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Many chemicals in day-to-day and industrial usage have the ability to cross the blood–brain barrier and develop neurotoxicity in humans. There are numerousinvitro,invivo, epidemiological andin silicostudies developed to test the neurotoxicity of such chemicals. This systematic review summarized the endpoints and biochemical markers generated frominvitromodels, organism-based models, human studies andin silicotools and how they are used to translate the data for risk assessment of neurotoxic chemicals. Increased evidence about different biomarkers through genomics and proteomics has developed data related to genes and proteins facilitating some understanding about the molecular mechanism of neurotoxicity. Fluid-based biomarkers such as those found in serum, plasma and urine from human studies act as indirect endpoints for neurotoxicity. Meanwhile, with improvement in knowledge of molecular mechanisms and different biomarkers, there is a potential to develop a translational platform that can integrate the biological data from different studies mechanistically and thereby translated across intra and interspecies for neurotoxicity assessment. Further, this review proposed an integrative translational framework combining experimental andin silicostudies like toxicokinetic models and integrative systems biology to assess the chemicals for neurotoxicity. This framework can be used to predict the inherent risk of neurotoxicity and extend to such chemicals where less experimental data exists.

Microplastics (MPs) are emerging pollutants detected everywhere in the environment, with the potential to harm living organisms. The present study investigated the concentration, morphology, and composition of MPs, between 20 μm and 5 mm, in a drinking water treatment plant (DWTP) located close to Barcelona (Catalonia, NE Spain). The sampling included different units of the DWTP, from influent to effluent as well as sludge line. Sampling strategy, filtration, allows sampling of large volumes of water avoiding sample contamination, and during 8 h in order to increase the representativeness of MPs collected. The pre-treatment of the samples consisted of advanced oxidation with Fenton's reagent and hydrogen peroxide, followed by density separation of the particles with zinc chloride solution. Visual identification was performed with an optical and stereoscopic microscope with final Fourier-transform infrared spectroscopic (FTIR) confirmation. MPs were found in all DWTP samples, with concentrations from 4.23 ± 1.26 MPs/L to 0.075 ± 0.019 MPs/L in the influent and effluent of the plant, respectively. The overall removal efficiency of the plant was 98.3%. The most dominant morphology was fibers followed by fragments and films. Twenty-two different polymer types were identified and synthetic cellulose, polyester, polyamide, polypropylene, polyethylene, polyurethane, and polyacrylonitrile were the most common. Although MPs could be incorporated from the distribution network, MPs intake from drinking water from this DWTP was not an important route compared to fish and seafood ingestion.

Since 2004, some legacy flame retardants (FRs) were restricted or removed from the European markets due to their concern on human health. Both organophosphorus FRs (OPFRs) and novel brominated FRs (NBFRs) have replaced them because they are presumably safer and less persistent emerging FRs (EFRs) and their exposure is currently occurring in indoor environments at high levels. Little is known about the neurotoxic potential risk of these EFRs in humans. The present study was aimed at assessing the acute neurotoxicity potential of Tris(1, 3-dichloro-2-propyl)phosphate (TDCPP), triphenyl phosphate (TPhP), Bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP) and 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) on human neuroblastoma cells (SH-SY5Y). SH-SY5Y were exposed to these EFRs at low concentrations -ranging 2.5-20 μM. during 2-24 h. We investigated viability, mitochondrial function, oxidative stress, inflammatory response, as well as neural plasticity and development. The results have demonstrated that selected EFRs (TDCPP, TPhP, EH-TBB and BEH-TBP) did not impair neural function on SH-SY5Y as acute response. To the best of our knowledge, this has been the first study focused on evaluating the neural affection of TPhP on SH-SY5Y cells and of EH-TBB and BEH-TBP on neural cells. We also assessed for the first time almost all endpoints after FR exposure on neural cell lines.

The blood-brain barrier (BBB) is a structural and functional interface between the plasma and the human brain. Predictive BBB in-vitro models like immortalized human capillary microvascular endothelial cells (HCMEC/D3) can be used to explore the BBB disruption potential of daily exposed chemicals. The present study was focused on investigating the human BBB permeation potential of one organophosphate pesticide, chlorpyrifos (CPF), and two pyrethroids, permethrin (PMT) and cyfluthrin (CFT). HCMEC/D3 cells were exposed to the chemical and the time-dependent pass across BBB along with permeation coefficient (Papp) was calculated. Transendothelial electrical resistance (TEER) was measured for the cells to check the monolayer formation and later to check the reduction in integrity after chemical exposure. Real time PCR was conducted to investigate the effect of chemicals on the expression BBB´s tight and adherens junction proteins. Calculated Papp value for three chemicals was in the following order: CPF>CFT>PMT, where CPF showed the highest permeation coefficient. TEER calculation showed that the integrity decreased after CPF exposure which was in concordance with Papp value whereas for other chemicals, no change in TEER after exposure was observed. In addition, the transwell study showed a higher efflux ratio (ER) (>2) of CFT indicating that CFT could be a substrate for active transport. For CPF and PMT, ER was less than 2, so no active transport seems to be involved. The evaluation of the mRNA expression analysis revealed a statistically significant decrease in Occludin (OCLN) gene expression for CPF, VE-Cadherin (CDH5) for PMT and Zonula Occludens (ZO1) expression for CFT. Our study showed that CPF has the highest potential for inducing cell death, higher permeation, and capability to induce BBB dysfunction than among the above-mentioned chemicals. Additionally, the results of the permeation study could be useful to build a human PBPK model using in vitro-to-in vivo extrapolation approach., This study was financially supported by Marie Skłodowska-Curie “Neurosome Project” under the grant agreement No. 766251. This publication reflects only the authors' views. The Community and other funding organizations are not liable for any use made of the information contained therein.

Identification of dominant airborne Particulate Matter (PM) sources is essential for maintaining high air quality standards and thus ensuring a good public health. In this study, different approaches were applied for source apportionment of three PM fractions (PM1, PM2.5 and PM10) at the outdoor of 14 schools of a coastal city with a significant land use interweaving such as Tarragona (Spain). PM were collected in 24h-quartz microfiber filters in two seasonal campaigns (cold and warm), together with nine local potential sources, so a total of 84 samples were chemically, mineralogically, and isotopically characterised. Source apportionment was assessed by (i) main chemical components, (ii) Principal Component Analysis (PCA), (iii) dual C and N isotope approach, and (iv) a Bayesian isotope mixing model. When chemical concentrations were grouped into marine, crustal, secondary inorganic aerosols and organic matter + elemental carbon categories, the unaccounted component reached 45% of PM mass. The PCA allowed to identify also traffic and industrial contributions, reducing the unaccounted mass to about 25%. Adding δ13C and δ15N values, secondary organic aerosol could be estimated and a continuous contribution of diesel combustion was identified together with a remarkable use of natural gas in winter. Isotopic values were better understood when considering air masses back trajectories and a possible long-distance contribution from coal-fired electric generating units (EGUs). Finally, using Bayesian dual isotope mixing models, the unaccounted PM mass was reduced up to 5% when adding these EGUs to marine-carbonate related, road traffic, domestic heating, waste incinerator and livestock waste contributions. The added value of the dual isotope approach combined with a Bayesian isotope mixing model, in comparison with conventional chemical approaches, was thus demonstrated for PM source apportionment in an urban and industrial site where many sources and processes converge and can then be applied to other complex cities.

