Human exposure to trace elements, aromatic amines and formaldehyde in swimsuits: Assessment of the health risks.

Nowadays, most of the swimsuits are mainly made of artificial fibres, which have interesting properties such as water repellence and fast drying. Swimsuits contain a wide range of additives, which can mean a hazard for the environment and/or human health. In this study, the concentrations of formaldehyde (free and water soluble), 24 aromatic amines, and 28 trace elements (Ag, Al, As, B, Ba, Be, Bi, Cd, Co, Cr, Cu, Fe, Hg, Mg, Mn, Mo, Ni, Pb, Sb, Sc, Se, Sm, Sr, Sn, Tl, Ti, V and Zn) were analysed in 39 swimsuits covering a wide range of materials, colours and brands. Dermal exposure and health risks were assessed for adults (men and women) aged > 18 years old, babies between 2 and < 3 years old, children (boys and girls) between 3 and < 6 years old and 6 and < 11 years old, and teenagers (boys and girls) between 11 and < 16 years old, wearing swimsuits for 4 h or 8 h. Formaldehyde and aromatic amines were below their respective detection limits in all samples (<16 and < 1.5 mg/kg, respectively). Regarding trace elements, Ti showed the highest mean levels (1844 mg/kg), being significantly higher in polyamide (3759 mg/kg) than in polyester (24.1 mg/kg) swimsuits. These high Ti levels were confirmed by environmental scanning electron microscope in a single sample made of polyamide. Increased concentrations of Cr were also observed, but only in polyamide black fabrics, with values ranging from 624 to 932 mg/kg. Non-cancer risks (hazard quotients) derived from the exposure to trace elements were in a safe zone for all analysed trace elements. Furthermore, the carcinogenic risks were evaluated for As, Cr and Pb, exhibiting values below the 10-5 threshold, with the exception of Cr in babies and children-girls. For Ti, health risks could not be calculated due to the lack of information on toxicological data. However, because Ti was the element with the highest concentrations in swimsuits, and taking into account the potential toxicity of TiO2 nanoparticles, further research is needed to assess the migration of this element from fibres to skin.

Environmental exposure to low-doses of ionizing radiation. Effects on early nephrotoxicity in mice.

Nuclear accidents of tremendous magnitude, such as those of Chernobyl (1986) and Fukushima (2011), mean that individuals living in the contaminated areas are potentially exposed to ionizing radiation (IR). However, the dose-response relationship for effects of low doses of radiation is not still established. The present study was aimed at investigating in mice the early effects of low-dose internal radiation exposure on the kidney. Adult male (C57BL/6J) mice were divided into three groups. Two groups received a single subcutaneous (s.c.) doses of cesium (137Cs) with activities of 4000 and 8000Bq/kg bw. A third group (control group) received a single s.c. injection of 0.9% saline. To evaluate acute and subacute effects, mice (one-half of each group) were euthanized at 72h and 10 days post-exposure to 137Cs, respectively. Urine samples were collected for biochemical analysis, including the measurement of F2-isoprostane (F2-IsoP) and kidney injury molecule-1 (KIM-1) levels. Moreover, the concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA damage, were measured in renal tissue. Urinary excretion of total protein significantly increased at 72h in mice exposed to Cs4000. Uric acid and lactate dehydrogenase (LDH) decreased significantly at both times post-exposure in animals exposed to Cs8000. After 72h and 10d of exposure to Cs4000, a significant increase in the γ-glutamil transferase (GGT) and N-acetyl-ß-D-glucosaminidase (NAG) activities was observed. In turn, F2-IsoP levels increased -mainly in the Cs4000 group- at 72h post-exposure. Following irradiation (137Cs), the highest level of KIM-1 was corresponded to the Cs4000 group at 72h. Likewise, the main DNA damage was detected in mice exposed to Cs4000, mainly at 10d after irradiation. The alterations observed in several biomarkers suggest an immediate renal damage following exposure to low doses of IR (given as 137Cs). Further investigations are required to clarify the mechanisms involved in the internal IR-induced nephrotoxicity.

