Distribution of Non-Persistent Endocrine Disruptors in Two Different Regions of the Human Brain

Non-persistent endocrine disrupting chemicals (npEDCs) can affect multiple organs and systems in the body. Whether npEDCs can accumulate in the human brain is largely unknown. The major aim of this pilot study was to examine the presence of environmental phenols and parabens in two distinct brain regions: the hypothalamus and white-matter tissue. In addition, a potential association between these npEDCs concentrations and obesity was investigated. Post-mortem brain material was obtained from 24 individuals, made up of 12 obese and 12 normal-weight subjects (defined as body mass index (BMI) > 30 and BMI < 25 kg/m2, respectively). Nine phenols and seven parabens were measured by isotope dilution TurboFlow-LC-MS/MS. In the hypothalamus, seven suspect npEDCs (bisphenol A, triclosan, triclocarban and methyl-, ethyl-, n-propyl-, and benzyl paraben) were detected, while five npEDCs (bisphenol A, benzophenone-3, triclocarban, methyl-, and n-propyl paraben) were found in the white-matter brain tissue. We observed higher levels of methylparaben (MeP) in the hypothalamic tissue of obese subjects as compared to controls (p = 0.008). Our findings indicate that some suspected npEDCs are able to cross the blood–brain barrier. Whether the presence of npEDCs can adversely affect brain function and to which extent the detected concentrations are physiologically relevant needs to be further investigated.Jana V. van Vliet-Ostaptchouk is supported by a Diabetes Funds Junior Fellowship from the Dutch Diabetes Research Foundation (project no. 2013.81.1673). This work was supported by the National Consortium for Healthy Ageing (NCHA) (NCHA NGI Grant 050-060-810), and the European Union’s Seventh Framework program (FP7/2007-2013) through the BioSHaRE-EU (Biobank Standardization and Harmonization for Research Excellence in the European Union) project, grant agreement 261433, and by the Danish Center on Endocrine Disrupters and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC)

Adipose tissue concentrations of non-persistent environmental phenols and local redox balance in adults from Southern Spain

The aim was to evaluate the associations of environmental phenol and paraben concentrations with the oxidative microenvironment in adipose tissue. This study was conducted in a subsample (n=144) of the GraMo cohort (Southern Spain). Concentrations of 9 phenols and 7 parabens, and levels of oxidative stress biomarkers were quantified in adipose tissue. Associations were estimated using multivariable linear regression analyses adjusted for potential confounders. Benzophenone-3 (BP-3) concentration was borderline associated with enhanced glutathione peroxidase (GPx) activity [exp(β)=1.20, p=0.060] and decreased levels of reduced glutathione (GSH) [exp(β)=0.55, p=0.070]. Concentrations of bisphenol A (BPA) and methylparaben (MeP) were associated to lower glutathione reductase (GRd) activity [exp(β)=0.83, exp(β)=0.72, respectively], and BPA was borderline associated to increased levels of oxidized glutathione (GSSG) [exp(β)=1.73, p-value=0.062]. MeP was inversely associated to both hemeoxygenase-1 (HO-1) and superoxide dismustase (SOD) activity, as well as to the levels of thiobarbituric acid reactive substances (TBARS) [0.75 < exp(β) < 0.79]. Our results suggest that some specific non-persistent pollutants may be associated with a disruption of the activity of relevant antioxidant enzymes, in addition to the depletion of the glutathione stock. They might act as a tissue-specific source of free radicals, contributing to the oxidative microenvironment in the adipose tissue.This research was supported in part by research grants from the European Union Commission (H2020-EJP-HBM4EU and SOE1/P1/F0082), Biomedical Research Networking Center-CIBER de Epidemiología y Salud Pública (CIBERESP), from the Institute of Health Carlos III, supported by European Regional Development Fund/FEDER (FIS-PI13/02406, FISPI14/ 00067, FIS-PI16/01820, FIS-PI16/01812, FIS-PI16/01858 and FIS-PI17/01743), and from the Consejería de Salud, Junta de Andalucía (PS-0506-2016). Funding for the equipment used was provided by Velux Fonden, Augustinus Fonden and Svend Andersen Fonden. The authors thank Kirsten og Freddy Johansens Fond and the International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC, Rigshospitalet, Copenhagen University) for economic support. Dr. Juan Pedro Arrebola is under contract within Ramón y Cajal Program (Ministerio de Economía, Industria y Competitividad de España, RYC-2016-20155)

Presence of Bisphenol A and Parabens in a Neonatal Intensive Care Unit: An Exploratory Study of Potential Sources of Exposure

This paper is part of the PhD thesis developed by L.M.I.-D. in the context of the“Clinical Medicineand Public Health Program”of the University of Granada.BACKGROUND:Newborns in neonatal intensive care units (NICUs) are in contact with a variety of medical products whose production might includesynthetic chemicals with hormonal activity.OBJECTIVES:