In 2012, the concentrations of trace elements (As, Be, Cd, Cr, Hg, Mn, Ni, Pb, Sn, Tl, and V) were measured in blood samples of the population living in the vicinity of a hazardous waste incinerator (HWI) located in Tarragona County (Catalonia, Spain). This study is part of a wide surveillance program aimed at assessing the impact of the facility on the public health conducted since 1998, before the HWI started operating. Lead was the metal occurring with the highest concentration (21.7 μg kg−1), followed by Mn (19.7 μg kg−1) and Hg (4.62 μg kg−1). Arsenic (6.99 μg kg−1) showed a low detection rate (49%), while the rest of the analyzed trace elements were not detected. In 2017, a new sampling campaign was conducted, and three new trace elements (Co, Cu, and Sb) were added. In the most recent survey, Cu reached a mean concentration of 931 μg kg−1, up to 60-fold higher than that corresponding to the remaining trace elements. Relatively high levels were also found for Sb (16.0 μg kg−1), Mn (13.9 μg kg−1), and Pb (13.0 μg kg−1). In comparison with the baseline study (1998), Hg, Mn, and Pb significantly decreased over time. Some trace elements showed significant differences according to sex, age, and area of residence. In general, the concentrations of trace elements in blood were similar to, or even lower than, those reported in the scientific literature. Hence, the exposure to trace elements does not mean any additional health risk for the population living near the HWI. This conclusion is in agreement with other studies carried out in the framework of this surveillance program, in which trace elements have been measured in different biological matrices, such as hair and autopsy tissues (brain, bone, kidney, liver, and lungs).

In 2016, total suspended particles (TSP) and fine particles (PM2.5) were collected near four e-waste recycling parks in a region of Southern China. TSP and PM2.5 levels and composition around these industrial activities were determined and the potential risks for human health due to the exposure to toxic elements contained on fine particles (PM2.5) were evaluated. Levels of TSP and PM2.5 were lower with advanced recycling methods than with small recycling e-waste workshops operating in the sampling region. The main trace elements in particles were Cu, Pb, and Ti, the same as those detected before the transition to advanced dismantling methods in e-waste recycling. Significantly higher levels of Cu, Pb, Sn, Te, Tl and NH4+ in TSP and Cu and Te in PM2.5 were found in e-waste recycling areas than in BG site. Taking Cu as the indicative element emitted from e-waste recycling activities, significant high positive correlations between Cu and W, and Cu and Te were found. These elements are present and can be released from electrical and electronical components during e-waste recycling processes. Exposure to elements for the population living near these e-waste recycling parks means carcinogenic risks above the acceptable threshold (>10-5).

Inhalation of particulate matter (PM) has been linked to serious adverse health effects, such as asthma, cardiovascular diseases and lung cancer. In the present study, coarse (PM10-2.5), accumulation mode (PM2.5-0.25), and quasi-ultrafine (PM0.25) particulates were collected inside twelve educative centers of Tarragona County (Catalonia, Spain) during two seasons (cold and warm). Chemical characterization of PM, as well as risk assessment were subsequently conducted in order to evaluate respiratory and digestive risks during school time for children. Levels and chemical composition of PM were very different among the 12 centers. Average PM levels were higher during the cold season, as well as the concentrations of most toxic metals. In most schools, PM levels were below the daily PM10 threshold established in the regulation (50 μg/m3), with the exception of school number 1 during the cold season. On average, and regardless of season, coarse PM was highly influenced by mineral matter, while organic matter and elemental carbon were prevalent in quasi-ultrafine PM. The concentrations of the toxic elements considered by the legislation (As, Cd, Pb, and Ni) were below their correspondent regulatory annual limits. Calculated risks were below the safety thresholds, being fine fractions (PM2.5-0.25 and PM0.25) the main contributors to both digestive and respiratory risks.

In the present study, we assessed the non-carcinogenic and carcinogenic human health risk due to exposure to trace elements in soil and indoor dust in Puchuncavi valley. We also determined the associations between trace element concentration in hair/toenails and the estimated chronic daily intake of trace elements in soil and indoor dust. We found statistically significant association between the trace element concentration in hair/toenails and the estimated chronic daily intake of soil and indoor dust. Indoor dust was more important than soil in terms of human exposure to trace elements in Puchuncavi, due to the high concentration of trace elements on this environmental media and long periods of time that the population spends at their households. With regards to non-carcinogenic risk, we found that there was no health risk associated to soil and indoor dust exposure in the Puchuncavi valley, because none of the hazard quotient values surpassed 1.0. However, carcinogenic risk due to arsenic exposure was above the threshold value of 1.0E-04 in the population of young children (from 1 to 5 years old) in all studied areas, including the control, and in the population of children (from 6 to

The concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were analyzed in 40 plasma samples of individuals living in zones under potential influence of the emissions of a hazardous waste incinerator (HWI) (Tarragona County, Catalonia, Spain). Samples corresponded to subjects of different gender, age and specific areas of residence. The levels of PCDD/Fs were compared to those obtained in a baseline study (1998), as well as in previous surveys (2002, 2007 and 2012). The current mean concentration of PCDD/Fs in plasma was 6.79 pg I-TEQ/g lipid, which was significantly lower than the baseline concentration (27.0 pg I-TEQ/g lipid). A significant decrease was also observed in comparison to the results obtained in 2002 and 2007 (15.7 and 9.4 pg I-TEQ/g, respectively), while the current PCDD/F levels were similar to those obtained in 2012 (6.18 pg I-TEQ/g lipid). This important reduction in plasma PCDD/F levels is in accordance with the decreasing trend in the daily dietary intake of PCDD/Fs, which diminished from 210.1 pg I-TEQ (baseline) to 8.54 pg WHO-TEQ (current). OCDD was the predominant congener in plasma, while 2,3,7,8-TeCDD and 1,2,3,4,7,8,9-HpCDF showed the lowest levels. Based on the above results, as well as other recent data on the levels of PCDD/Fs in human milk, we conclude that the presence of the HWI does not mean additional and significant risks –as regards to PCDD/F exposure-for the population living in the neighborhood of the facility.

Chemical industries and oil refineries are known emission sources of environmental contaminants, such as metals/metalloids, polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), among others. Based on the toxicological potential of these pollutants, harmful health effects can be expected for the population living near these facilities. One of the largest chemical/petrochemical complexes in Europe is located in Tarragona County (Catalonia, Spain). In the last two decades, a number of investigations aimed at assessing the environmental impact of air pollutants potentially emitted by this industrial complex have been carried out. The present paper is a review of the available scientific information on the levels of air pollutants related with the activities of this chemical/petrochemical complex. Although there are currently some data on the environmental burdens of metals/metalloids, PAHs, VOCs and PCDD/Fs, there is an evident lack of specific biological monitoring studies on human health. Taking into account the amount of chemicals released to air and their toxicity, it is essential to perform an in-depth analysis of the current health status of the population living in Tarragona County.

