Biochar dust emission: Is it a health concern? Preliminary results for toxicity assessment.

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 (

The Designer Drug αPHP Affected Cell Proliferation and Triggered Deathly Mechanisms in Murine Neural Stem/Progenitor Cells.

Increasing reports of neurological and psychiatric outcomes due to psychostimulant synthetic cathinones (SCs) have recently raised public concern. However, the understanding of neurotoxic mechanisms is still lacking, particularly for the under-investigated αPHP, one of the major MDPV derivatives. In particular, its effects on neural stem/progenitor cell cultures (NSPCs) are still unexplored. Therefore, in the current in vitro study, the effects of increasing αPHP concentrations (25-2000 µM), on cell viability/proliferation, morphology/ultrastructure, genotoxicity and cell death pathways, have been evaluated after exposure in murine NSPCs, using a battery of complementary techniques, i.e., MTT and clonogenic assay, flow cytometry, immunocytochemistry, TEM, and patch clamp. We revealed that αPHP was able to induce a dose-dependent significant decrease of the viability, proliferation and clonal capability of the NSPCs, paralleled by the resting membrane potential depolarization and apoptotic/autophagic/necroptotic pathway activation. Moreover, ultrastructural alterations were clearly observed. Overall, our current findings demonstrate that αPHP, damaging NSPCs and the morpho-functional fundamental units of adult neurogenic niches may affect neurogenesis, possibly triggering long-lasting, irreversible CNS damage. The present investigation could pave the way for a broadened understanding of SCs toxicology, needed to establish an appropriate treatment for NPS and the potential consequences for public health.

Effect of Musical Stimulation on Placental Programming and Neurodevelopment Outcome of Preterm Infants: A Systematic Review.

BACKGROUND: The fetal environment is modulated by the placenta, which integrates and transduces information from the maternal environment to the fetal developmental program and adapts rapidly to changes through epigenetic mechanisms that respond to internal (hereditary) and external (environmental and social) signals. Consequently, the fetus corrects the trajectory of own development. During the last trimester of gestation, plasticity shapes the fetal brain, and prematurity can alter the typical developmental trajectories. In this period, prevention through activity-inducing (e.g., music stimulation) interventions are currently tested. The purpose of this review is to describe the potentialities of music exposure on fetus, and on preterm newborns in the Neonatal Intensive Care Unit evaluating its influence on neurobehavioral development. METHODS: Databases were searched from 2010 to 2022 for studies investigating mechanisms of placental epigenetic regulation and effects of music exposure on the fetus and pre-term neonates. RESULTS: In this case, 28 selected papers were distributed into three research lines: studies on placental epigenetic regulation (13 papers), experimental studies of music stimulation on fetus or newborns (6 papers), and clinical studies on premature babies (9 papers). Placental epigenetic changes of the genes involved in the cortisol and serotonin response resulted associated with different neurobehavioral phenotypes in newborns. Prenatal music stimulation had positive effects on fetus, newborn, and pregnant mother while post-natal exposure affected the neurodevelopment of the preterm infants and parental interaction. CONCLUSIONS: The results testify the relevance of environmental stimuli for brain development during the pre- and perinatal periods and the beneficial effects of musical stimulation that can handle the fetal programming and the main neurobehavioral disorders.

Benzene Exposure and MicroRNAs Expression: In Vitro, In Vivo and Human Findings.