Ritter reaction-mediated syntheses of 2-oxaadamantan-5-amine, a novel amantadine analog.

Two alternative syntheses of 2-oxaadamantan-5-amine, a novel analog of the clinically approved drug amantadine, are reported. The compound has been tested as an anti-influenza A virus agent and as an NMDA receptor antagonist. While the compound was not antivirally active, it displayed moderate activity as an NMDA receptor antagonist.

Tryptophanol-derived oxazolopiperidone lactams: identification of a hit compound as NMDA receptor antagonist.

N-Methyl-D-aspartate receptors (NMDAR) exacerbated activation leads to neuron death through a phenomenon called excitotoxicity. These receptors are implicated in several neurological diseases (e.g., Alzheimer and Parkinson) and thus represent an important therapeutic target. We herein describe the study of enantiopure tryptophanol-derived oxazolopiperidone lactams as NMDA receptor antagonists. The most active hit exhibited an IC50 of 63.4 µM in cultured rat cerebellar granule neurons thus being 1.5 fold more active than clinically approved NMDA antagonist amantadine (IC50=92 µM).

In vitro neurotoxic potential of emerging flame retardants on neuroblastoma cells in an acute exposure scenario.

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.

Emerging and legacy flame retardants in indoor air and dust samples of Tarragona Province (Catalonia, Spain).

Flame retardants (FRs) are widely used in consumer products including furniture foam and electronic equipment such as computers, monitors and TVs. Over time, FRs can easily migrate into the surrounding environments. Since brominated FRs (BFRs) has been determined of high concern due to their environmental persistence, bioaccumulation and potential toxicity, novel FRs have emerged. The present study was aimed at identifying and quantifying the indoor levels of 41 legacy and novel FRs, which include 20 OPFRs and 21 HFRs (8 PBDEs, 3 HBCDDs, 5 NBFRs and 5 DECs) in Tarragona Province (Catalonia, Spain). The results have confirmed the presence of both legacy and novel FRs in air and dust of homes, schools and offices. To the best of our knowledge, this is the first European study measuring OPFRs at office environments and also confirming the presence of the following OPFRs: TEP, TCIPP, T2IPPP, TPPO, DCP, TMCP and B4IPPPP in indoor air, even some of them at high levels. OPFRs in general and TCIPP in particular showed high concentrations in air (94,599 pg/m3 and 72,281 pg/m3, respectively) and dust (32,084 ng/g and 13,496 ng/g, respectively) samples collected in indoor environments. HBCDDs were found at high levels in dust (32,185 ng/g), whereas the presence of PBDEs and DECs were low in both matrices (<160 pg/m3 in air and <832 ng/g in dust). NBFRs showed higher levels than the two legacy FRs groups, which is supported by the current restrictions of these FRs (640 pg/m3 in air and 1291 ng/g in dust). Samples of schools had significantly lower levels of NBFRs, but significantly higher concentrations of HFRs in air than in home samples, while dust levels of HFRs were significantly lower than those in samples of offices. Regarding human health risks, the current assessment suggests that those derived from exposure to FRs were lower -although close- to assumable risks, evidencing the potential of FRs for non-carcinogenic and carcinogenic risks, mainly due to the exposure to TCIPP, which was the main contributor together with ΣHBCDDs and also EHDPP.

Chlorpyrifos, permethrin and cyfluthrin effect on cell survival, permeability, and tight junction in an in-vitro model of the human blood-brain barrier (BBB).

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.

Concentrations of arsenic and vanadium in environmental and biological samples collected in the neighborhood of petrochemical industries: A review of the scientific literature.