Microplastics (MPs) are accessible for organisms with active filter feeding strategies, as are many marine molluscs, which live attached or semi-buried in sediments. In the present study, MPs (from 0.02 to 5 mm) concentration, morphology, and composition were determined in consumed mollusc species of the Catalan coast (NW Mediterranean Sea). Microplastic concentrations, morphologic characteristics and composition were studied according to species, catchment zones and depuration condition. Finally, human intake of MPs through molluscs' consumption was determined.2300 individuals were analysed, being 1460 MPs extracted and their size, and polymeric composition registered. Big oysters and mussels showed the highest MPs concentration by individual, with levels of 22.8 ± 14.4 and 18.6 ± 23.0 MPs/individual, respectively. Mean annual MPs (≥20 μm) consumption for adult population was estimated in 8103 MPs/year, with a 95th percentile of 19,418 MPs/year. It suggests that the consumption of molluscs is an important route of MPs exposure for the Catalan population.

Mediterranean Sea has been proposed as the sixth greatest accumulation zone for marine litter and the most affected regarding to microplastics (MPs). Tarragona (Catalonia, NE Spain) coastal region suffers high pressure due to urbanization, tourism, industrial harbour and petrochemical/plastic industries. The present study aims to quantify and characterize in size, morphology and composition the MPs present in sandy beaches, marine sediments, and surface seawaters of Tarragona coastal region. MPs mean abundance were 1.30 items/m3 in surface seawaters, 32.4 items/kg in marine sediments, and 10.7 items/kg in sandy beaches. Polyester fibres were dominant MPs in bottom sediments and seawater meanwhile polyethylene and polypropylene fragments were the main MPs in beaches. The fibres balls associated with bottom sediments, organic matter and plankton were abundant, masking the real quantity of fibres in each reservoir. The abundance by volume of seawater MPs was higher to those found in oceanic areas and similar to other areas of Mediterranean Sea, corroborating that Western Mediterranean Sea as a region of MPs accumulation. MPs composition and abundance suggested the input of numerous land-base-sources, WWTP (wastewater treatment plants) effluents discharges, and emissaries as the most important. Marine MPs pollution were studied from an integrative point of view, that includes superficial sea water, sand from beaches and sediments. The dynamics of MPs in Tarragona coast were characterized by seawater as the media that receive and facilitate dispersion and fragmentation. The shoreline acts as an intermediate reservoir with constant weathering and active exchange with seawater surface and the sediments acts as a significant sink for medium MPs sizes. It is necessary to develop protocols and guidelines for MPs analysis to obtain harmonized and comparable results.

This paper was aimed at reviewing recent studies related with the impact on environment and human health of metals and PCDD/Fs near cement plants. It has been particularly focused on the impact of cement plants located in Catalonia, Spain, which have been monitored by our research for more than ten years. Environmental monitoring studies were performed under different cement plant conditions. While some of our studies examined temporal trends of the levels of the above indicated pollutants, the main goal of other surveys was to assess the impact of implementing alternative fuels in the facilities. Even one of the studies was performed before and after the cement plant temporally ceased its industrial activity. The impact of cement plants burning alternative fuels on the emissions of metals and PCDD/Fs elsewhere was also reviewed. Regarding the cement plants in Catalonia, no significant differences were found, neither in the long-term follow-up studies, nor when alternative fuels are used, nor when a cement plant temporally stopped its activity. These results are in agreement with those reported for several stack emissions of other cement plants working under different conditions. We conclude that emissions of metals and PCDD/Fs by cement plants working with the best available techniques (BAT), should not cause a significant negative impact neither on the surrounding environment, nor on the human health of the population living in the neighborhood.

Air pollution by airborne particles is a serious health problem worldwide. The present study was aimed at investigating the concentrations and composition of total suspended particles (TSPs) and PM2.5 at various industrial/commercial sites of Guangzhou, a megacity of Southern China. Major and trace elements, ions and carbonaceous fraction were determined and main components were calculated. In addition, in order to assess the potential toxic on the respiratory system of these PM, cytotoxicity of size-fractionated particles (PM10-5.6, PM5.6-3.3, PM3.3-1.1, PM1.1-0.43) for a human lung cancer cell line (A549) was also investigated. Correlations between PM constituents and toxicity were assessed. Median levels of TSPs and PM2.5 in industrial/commercial sites were 206 and 57.7 μg/m3, respectively. Nickel, Cu, Mo, Mn, Pb, and Ti were the most abundant metals in TSPs and PM2.5. Industrial activities and coal combustion were the most important sources of carbonaceous particles in the zone. MTT assays showed that PM10-5.6 and PM1.1-0.43 had the highest and the lowest cytotoxicity to A549 cell lines, respectively. Inhalable particles around the manufacturing of metal facilities and formal waste treatment plants showed a high cytotoxicity to A549 cell lines. In general terms, no significant correlations were found between main components of PM and toxicity. However, W showed a significant correlation with cell viability.

The widespread use of Perfluorooctanesulfonate(PFOS) in everyday life, its long half-life, and the lipophilicity that makes it easily accumulate in the body, raises the question of its safe exposure among different population groups. There are currently enough epidemiological studies showing evidence of PFOS exposure and its associated adverse effects on humans. Moreover, it is already known that physiological changes along with age e.g. organ volume, renal blood flow, cardiac output andalbuminconcentrations affect chemicals body burden. Human biomonitoring cohort studies have reported PFOS concentrations in blood and autopsy tissue data with PFOS present in sensitive organs across all human lifespan. However, to interpret such biomonitoring data in the context ofchemical risk assessment, it is necessary to have a mechanistic framework that explains show the physiological changes across age affects the concentration of chemical inside different tissues of the human body.PBPKmodel is widely and successfully used in the field of risk assessment. The objective of this manuscript is to develop a dynamic age-dependent PBPK model as an extension of the previously published adult PFOS model and utilize this model to predict and compare the PFOS tissue distribution and plasma concentration across different age groups. Different cohort study data were used for exposure dose reconstruction and evaluation of time-dependent concentration in sensitive organs. Predicted plasma concentration followed trends observed in biomonitoring data and model predictions showed the increased disposition of PFOS in the geriatric population. PFOS model is sensitive to parameters governing renalresorptionand elimination across all ages, which is related to PFOS half-life in humans. This model provides an effective framework for improving the quantitative risk assessment of PFOS throughout the human lifetime, particularly in susceptible age groups. The dynamic age-dependent PBPK model provides a step forward for developing such kind of dynamic model for other perfluoroalkyl substances.