MicroRNAs (miRNAs) are important regulators of gene expression and define part of the epigenetic signature. Their influence on human health is established and interest in them is progressively increasing. Environmental and occupational risk factors affecting human health include chemical agents. Benzene represents a pollutant of concern due to its ubiquity and because it may alter gene expression by epigenetic mechanisms, including miRNA expression changes. This review summarizes recent findings on miRNAs associated with benzene exposure considering in vivo, in vitro and human findings in order to better understand the molecular mechanisms through which benzene induces toxic effects and to evaluate whether selected miRNAs may be used as biomarkers associated with benzene exposure. Original research has been included and the study selection, data extraction and assessments agreed with PRISMA criteria. Both in vitro studies and human results showed a variation in miRNAs' expression after exposure to benzene. In vivo surveys also exhibited this trend, but they cannot be regarded as conclusive because of their small number. However, this review confirms the potential role of miRNAs as "early warning" signals in the biological response induced by exposure to benzene. The importance of identifying miRNAs' expression, which, once validated, might work as sentinel molecules to better understand the extent of the exposure to xenobiotics, is clear. The identification of miRNAs as a molecular signature associated with specific exposure would be advantageous for disease prevention and health promotion in the workplace.

A follow-up study on workers involved in the graphene production process after the introduction of exposure mitigation measures: evaluation of genotoxic and oxidative effects.

During nanomaterial (NM) production, workers could be exposed, particularly by inhalation, to NMs and other chemicals used in the synthesis process, so it is important to have suitable biomarkers to monitor potential toxic effects. Aim of this study was to evaluate the effectiveness of the introduction of exposure mitigation measures on workers unintentionally exposed to graphene co-pollutants during production process monitoring the presumable reduction of workplace NM contamination and of early genotoxic and oxidative effects previously found on these workers. We used Buccal Micronucleus Cytome (BMCyt) assay and Fpg-comet test, resulted the most sensitive biomarkers on our first biomonitoring work, to measure the genotoxic effects. We also detected urinary oxidized nucleic acid bases 8-oxoGua, 8-oxoGuo and 8-oxodGuo to evaluate oxidative damage. The genotoxic and oxidative effects were assessed on the same graphene workers (N = 6) previously studied, comparing the results with those found in the first biomonitoring and with the control group (N = 11). This was achieved 6 months after the installation of a special filter hood (where to perform the phases at higher risk of NM emission) and the improvement of environmental and personal protective equipment. Particle number concentration decreased after the mitigation measures. We observed reduction of Micronucleus (MN) frequency and oxidative DNA damage and increase of 8-oxodGuo excretion compared to the first biomonitoring. These results, although limited by the small subject number, showed the efficacy of adopted exposure mitigation measures and the suitability of used sensitive and noninvasive biomarkers to bio-monitor over time workers involved in graphene production process.

A Comprehensive Review on Multifaceted Mechanisms Involved in the Development of Breast Cancer Following Adverse Childhood Experiences (ACEs).

BACKGROUND AND AIM OF THE WORK: Adverse Childhood Experiences (ACEs) may give rise to harmful effects on health throughout life. Epigenetic changes explain how preexisting risk factors may contribute to produce altered biological responses and cancer risk. The main aim of the review is to summarize studies examining the means in which Adverse Childhood Experiences (ACEs) can modulate individual vulnerability to breast cancer (BC) development through multifaceted mechanisms. METHODS: Studies selection, data extraction, and assessments agreed to PRISMA criteria. We included original research with clinical samples following BC interventions, investigating potential mechanisms linking ACEs and BC in adults. RESULTS: From the 3321 papers found, nine articles involving 2931 participants were selected. All studies included ACEs retrospective assessments and psychological measures, and seven of them considered biomarkers. Individuals exposed to greater ACEs were at increased BC risk compared with individuals with no ACEs. Associations were found between child abuse and/or neglect, depression, perceived stress, fatigue, and plasma levels of cytokines interleukin (IL-6), C-reactive protein (CRP), soluble tumor necrosis factor receptor type II (sTNF-RII), interleukin IL-1 receptor antagonist (IL-1ra), and psycho-physiological adjustments that may lead to BC. CONCLUSIONS: Exposure to multiple ACEs appears a risk factor for BC development in adulthood. Although the clinical relevance of findings such as this is ambiguous, the review added evidence for a link between the presence of childhood adversity and BC occurrence, pointing to psychological, hormonal, and immunological dysregulations.

