Benzene induces gene-duplicating but not gene-inactivating mutations at the glycophorin A locus in exposed humans.

Occupational exposure to benzene is known to cause leukemia, but the mechanism remains unclear. Unlike most other carcinogens, benzene and its metabolites are weakly or nonmutagenic in most simple gene mutation assays. Benzene and its metabolites do, however, produce chromosomal damage in a variety of systems. Here, we have used the glycophorin A (GPA) gene loss mutation assay to evaluate the nature of DNA damage produced by benzene in 24 workers heavily exposed to benzene and 23 matched control individuals in Shanghai, China. The GPA assay identifies stem cell or precursor erythroid cell mutations expressed in peripheral erythrocytes of MN-heterozygous subjects, distinguishing the NN and N phi mutant variants. A significant increase in the NN GPA variant cell frequency (Vf) was found in benzene-exposed workers as compared with unexposed control individuals (mean +/- SEM, 13.9 +/- 1.7 per million cells vs. 7.4 +/- 1.1 per million cells in control individuals; P = 0.0002). In contrast, no significant difference existed between the two groups for the N phi Vf (9.1 +/- 0.9 vs. 8.8 +/- 1.8 per million cells; P = 0.21). Further, lifetime cumulative occupational exposure to benzene was associated with the NN Vf (P = 0.005) but not with the N phi Vf (P = 0.31), suggesting that NN mutations occur in longer-lived bone marrow stem cells. NN variants result from loss of the GPA M allele and duplication of the N allele, presumably through recombination mechanisms, whereas NO variants arise from gene inactivation, presumably due to point mutations and deletions. Thus, these results suggest that benzene produces gene-duplicating mutations but does not produce gene-inactivating mutations at the GPA locus in bone marrow cells of humans exposed to high benzene levels. This finding is consistent with data on the genetic toxicology of benzene and its metabolites and adds further weight to the hypothesis that chromosome damage and mitotic recombination are important in benzene-induced leukemia.

Inconsistencies in Guidelines for Visual Health Surveillance of VDT Workers

Objectives: In Europe, 25% of workers use video display terminals (VDTs). Occupational health surveillance has been considered a key element in the protection of these workers. Nevertheless, it is unclear if guidelines available for this purpose, based on EU standards and available evidence, meet currently accepted quality criteria. The aim of this study was to appraise three sets of European VDT guidelines (UK, France, Spain) in which regulatory and evidence-based approaches for visual health have been formulated and recommendations for practice made. Methods: Three independent appraisers used an adapted AGREE instrument with seven domains to appraise the guidelines. A modified nominal group technique approach was used in two consecutive phases: first, individual evaluation of the three guidelines simultaneously, and second, a face-to-face meeting of appraisers to discuss scoring. Analysis of ratings obtained in each domain and variability among appraisers was undertaken (correlation and kappa coefficients). Results: All guidelines had low domain scores. The domain evaluated most highly was Scope and purpose, while Applicability was scored minimally. The UK guidelines had the highest overall score, and the Spanish ones had the lowest. The analysis of reliability and differences between scores in each domain showed a high level of agreement. Conclusions: These results suggest current guidelines used in these countries need an update. The formulation of evidence-base European guidelines on VDT could help to reduce the significant variation of national guidelines, which may have an impact on practical application.

Alteraciones oculares y visuales en personas que trabajan con ordenador y son usuarias de lentes de contacto: una revisión bibliográfica

Fundamentos: El elevado número de personas que trabajando con ordenador utiliza lentes de contacto plantea la cuestión sobre si la suma de estos dos factores de riesgo para la salud visual puede originar un agravamiento del Síndrome Visual Informático. El objetivo de esta revisión es sintetizar el conocimiento científico sobre las alteraciones oculares y visuales relacionadas con la exposición a ordenador en usuarios de lentes de contacto. Métodos: Revisión de artículos científicos (2003-2013) en español e inglés, realizando una búsqueda bibliográfica, en Medline a través de PubMed y en Scopus. Resultados: La búsqueda inicial aportó 114 trabajos, después de aplicar criterios de inclusión/exclusión se incluyeron seis artículos. Todos ellos ponen de manifiesto que las alteraciones al utilizar el ordenador son más frecuentes en las personas usuarias de lentes de contacto, con prevalencias que oscilan de 95,0% al 16,9% que en las que no utilizan lentes de contacto, cuya prevalencia va del 57,5% al 9,9% y con una probabilidad cuatro veces mayor de padecer ojo seco [OR: 4,07 (IC 95%: 3,52-4,71)]. Conclusiones: Las personas usuarias de ordenador padecen más alteraciones oculares y visuales cuando además son usuarias de lentes de contacto, pero los estudios son escasos y poco contundentes. Se precisan nuevas investigaciones que analicen la influencia según los tipos de lentes y sus condiciones de uso, tanto en la sintomatología como en la calidad de la lágrima y la superficie ocular. Las lentes de hidrogel de silicona son las que se asocian a mayor confort.

