Benzene: A public health concern

Benzene: A public health concern

S8 Abstracts / Toxicology Letters 259S (2016) S4–S62 S03-2 Effects of low-level lead exposure on blood pressure in a population-based study in South...

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Abstracts / Toxicology Letters 259S (2016) S4–S62

S03-2 Effects of low-level lead exposure on blood pressure in a population-based study in Southern Brazil

S03-3 Benzene: A public health concern

A.C.B. Almeida Lopes 1,∗ , E.K. Silbergeld 2 , A. Navas-Acien 2 , R. Zamoiski 3 , A.C. Martins Jr. 4 , A.E.I. Camargo 5 , M.R. Urbano 1,6 , A.E. Mesas 1,7 , M.M.B. Paoliello 1

Representative of Brazilian Petroleum, Gas and Biofuels Institute (IBP), in the Brazilian Permanent Benzene Commission (CNPBz), Rio de Janeiro, RJ, Brazil


Introduction: Benzene is one of the world’s major commodity chemicals. Benzene is a natural component of crude oil and other petroleum products, might be in by-products of operations in coke oven industry and in tobacco smoke. Its primary use is as an intermediate in the production of other chemicals, predominantly styrene, cumene, and cyclohexane. Benzene is an important raw material for the manufacture of synthetic rubbers, gums, lubricants, dyes, pharmaceuticals, and agricultural chemicals. Airborne benzene is a ubiquitous environmental air pollutant. Occupational exposure: Workers employed in industries such as extraction of crude oil and natural gas, petroleum refineries, transport and distribution of petroleum products, gasoline stations, car repair shops, chemical industry, coke oven industry and shoe manufacturing using benzene-based glues are potentially exposed to benzene. Environmental exposure: Benzene is widespread in the environment. Benzene is a component of both indoor and outdoor air pollution. Airborne benzene is usually produced by processes associated with chemical manufacturing or the gasoline industry, including gasoline bulk-loading and discharging facilities and combustion engines. Leakage from underground storage tanks and seepage from landfills or improper disposal of hazardous wastes has resulted in benzene contamination of groundwater used for drinking. Effluent from industries is also a source of groundwater contamination. People living around hazardous waste sites, petroleum-refining operations, petrochemical manufacturing sites, or gas stations may be exposed to higher levels of benzene in air. U.S. EPA has imposed benzene emissions restrictions from industrial solvent use, waste operations, transfer operations, and gasoline marketing, and set a maximum contaminant level of benzene in drinking water. Food and Drug Administration (FDA) mandated that benzene can only be an indirect food additive in adhesives used for food packaging. Benzene toxicity: Benzene is a ubiquitous pollutant that causes health effects. Although the mechanism by which benzene causes toxicity is unclear, metabolism is required. The hematopoietic system and the cells of the bone marrow are the most sensitive target organs for benzene exposure. Repeated occupational benzene exposure over long periods of time may affect several parameters related to the hematological system, including the immune system, causing bone marrow depression expressed as anemia, leucopenia and thrombocytopenia. Benzene has been classified as a human carcinogen by the World Health Organization (WHO) and International Agency for Research on Cancer (IARC). Benzene and metabolites may induce a number of chromosomal aberrations including mitotic recombination, DNA strand breaks, chromosomal translocations, and aneuploidy in hematopoietic stem or progenitor cells. Many different epidemiological studies have been performed on the relation between benzene exposure and leukemia. Relatively low level exposure to benzene was associated with increased risk of myelodysplastic syndrome (MDS), suggesting that MDS maybe the more relevant health risk for lower benzene exposures. Benzene health risk is consistently elevated among exposed workers for lymphohaematopoietic (LH) cancers combined and for some subgroups. There was little evidence of a relationship between benzene