Sex Difference and Benzene Exposure: Does It Matter?

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.

Environmental/Occupational Exposure to Radon and Non-Pulmonary Neoplasm Risk: A Review of Epidemiologic Evidence.

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.

Overexpression of microRNA­486 affects the proliferation and chemosensitivity of mesothelioma cell lines by targeting PIM1.

Dysregulated levels of microRNAs (miRNAs or miRs), involved in oncogenic pathways, have been proposed to contribute to the aggressiveness of malignant pleural mesothelioma (MPM). Previous studies have highlighted the downregulation of miRNA miR­486­5p in patients with mesothelioma and the introduction of miRNA mimics to restore their reduced or absent functionality in cancer cells is considered an important therapeutic strategy. The aim of the present study was to evaluate the mechanisms through which miRNAs may influence the functions, proliferation and sensitivity to cisplatin of MPM cells. In the present study, a miR­486­5p mimic was transfected into the H2052 and H28 MPM cell lines, and cell viability, proliferation, apoptosis and mitochondrial membrane potential were monitored. miR­486­5p overexpression led to a clear impairment of cell proliferation, targeting CDK4 and attenuating cell cycle progression. In addition, transfection with miR­486­5p mimic negatively regulated the release of inflammatory factors and the expression of Provirus integration site for Moloney murine leukaemia virus 1 (PIM1). The sensitivity of the cells to cisplatin was enhanced by enhancing the apoptotic effects of the drug and impairing mitochondrial function. On the whole, the present study demonstrates that miR­486­5p may play an important role in MPM treatment by targeting multiple pathways involved in tumour development and progression. These activities may be mostly related to the downregulation of PIM1, a crucial regulator of cell survival and proliferation. Furthermore, these results provide support for the combined use of miR­486­5p with chemotherapy as a therapeutic strategy for MPM.

Exposure to nanoparticles derived from diesel particulate filter equipped engine increases vulnerability to arrhythmia in rat hearts.

Air pollution is well recognized as a central player in cardiovascular disease. Exhaust particulate from diesel engines (DEP) is rich in nanoparticles and may contribute to the health effects of particulate matter in the environment. Moreover, diesel soot emitted by modern engines denotes defective surfaces alongside chemically-reactive sites increasing soot cytotoxicity. We recently demonstrated that engineered nanoparticles can cross the air/blood barrier and are capable to reach the heart. We hypothesize that DEP nanoparticles are pro-arrhythmogenic by direct interaction with cardiac cells. We evaluated the internalization kinetics and the effects of DEP, collected from Euro III (DEPe3, in the absence of Diesel Particulate Filter, DPF) and Euro IV (DEPe4, in the presence of DPF) engines, on alveolar and cardiac cell lines and on in situ rat hearts following DEP tracheal instillation. We observed significant differences in DEP size, metal and organic compositions derived from both engines. DEPe4 comprised ultrafine particles (<100 nm) and denoted a more pronounced toxicological outcome compared to DEPe3. In cardiomyocytes, particle internalization is fastened for DEPe4 compared to DEPe3. The in-vivo epicardial recording shows significant alteration of EGs parameters in both groups. However, the DEPe4-instilled group showed, compared to DEPe3, a significant increment of the effective refractory period, cardiac conduction velocity, and likelihood of arrhythmic events, with a significant increment of membrane lipid peroxidation but no increment in inflammation biomarkers. Our data suggest that DEPe4, possibly due to ultrafine nanoparticles, is rapidly internalized by cardiomyocytes resulting in an acute susceptibility to cardiac electrical disorder and arrhythmias that could accrue from cellular toxicity. Since the postulated transfer of nanoparticles from the lung to myocardial cells has not been investigated it remains open whether the effects on the cardiovascular function are the result of lung inflammatory reactions or due to particles that have reached the heart.

