupationally exposed to benzene and had one or more abnormal hematological parameter (cases) and 184 subjects with a similar exposure scenario, free from any abnormal hematological parameters (referent) were studied. Atmospheric concentrations of benzene were measured and GSTM1 and GSTT1 genotypes were evaluated using the multiplex polymerase chain reaction (PCR) technique. Additionally, GSTP1 and CYP2E1 genotypes were determined by PCR- restriction fragment length polymorphism (PCR-RFLP). The frequency of null GSTT1 genotype in cases was significantly higher than that of referent group (32.3 vs. 18.5%, OR 2.1, 95% CI 1.23-3.56, p = 0.004). The mean value of platelets in subjects with null GSTT1 genotype was significantly lower than that of individuals with positive GSTT1 genotype (p = 0.015). Conversely, the mean value of leukocytes was significantly higher in subjects with null GSTM1 genotype as compared to those with positive GSTM1 genotype (p = 0.026). Logistic regression analysis showed that, subjects with null GSTT1 genotype had a significantly higher risk for hematological disorders, as compared to those with positive GSTT1 genotype (OR 2.1, 95% CI 1.23-3.56). Moreover, subjects with both null GSTT1 and GSTM1 genotypes had a significantly higher risk for hematological disorders as compared to subjects with positive GSTT1 and GSTM1 genotypes (OR 2.35, 95% CI 1.14-4.8). The results of this study showed that, individuals carrying null GSTT1 or both null STT1 and GSTM1 genotypes had a higher risk and were more susceptible to benzene-induced hematological disorders.

Culture scale-up and immobilisation of a mixed methanotrophic consortium for methane remediation in pilot-scale bio-filters.

Robust methanotrophic consortia for methane (CH4) remediation and by-product development are presently not readily available for industrial use. In this study, a mixed methanotrophic consortium (MMC), sequentially enriched from a marine sediment, was assessed for CH4 removal efficiency and potential biomass-generated by-product development. Suitable packing material for bio-filters to support MMC biofilm establishment and growth was also evaluated. The enriched MMC removed ∼7-13% CH4 under a very high gas flow rate (2.5 L min-1; 20-25% CH4) in continuous-stirred tank reactors (∼10 L working volume) and the biomass contained long-chain fatty acids (i.e. C16 and C18). Cultivation of the MMC on plastic bio-balls abated ∼95-97% CH4 in pilot-scale non-sterile outdoor-operated bio-filters (0.1 L min-1; 1% CH4). Contamination by cyanobacteria had beneficial effects on treating low-level CH4, by providing additional oxygen for methane oxidation by MMC, suggesting that the co-cultivation of MMC with cyanobacterial mats does not interfere with and may actually be beneficial for remediation of CH4 and CO2 at industrial scale.

Analysis of inflammatory markers and metals in nasal lavage fluid of welders.

Welding fumes may produce adverse health effects in the respiratory tract. To assess the relationship between exposure to welding fumes and inflammation in the upper airways, 190 male welders were examined from the WELDOX study (median age 40 yr, 54.7% smokers, and 32.9% atopics). Inhalable welding fumes were collected in the breathing zone of welders during a single shift. Chromium (Cr), nickel (Ni), manganese (Mn), and iron (Fe) were measured in the welding-fume samples and in postshift nasal lavage fluid (NALF). In addition, the numbers of particles and inflammatory biomarkers, including total and differential cell counts, interleukin (IL)-8, leukotriene (LT) B4, 8-isoprostane (8-iso-PGF2α), tissue inhibitor of metalloproteinase-1 (TIMP-1), and immunoreactive matrix metalloproteinase (MMP)-9, were determined. Metal concentrations in NALF correlated with airborne concentrations. No significant association was found between airborne metal concentrations and biomarkers of inflammation in NALF, whereas increasing metal concentrations in NALF resulted in increased concentrations of total protein, IL-8, MMP-9, and TIMP-1. LTB4 and 8-iso PGF2α were elevated at higher concentrations of Cr or Ni in NALF. The same was true for Fe, although the effects were less pronounced and of borderline significance. In conclusion, our results showed a significant association between the concentrations of metals and soluble inflammatory markers in the NALF of welders. The noninvasive collection of NALF is applicable in field studies, where it may serve as a suitable matrix to simultaneously assess biomarkers of exposure and effect in the upper respiratory tract in workers who are occupationally exposed to airborne hazardous substances.

Diazepam influences urinary bioindicator of occupational toluene exposure.

In the present study, we investigated the influence of diazepam (DZP) on the excretion of TOL by examining their urinary metabolites, hippuric acid (HA) and ortho-cresol (o-C). Male Wistar rats were exposed to TOL (20ppm) in a nose-only exposure chamber (6h/day, 5days/week for 6 weeks) with simultaneous administration of DZP (10mg/kg/day). Urinary o-C levels were determined by GC-MS, while HA, creatinine (CR), DZP and its metabolite, nordiazepam, were analysed by HPLC-DAD. The results of a Mann-Whitney U test showed that DZP influenced the urinary excretion of o-C (p<0.05). This pioneering study revealed that there was an interaction between DZP and TOL, probably by the inhibition of the CYP isoforms (CYP2B6, CYP2C8, CYP2E1, and CYP1A2) involved in the oxidative metabolism of the solvent. This is relevant information to be considered in the biomonitoring of occupational toluene exposure.