Graduate Program in Public Health, State University of Londrina –UEL, Londrina, Paraná, Brazil 2 Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA 3 Radiation Epidemiology Branch of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Washington, DC, USA 4 Graduate Program in Toxicology, Faculty of Pharmaceutical Sciences of University of São Paulo – USP, Ribeirão Preto, São Paulo, Brazil 5 Graduate Program in Health Sciences, Center of Health Sciences, State University of Londrina – UEL, Londrina, Paraná, Brazil 6 Department of Statistics, State University of Londrina – UEL, Londrina, Paraná, Brazil 7 Department of Public Health, State University of Londrina – UEL, Londrina, Paraná, Brazil Introduction: Environmental lead exposure is a public health issue, due to its ability to accumulate in the organism for a long period of time, and also to the absence of a safe concentration in the exposure to this metal. Low levels of lead exposure among adults in the general population may increase blood pressure and enhance the risk of hypertension. Objective: to evaluate the relationship of blood lead levels (BLL) with blood pressure and hypertension in a population-based sample of adults living in a city in Southern Brazil. Methods: A total of 948 adults, aged 40 years or older, were randomly selected. Information on socioeconomic, dietary, lifestyle and occupational background was obtained by orally administered household interviews. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) was measured according to the guidelines VI Brazilian Guidelines on Hypertension. Participants were considered as hypertensive if any of the following criteria were present: a systolic blood pressure of 140 mm Hg or higher, a diastolic blood pressure of 90 mm Hg or higher, or self-reported use of antihypertensive medication. BLL were measured by ICP-MS technique. Multiple logistic regression was used to examine associations of BLL with hypertension status and with elevated SBP and DBP. Results: The overall geometric mean of BLL was 1.97 ␮g/dl (95% CI: 1.90–2.04 ␮g/dl), and the means for the blood lead quartiles ranged from 0.96 ␮g/dl to 4.21 ␮g/dl in the lowest and higher quartile, respectively. We found that adults in the highest blood lead quartile had increased odds of DBP (OR: 2.57; 95% CI: 1.51–4.39) and of hypertension (OR: 2.54; 95% CI: 1.17–5.53) compared to those in the lowest quartile. Participants in the 90th percentile of blood lead distribution had 0.07 mmHg (95% CI: 0.03–0.11) higher DBP, and higher OR for hypertension, compared with those participants in the 10th percentile of blood lead. Conclusions: At low concentrations, BLL were positively associated with DBP and with the odds for hypertension in adults aged 40 or older. Financial support: Coordination for the Improvement of Higher Level or Education Personnel (CAPES), through the Ministry of Health, Brazil.

E.M. Barbosa

Abstracts / Toxicology Letters 259S (2016) S4–S62

exposure and chronic lymphoid leukemia (CLL), chronic myeloid leukemia (CML) or myeloproliferative disease (MPD). Conclusions: It is necessary more powerful studies with a wider range of benzene exposure to establish LH cancer risk, and the biological plausibility further examined from a mechanistic viewpoint. Although the most of research on benzene-induced leukemia has been primarily focused on occupational benzene poisoning, several epidemiological studies have indicated that increased exposure to benzene from the environment is a major cause of childhood leukemia. The U.S. EPA Children’s Guidance describes evidence that early life exposure may result in increased cancer risk by contrast to exposure as an adult. S03-4 Health risk assessment for air pollutants: Lung inflammation and extra pulmonary adverse events are correlated to particulate matter size, origin and season of collection P. Palestini Department of Medicine and Surgery, POLARIS Centre, University of Milano-Bicocca, Monza, Italy Epidemiological studies have indicated associations between exposure to ambient air particulate matter (PM) and increased mortality from cardiopulmonary diseases, including lung cancer, chronic obstructive lung disease and myocardial infarction. The adverse health effects related to PM depend on the sampling area (spatial variability), season (temporal variability) and particle size fraction. Therefore, there is substantial variation in the inflammation and oxidative stress potential of PM sampled at different locations or times. PM10 causes the most serious effects on human health. In particular, the summer fraction could contain biogenic materials, such as Gram-negative bacteria, pollen, endotoxin and spores. Also transition metals and endotoxins are potential mediators of PM10 adverse effects, causing reactive oxygen species and inflammatory mediator production. PM2.5 toxicity was emphasized because of particles deposition into the deep airways and terminal alveoli. Various kind of chemicals are adsorbed onto fine particulate matter collected during winter season, such as trace of metals and polycyclic aromatic hydrocarbons. These chemicals are known to dissolve and translocate into blood circulation after particles deposition in the lungs, and are able to initiate redox reactions, thus producing reactive oxygen species, implicated in inflammation and adverse health effects. The lung inflammation plays a key role in enhancing the extra-pulmonary translocation of smallest particles. Moreover, ultrafine particles (UFPs <0.1 ␮m) are able to over-pass the lung clearance process and enter into the alveolar epithelium. On the other hand, UFPs source and consequently their chemical composition could be responsible for the activation of molecular mechanisms ad hoc. Indeed, both in respiratory and cardiovascular system DEP (from EURO 4 diesel engine emission), enriched in Zn, Al and PAH, induces greater oxidative stress than BM (from pellet boiler biomass emission) enriched in K and Mn. In conclusion, it could be hypothesized the existence of a stratified hierarchical response to PM at three levels: the primer event is oxidative stress and a putative adaptive response; whether this does not occur, the oxidative stress stimulates inflammation leading to the second level; finally, cell death relates to the third level.


