Exposure to individual and multiple carcinogenic metals during paediatric age: an experience from an Italian urban scenario.

BACKGROUND: Exposure to single and multiple carcinogenic metals and/or semimetals represents a major environmental risk factor for public health. In particular, children are more susceptible to environmental pollutants than adults, but specific studies are still limited. The aims of the present study were: 1) to trace the exposure and co-exposure profiles to eight known or suspected carcinogenic metals and semimetals (As, Be, Cd, Co, Cr, Ni, Pb, and Sb); and: 2) to evaluate the influence of some possible interfering/confounding factors on the exposure to these elements during childhood. STUDY DESIGN: Cross-sectional study. METHODS: We recruited 159 healthy Italian children attending a primary school of the urban area of Rome, Italy. Selected metals were determined by inductively coupled plasma mass spectrometry on urinary samples collected at the end of a "typical" day (one sample for each child), while information about possible confounding/interfering factors were collected via questionnaires. RESULTS: The great part of the studied children resulted co-exposed to the monitored metals: 83.2%, 69.2%, 51.0% and 29.3% of the participants were concurrently exposed to at least two, three, four and five trace elements, respectively. Gender was the only one among the investigated variable that significantly influenced the co-exposure, with females resulting at lower risk (OR = 0.392; 95 IC = 0.156 - 0.989; p < 0.047). CONCLUSIONS: Given the importance of protecting child's health and the risks related to the exposure to carcinogenic metals, especially when they occur simultaneously, other researches in this field are strongly recommended.

Urinary biomarkers of exposure and of oxidative damage in children exposed to low airborne concentrations of benzene.

The aim of this work was to evaluate the oxidative damage to nucleic acids in children (5-11 years) associated with exposure to environmental pollutants and tobacco smoke (ETS). For each subject, urinary sampling was done twice (evening and next morning) to measure by tandem LC-MS-MS such oxidated products of nucleic acids as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and 8-oxo-7,8-dihydroguanine (8-oxoGua). Methyl tert-butyl ether (U-MTBE), benzene (U-Benz), and its metabolites (t,t-muconic and S-phenylmercapturic acids, t,t-MA and S-PMA, respectively) were determined as biomarkers of exposure to air pollution, and cotinine as a biomarker of exposure to ETS. Biomarkers of exposure (S-PMA and U-MTBE) and of DNA oxidation (8-oxodGuo) were dependent on the urbanization and industrialization levels and increased in the evening sample as compared to next morning (p<0.05). In both evening and next morning samples, 8-oxodGuo and 8-oxoGuo correlated with each other (r=0.596 and r=0.537, respectively, p<0.01) and with biomarkers of benzene exposure, particularly S-PMA (r=0.59 and r=0.45 for 8-oxodGuo and r=0.411 and r=0.383 for 8-oxoGuo, p<0.01). No such correlations were observed for U-MTBE and cotinine. Multiple linear regression analyses showed that 8-oxodGuo was positively associated with S-PMA at both sampling times (ß=0.18 and ß=0.14 for evening and next morning sampling, respectively; p<0.02) and weakly with U-MTBE (ß=0.07, p=0.020) only in the evening urines. These results suggest that the selected biomarkers of exposure to benzene, particularly S-PMA, are good tracers of exposure to complex mixtures of oxidative pollutants and that the associated oxidative damage to nucleic acids is detectable even at very low levels of exposure.

Synergistic interactions between PBDEs and PCBs in human neuroblastoma cells.

Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants. Exposure to these chemicals has been associated with developmental neurotoxicity, endocrine dysfunction, and reproductive disorders. Humans and wildlife are generally exposed to a mixture of these environmental pollutants, highlighting the need to evaluate the potential effects of combined exposures. In this study, we investigated the cytotoxic effects of the combined exposure to two PBDEs and two PCBs in a human neuronal cell line. 2,2',4,4'-Tetrabromodiphenyl ether, 2,2',4,4',5-pentabromodiphenyl ether, PCB-126 (3,3',4,4',5-pentachlorobiphenyl; a dioxin-like PCB), and PCB-153 (2,2',4,4',5,5'-hexachlorobiphenyl; a non-dioxin-like PCB) were chosen, because their concentrations are among the highest in human tissues and the environment. The results suggest that the nature of interactions is related to the PCB structure. Mixtures of PCB-153 and both PBDEs had a prevalently synergistic effect. In contrast, mixtures of each PBDE congener with PCB-126 showed additive effects at threshold concentrations, and synergistic effects at higher concentrations. These results emphasize the concept that the toxicity of xenobiotics may be affected by possible interactions, which may be of significance given the common coexposures to multiple contaminants.