Occupational exposure to graphene and silica nanoparticles. Part II: pilot study to identify a panel of sensitive biomarkers of genotoxic, oxidative and inflammatory effects on suitable biological matrices.

The available biomonitoring studies on workers producing/handling nanomaterials (NMs) focused on potential effects on respiratory, immune and cardio-vascular system. Aim of this study was to identify a panel of sensitive biomarkers and suitable biological matrices to evaluate particularly genotoxic and oxidative effects induced on workers unintentionally exposed to graphene or silica nanoparticles during the production process. These nanomaterials have been chosen for 'NanoKey' project, integrating the workplace exposure assessment (reported in part I) with the biomonitoring of exposed workers reported in the present work. Simultaneously to workplace exposure characterization, we monitored the workers using: Buccal Micronucleus Cytome (BMCyt) assay, fpg-comet test (lymphocytes), oxidized DNA bases 8-oxoGua, 8-oxoGuo and 8-oxodGuo measurements (urine), analysis of oxidative stress biomarkers in exhaled breath condensate (EBC), FENO measurement and cytokines release detection (serum). Since buccal cells are among the main targets of NM occupational exposure, particular attention was posed to the BMCyt assay that represents a noninvasive assay. This pilot study, performed on 12 workers vs.11 controls, demonstrates that BMCyt and fpg-comet assays are the most sensitive biomarkers of early, still reparable, genotoxic and oxidative effects. The findings suggest that these biomarkers could represent useful tools for the biomonitoring of workers exposed to nanoparticles, but they need to be confirmed on a high number of subjects. However, such biomarkers don't discriminate the effects of NM from those due to other chemicals used in the NM production process. Therefore, they could be suitable for the biomonitoring of workers exposed to complex scenario, including nanoparticles exposure.

Welding Fumes, a Risk Factor for Lung Diseases.

(1) Background: Welding fumes (WFs) are composed of fine and ultrafine particles, which may reach the distal airways and represent a risk factor for respiratory diseases. (2) Methods: In vitro and in vivo studies to understand WFs pathogenesis were selected. Epidemiological studies, original articles, review, and meta-analysis to examine solely respiratory disease in welders were included. A systematic literature search, using PubMed, National Institute for Occupational Safety and Health Technical Information Center (NIOSHTIC), and Web of Science databases, was performed. (3) Results: Dose, time of exposure, and composition of WFs affect lung injury. Inflammation, lung defense suppression, oxidative stress, DNA damage, and genotoxic effects were observed after exposure both to mild and stainless steel WFs. (4) Conclusions: The detection of lung diseases associated with specific occupational exposure is crucial as complete avoidance or reduction of the exposure is difficult to achieve. Further studies in the area of particle research may aid the understanding of mechanisms involved in welding-related lung disease and to expand knowledge in welding-related cardiovascular diseases.

The Relationship Between Widespread Pollution Exposure and Oxidized Products of Nucleic Acids in Seminal Plasma and Urine in Males Attending a Fertility Center.

BACKGROUND: In recent decades, there has been an increase in male infertility, and in many cases, the etiology remains unclear. Several studies relate male hypo-fertility to xenobiotic exposure, even if no data exist about multiple exposure at the environmental level. METHODS: The study involved 86 males with diagnosis of idiopathic male infertility (IMI), and 46 controls with no alteration in sperm characteristics. Seminal plasma (SP) and urine samples were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) to quantify biomarkers of exposure (the main metabolites of benzene, toluene, 1,3-butadiene, 3-monochloropropanediol, styrene, and naphthol) and effect (oxidized products of nucleic acids). RESULTS: Biomarker concentrations were similar in subjects with IMI and controls even if a stronger correlation between biomarkers of exposure and effects were observed in SP. Data show that, both in SP and urine, most metabolites were inter-correlated, indicating a simultaneous co-exposure to the selected substances at the environmental level. Principal component analysis showed in SP the clustering of mercapturic acids indicating a preferential metabolic pathway with Glutathione (GSH) depletion and, consequently, an increase of oxidative stress. This result was also confirmed by multivariable analysis through the development of explanatory models for oxidized products of nucleic acids. CONCLUSIONS: This study highlights how oxidative stress on the male reproductive tract can be associated with a different representation of metabolic pathways making the reproductive tract itself a target organ for different environmental pollutants. Our results demonstrate that SP is a suitable matrix to assess the exposure and evaluate the effects of reproductive toxicants in environmental/occupational medicine. The statistical approach proposed in this work represents a model appropriate to study the relationship between multiple exposure and effect, applicable even to a wider variety of chemicals.