A reliable and valid questionnaire was developed to measure computer vision syndrome at the workplace

Objectives: To design and validate a questionnaire to measure visual symptoms related to exposure to computers in the workplace. Study Design and Setting: Our computer vision syndrome questionnaire (CVS-Q) was based on a literature review and validated through discussion with experts and performance of a pretest, pilot test, and retest. Content validity was evaluated by occupational health, optometry, and ophthalmology experts. Rasch analysis was used in the psychometric evaluation of the questionnaire. Criterion validity was determined by calculating the sensitivity and specificity, receiver operator characteristic curve, and cutoff point. Testeretest repeatability was tested using the intraclass correlation coefficient (ICC) and concordance by Cohen’s kappa (k). Results: The CVS-Q was developed with wide consensus among experts and was well accepted by the target group. It assesses the frequency and intensity of 16 symptoms using a single rating scale (symptom severity) that fits the Rasch rating scale model well. The questionnaire has sensitivity and specificity over 70% and achieved good testeretest repeatability both for the scores obtained [ICC 5 0.802; 95% confidence interval (CI): 0.673, 0.884] and CVS classification (k 5 0.612; 95% CI: 0.384, 0.839). Conclusion: The CVS-Q has acceptable psychometric properties, making it a valid and reliable tool to control the visual health of computer workers, and can potentially be used in clinical trials and outcome research.

Characterization of Organophosphate Pesticides in Urine and Home Environment Dust in an Agricultural Community

Thesis (Master's)--University of Washington, 2016-06

Influence of body iron store status and cigarette smoking on cadmium body burden of healthy Thai women and men

The influence of cigarette smoking, body iron store status and gender on cadmium (Cd) body burden was examined in a group of 197 healthy Thais with overall mean age of 30.5 year (19-47 year). The lowest, geometric mean, and the highest urinary Cd excretion rate was 0.04, 0.46 and 3.84 mug/g creatinine, respectively. The prevalence of low iron stores (serum ferritin

Parental occupation and Ewing's sarcoma: Pooled and meta-analysis

Etiologic data on Ewing's sarcoma family of tumors (ESFT) are limited, with only 5 case-control studies reported. Interesting associations, particularly related to parental occupation, have been noted, but results are somewhat inconsistent. We conducted a pooled analysis of 3 case-control studies to assess the overall associations between parental occupation and ESFT. The pooled analysis provided data on parental occupational exposure on 199 cases of ESFT and 1,451 controls. The pooled odds ratio for the periconception and gestation periods were 2.3 (95% CI = 1.3-4.1) for children whose fathers had worked on farms and 3.9 (95% CI 1.6-9.9) for those whose mothers had farmed. For the periconception and gestation periods, there was a 3.5-fold increased risk for those with both parents having farmed and a doubling of risk for those with at least one parent having farmed; pattern of increasing risk with increasing number of years of postnatal parental exposure to farms was seen. No other occupational group (or more narrowly defined occupations) had other than minor inconsistent associations with the occurrence of ESFT. In addition, we conducted a meta-analysis of farm occupation (a main risk factor) including all 4 case-control studies that collected required information to consider parental occupation. Results of the meta-analysis were consistent with those from the pooled analysis. This collaborative analysis of available individual data on parental occupation and ESFT in the offspring provides evidence supporting the hypothesis of an association between ESFT and parental occupation in farming. © 2005 Wiley-Liss, Inc.