[Interpretative strategies of lung function tests: obstructive pattern]. / Strategie interpretative del deficit ostruttivo all'esame spirometrico.

INTRODUCTION: Periodic spirometric assessment is critical in the health surveillance of workers who are exposed to respiratory pollutants and plays a key role in the prevention of occupational lung diseases. OBJECTIVES: The aim of this review is to provide updates on the proper spirometry examination procedure and the criteria for data interpretation, in order to correctly diagnose obstructive impairment and longitudinal decline of pulmonary function. METHODS: A review of the most recent scientific literature was carried out focusing on those papers dealing with spirometric techniques, choice of reference values, and criteria for data interpretation. RESULTS: Over the years, the use of different diagnostic algorithms and reference values have led to poor clarity among users as well as diagnostic misclassifications. CONCLUSIONS: For spirometric data reliability it is mandatory to perform appropriate pulmonary function tests, make a correct selection of reference values and use updated interpretive criteria.

[New perspectives in biomonitoring of metallic elements: the example of hexavalent chromium]. / Nuove prospettive nel monitoraggio biologico degli elementi metallici: l'esempio del cromo esavalente.

Plating industry is an important productive sector in all the national territory, because of its contribution to a high number of industrial products and crafts. In the chrome plating sector there is a specific chemical risk due to the exposure to compounds containing hexavalent Chromium [Cr(VI)]. Exhaled breath condensate (EBC) has been used to study both acute and long term exposure to Cr(VI) in chrome plating workers. Cr-EBC correlates with specific oxidative stress biomarkers. Moreover, both total Cr and its hexavalent fraction can be measured in EBC, which therefore is a promising biological fluid to assess the absorbed dose at the target organ level, the pulmonary reduction kinetics of Cr(VI) and in general its local pneumotoxic effects. EBC collection and analysis could give additional information to the traditional measures performed during biomonitoring.

[Sleep disorders, risk of accidents and traffic accidents in a group of drivers of public transport]. / Disturbi del sonno, rischio infortunistico e incidenti stradali in un gruppo di autisti di mezzi pubblici.

In order to evaluate the prevalence of sleep disorders and visuomotor performance, a survey was conducted on 253 drivers of public transport company, aged between 25 and 64 years. Biometric data (BMI, neck circumference and waist, PA) were collected and three questionnaires were administered to investigate sleep disorders. Simple and multiple choice reaction times were administered using a computerized test battery. Records on road accidents in the period 2005-2011 and all accidents in the period 2002-2010 were analyzed. On the basis of clinical and anamnestic questionnaire, workers were divided into two groups: 194 drivers (group 1) without suspicion of sleep disorders and 59 drivers (group 2) with suspected sleep disorders, and 41 with suspected obstructive sleep apnea syndrome (OSAS). The drivers with suspicion of sleep disorders, in particular those with suspected diagnosis of OSAS, showed reaction times significantly prolonged as compared to the drivers of the group 1. In group 2, a higher incidence of (all) accidents was found, whereas the incidence of road accidents was significantly increased only in drivers with suspected OSAS. In addition to the sleep disorders, the use of drugs altering vigilance (antihistamines and benzodiazepines) were significant determinants. In-depth clinical examinations are in progress to confirm the suspected diagnosis of sleep disorders.

Association between environmental exposure to benzene and oxidative damage to nucleic acids in children.