Biomarkers of exposure to aromatic hydrocarbons and methyl tert-butyl ether in petrol station workers.

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.

Inter- and intra-subject variability of kinetics of airway exhalation and deposition of particulate matter in indoor polluted environments.

PM(2.5) generated by indoor combustion activities can contribute significantly to personal PM exposure. The aims of this study were: (1) to validate a device specifically designed to study the kinetics of particle exhalation and the percentage of airway particle deposition (%DEP) in polluted indoor environments (welding fumes, environmental tobacco smoke - ETS) and (2) to assess the intra- and inter-subject variability of the signal. The device was tested on 14 subjects exposed to welding fumes and 10 subjects exposed to environmental tobacco smoke (ETS), performing repeated measures at different environmental PM concentrations. The intra-subject variability of the signal for particles with diameter 0.3-1.0 µm showed a geometric mean of %CV always below 6%, despite the values of %DEP. In the welding fume study, the increase in airborne 0.5-1.0 µm PM concentrations between the consulting room and production department was explainable in terms of increased density due to the metallic composition of particles. The %DEP of 0.3-1.0 µm ETS particles decreased with airborne PM concentration due to the technical limits of a laser particle counter and the perturbation induced by the physical characteristics of ETS PM. However, also at those extreme conditions, the signal remained repeatable and the individual susceptibility to PM remained substantially unaltered. In conclusion, the versatility and portability of our device, together with the repeatability of the signal, confirmed that the kinetics of exhaled particles and %DEP could be routinely measured in polluted environments and used to define individual susceptibility to airborne particles.

Developmental exposure to methylmercury and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) affects cerebral dopamine D1-like and D2-like receptors of weanling and pubertal rats.

MeHg (0.5 mg/kg/day) and/or PCB153 (5 mg/kg/day) effects, administered orally to rat dams (GD7-PND21), were explored in PND21 and PND36 offspring brain in terms of density (Bmax) and affinity (Kd) of dopamine D1-like (D1-Rs) and D2-like receptors (D2-Rs), by saturation binding studies. D1-Rs decreased density in both cortex and striatum (15-30%) by MeHg and PCB153, either alone or combined, without additivity in PND21 males. Changes disappeared by PND36. In females, only MeHg caused a 15% Bmax decrease in striatum. D2-Rs enhanced density (23-50%) and reduced affinity in cortex to a similar extent by all treatments in both weanling and pubertal males. Affinity was also decreased in females by all types of exposure at both ages, while density was enhanced by PCB153 only in a delayed manner (PND36). No changes were detected in striatum. In MeHg and MeHg + PCB153 pup cortex, Hg concentrations ranged, on PND21, between 0.25 and 0.89 and 0.94-1.40 µg/g tissue, respectively, and were 5- to sixfold lower 2 weeks later. PCB153 levels, in PCB153 ± MeHg treated rats, were about 15 µg/g tissue (PND21) and 4-8 µg/g tissue (PND36). In striatum, the Hg and PCB153 concentrations were similar to those in cortex. Brain kinetics trend also applied to blood PCB153 or Hg levels. Perinatal exposure to MeHg and/or PCB153 affects D1- and D2-Rs in a gender-, time-, and brain area-dependent manner. Combined treatment does not exacerbate the neurochemical effects of the individual compounds.

