Air concentrations of trace elements in a municipality under the influence of Tarragona petrochemical complex: Human health risks.

One of the largest petrochemical complexes of southern Europe is located in Tarragona County (Catalonia, Spain). Despite environmental monitoring is routinely conducted in the area, the long-term occurrence of airborne trace elements has been poorly investigated. In the present study, the concentrations of arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), lead (Pb) and vanadium (V) were analysed in air samples collected in El Morell, a town potentially impacted by the petrochemical. Air samples were simultaneously collected in the town of Cambrils, as a background site. Meteorological data and retro trajectories analysis were used to evaluate the impact of the petrochemical industry on the levels of trace elements in air. Subsequently, human health risks due to inhalation exposure to the trace elements were also assessed. Except for V, air concentrations were significantly higher near the oil refinery than the background levels. Human health risks were also estimated to be higher in the vicinity of the petrochemical complex. In turn, air inhalation of Pb and V was higher than their dietary intakes. The present data should be considered only as preliminary, since the sampling was taken during only three weeks, which is an insufficient period to extract reliable conclusions. Further long-term studies should be focused on assessing the influence of temporary variables, such as meteorological conditions and fugitive or sporadic emissions.

Framework for risk assessment of PFAS utilizing experimental studies and in-silico models.

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.

Unravelling sex-specific BPA toxicokinetics in children using a pediatric PBPK model.

Bisphenol A (BPA) is a widely known endocrine disruptor (ED) found in many children's products such as toys, feeding utensils, and teething rings. Recent epidemiology association studies have shown postnatal BPA exposure resulted in developing various diseases such as diabetes, obesity, and neurodegeneration, etc., later in their lives. However, little is known about its sex-specific metabolism and consequently internal exposure. The aim of this study was to develop a sex-specific pediatric physiologically based pharmacokinetic model (PBPK) for BPA to compare their toxicokinetic differences. First, the published adult PBPK model was re-validated, and then this model was extended by interpolation to incorporate pediatric sex specific physiological and biochemical parameters. We used both the classical body weight and ontogeny-based scaling approach to interpolate the metabolic process. Then, the pharmacokinetic attributes of the models using the two-scaling approach mentioned above were compared with adult model. Further, a sex-specific PBPK model with an ontogeny scaling approach was preferred to evaluate the pharmacokinetic differences. Moreover, this model was used to reconstruct the BPA exposure from two cohorts (Helix and PBAT Cohort) from 7 EU countries. The half-life of BPA was found to be almost the same in boys and girls at the same exposure levels. Our model estimated BPA children's exposure to be about 1500 times higher than the tolerable daily intake (TDI) recently set by European Food Safety Authority (EFSA) i.e., 0.04 ng/kg BW/day. The model demonstrated feasibility of extending the adult PBPK to sex-specific pediatric, thus investigate a gender-specific health risk assessment.

EDC-induced mechanisms of immunotoxicity: a systematic review.

Endocrine-disrupting chemicals (EDCs) refer to a group of chemicals that cause adverse effects in human health, impairing hormone production and regulation, resulting in alteration of homeostasis, reproductive, and developmental, and immune system impairments. The immunotoxicity of EDCs involves many mechanisms altering gene expression that depend on the activation of nuclear receptors such as the aryl hydrocarbon receptor (AHR), the estrogen receptor (ER), and the peroxisome proliferator-activated receptor (PPAR), which also results in skin and intestinal disorders, microbiota alterations and inflammatory diseases. This systematic review aims to review different mechanisms of immunotoxicity and immunomodulation of T cells, focusing on T regulatory (Treg) and Th17 subsets, B cells, and dendritic cells (DCs) caused by specific EDCs such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), bisphenols (BPs) and polyfluoroalkyl substances (PFASs). To achieve this objective, a systematic study was conducted searching various databases including PubMed and Scopus to find in-vitro, in-vivo, and biomonitoring studies that examine EDC-dependent mechanisms of immunotoxicity. While doing the systematic review, we found species- and cell-specific outcomes and a translational gap between in-vitro and in-vivo experiments. Finally, an adverse outcome pathway (AOP) framework is proposed, which explains mechanistically toxicity endpoints emerging from different EDCs having similar key events and can help to improve our understanding of EDCs mechanisms of immunotoxicity. In conclusion, this review provides insights into the mechanisms of immunotoxicity mediated by EDCs and will help to improve human health risk assessment.