Genotoxicity of inorganic lead salts and disturbance of microtubule function

Lead compounds are known genotoxicants, principally affecting the integrity of chromosomes. Lead chloride and lead acetate induced concentration-dependent increases in micronucleus frequency in V79 cells, starting at 1.1 μ M lead chloride and 0.05 μ M lead acetate. The difference between the lead salts, which was expected based on their relative abilities to form complex acetato-cations, was confirmed in an independent experiment. CREST analyses of the micronuclei verified that lead chloride and acetate were predominantly aneugenic (CREST-positive response), which was consistent with the morphology of the micronuclei (larger micronuclei, compared with micronuclei induced by a clastogenic mechanism). The effects of high concentrations of lead salts on the microtubule network of V79 cells were also examined using immunofluorescence staining. The dose effects of these responses were consistent with the cytotoxicity of lead(II), as visualized in the neutral-red uptake assay. In a cell-free system, 20-60 μ M lead salts inhibited tubulin assembly dose-dependently. The no-observed-effect concentration of lead(II) in this assay was 10 μ M. This inhibitory effect was interpreted as a shift of the assembly/disassembly steady-state toward disassembly, e.g., by reducing the concentration of assembly-competent tubulin dimers. The effects of lead salts on microtubule-associated motor-protein functions were studied using a kinesin-gliding assay that mimics intracellular transport processes in vitro by quantifying the movement of paclitaxel-stabilized microtubules across a kinesin-coated glass surface. There was a dose-dependent effect of lead nitrate on microtubule motility. Lead nitrate affected the gliding velocities of microtubules starting at concentrations above 10 μ M and reached half-maximal inhibition of motility at about 50 μ M. The processes reported here point to relevant interactions of lead with tubulin and kinesin at low dose levels. Environ. Mal. Mutagen. 45:346-353, 2005. © 2005 Wiley-Liss, Inc.

Cadmium-induced nephropathy in the development of high blood pressure

In recognition of a central role of the kidney in long-term blood pressure control, we undertook an in-depth analysis of the relationship between blood pressure and kidney damage caused by environmental exposure to the common pollutants cadmium and lead. The subjects were 200 healthy Thais, 16 and 60 years of age (100 female non-smokers, 53 male non-smokers, and 47 male smokers). None of these subjects had been exposed to Cd or Pb in the workplace and their urinary Cd concentrations ranged from 0.4 to 37 nM, whereas their urinary Pb concentrations ranged from 0.1 to 30 nM. The prevalence of high blood pressure was 2%, 8% and 19%, respectively in subjects with low, average and high Cd-burden (linear trend chi(2) = 6.4, P = 0.01). Multiple regression analysis revealed a significant positive association between Cd-burden and blood pressure in male nonsmokers (adjusted beta = 0.31, P = 0.02) and an inverse association between blood pressure and urinary Pb excretion rate in male smokers (adjusted beta = -0.38, P = 0.005). Associations between Cd-burden and nephropathies were evidenced by increases in urinary excretion of beta 2-microglobutin (P = 0.02) and N-acetyl-beta-D-glucosaminidase (P = 0.005) in subjects with high Cd-burden, compared with the subjects with average Cd-burden. In addition, an association between Cd-related nephropathy and high blood pressure was evidenced by a 20% increase in the prevalence of high blood pressure in people with NAG-uria (linear trend chi(2) = 4.3, P = 0.04). Our present study provides first evidence for a possible link between renal tubular damage and dysfunction caused by environmental Cd exposure and increased risk of high blood pressure. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Biological monitoring and Biological Limit Values (BLV): The strategy of the European Union

Occupational standards concerning allowable concentrations of chemical compounds in the ambient air of workplaces have been established in several countries worldwide. With the integration of the European Union (EU), there has been a need of establishing harmonised Occupational Exposure Limits (OEL). The European Commission Directive 95/320/EC of 12 July 1995 has given the tasks to a Scientific Committee for Occupational Exposure Limits (SCOEL) to propose, based on scientific data and where appropriate, occupational limit values which may include the 8-h time-weighted average (TWA), short-term limits/excursion limits (STEL) and Biological Limit Values (BLVs). In 2000, the European Union issued a list of 62 chemical substances with Occupational Exposure Limits. Of these, 25 substances received a skin notation, indicating that toxicologically significant amounts may be taken up via the skin. For such substances, monitoring of concentrations in ambient air may not be sufficient, and biological monitoring strategies appear of potential importance in the medical surveillance of exposed workers. Recent progress has been made with respect to formulation of a strategy related to health-based BLVs. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Asma, abitudini e stile di vita "Analisi retrospettiva di un campione di pazienti asmatici seguito in ambulatorio di terzo livello"