OBJECTIVES: To evaluate the association between environmental exposure to benzene and oxidative damage to nucleic acids in children, also considering the role of Environmental Tobacco Smoke (ETS). METHODS: 396 children living in central Italy were recruited in districts with different urbanization and air pollution. All biomarkers were determined in spot urine samples by mass spectrometric techniques to assess exposure [benzene (U-Benz), and its metabolites (t,t-muconic and S-phenylmercapturic acids, t,t-MA and S-PMA, respectively), cotinine] and nucleic acid oxidation [8-oxo-7, 8-dibydro-2'-deoxyguanosine (8-oxodGuo), 8-oxo-7, 8-dihydroguanosine (8-oxoGuo), and 8-oxo-7, 8-dihydroguanine (8-oxoGua)]. RESULTS: Biomarkers of exposure and nucleic acid oxidation increased with urbanization and were correlated with each other (r > 0.18, p < 0.005). In a multiple linear regression model, benzene exposure, assessed by S-PMA and t,t-MA, was associated (p < 0.0001) with both 8-oxodGuo (R2 = 0.392) and 8-oxoGuo (R2 = 0.193) in all areas of residence, with similar slopes. CONCLUSIONS: (i) Biomarkers of exposure to benzene increased as a function of environmental air pollution and urbanization level; (ii) U-Benz clearly distinguished both exposure to ETS and areas of residence, whereas benzene metabolites were associated only with the latter; (iii) the variance of 8-oxodGuo and 8-oxoGuo was accounted for by environmental benzene exposure, thus suggesting that benzene is a good tracer of other components of complex mixtures of pollutants causing oxidative damage to nucleic acids.

[Environmental and biological monitoring of exposure to monoaromatic hydrocarbons and to methyl tert-butyl ether in a group of petrol station workers]. / Monitoraggio ambientale e biologico dell'esposizione ad idrocarburi mono-aromatici ed a metil tert-butil etere in un gruppo di lavoratori addetti all'erogazione di carburanti.

The aim of the study was to evaluate biomarkers of exposure to gasoline in petrol station workers by a combined approach of environmental and biological monitoring. The personal exposure to benzene, toluene, ethylbenzene and xylene (BTEX) and the urinary levels of BTEX, methyl tert-butyl ether (U-MTBE), trans,trans-muconic (t,t-MA) and S-phenylmercapturic acids (S-PMA) and cotinine were determined by mass spectrometry coupled chromatographic techniques. U-MTBE levels were strictly influenced by occupational exposure to gasoline, whereas both U-B and S-PMA levels depended from smoking habits and occupational exposure.

[Biological monitoring and exposure to silica: application of new dose and effect biomarkers]. / Monitoraggio biologico ed esposizione a silice: applicazione di nuovi indicatori di dose e di effetto.

Si-CAE was measured in 16 composite marble industry workers furthermore, a spirometry was performed and 8oxoGua, 8oxoGuo 8oxodGuo, SP-A, SP-D, CC16 and HO-1 were dosed. A lower spirometric values (FEV1 and FVC) were observed among workers compared with controls and the following markers were increased: Si-CAE, 8oxoGuo and HO-1 expression. This study shows that exposure to silica can increase the levels of Si-CAE, which can be used to estimate the dose to the target. Finally, nonspecific spirometric abnormalities and an increase in biomarkers of effect were observed.

[Early molecular diagnosis of lung cancer: a method to rule out the disease]. / Diagnosi molecolare precoce del tumore polmonare: un metodo per escludere la malattia.

Aim of this study was the determination of new markers for the diagnosis of lung cancer. 61 patients with non-small cell lung cancer (NSCLC) and 42 controls were enrolled. In the NSCLC patients the following markers were increased: H2O2 in exhaled breath condensate, pentane, hexane, nonenal, trans-2-heptanal, trans-2-nonenal in exhaled breath, while pentanal was decreased. Using multivariate statistical models, a sensitivity of 73.8% and a specificity of 76.8% were calculated. This study shows that with this non-invasive test followed by a most powerful test on positives (e.g. PET) it is possible to decrease the number of false positives.

[Acute lead poisoning: a singular case of hemolytic anemia and lead colic]. / Intossicazione acuta da piombo: un caso singolare di anemia emolitica e colica saturnina.