In the present study, the presence of a wide spectrum of major and trace elements (As, Ag, Al, Ba, Cd, Co, Cr, Cu, Hg, Mn, Ni, Sr, Sb, Se, Sn, Pb, V, and Zn), fatty acids, as well as some pollutants like free and total BPA and tetrabromobisphenol A (TBBPA), was analysed in human milk (n = 53) and infant formula (n = 50) samples. In addition, the infant exposure to these chemicals was assessed. The content of free BPA and several elements (Al, Ca, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Sn, Sr, and Zn) was higher (p 0.01) in infant formula samples. Furthermore, human milk contained levels of BPA and elements that, in almost all cases, were well below their respective EFSA and/or WHO thresholds, being also independent of the maternal characteristics (e.g., age, BMI or breastfeeding period). The fatty acid profiling also revealed major differences between human milk and infant formulas, which should be taken in account in the development of new formulas as well as in specific recommendations for the diet of breastfeeding mothers. Anyway, the results of this study reinforce that breastfeeding should be always the first feeding option in early life.

Perfluoroalkyl substances (PFAS), especially PFOS and PFOA, are two widely used synthetic chemicals that can impact human health based on evidence from animal and epidemiologic studies. In this paper, we have reviewed and summarized the influence of PFAS exposure on health, pointing the quality of evidence, and applied translational techniques to integrate evidence for PFAS policy making. This is the first review where highly referred articles on PFAS used for policymaking by several regulatory agencies were collected and evaluated based on the review guidelines developed by the US National Toxicology Program's Office of Health Assessment and Translation (OHAT) review guidelines. Several limitations were observed, including co-exposure to multiple chemicals and limited measurement of primary and secondary outcomes related to specific toxicity. However, data from all the studies provided a moderate to strong level of confidence for link between PFAS exposure and different adverse outcomes. Secondly, for translating the risk to humans, an in-silico model and scaling approach was utilized. Physiologically based pharmacokinetic model (PBPK) was used to calculate the human equivalent dose (HED) from two widely accepted studies and compared with tolerable daily intakes (TDIs) established by various regulatory agencies. Inter-species dose extrapolation was done to compare with human the relevance of dosing scenarios used in animals. Overall, a framework for translation of risk was proposed based on the conclusions of this review with the goal of improving policymaking. The current paper can improve the methodological protocols for PFAS experimental studies and encourage the utilization of in-silico models for translating risk.

In 2009, a cement plant located in Alcanar (South Catalonia, Spain) started co-processing a special kind of refuse-derived fuel (RDF) called ENERFUEL™. In April 2014 and 2017, 5 and 8 years after RDF co-processing, the concentrations of metals and metalloids (As, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Sb, Tl, V and Zn) and PCDD/Fs were measured in samples of soils, herbage and air collected in the vicinity of the facility. The comparison of the current concentrations with those obtained in a baseline study (2008), when fossil fuels were used solely, has shown that the environmental concentrations of metals, metalloids and PCDD/Fs were not significantly modified. The concentrations of metals, metalloids and PCDD/Fs in soil, vegetation and air of Alcanar are in the low part of the ranges found around other cement plants in Catalonia (in general, below 50th percentile). Non-carcinogenic risks due to exposure to metals, metalloids and PCDD/Fs were lower than the safety value (HQ

In this pilot study three fractions of particulate matter (PM0.25, PM2.5-(0.25), and PM10-2.5) were collected in three environments (classroom, home, and outdoors) in a village located nearby an industrial complex. Time-activity pattern of 20 students attending the classroom was obtained, and the dose of particles reaching the children's lungs under actual environmental conditions (i.e. real dose) was calculated via dosimetry model. The highest PM concentrations were reached in the classroom. Simulations showed that heavy intensity outdoor activities played a major role in PM deposition, especially in the upper part of the respiratory tract. The mass of PM10-2.5 reaching the alveoli was minor, while PM2.5-0.25 and PM0.25 apportion for most of the PM mass retained in the lungs. Consequently, PM(2.5-0.25 )and PM0.25 were the only fractions used in two subsequent toxicity assays onto alveolar cells (A549). First a cytotoxicity dose- response assay was performed, and doses corresponding to 5% mortality (LC5) were estimated. Afterwards, two LC-MS metabolomic assays were conducted: one applying LC5, and another applying real dose. A lower estimated LC5 value was obtained for PM0.25 than PM2.5-0.25 (8.08 and 73.7 ng/mL respectively). The number of altered features after LC5 exposure was similar for both fractions (39 and 38 for PM0.25 and PM2.5-0.25 respectively), while after real dose exposure these numbers differed (10 and 5 for PM(0.25 )and PM2.5-0.25 respectively). The most metabolic changes were related to membrane and lung surfactant lipids. This study highlights the capacity of PM to alter metabolic profile of lung cells at conventional environmental levels. (C) 2018 Elsevier Ltd. All rights reserved.

In 1996-1998, a wide surveillance program was initiated in the vicinity of a new hazardous waste incinerator (HWI) placed in Constantí (Catalonia, Spain), which started its regular operations in 1999. The program was aimed at assessing the environmental impact of the facility on the surrounding environment, as well as to evaluate the potential risks for the population living in the neighborhood. Since then, among other measurements, the concentrations of polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) have been periodically determined in soil and herbage samples. This study shows the results, corresponding to the period 2013-2016. Data were compared with those obtained in the baseline survey (1996-1998), as well as with those of the previous survey (2011-2012). The median PCDD/F concentrations in soils were 0.44 and 0.33 ng toxic equivalent (I-TEQ)/kg in 2015 and 2016, respectively, with a significant decrease in relation to the baseline survey, and a non-significant decrease between 2015 and 2016. In turn, PCDD/F levels in vegetation showed some fluctuations over time, being the concentrations of PCDD/Fs in 2013 very similar to those found in 2012 (1.11 and 1.23 ng I-TEQ/kg, respectively). These concentrations notably decreased along the three last campaigns (0.16, 0.23, and 0.17 ng I-TEQ/kg in 2014, 2015, and 2016, respectively). These changes would be more related to a number of environmental factors rather than to a variation of PCDD/F emissions by the HWI. With respect to human health risks, exposure to PCDD/Fs in the area under potential influence of the HWI is not of concern, as the current environmental concentrations of PCDD/Fs do not mean additional carcinogenic or non-carcinogenic risks for the local population.