Growing evidence suggest the importance of different environments in promoting the pathogenesis and/or exacerbation of asthma. Indoor air pollution is a major contributor to human exposure, since people spend up to 90% of their day indoors. Apart from active smoking, indoor pollution is considered one of the major preventable risk factors of chronic respiratory diseases. The professional activity can also be dangerous because it exposes the subject to environments that can promote the onset of asthma or worsening of the latter in those already affected. Even bad habits such as incorrect diet, lead to more difficulty in controlling their disease. However asthma is a multifactorial disease in nature so it is not easy to distinguish the role of occupational exposure, pollution and normal habits such as smoking, nutrition, sports, etc. This retrospective study was conducted on a sample of asthma patients residing in the metropolitan area of Parma. 116 patients were selected among those who are followed up at least two years at the Asthma outpatient Clinic of Parma University Hospital. The sample in question is therefore closely controlled and monitored; it comes to patients who are well educated on the control of their disease, are able to take appropriate measures to minimize the symptomatology. With this tight approach is proposed to minimize the effect of confounding and then traced with greater certainty the possible cause of the failure to control the disease. For this purpose, each patient was subjected to regular checkups; we took as a reference the period of time between April and October 2015. During each visit, in addition to general data for each patient, we were collected personal information about their habits and way of life through a validated questionnaire delivered and completed by the patient during the visit in the presence of the permanent staff. The questionnaire covers mainly the qualification of the patient, its possible occupational exposure, his home, with information about nearby traffic, time spent outside, physical activity (place and time), exposure to chemicals, exposure to various fumes (fireplace or stove) and cigarette smoke, comorbidities and any drugs taken during the visits considered. Regarding the respiratory conditions of patients during every examination we were considered: Asthma Control Test (a test performed by patients to assess the state of the disease during the month preceding the test), the measurement of exhaled nitric oxide (FeNO) as an index of airways inflammation, measuring the resistance level of small airways (R5-R20) and some spirometric values observed in experiment; in particular the forced vital capacity (FVC), forced expiratory volume in the first second (FEV 1), FEV1/FVC ratio, forced expiratory flow rate over the middle 50% of the FVC (FEF25–75) and FEF25-75/FVC were recorded. The sample has been studied considering both the changes of the respiratory parameters for every patient in their examinations, and the respiratory parameters of all the examinations took as a whole in relation with the variables considered. From the results obtained, the patients are clinically stable; their adopted lifestyle and the exposure to possible sources of outdoor pollution, seems not affect the overall control of their disease. Some findings of our study are of interest. First, the subjects who carry a steroid therapy show a clinical worst, as revealed by the decrease of most spirometric indices, particularly FEF25, FEF75, FEF25-75 and R5-R20; also, the presence of comorbidities and the subsequent intake of other drugs, in addition to normal therapy for asthma, seem to be conditions associated with poorer performance in the functional respiratory parameters in particular FEV1/FVC, FEF75 and FEF25-75. Spirometric indexes that are down are mainly those related to obstruction imposed on small airways; this suggests a neglect to the latter on the contrary should be further explored and treated accordingly. It is also observed that both patients are overweight than those living on the lower floors and/or who have the most windows exposed to traffic, showed a decrease of pulmonary function, especially those relate to an obstruction at the small airways level. In conclusion, our results provided the evidence that a most appropriate therapy, specific to reach the small airways, associated with a healthy lifestyle, can help improve the management of asthma.