BACKGROUND: Acute lead poisoning due to food intake is exceptional in adults and often associated with mental illness OBJECTIVES: to describe a case report of acute lead intoxication with haemolytic anemia and lead colic. METHODS: A 41-year old male patient was admitted to hospital for abdominal pain and persistent constipation. Abdominal X-ray showed a radiopaque mass in the caecum and progressive anaemia was observed The patient was discharged with a diagnosis of bowel obstruction. Due to persistence of the symptoms he was again hospitalized; abdominal X-ray showed diffuse radiopaque particles in the colon and haemoglobin (hb) had dropped to 8.7 g/dl. Blood levels of lead and zinc protoporphryin were 106.7 microg/dl and 6.6 microg/gHb, respectively. The timely start of chelating therapy led to a rapid return to normal peripheral blood counts and a decline in blood lead levels. RESULTS: Although acute lead poisoning due to intake with food is exceptional in adults and often associated with mental illness, in this case, it was not possible to clarify the route and vehicle of ingestion of the toxic. Lead body burden was shown as a caecal mass, probably as a result of ingesting a single bolus of lead dust which, considering the size and density of the mass, was estimated as weighing several grammes. This acute lead intake induced an acute haemolysis due to enhanced fragility of the erythrocyte membrane. CONCLUSIONS: In the course of acute lead intoxication, the critical organ is not the bone marrow, but rather the red blood cell, leading to haemolysis and anaemia.

[Laboratory animal; allergy; asthma]. / Allergia da animali da laboratorio.

Laboratory animal allergy (LAA) may develop when susceptible persons are exposed to allergens produced by laboratory animals. LAA is associated with exposure to urine, fur, and salivae of rats, guinea pigs, dogs and rabbits. Approximately 30% of persons who are exposed to laboratory animals may develop LAA and some will also develop asthma. LAA is most likely to occur in persons with previously known allergies, especially to domestic pets. The majority of LAA sufferers experience symptoms within six months their first exposure to laboratory animals; almost all develop symptoms within three years. The most common symptoms are watery eyes and an itchy, runny nose, although skin symptoms and lower respiratory tract symptoms may also occur. Feeding and handling laboratory animals or cleaning their cages generates ten times the amount of allergens compared with undisturbed conditions. Prevention of animal allergy depends on control of allergenic material in the work environment and on organizational and individual protection measures. Pre-placement evaluation and periodic medical surveillance of workers are important pieces of the overall occupational health programme. The emphasis of these medical evaluations should be on counselling and early disease detection.

Methylmercury at low doses modulates the toxicity of PCB153 on PC12 neuronal cell line in asynchronous combination experiments.

Me-Hg and PCB153 are known neurotoxic contaminants which tend to accumulate in food, particularly in fish. Aim of this study was to perform asynchronous and combined exposure to Me-Hg and PCB153 in a neuronal rat cell line (PC12) to better characterise the antagonism observed at some combination concentrations. PC12 cells were treated with three concentrations of Me-Hg (0.1-0.5-1.0 microM) and PCB153 at one concentration (175 microM) in single and combined asynchronous exposures, using viability (MTT assay) as end-point. At all concentrations used, a statistically significant antagonistic effect was observed when Me-Hg preceded PCB153 exposure, while effect was additive when PCB153 preceded Me-Hg exposure. The antagonism is particularly evident at low concentrations of Me-Hg (0.1 microM). In conclusion, combined asynchronous exposure showed that whereas Me-Hg can modulate PCB153 toxicity, the opposite seems not to be true. Therefore, the use of asynchronous exposure could be a promising approach to study the mechanisms of toxicity of binary mixtures.

Opinion of hepatic transplant waiting list patients regarding split liver transplantation.

BACKGROUND: Split liver transplantation (SLT) increases organ supply for hepatic transplantation. Long-term patient survival and complication rates seem to be equivalent between orthotopic liver transplantation (OLT) and SLT. There are controversies among transplant physicians due to an ethical dilemma between benefiting individual needs or those of society. Barshes and Goss (Am J Transplant 5:2047, 2005) demonstrated that the majority of adult liver transplant candidates are favorable to SLT. The aim of our study was to evaluate the opinions of patients at a Brazilian university hospital regarding SLT. MATERIALS AND METHODS: A questionnaire with 14 questions was applied to 50 patients included in a hepatic transplant waiting list regarding SLT. RESULTS: The overall attitudes of 66% of the participants were classified as utilitarian, 31% were classified as self-preserving, and 3% were undecided. Ninety-one percent of patients would be willing to share even if their expected survival after SLT was shorter than that with OLT. For 77% of patients, children must have priority over adults. However, 83% were unaware of the donors for pediatric transplantations. CONCLUSIONS: SLT is a consistent solution for organ demand despite controversies among transplant physicians. The present study demonstrated that most patients were favorable to SLT. In conclusion, attitudes toward graft sharing are not barriers to SLT.