Risk Assessment of Perfluorooctane Sulfonate (PFOS) using Dynamic Age Dependent Physiologically based Pharmacokinetic Model (PBPK) across Human Lifetime.

The widespread use of Perfluorooctane sulfonate (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 and albumin concentrations 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 of chemical 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. PBPK model 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 renal resorption and 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.

Characterization of airborne particles and cytotoxicity to a human lung cancer cell line in Guangzhou, China.

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.

Environmental levels and human health risks of metals and PCDD/Fs near cement plants co-processing alternative fuels in Catalonia, NE Spain: a mini-review.

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.

An integrative translational framework for chemical induced neurotoxicity - a systematic review.

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 numerous in vitro, in vivo, epidemiological and in silico studies developed to test the neurotoxicity of such chemicals. This systematic review summarized the endpoints and biochemical markers generated from in vitro models, organism-based models, human studies and in silico tools 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 and in silico studies 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.

Development and evaluation of a harmonized whole body physiologically based pharmacokinetic (PBPK) model for flutamide in rats and its extrapolation to humans.

By their definition, inadvertent exposure to endocrine disrupting compounds (EDCs) intervenes with the endocrine signalling system, even at low dose. On the one hand, some EDCs are used as important pharmaceutical drugs that one would not want to dismiss. On the other hand, these pharmaceutical drugs are having off-target effects and increasingly significant exposure to the general population with unwanted health implications. Flutamide, one of the top pharmaceutical products marketed all over the world for the treatment of prostate cancer, is also a pollutant. Its therapeutic action mainly depends on targeting the androgen receptors and inhibiting the androgen action that is essential for growth and survival of prostate tissue. Currently flutamide is of concern with respect to its categorization as an endocrine disruptor. In this work we have developed a physiologically based pharmacokinetic (PBPK) model of flutamide that could serve as a standard tool for its human risk assessment. First we built the model for rat (where many parameters have been measured). The rat PBPK model was extrapolated to human where the re-parameterization involved human-specific physiology, metabolic kinetics derived from in-vitro studies, and the partition coefficient same as the rat model. We have harmonized the model by integrating different sets of in-vitro, in-vivo and physiological data into a PBPK model. Then the model was used to simulate different exposure scenarios and the results were compared against the observed data. Both uncertainty and sensitivity analysis was done. Since this new whole-body PBPK model can predict flutamide concentrations not only in plasma but also in various organs, the model may have clinical applications in efficacy and safety assessment of flutamide. The model can also be used for reverse dosimetry in the context of interpreting the available biomonitoring data to estimate the degree to which the population is currently being exposed, and a tool for the pharmaceutical companies to validate the estimated Permitted Daily Exposure (PDE) for flutamide.

Health risks for the population living near petrochemical industrial complexes. 1. Cancer risks: A review of the scientific literature.

Petrochemical complexes and oil refineries are well known sources of a wide range of environmental pollutants. Consequently, the potential harmful health effects of living near these facilities is a topic of concern among the population living in the neighborhood. Anyhow, the number of studies carried out on this issue is rather limited and, in some cases, results are even slightly contradictory. The present Review was aimed at assessing whether living in the vicinity of petrochemical industries and oil refineries is associated with a higher incidence of cancer and cancer mortality. In this sense, up to 23 investigations were found in PubMed and Scopus databases. According to the type of cancer, leukemia and other hematological malignancies were reported as the main types of cancer for populations living in the neighborhood of petrochemical industries. This was concluded based on studies performed in Taiwan, Spain, United Kingdom, Italy and Nigeria. In contrast, no association was found in 4 different investigations conducted in Sweden, Finland and USA with the same purpose. Other scientific studies reported a high incidence of lung and bladder cancer in Taiwan, Italy and USA, as well as an excess mortality of bone, brain, liver, pleural, larynx and pancreas cancers in individuals living near petrochemical complexes from Taiwan, Spain, Italy, United Kingdom and USA. Thus, human exposure to certain carcinogenic pollutants emitted from petrochemical industries might increase the incidence of some cancers and cancer mortality. Anyway, since the limited number of investigations conducted until now, further studies are required in order to corroborate -in a more generalized way-this conclusion.