Cadmium in the environment and high risk population groups

Cadmium has been widely used in various industries for the past fifty years, with current world production standing at around 16,755 tonnes per year. Very little cadmium is ever recycled and the ultimate fate of all cadmium is the environment. In view of reports that cadmium in the environment is increasing, this thesis aims to identify population groups 'at risk' of receiving dietary intakes of cadmium up to or above the current Food and Agricultural Organisation/World Health Organisation maximum tolerable intake of 70 ug/day. The study involves the investigation of one hundred households (260 individuals) who grow a large proportion of their vegetable diet in garden soils in the Borough of Walsall, part of an urban/industrial area in the United Kingdom. Measurements were made of the cadmium levels in atmospheric deposition, soil, house dust, diet and urine from the participants. Atmospheric deposition of cadmium was found to be comparable with other urban/industrial areas in the European Community, with deposition rates as high as 209 g ha-1 yr-1. The garden soils of the study households were found to contain up to 33 mg kg-1 total cadmium, eleven times the highest level usually found in agricultural soils. Dietary intakes of cadmium by the residents from food were calculated to be as high as 68 ug/day. It is suggested that with intakes from other sources, such as air, adventitious ingestion, smoking and occupational exposure, total intakes of cadmium may reach or exceed the FAO/WHO limit. Urinary excretion of cadmium amongst a non-smoking, non-occupationally exposed sub-group of the study population was found to be significantly higher than that of a similar urban population who did not rely on home-produced vegetables. The results from this research indicate that present levels of cadmium in urban/industrial areas can increase dietary intakes and body burdens of cadmium. As cadmium serves no useful biological function and has been found to be highly toxic, it is recommended that policy measures to reduce human exposure on the European scale be considered.

Caracterização do material particulado e avaliação do risco ocupacional e mecanismos moleculares associados à queima artesanal da castanha de caju

Brazil is among the largest cashew nut producers of the world. However, the roasting process is still carried out artisanally, especially in the Brazilian semiarid region. In face of this occupational problem, the aim of this study was to perform a physical-chemical characterization of the particulate matter (PM) emitted by the roasting of cashew nuts, as well as to determine the occupational risk and molecular mechanisms associated. The most evident PM characteristics were the prevalence of fine particles, typical biomass burning morphologies such as tar ball and the presence of the elements K, Cl, S, Ca and Fe. In addition, atmospheric modeling analyses suggest that these particles can reach neighboring regions of the emission source. Polycyclic aromatic hydrocarbons (PAHs) with carcinogenic potential, such as benzo[a]pyrene, dibenz[a,h]anthracene, benzo[a]anthracene, benzo[b]fluoranthene, chrysene, benzo[k]fluoranthene, indeno[1,2,3-c,d]pyrene and benzo[j]fluoranthene were the most abundant PAHs found in the two air monitoring campaigns. Among the identified oxy-PAH the benzanthrone (7H-benz[d,e]anthracen-7-one) had the highest concentration and the evaluation of lifetime cancer risk showed an increase of 12 to 37 cases of cancer for every 10,000 exposed people. Chemical analysis of roasted cashew nuts identified the PAHs: phenanthrene, benzo[g,h,i]perylene, pyrene and benzo[a]pyrene, besides the 3-pentadecilfenol allergen (urushiol analogue) as prevalent. Occupational exposure to PAHs was confirmed by the increase of urinary 1-hydroxypyrene levels and genotoxic effects were evidenced by the increase on micronuclei and nuclear bud frequency in exfoliated buccal mucosa cells among the exposed workers. Other biomarkers of effects such as karyorrhexis, pyknotic, karyolytic, condensed chromatin and binucleated cells also have their frequencies increased when compared to an unexposed control group. The investigation of the molecular mechanisms associated with the PM organic extract showed cytotoxicity in human lung cell lines (A549) at concentrations ≥ 4 nM BaPeq. Using non-cytotoxic doses the extract was able to activate proteins involved in the DNA damage response pathway (Chk1 and p53). Moreover, the specific contribution of the four most representative PAHs in the cashew nut roasting sample showed that benzo[a]pyrene was the most efficient to activate Chk1 and p53. Finally, the organic extract was able to increase persistently the mRNA expression involved in the PAHs metabolism (CYP1A1 and CYP1B1), inflammatory response (IL-8 and TNF-α) and cell cycle arrest (CDKN1A) for DNA repair (DDB2). The high PM concentrations and its biological effects associated warn of the serious harmful effects of artisanal cashew nut roasting and urgent actions should be taken to the sustainable development of this activity.