S03-5 Particulate matter disrupts the glutamate uptake in cerebellar glia cells: Implications for glutamatergic transmission E. Suárez-Pozos ∗ , A. De Vizcaya-Ruiz, A. Ortega Departamento de Toxicología, Cinvestav, Ciudad de México, Mexico Introduction: Glutamate, the main excitatory amino acid transmitter triggers a wide variety of signal transduction cascades that regulate protein synthesis at the transcriptional and translational levels. Activity dependent differential gene expression has been attributed to the activation of both membrane glutamate receptors and transporters. The bulk of glutamate uptake takes place in glia cells. Recent studies have linked exposure to fine particulate matter with toxicity at a neurological level, given that some of its components can reach the brain and instigate damage locally or systemically. Within the cerebellum, Bergmann glia cells (BGC) are responsible for most of the glutamate uptake activity through the Na+ dependent glutamate/aspartate transporter (GLAST/EAAT-1). Objective: Taking into consideration the functional role of Bergmann glia, in terms of the recycling of glutamate, the supply to neurons of lactate and the prevention of neurotoxic insults, we decided to investigate if air pollution particulate matter (PM) targets glia cells that surround glutamatergic synapses and by these means alter the major excitatory transmitter system in the brain. Materials and methods: Cultured chick cerebellar Bergmann glia cells were exposed to fine PM isolated and concentrated from Mexico City and [35S]-methionine incorporation into newly synthesized polypeptides, eukaryotic translation factors phosphorylation and [3H]-D-Aspartate uptake activity were measured in a time and dose dependent manner. Results: A translational-dependent modulation of uptake activity was observed. Furthermore, PM treatment resulted in the activation of a signaling cascade that included Ca2+ influx through the Na+ /Ca2+ exchanger, eIF2-alpha, eEF2 phosphorylation, activation of p60src and p42/44MAPK, reduced glutamate transporters translation and finally reduced glutamate uptake. Conclusions: These results suggest that air pollutants deleterious effects in the CNS targets glia cells, compromising glutamatergic synaptic neurotransmission. Financial support: Conacyt 79502, Fundación Pandea. Symposia S04: In vitro microphysiological systems to predict toxicity S04-1 Chip based microphysiological systems – A step toward emulation of systemic aspects of human biology in vitro R. Horland 1 , I. Maschmeyer 1 , M. Dehne 1 , T. Hasenberg 1 , A. Ramme 1 , A. Lorenz 1 , A. Jaenicke 1 , J. Hübner 2 , K. Schimek 2 , B. Atac-Wagegg 1 , R. Lauster 2 , U. Marx 1 1

TissUse GmbH, Berlin, Germany Department of Medical Biotechnology, Technische Universität Berlin, Berlin, Germany 2

Introduction: Drug discovery, safety assessment and hazard identification of drug substances, chemicals and other compounds rely historically on the use of animal models. The phylogenetic distance between animals and humans reduces the predictive