New techniques for assessment of occupational respiratory diseases.

Recently, as several studies have demonstrated, these non-invasive techniques, such as induced sputum (IS) or analysis of the exhaled air; exhaled nitric oxide (eNO) or exhaled breath condensate (EBC) provide fairly reliable results that correlate with those of "gold standard" methods (bronchoscopy, bronchoalveolar lavage) which are more invasive and uncomfortable for patients. Although novel approaches have attracted the attention of scientists, they have not been examined in relation to occupational settings and professional diseases. The IS is a useful biological medium for the diagnosis of occupational asthma and for the assessment of exposures to harmful dust at workplaces. The eNO analysis can serve as an easy and comfortable diagnostic tool for the professional asthma after exposure to various allergens. The examination of EBC biomarkers evaluates local doses of hard metals in the lung, as well as detection of oxidative stress markers (malondialdehyde, H2O2). Due to the need to standardize the procedures for EBC collection, further studies on EBC validation and the subsequent application in the clinical and epidemiological fields are required. The techniques listed in this article may serve as optimal tools for diagnosis of occupational respiratory diseases and for screening/monitoring programs following inhalation exposures in future (ref 64).

[Non-invasive assessment of lung pathobiology in hairdressers]. / Valutazione non invasiva della patobiologia polmonare in una coorte di lavoratori del settore acconciatura.

BACKGROUND: Hairdressers are exposed to chemical agents with potentially irritant and sensitizing effects on airways. OBJECTIVES: To asses the presence of respiratory symptoms and biochemical and functional changes of the airways in a cohort of hairdressers. METHODS: Respiratory symptoms, lung function tests, fractional exhaled nitric oxide (FE(NO)50) and selected oxidative stress biomarkers [hydrogen peroxide (H2O2), malondialdehyde (MDA) and 4-hydroxynonenal (HNE)] in exhaled breath condensate (EBC) were assessed in 23 hairdressers on a rest day (Group 1); 12 workers (Group 2) were willing to perform the same tests at the beginning (BS) and at the end of a shift (ES) on the same working day. Eighteen subjects not occupationally exposed to airways irritants formed the control group. RESULTS: Most of the hairdressers reported respiratory symptoms during work; however, all (except one) showed normal spirometry indexes. FE(NO)50 levels were within the reference limits and did not change comparing BS vs. ES sampling. H2O2 and HNE values in EBC were higher in Group 1 (H2O2: 0,16 [0,05-0,19] microM; HNE: 0,94 [0,82-1,22] nM) than in controls (H2O2: 0,05 [0,02-0,09] microM; HNE: 0,61 [0,49-0,78] nM, p < 0,001). In Group 2, H2O2 and MDA levels were higher in EBC collected at ES (0,56 [0,23-3,62] mM and 5,21 [4,93-5,95] nM) in comparison with the BS values (0,11 [0,03-0,28] mM and 4,12 [3,46-5,16] nM, p < 0,001 and p < 0,02, respectively). CONCLUSIONS: Increased levels of oxidative stress biomarkers are detectable in EBC of hairdressers, without impairment in respiratory function. Exhaled biomarkers of oxidative stress may be sensitive end points for evaluating early biochemical changes in the airways of hairdressers.

Environmental risk factors for Parkinson's disease and parkinsonism: the Geoparkinson study.