Previously to the modernization of the municipal solid waste incinerator (MSWI) of Campdora (Girona, Catalonia, Spain) two sampling campaigns (2015 and 2016) were conducted. In each campaign, 8 soil and 4 air samples (PM10 and total particle phase and gas phase) were collected. The levels of As, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Sb, Sn, Tl and V, and PCDD/Fs were analysed at different distances and wind directions around the MSWI. Environmental levels of trace elements and PCDD/Fs were used to assess exposure and health risks (carcinogenic and non-carcinogenic) for the population living around the facility. In soils, no significant differences were observed for trace elements and PCDD/Fs between both campaigns. In air, significant higher levels of As, Cd, Co, Mn, Ni, Pb, Tl and V were detected in 2016. Regarding soil levels, only Cd (distances) and As, Cu, Mn, and Ni (wind directions) showed significant differences. No differences were noted in the concentrations of trace elements and PCDD/Fs in air levels with respect to distances and directions to the MSWI. No differences were registered in air levels (elements and PCDD/Fs) between points influenced by MSWI emissions and background point. However some differences in congener profile were noted regarding from where back-trajectories come from (HYSPLIT model results), pointing some influence of Barcelona metropolitan area. The concentrations of trace elements and PCDD/Fs were similar -or even lower- than those reported around other MSWIs in Catalonia and various countries. Non-carcinogenic risks were below the safety limit (HQ

Recent studies suggest universal fetal exposure to Bisphenol A (BPA) and its association with the adverse birth outcomes. Estimation of the fetal plasma BPA concentration from the maternal plasma BPA would be highly useful to predict its associated risk to this specific population. The objective of current work is to develop a pregnancy-physiologically based pharmacokinetic (P-PBPK) model to predict the toxicokinetic profile of BPA in the fetus during gestational growth, and to evaluate the developed model using biomonitoring data obtained from different pregnancy cohort studies. To achieve this objective, first, the adult PBPK model was developed and validated with the human BPA toxicokinetic data. This validated human PBPK model was extended to develop a P-PBPK model, which included the physiological changes during pregnancy and the fetus sub-model. The developed model would be able to predict the BPA pharmacokinetics (PKs) in both mother and fetus. Transplacental BPA kinetics parameters for this study were taken from the previous pregnant mice study. Both oral and dermal exposure routes were included into the model to simulate total BPA internal exposure. The impact of conjugation and deconjugation of the BPA and its metabolites on fetal PKs was investigated. The developed P-PBPK model was evaluated against the observed BPA concentrations in cord blood, fetus liver and amniotic fluid considering maternal blood concentration as an exposure source. A range of maternal exposure dose for the oral and dermal routes was estimated, so that simulation concentration matched the observed highest and lowest mother plasma concentration in different cohorts' studies. The developed model could be used to address the concerns regarding possible adverse health effects in the fetus being exposed to BPA and might be useful in identifying critical windows of exposure during pregnancy.

Background: In February 2017, some buildings of La Pineda (Catalonia, NE Spain) a rather small town, located near to the Tarragona harbor, were affected by a contamination episode that dirtied external walls, windows, doors and floors of these buildings with a black dust. This study was aimed at assessing the origin of the black dust appeared in the buildings. Methods: Black dust samples were collected in the railings of balconies, windows, and exterior doors of two buildings in La Pineda, as well as in the ground of the breakwater of the Tarragona harbor, at few meters from the open air coal storage area. Elemental analysis of the black dust (C, N, H and S) was performed. A daily sample of PM10 was also collected and analyzed for five consecutive days. Results: The total carbon content of the collected dust was 25.8%, 29.4% and 33.9% in the two buildings of La Pineda and the breakwater, respectively. In turn, the contribution of carbon from carbonates was 0.0%, 1.3% and 5.1%, in the samples of the two buildings and the breakwater, respectively. PM10 showed levels between 18 and 39 µg/m3, with mean and median levels of 29 µg/m3. Conclusion: The elemental analysis indicated that the two black dust samples collected in the two buildings of La Pineda were similar to the sample collected at the breakwater of the port of Tarragona, showing a common origin: The bulk coal storage area of Tarragona harbor. Because information on the human health risks derived from the important activities conducted in the port of Tarragona is currently non-existent, an exhaustive assessment of all pollutants involved in the activities of the port is strongly recommended.

Humans are exposed to a cocktail of heavy metal toxicants in the environment. Though heavy metals are deleterious, there is a paucity of information on the toxicity of mixtures. In this study, four common neurotoxicity heavy metals lead (Pb) cadmium (Cd), arsenic (As), and methylmercury (MeHg) were exposed individually and as mixtures to HT-22 cell line for 8days. The study established that low dose exposures induced toxicity to the HT-22 cell line during 8days. The results indicates potency dependent response, the toxicity of single metals on the HT-22 cells; MeHg > As > Cd > Pb. The cytotoxicity data of single metals were used to determine the mixtures interaction profile by using the dose additivity and effect additivity method. Metal mixtures showed higher toxicities compared to individual metals. Synergistic, antagonistic or additive effects of the toxicity were observed in different mixtures in low dose exposure. The interactive responses of mixtures depend on the co-exposure metal and their respective concentration. We concluded that the combined effects should be considered in the risk assessment of heavy metal co-exposure and potency. In future, comprehensive mechanistic based investigations needed for understanding the real interactive mixtures effects at molecular level.

Microalgae growth inhibition assays are candidates for referent ecotoxicological assays, and are a fundamental part in the strategy to reduce the use of fish and other animal models in aquatic toxicology. In the present work, the performance of Raphidocelis subcapitata exposed to heavy metals following standardized growth inhibition assays has been assessed in three different scenarios: 1) dilutions of single heavy metals, 2) artificial mixture of heavy metals at similar levels than those found in natural rivers and, 3) natural samples containing known mixtures of contaminants (heavy metals). Chemical speciation of heavy metals has been estimated with Eh-pH diagram and Visual MINTEQ software; heavy metal and free heavy metal ion concentrations were used as input data, together with microalgae growth inhibition, for Dr. Fit software. The final goal was to assess the suitability of the ecotoxicological test based on the growth inhibition of microalgae cultures, and the mathematic models based on these results, for regulatory and decision-making purposes. The toxicity of a given heavy metal is not only determined by its chemical speciation; other chemical and biological interaction play an important role in the final toxicity. Raphidocelis subcapitata 48h-h-EC50 for tested heavy metals (especially Cu and Zn) were in agreement with previous studies, when ion metal bioavailability was assumed to be 100%. Nevertheless, the calculated growth inhibition was not in agreement with the obtained inhibition when exposed to the artificial mixture of heavy metals or the natural sample. Interactions between heavy metal ions and the compounds of the culture media and/or the natural sample determine heavy metal bioavailability, and eventually their toxicity. More research is needed for facing the challenge posed by pollutant mixtures as they are present in natural environments, and make microalgae-based assays suitable for pollution management and regulatory purposes.

The aim of this work is to predict the bioavailability of the Potentially Toxic Elements (PTEs) Cd, Pb, Hg, Ni, Cu, Zn, As, Cr and Se in 6 sites within the Ebro River basin. In situ Diffusive gradient in thin-films (DGTs) and classical sampling have been used and compared. The potentially bioavailable fractions of each PTE was estimated by modelling their chemical speciation using three programs (WHAM 7.0, Visual MINTEQ 3.1 and Bio-met), following the suggestions published in recent European regulations. Results of the equilibrium-based models WHAM 7.0 and Visual MINTEQ 3.1 indicate that As, Cd, Ni, Se and Zn, predominate as free metals ions or forming inorganic soluble complexes. Copper, Pb and Hg bioavailability is conditioned by their affinity to dissolved humic substances. According to Visual MINTEQ 3.1, Cr is subjected to redox reactions, being Cr (VI) present (at low concentrations) in the studied rivers. According to Bio-met model, the bioavailability of Cu and Zn is highly influenced by soluble organic matter and water hardness, respectively. For most PTEs, the bioavailability estimated by deploying DGTs in river waters tends to be slightly lower than the estimation obtained with speciation models, since in real conditions more environmental factors take place comparing to the finite number of parameters considered in models.