Petrochemical facilities, including oil refineries, are emission sources of a wide range of environmental pollutants such as trace elements, volatile organic compounds, and polycyclic aromatic hydrocarbons, among others. Populations living near this kind of facilities may be potentially exposed to contaminants, which are, in turn, associated with a wide range of adverse effects. In our laboratory, we have shown that the environmental concentrations of trace elements near the petrochemical complex of Tarragona County (Spain), which is among the largest complexes in the European Union, should not be a relevant pollution source for these elements, with the exception of arsenic (As) and vanadium (V). Moreover, the International Agency for Research on Cancer (IARC) classified As and V as Group 1 and Group 2B, respectively. Based on it, the present paper was aimed at reviewing the available scientific information on the occurrence of As and V in the vicinity of petrochemical complexes worldwide, considering environmental matrices (air, dust, sediments, soil, and water), as well as biological samples (blood, hair, and urine). In general, levels of As and V in environmental matrices showed higher fluctuation throughout the world and was highly dependent on the samples zone while levels of both elements in urinary samples from subjects living near a petrochemical area were higher than those of population living further.

Trace Elements in Blood of the Population Living near a Hazardous Waste Incinerator in Catalonia, Spain.

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).

Maternal exposure to mixtures of dienestrol, linuron and flutamide. Part I: Feminization effects on male rat offspring.

Exposure to endocrine-disrupting compounds (EDCs) during pregnancy can result in negative health effects in later generations, including sex changes and feminization. The present study assessed the feminization effects on male offspring rats of three EDCs: Dienestrol (DIES), Linuron (LIN), and Flutamide (FLU). Sexually mature female rats were exposed from gestation day (GD) 6 until postnatal day (PND) 21 to: 0.37, 0.75, 1.5, 3.12 or 6.25 µg/kg/day of DIES, 1.5, 3, 6, 12.5, 25 or 50 mg/kg/day of LIN, 3.5, 6.7, 12.5, 25 or 50 mg/kg/day of FLU, and the following mixtures: FLU + DIES (mg/kg/day+µg/kg/day), 3.5 + 0.37, or 3.5 + 3, 25 + 0.37, or 25 + 3; FLU + LIN (mg/kg/day + mg/kg/day), 3.5 + 12.5, or 25 + 12.5; and DIES + LIN (µg/kg/day + mg/kg/day), 0.37 + 12.5, or 3 + 12.5. Anogenital distance (AGD), nipple retention (NR) and cryptorchidism were evaluated. FLU produced a decrease of AGD, an increase of NR, and an increase of cryptorchidism at the highest dose. None of these three endpoints were significantly affected by LIN or DIES treatments alone. Combinations of FLU + LIN and FLU + DIES increased NR, and decreased AGD, while DIES + LIN did not produce any effects in male pups. Results show that FLU is able to induce feminization in male pups, while binary combinations of LIN and DIES did not modify the effects produced by FLU.

Biomonitoring of Trace Elements in Hair of Schoolchildren Living Near a Hazardous Waste Incinerator-A 20 Years Follow-Up.

Since 1998, a monitoring program is periodically performed to assess the environmental and human health impact of air chemicals potentially emitted by a hazardous waste incinerator (HWI) located in Constantí (Catalonia, Spain). In 2017, samples of hair were collected from 94 schoolchildren (aged 10-13 years) living nearby and the levels of 11 trace elements (As, Be, Cd, Cr, Hg, Mn, Ni, Pb, Sn, Tl and V) were determined. The concentrations showed the following descending order: Pb > Hg > Ni > Sn > Mn > Cr. In turn, As, Be and Tl were not detected, while Cd and V were found only in a few samples. Some metal levels were significantly, positively correlated. Some significant differences were also noticed according to the gender and the specific zone of residence. Finally, the levels of trace elements showed fluctuations through time. Cr and Pb showed a significant decrease in comparison to the concentrations obtained in the baseline study (1998). According to the current results, metal emissions from the HWI are not relevant in terms of human health impact since their levels were similar and even lower than those reported in other contaminated areas.

Effect of Radiation on the Expression of CVD-related miRNAs, Inflammation and Endothelial Dysfunction of HUVECs.