Adverse health effects for populations living near waste incinerators with special attention to hazardous waste incinerators. A review of the scientific literature.

Incinerators of municipal, hazardous and medical wastes are sources of emissions of toxic pollutants, being polychlorinated dibenzo-p-dioxins and dibenzofurans, as well as a number of heavy metals of special concern. Moreover, waste incineration also generates ashes that must be properly disposed. In all countries, waste management is currently being an issue of tremendous importance. While the treatment and disposal of municipal solid waste (MSW) is a problem in the entire world, in industrialized countries, the management of hazardous waste (HW) is an additional issue of important concern. While the available scientific information on the environmental impact and the health risks of MSWIs is quite considerable, that related with the potential adverse health effects for the populations living near HWIs is much more reduced. In this paper, we have reviewed the information on health effects-including the incidence of cancer and cancer mortality-for the people residing in the vicinity of HWIs. For a better understanding of the problem, some studies on cancer and other adverse health effects near MSWIs have been also reviewed. Special attention has been paid to the HWI of Constantí (Catalonia, Spain) on which the most complete information among all HWIs in the entire world is available. In our conclusions, a series of important issues/questions are raised: is really safe the limit value of 0.1 ng TEQ/Nm3 for PCDD/Fs to protect human health? Where are the evidences on this? On the other hand, to date, risk assessment studies have been only focused on certain substances; heavy metals and PCDD/Fs. Studies have not included those chemicals that are not routinely analyzed, being even some of them probably unknown right now. Moreover, what about potential interactions among chemicals in order to estimate the carcinogenic and non-carcinogenic risks for the population living near incinerators? Complete epidemiological studies are clearly necessary.

Organophosphate metabolite concentrations in maternal urine during pregnancy.

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 (<0.40) to fair (0.40-0.60). Statistically significant differences were observed for the creatinine adjusted concentrations of the most abundant OP metabolites in these trimesters when examined with the Wilcoxon signed rank test for paired data. In general, no association was found between urinary OP metabolites and most demographic and lifestyle predictors. However, a positive significant association was observed for women with vegetarian diet and for women of higher economic status and eventual consumption of organic food which showed higher PNP concentrations. These results suggest that higher fruit and vegetable consumption may involve higher OP pesticide ingestion but the overall association was weak.

Changes of organochlorine compound concentrations in maternal serum during pregnancy and comparison to serum cord blood composition.

The concentrations of organochlorine compounds (OCs), including pentachlorobenzene, hexachlorobenzene (HCB), hexachlorocyclohexanes (α-, ß-, γ- and δ-HCH), polychlorobiphenyls (PCBs 28, 52, 101, 118, 138, 153 and 180), DDT and metabolites, were measured in maternal serum samples collected at the first trimester of pregnancy, at delivery and in umbilical cord from a cohort of mother-newborn pairs from Tarragona (Spain) (n = 50), representing general population of a Mediterranean area from Southern Europe. The observed concentrations were generally low in comparison with previous studies in other world areas. Higher OC concentrations were observed in the maternal serum collected at delivery than in the first trimester and the cord blood concentrations were lower than the maternal levels. These results show for the first time a small but statistically significant increase in maternal venous concentration of OCs between the first trimester and delivery when measured in ng/ml. HCB, ß-HCH and the PCB congeners in cord blood were significantly correlated with the concentrations of these compounds in maternal venous blood and the coefficients were stronger for the samples collected at delivery which was consistent with OC transfer from mother to foetus. In the case of DDT compounds, only 4,4'-DDT showed maternal-cord blood correlation which documented the low metabolic capacity of newborns for OC transformation, e.g. DDT into DDE. Maternal age was the most significant driver of the observed maternal venous OC concentrations in both periods, older ages involving higher concentrations. Higher body mass index was only significantly correlated with higher 4,4'-DDE concentrations in maternal venous blood and cord blood. In some cases, social class and education level were significantly correlated with OC concentrations, e.g. 4,4'-DDE in maternal venous blood from the first trimester and cord blood and PCB153 in maternal venous blood at delivery. In these cases, highest concentrations were found in the women with highest education level and most affluent social class. Comparison of the maternal OC concentrations of this cohort with those observed in 2002 in population of the same geographic area and age range shows decreases between two and ten times over this fourteen-year period.