Determination of aldehydes in exhaled breath of patients with lung cancer by means of on-fiber-derivatisation SPME-GC/MS.

A number of volatile organic compounds (VOCs) have been identified and used in preliminary clinical studies of the early diagnosis of lung cancer. The aim of this study was to evaluate the potential of aldehydes (known biomarkers of oxidative stress) in the diagnosis of patients with non-small cell lung cancer (NSCLC). We used an on-fiber-derivatisation SPME sampling technique coupled with GC/MS analysis to measure straight aldehydes C3-C9 in exhaled breath. Linearity was established over two orders of magnitude (range: 3.3-333.3×10(-12) M); the LOD and LOQ of all the aldehydes were respectively 1×10(-12) M and 3×10(-12) M. Accuracy was within 93% and precision calculated as % RSD was 7.2-15.1%. Aldehyde stability in a Bio-VOC(®) tube stored at +4°C was 10-17 h, but this became >10 days using a specific fiber storage device. Finally, exhaled aldehydes were measured in 38 asymptomatic non-smokers (controls) and 40 NSCLC patients. The levels of all of the aldehydes were increased in the NSCLC patients without any significant effect of smoking habits and little effect of age. The good discriminant power of the aldehyde pattern (90%) was confirmed by multivariate analysis. These results show that straight aldehydes may be promising biomarkers associated with NSCLC, and increase the sensitivity and specificity of previously identified VOC patterns.

Occupational exposure to low levels of benzene: Biomarkers of exposure and nucleic acid oxidation and their modulation by polymorphic xenobiotic metabolizing enzymes.

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).

Nitrous oxide determination in postmortem biological samples: a case of serial fatal poisoning in a public hospital.

In a public hospital, eight cases of fatal poisoning by nitrous oxide (N(2)O) occurred under oxygen administration, due to an erroneous swapping of the lines in the gas system. The aim of the study was to clarify the factors involved in asphyxia by characterizing gases from different lines and measuring N(2)O concentrations in postmortem biological samples from bodies exhumed. Analyses carried out on the gas system confirmed the erroneous substitution of O(2) line with N(2)O and air line with O(2). Consequently, high N(2)O amounts were revealed in several tissues and gaseous biological samples. All specimens were analyzed by headspace gas chromatography technique. A rigorous quantitative analysis was possible only in blood (11.29-2152.04 mg/L) and urine (95.11 mg/L) and in air samples from stomach and trachea (from 5.28 to 83.63 g/m(3)). This study demonstrates that N(2)O can be detected in biological samples even 1 month after death.

Low concentrations of the brominated flame retardants BDE-47 and BDE-99 induce synergistic oxidative stress-mediated neurotoxicity in human neuroblastoma cells.

Polybrominated diphenyl ether (PBDE) flame retardants have become widespread environmental contaminants. The highest body burden has been found in toddlers and infants, due to their exposure through breast milk and house dust, and the current concern for potential adverse health effects of PBDEs relates to their developmental neurotoxicity. The mechanisms underlying the neurotoxicity of PBDEs are largely not understood, though there is evidence that PBDEs may elicit oxidative stress. In this study, two different mathematical models were used to evaluate the interaction between BDE-47 and BDE-99 on viability of neuronal cells. The combined exposure to these compounds induced synergistic effects at concentrations of BDE-47 below its threshold doses, and in a wide range of BDE-99 concentrations below its IC(50). In contrast, at concentrations of BDE-47 near its IC(50) value, and in a wide range of BDE-99 concentrations, antagonistic effects were observed. The interactions observed on cell viability were confirmed by an assessment of induction of oxidative stress. The finding that co-exposure to BDE-47 and BDE-99 could induce synergistic neurotoxic effects, in particular at low doses of BDE-47, is of much toxicological interest, as humans are exposed to mixtures of PBDEs, most notably tetra- and penta-BDE congeners.