BACKGROUND/AIM: Radiotherapy (RT) can lead to cardiovascular disease (CVD). Evidence suggests that radiation modulates miRNA levels. Our purpose was to assess the acute response to radiation-induced modulation of the expression of miRNA-146a, miRNA-155, miRNA-221, and miRNA-222, inflammatory response and endothelial dysfunction on endothelial cells. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to 2 Gy RT, and intracellular levels of selected miRNAs were measured by real-time polymerase chain reaction at 2 and 24 h. Cytokine and adhesion molecule release were also assessed. RESULTS: Results showed that 2 Gy significantly increased the expression of miRNA-221 and miRNA-222, and reduced the level of miRNA-155 after 2 h; whereas miRNA-146a and miRNA-155 were significantly overexpressed and miRNA-222 was significantly down-regulated at 24 h. Interleukin-8 and soluble vascular cell adhesion molecule 1 levels were not affected by the studied RT. CONCLUSION: RT at 2 Gy modulated expression of selected miRNAs by endothelial cells after 2 and 24 h, which might be related to CVD development in patients who receive RT.

Effect of radiotherapy on the expression of cardiovascular disease-related miRNA-146a, -155, -221 and -222 in blood of women with breast cancer.

Breast cancer (BC) is one of the most important neoplasias among women. Many patients receive radiotherapy (RT), which involves radiation exposure of the thoracic zone, including the heart and blood vessels, leading to the development of cardiovascular disease (CVD) as a long-term side effect. The severity of CVD-related pathologies leads research on assessing novel CVD biomarkers as diagnostic, prognostic or therapeutic agents. Currently, the possible candidates include blood microRNAs (miRNAs). Previous studies have supported a role for miRNA-146a, -155, -221, and -222 in the progression of CVD. Our purpose was to evaluate the RT-induced modulation of the expression of these miRNAs in the blood of women with BC. Pre-RT control and post-RT blood samples were collected, and after miRNA isolation and reverse transcription, the levels of the selected miRNAs were measured by real-time PCR. Our results showed that miRNA-155 exhibited the lowest expression, while miRNA-222 exhibited the highest expression, followed by miRNA-221. The expression of each individual miRNA was positively correlated with that of the others both pre-RT control and post-RT and inversely correlated with age before RT. Furthermore, RT promoted the overexpression of the selected miRNAs. Their levels were also affected by CVD-linked clinical parameters, treatment and BC side. Modulation of the expression of the selected miRNAs together with other risk factors might be associated with the development of future cardiovascular pathologies. Further confirmatory studies are needed to assess their potential as possible biomarkers in the progression of or as therapeutic targets for RT-induced CVD in BC patients.

Renal and hepatic effects following neonatal exposure to low doses of Bisphenol-A and 137Cs.

137-Cesium (137Cs) is one of the most important distributed radionuclides after a nuclear accident. Humans are usually co-exposed to various environmental toxicants, being Bisphenol-A (BPA) one of them. Exposure to IR and BPA in early life is of major concern, due to the higher vulnerability of developing organs. We evaluate the renal and hepatic effects of low doses of ionizing radiation (IR) and BPA. Sixty male mice (C57BL/6J) were randomly assigned to six experimental groups (n=10) and received a single subcutaneous dose of 0.9% saline solution, 137Cs and/or BPA on postnatal day 10: control, BPA (25 µg/kgbw), Cs4000 (4000 Bq 137Cs/kgbw), Cs8000 (8000 Bq 137Cs/kgbw), BPA/Cs4000 and BPA/Cs8000. At the age of two months, urines (24h) and blood samples were collected from animals of each group to determine biochemical parameters. Finally, kidneys and liver were removed to quantify DNA damage (8-OHdG), as well as to determine CYP1A2 mRNA expression. Data suggest that both BPA and 137Cs induced renal and liver damage evidenced by oxidative stress. However, when there is a co-exposure, it seems that there are compensatory mechanisms that may reverse the damage induced by each toxic itself. Notwithstanding, more studies are necessary to better understand the synergistic mechanisms behind.