In May 2016, a big fire occurred in an illegal landfill placed in Seseña (Toledo, Spain), where between 70,000 and 90,000 tons of tires had been accumulated during years. Just after the fire, and because of the increase of airborne PAHs, we found that cancer risks for the population living in the neighborhood of the landfill were 3-5 times higher than for the rest of inhabitants of Seseña. Some months after our initial (June 2016) study, two sampling campaigns (December 2016 and May 2017) were performed to assess the temporal trends of the environmental levels of PAHs, as well as to reassure that these chemicals did not pose any risk for the human health of Seseña inhabitants. In soils, the total concentrations of the 16 PAHs (December 2016), as well as the sum of the seven carcinogenic PAHs, showed values between 8.5 and 94.7 ng g

Heavy metals are considered some of the most toxic environmental pollutants. Exposure to heavy metals including lead (Pb), cadmium (Cd), arsenic (As), and methyl mercury (MeHg) has long been known to cause damage to human health. Many recent studies have supported the hippocampus as the major target for these four metals for inflicting cognitive dysfunction. In the present study, we proposed hippocampal relevant in vitro toxicity of Pb, Cd, As, and MeHg in HT-22 cell line. This study reports, initially, cytotoxic effects in acute, subchronic, chronic exposures. We further investigated the mechanistic potency of DNA damage and apoptosis damage with the observed cytotoxicity. The genotoxicity and apoptosis were measured by using the comet assay, annexin-V FTIC / propidium iodide (PI) assay, respectively. The results of cytotoxicity assay clearly demonstrated significant concentration and time-dependent effects on HT-22 cell line. The genotoxic and apoptosis effects also concentration-dependent fashion with respect to their potency in the range of IC10-IC30, maximal level of damage observed in MeHg. In conclusion, the obtained result suggests concentration and potency-dependent response; the maximal level of toxicity was observed in MeHg. These novel findings support that Pb, Cd, As, and MeHg induce cytotoxic, genotoxic, and apoptotic effects on HT-22 cells in potency-dependent manner; MeHg> As> Cd> Pb. Therefore, the toxicity of Pb, Cd, As, and MeHg could be useful for knowing the common underlying molecular mechanism, and also for estimating the mixture impacts on HT-22 cell line.

Mixture of metals and herbicides in rivers may pose relevant risks for the health of surrounding communities. Humans may be exposed to river pollution through intake of contaminated water and fish, as well as irrigated agricultural products. The aim of this study was to assess the human health risks of environmental exposure to metals and herbicides through water and fish intake in the Pardo River. Metals (Al, As, Be, Cd, Cr, Cu, Pb, Mn, Hg, Ni, Tl, Sn, V, and Zn) were analyzed in river water and in edible fish. Herbicides (ametryn, atrazine, diuron, hexazinone, simazine, and tebuthiuron) were analyzed in river water. Seasonal variances were also studied. Aluminum, Cd, Cu, Mn, Pb, and Zn levels in river water were higher than the USEPA benchmarks. Non-carcinogenic risks due to pollutants mixture exposure were above the limit, and carcinogenic risks of As exposure were >10−6 in the sampling points during the rainy season. Metal levels in fish were lower than the Brazilian legislation and do not pose a threat to public health. Herbicides were detected in four sampling points, with atrazine concentrations (range 0.16–0.32 μg/L) below the Brazilian standard (2.0 μg/L), but above the European Union standard (0.1 μg/L). Considering the water supply needs of cities located in the Pardo River Basin and the persistence of metals and herbicides, the present study indicated that there was a seasonal influence on non-carcinogenic and carcinogenic risks to human health, especially in the rainy season. Studies for water treatment plants implantation should consider the risks of exposure to persistent substances, in order to protect the population.

The concentrations of trace elements were analysed in samples of home textiles (i.e. towels, bedclothes and pyjamas). Arsenic, Be, Cd, Sc, Se, Sm and Tl levels were below their respective detection limits, while Hg, Mo and V could be only detected in a few samples. The highest mean levels corresponded to Mg, Cu andSb. In agreement with previous findings in casual wear, home textiles made of polyester, either exclusively or partially, showed significantly higher levels of Sb than those made of cotton, while Ti levels were also significantly higher in synthetic fibre items. The levels of Cr and Cu were especially relevant in colour clothes. The dermal absorption of trace elements during sleeping and towels use were also estimated, being the health risks subsequently assessed. The maximum hazard quotient (HQ) for all elements was well below 0.01, indicating a safe situation. The only exception was Sb, whose HQ due to bedclothes/pyjamas and towels use was 0.4 and >1, respectively. Comparing with other...

This study was aimed at comparing the toxicity effects on cell viability and the obesogenic activity of Bisphenol A (BPA) and its analogues, Bisphenol S (BPS) and Bisphenol F (BPF), by in vitro assays with a preadipocytic 3T3-L1 cell line. To compare the toxic potential and select the concentrations of each chemical not showing a decrease in cell viability, MTT assay was performed. The cell phenotype was determined in differentiated 3T3-L1 adipocytes by red oil O staining. To determine the expression levels of the different adipogenic proteins the Western Blot test was performed. The results from MTT assay showed a greater toxic effect of BPA - at equal and even lower concentrations-than its analogues. However, BPS followed by BPF showed a greater neutral lipid storage capacity than BPA, which was reflected in the increase of the protein expression of CCAAT/enhancer binding protein α (C/EBPα), peroxisome proliferator-activated receptor gamma γ (PPARγ) and acid-binding protein 4 (FABP4). In summary, these BPA analogues -especially BPS- present a greater endocrine potential activity than BPA.

Phthalates are known endocrine disruptors (EDs) and are associated with potential diseases, such as obesity and diabetes. In 2002, the plasticizer 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) was introduced as an alternative to phthalates in the European market. The objective of this study was to evaluate the total exposure to phthalate and DINCH metabolites from EXHES Tarragona, Spain cohort of pregnant women. On the one hand, the analytical determination of phthalate and DINCH metabolites in urine was carried out. On the other hand, the reconstructed exposure was calculated for phthalates and DINCH using their metabolites concentration measured in the urine. Thirteen different phthalate metabolites and two metabolites of DINCH were measured and detected in almost all pregnant women's urine samples (n = 60). There were significant correlations between metabolites of the same parent compounds, and also between DEHP and MBzP metabolites, DiNP and BBZP metabolites, and DEHP and DiNP metabolites respectively. The exposure of pregnant women to phthalate and DINCH parent compounds were also back calculated using the levels of each metabolite found in pregnant women urine (reconstructed exposure). Besides, to demonstrate the utility of this approach, the physiologically based pharmacokinetic (PBPK) model was used to predict the cumulative amount of MEHP (a principal metabolite of DEHP in urine). To proceed with that, DEHP reconstructed exposure and estimated exposure from the same cohort (previously studied by the same authors) were simulated using the PBPK model. Results showed that the reconstructed-PBPK simulation was closer to the 24 h biomonitoring data than the estimated PBPK-simulation., This clearly shows that the combination of reconstructed exposure with the PBPK model is a good tool to predict chemicals exposure. However, some discrepancies between simulated and biomonitored values were found. This can be associated with other sources that contribute to the total exposure and emphasises the need to consider multi-routes exposure for the widely distributed chemicals like phthalates and DINCH.