Human biomonitoring to evaluate exposure to toxic and essential trace elements during pregnancy. Part B: Predictors of exposure.

Maternal exposure to toxic and essential trace elements represents a surrogate of exposure to the unborn child. Variables of exposure as sociodemographic, lifestyles and diet may contribute to different exposure of pregnant women to specific trace elements. Blood, urine and cord blood samples of 53 pregnant women of the HEALS-EXHES cohort, recruited in Reus (Catalonia, Spain) between 2016 and 2017, were analysed for the concentrations of As, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Se and Zn. Univariate and multivariate models were built in order to assess associations between element concentrations in each matrix, and variables obtained by questionnaires on mothers' characteristics and dietary habits. Results showed several significant associations between various variables and essential trace and toxic elements. Age was associated with higher levels of Cd and Pb in cord blood samples. Multiparous women showed lower levels of Cd in maternal blood and Pb in both maternal and cord blood than nulliparous women. Hispanic mothers presented higher levels of blood As and lower levels of blood Se compared to mothers of different ethnicity. Higher education level was associated with higher As and Hg concentrations in both maternal and cord blood samples. Higher annual income diminished the level of Pb in maternal blood. Smoking in pregnancy incremented the levels of Cd in mothers' blood. Alcohol consumption may affect the absorption of Cu, Mn and Zn. Supplementations with multivitamins, folic acid and iron showed effects on elements as Cr, Mn, Se and Zn. Regarding food group intake, bluefish incremented Pb levels, while canned fish and seafood affected levels of some elements as As, Hg, Cu and Se. Other elements such as Mn and Pb were influenced by the intake of different kinds of foods. The present results showed that some modifiable lifestyles and food intakes could be the target of interventions to help pregnant women to maintain suitable concentrations of essential elements and lower levels of toxic ones, and to improve consequently neonatal health outcomes.

Monitoring dioxins and furans in plasma of individuals living near a hazardous waste incinerator: Temporal trend after 20 years.

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.

Metals in biological tissues of the population living near a hazardous waste incinerator in Catalonia, Spain: Two decades of follow-up.

During the period 1996-1998, a hazardous waste incinerator (HWI) was built in Constantí (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.

Seasonal characterization and dosimetry-assisted risk assessment of indoor particulate matter (PM10-2.5, PM2.5-0.25, and PM0.25) collected in different schools.

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.

Human biomonitoring to evaluate exposure to toxic and essential trace elements during pregnancy. Part A. concentrations in maternal blood, urine and cord blood.

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.

Physiology-based toxicokinetic modelling in the frame of the European Human Biomonitoring Initiative.

Given the opportunities provided by internal dosimetry modelling in the interpretation of human biomonitoring (HBM) data, the assessment of the links between exposure to chemicals and observed HBM data can be effectively supported by PBTK modelling. This paper gives a comprehensive review of available human PBTK models for compounds selected as a priority by the European Human Biomonitoring Initiative (HBM4EU). We highlight their advantages and deficiencies and suggest steps for advanced internal dose modelling. The review of the available PBTK models highlighted the conceptual differences between older models compared to the ones developed recently, reflecting commensurate differences in research questions. Due to the lack of coordinated strategies for deriving useful biomonitoring data for toxicokinetic properties, significant problems in model parameterisation still remain; these are further increased by the lack of human toxicokinetic data due to ethics issues. Finally, questions arise as well as to the extent they are really representative of interindividual variability. QSARs for toxicokinetic properties is a complementary approach for PBTK model parameterisation, especially for data poor chemicals. This approach could be expanded to model chemico-biological interactions such as intestinal absorption and renal clearance; this could serve the development of more complex generic PBTK models that could be applied to newly derived chemicals. Another gap identified is the framework for mixture interaction terms among compounds that could eventually interact in metabolism. From the review it was concluded that efforts should be shifted toward the development of generic multi-compartmental and multi-route models, supported by targeted biomonitoring coupled with parameterisation by both QSAR approach and experimental (in-vivo and in-vitro) data for newly developed and data poor compounds.

Early-life intake of major trace elements, bisphenol A, tetrabromobisphenol A and fatty acids: Comparing human milk and commercial infant formulas.

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.