OBJECTIVE: To investigate the associations between Parkinson's disease and other degenerative parkinsonian syndromes and environmental factors in five European countries. METHODS: A case-control study of 959 prevalent cases of parkinsonism (767 with Parkinson's disease) and 1989 controls in Scotland, Italy, Sweden, Romania and Malta was carried out. Cases were defined using the United Kingdom Parkinson's Disease Society Brain Bank criteria, and those with drug-induced or vascular parkinsonism or dementia were excluded. Subjects completed an interviewer-administered questionnaire about lifetime occupational and hobby exposure to solvents, pesticides, iron, copper and manganese. Lifetime and average annual exposures were estimated blind to disease status using a job-exposure matrix modified by subjective exposure modelling. Results were analysed using multiple logistic regression, adjusting for age, sex, country, tobacco use, ever knocked unconscious and family history of Parkinson's disease. RESULTS: Adjusted logistic regression analyses showed significantly increased odds ratios for Parkinson's disease/parkinsonism with an exposure-response relationship for pesticides (low vs no exposure, odds ratio (OR) = 1.13, 95% CI 0.82 to 1.57, high vs no exposure, OR = 1.41, 95% CI 1.06 to 1.88) and ever knocked unconscious (once vs never, OR = 1.35, 95% CI 1.09 to 1.68, more than once vs never, OR = 2.53, 95% CI 1.78 to 3.59). Hypnotic, anxiolytic or antidepressant drug use for more than 1 year and a family history of Parkinson's disease showed significantly increased odds ratios. Tobacco use was protective (OR = 0.50, 95% CI 0.42 to 0.60). Analyses confined to subjects with Parkinson's disease gave similar results. CONCLUSIONS: The association of pesticide exposure with Parkinson's disease suggests a causative role. Repeated traumatic loss of consciousness is associated with increased risk.

Gene-environment interactions in parkinsonism and Parkinson's disease: the Geoparkinson study.

OBJECTIVES: To investigate associations of Parkinson's disease (PD) and parkinsonian syndromes with polymorphic genes that influence metabolism of either foreign chemical substances or dopamine and to seek evidence of gene-environment interaction effects that modify risk. METHODS: A case-control study of 959 prevalent cases of parkinsonism (767 with PD) and 1989 controls across five European centres. Occupational hygienists estimated the average annual intensity of exposure to solvents, pesticides and metals, (iron, copper, manganese), blind to disease status. CYP2D6, PON1, GSTM1, GSTT1, GSTM3, GSTP1, NQO1, CYP1B1, MAO-A, MAO-B, SOD 2, EPHX, DAT1, DRD2 and NAT2 were genotyped. Results were analysed using multiple logistic regression adjusting for key confounders. RESULTS: There was a modest but significant association between MAO-A polymorphism in males and disease risk (G vs T, OR 1.30, 95% CI 1.02 to 1.66, adjusted). The majority of gene-environment analyses did not show significant interaction effects. There were possible interaction effects between GSTM1 null genotype and solvent exposure (which were stronger when limited to PD cases only). CONCLUSIONS: Many small studies have reported associations between genetic polymorphisms and PD. Fewer have examined gene-environment interactions. This large study was sufficiently powered to examine these aspects. GSTM1 null subjects heavily exposed to solvents appear to be at increased risk of PD. There was insufficient evidence that the other gene-environment combinations investigated modified disease risk, suggesting they contribute little to the burden of PD.

Antagonistic effects of methyl-mercury and PCB153 on PC12 cells after a combined and simultaneous exposure.

The study of interactions for those substances which tend to accumulate in food and affect the nervous system appears to be a fundamental point to characterize the combined exposure in vitro. In this study we included two food contaminants which are known neurotoxicants: methyl-mercury (Me-Hg) and the ortho-substituted PCB 153. PC12 cells were treated with Me-Hg (range 1e-7, 2e-6 M) and PCB153 (range 1e-5, 4e-4 M) in single and combined synchronous experiments and a mathematical model was set up according to the Loewe additivity criterion to evaluate the level of interaction between toxicants, using viability as end-point. At some concentrations (Me-Hg 5e-7 M and PCB153 1e-4 and 2e-4 M; Me-Hg 1e-6M and PCB153 5e-5 M; Me-Hg 1e-7 M and PCB153 4e-4 M), a statistically significant antagonist effect was observed. No interaction was observed for other combinations. The analysis of other toxicological parameters known to be modified in single exposure experiments (TBARS and intra-cellular dopamine) confirmed the viability results. The results of our work represent a starting point to generate novel information on the interactions between PCB153 and Me-Hg in vitro, as well as a new relevant experimental and mathematical approach useful to investigate the effects of different toxicant mixtures.