We present a model to predict the long-term distribution and concentrations of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) in estuaries comprising multiple intercommunicated sub-embayments. To that end, a mass balance model including rate constants and time-varying water inputs was designed to calculate levels of these compounds in water and sediment for every sub-embayment. Subsequently, outflows and tidal water exchanges were used to interconnect the different regions of the estuary. To calculate plausible risks to population, outputs of the model were used as inputs in a previously designed model to simulate concentrations of PFOA and PFOS in a sport fish species (Cymatogaster aggregata). The performance of the model was evaluated by applying it to the specific case of San Francisco Bay, (California, USA), using 2009 sediment and water sampled concentrations of PFOA and PFOS in North, Central and South regions. Concentrations of these compounds in the Bay displayed exponential decreasing trends, but with different shapes depending on region, compound, and compartment assessed. Nearly stable PFOA concentrations were reached after 50 years, while PFOS needed close to 500 years to stabilize in sediment and fish. Afterwards, concentrations stabilize between 4 and 23 pg/g in sediment, between 0.02 and 44 pg/L in water, and between 7 and 104 pg/g wet weight in fish, depending on compound and region. South Bay had the greatest final concentrations of pollutants, regardless of compartment. Fish consumption is safe for most scenarios, but due to model uncertainty, limitations in monthly intake could be established for North and South Bay catches.

The burden of organophosphate (OP) pesticides in pregnant women from Tarragona (n = 157), a Mediterranean area of intense agricultural activity, has been assessed from the study of hydroxylated organic metabolites in urine samples in the three trimesters of pregnancy. 2-Diethylamino-6-methylpyrimidin-4-ol (DEAMPY), a metabolite of pirimiphos, was the compound found in higher concentration, medians 0.66–2.8 μg/g creatinine. 4-Nitrophenol (PNP), a metabolite of parathion, medians 0.24–0.41 μg/g creatinine, was the second most abundant compound. 2-Isopropyl-6-methyl-4-pyrimidol (IMPY), a metabolite of diazinon, was also present but in lower concentrations. Except for DEAMPY, the concentrations found in this cohort were lower than those reported in studies from other countries. Intraclass correlation coefficients (ICCs) were calculated for the compounds found in more than the 35% of the samples, the reliability between trimesters was poor (, This paper was supported by funding from the European Union projects: HEALS (FP7-ENV-2013- 603946), Neurosome (H2020-MSCA-ITN-2017 SEP-210411486) and EDC-MET (H2020-HEALTH/0490–825762). J. Rovira received funds from the Health Department of Catalonia Government trough “Pla Estratègic de Recerca i Innovació en salut” (PERIS 2016–2020).

The purpose of this study was to assess the impact to human health of air pollutants, through the integration of different technics: data statistics (spatial and temporal trends), population attributable fraction using AIRQ+ model developed by the WHO, and burden of disease using Disability-Adjusted Life Years (DALYs). The levels of SO

During the period 1996–1998, a hazardous waste incinerator (HWI) was built in Constanti (Tarragona County, Catalonia, Spain). Because of the potential adverse effects of toxic emissions, mainly metals and dioxins and furans, waste incinerators in general have been an important cause of concern for the public opinion. For that reason, to assess its environmental impact on the surroundings, as well as the potential human health risks of the HWI, environmental and biological monitoring studies have been carried out since 1996–1998, when the baseline concentrations were established. This article summarizes all the results corresponding to metals in biological tissues of the population living near the HWI, two decades after the construction of the facility. In 1996–1998, the baseline concentrations of a number of elements (As, Be, Cd, Cr, Hg, Mn, Ni, Pb, Sn, Tl and V) were determined in samples of hair, blood and autopsy tissues (bone, brain, liver, lung and kidney) of subjects living in the area. In successive 5-year periods, new surveys were conducted to periodically measure the levels of metals in the same biological tissues. The daily dietary intake of these metals was also estimated for the population of the area. The results of this surveillance program do no suggest additional adverse health risks of metals for the population living near the HWI. However, special attention should be paid to Cr, due not only to the increases of this element observed in most analyzed biological tissues, but also in its dietary intake.

In 2016, total suspended particles (TSP) and fine particles (PM

Exposures to toxic elements or deficiencies of essential elements during pregnancy may be associated to various birth complications or even diseases in early life. The aim of this paper was to assess the concentrations of selected toxic (As, Cd, Cr, Hg, Ni, Pb) and essential trace elements (Co, Cu, Mn, Se and Zn) in blood and urine samples of delivering women at different periods of gestation and cord blood, as well as to evaluate the placental permeability for these elements. A total of 53 women participating in the HEALS-EXHES study were enrolled. In particular, 48 blood samples from 1st trimester of pregnancy, 40 blood samples at delivery, and 31 cord blood at delivery were collected. Moreover, mothers' urine were sampled at the 1st (53 samples), 2nd (53 samples) and 3rd trimester (49 samples) of pregnancy. Results showed that Hg and Mn levels in cord blood were about 2.0 times higher than in maternal blood, suggesting that these elements may be transferred from mother to fetus. The cord blood levels of As and Pb were lower (ca. the 65%) than those in maternal blood, showing that the placenta modulates the rate of transfer for these elements. Essential elements as Cu and Zn showed significantly lower levels in cord than in maternal blood suggesting that the transplacental transfer of these nutrients was very limited. In addition, correlation between paired maternal and cord blood samples for As, Hg and Pb was statistically significant indicating that the fetal body burden may reflect the maternal exposure. Cadmium, Co, Cr, Ni and Se levels did not show significant correlations between maternal and cord blood. Maternal urinary concentrations of trace elements, including As, Cr, Cu, Hg, Se and Zn decreased along pregnancy, which may cause variations in fetal exposure. The levels of toxic and essential elements in maternal blood and urine, as well as in cord blood, were for most elements at the lower end of the ranges found in the scientific literature not being of special concern for pregnant women and the unborn.

This study was aimed at assessing the prenatal exposure to perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in a cohort of pregnant women living in Reus (Tarragona County, Catalonia, Spain). These chemicals were biomonitored in maternal plasma during the first trimester of pregnancy, at delivery, and in cord blood. The dietary exposure of PFOS and PFOA was estimated by using questionnaires of food frequency and water intake, as well as data on food levels previously reported in the same area. In addition, the exposure through air inhalation and indoor dust ingestion was also calculated. Finally, a physiologically-based pharmacokinetic (PBPK) model was applied in order to establish the prenatal exposure of the fetus/child and to adjust exposure assessment vs. biomonitoring results. Probabilistic calculations of fetal exposure were performed by forward internal dosimetry and Monte-Carlo simulation. Mean plasma levels of PFOA were 0.45, 0.13 and 0.12 ng/mL at the first trimester, at delivery and in cord plasma, while those of PFOS were 2.93, 2.21, and 1.17 ng/mL, respectively. Traces of PFOS were found in all samples in the trimester and at delivery, and almost in all cord blood samples. Transplacental transfers of PFOS and PFOA were estimated to be around 70% and 60%, respectively. A temporal decrease trend in plasma levels of PFOS and PFOA was noticed, when comparing current values with data obtained 10 years ago in the same area. In agreement with many other studies, dietary intake was the main route of exposure to PFOS and PFOA in our cohort of pregnant women. It is an important issue to establish the exposure in critical windows periods such as fetal development to perfluoroalkylated substances, but also to other endocrine disrupting chemicals.

Inhalation of particulate matter (PM) has been linked to serious adverse health effects, such as asthma, cardiovascular diseases and lung cancer. In the present study, coarse (PM

Human exposure to toxic heavy metals is a global challenge. Concurrent exposure of heavy metals, such as lead (Pb), cadmium (Cd), arsenic (As) and methylmercury (MeHg) are particularly important due to their long lasting effects on the brain. The exact toxicological mechanisms invoked by exposure to mixtures of the metals Pb, Cd, As and MeHg are still unclear, however they share many common pathways for causing cognitive dysfunction. The combination of metals may produce additive/synergetic effects due to their common binding affinity with NMDA receptor (Pb, As, MeHg), Na+ - K+ ATP-ase pump (Cd, MeHg), biological Ca+2 (Pb, Cd, MeHg), Glu neurotransmitter (Pb, MeHg), which can lead to imbalance between the pro-oxidant elements (ROS) and the antioxidants (reducing elements). In this process, ROS dominates the antioxidants factors such as GPx, GS, GSH, MT-III, Catalase, SOD, BDNF, and CERB, and finally leads to cognitive dysfunction. The present review illustrates an account of the current knowledge about the individual metal induced cognitive dysfunction mechanisms and analyse common Mode of Actions (MOAs) of quaternary metal mixture (Pb, Cd, As, MeHg). This review aims to help advancement in mixture toxicology and development of next generation predictive model (such as PBPK/PD) combining both kinetic and dynamic interactions of metals.

In May 2016, a fire occurred in one of the largest landfills in Europe (Seseña, Toledo, Spain), where 70,000–90,000 tons of tires had been illegally accumulated for >15 years. Because of the proximity of population nuclei and the duration of the episode (>20 days), we conducted a preliminary human health risk assessment study just after the tire fire. Samples of air and soil were collected in 3 areas surrounding the landfill (El Quiñón, at only 500 m, and Seseña Nuevo and Seseña Viejo, both at 4 km), as well as in background sites. In addition, samples of crops (barley, wheat, cabbage and lettuce) were also obtained from local farmers. The concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs) and a number of trace elements (As, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Sb, Sn, Tl, and V) were analyzed in all the samples. The concentrations of all the target pollutants, excepting PAHs, were relatively similar at the different sampling zones, irrespective of the distance to the landfill. In turn, a significant increase of PAHs was noted near the tire landfill, with air levels up to 6-times higher than those found at 4 km (134 vs. 19.5–22.7 ng/m3). Similarly, PAH concentrations in lettuce were relatively higher than those typically found in monitoring programs of food safety. Because of the increase of airborne PAHs, cancer risks due to exposure to environmental pollutants for the population living at El Quiñón, near the landfill, were between 3- and 5-times higher than those estimated for the inhabitants of Seseña. After this preliminary study, further investigations, focused only on PAHs, but more extensive in terms of number of samples, should be conducted to assure that PAHs have been progressively degraded through time. Keywords: Tire landfill fire, Seseña, Spain, Human exposure, Polycyclic aromatic hydrocarbons, Cancer risks

In June 2010, the cement plant of Montcada i Reixac (MR) (Catalonia, Spain) began a gradual implementation of alternative fuel to replace fossil fuel. Between December 2010 and November 2014, we conducted three monitoring surveys to evaluate the state of the environment around the facility. Data were compared with results from three monitoring surveys performed in 2008-2009. In all these studies, samples of soil, vegetation, and air were collected, being the content of a number of trace elements and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in these matrices determined. In general terms, a decrease of metal and PCDD/F concentrations was found. Human health risks followed a similar temporal trend, being acceptable according to national and international standards and independent on the fuel used. The Disability-Adjusted Life Year and the costs of cancer cases were also estimated for the population living around the MR cement plant, accounting for 4 years and 31,000 €/year, respectively.

The concentrations of a considerable number of trace elements (Ag, Al, As, B, Ba, Be, Bi, Cd, Co, Cr, Cu, Fe, Hg, Mg, Mn, Mo, Ni, Pb, Sb, Sc, Se, Sm, Sn, Sr, Ti, Tl, V and Zn) were determined in various skin-contact clothes (T-shirts, blouses, socks, baby pajamas and bodies) from the Catalan (Spain) market. In addition, migration experiments with artificial acidic sweat were conducted in order to establish the migration rates of these elements. High levels of Zn (186–5749 mg/kg) were found in zinc pyrithione labeled T-shirts, while high concentrations of Sb and Cr were found in polyester and black polyamide fabrics, respectively. An environmental scanning electron microscope (ESEM) confirmed the presence of Ag and Ti particles and aggregates in several clothing items. The use of the ESEM complemented the results of the elemental analysis and migration experiments. Dermal exposure to trace elements was subsequently calculated, and the human health risks were assessed. Antimony showed the highest mean hazard quotient (HQ = 0.4) for male and female adults wearing polyester clothes; for one of the examined items (polyester T-shirt) the HQ was even above the safety limit (HQ > 1). Exposure to Sb from polyester textile could mean potential health risks in subpopulation groups who frequently wear these clothes, and for long time periods. The migration experiments with artificial sweat showed to be essential for establishing the exposure to trace elements through cloth with direct contact with skin.

Physiologically-based pharmacokinetic (PBPK) models are mathematical representations of the human body aimed at describing the time course distribution of chemicals in human tissues. Since parameterization of PBPK models is based on empirical estimation and experimental data, simulation results may have high degree of uncertainty. As a consequence, the reliability of model validation is highly affected. In this study, the parametric uncertainty associated with PBPK models developed for perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) were analyzed and the different validation approaches were discussed for a case-study in Tarragona County (NE of Spain). Physicochemical parameters and dietary intake of PFOS and PFOA were estimated from previous investigations performed in Tarragona County. A sensitivity analysis (SA) was performed to understand the degree of influence of input parameters on the final outcomes. The uncertainty of the PBPK models' outcome was assessed by propagating the parametric uncertainty using the Latin Hypercube Sampling (LHS) technique. The elimination constants (Tm and Kt) as well as the Free fraction and the Intake, were the most influential parameters according to the SA results, being up to 83% for PFOS and 99.9% for PFOA. The validation of the PBPK model, which was performed using different approaches, showed clear discrepancies in the visual validation when compared with the statistical analysis.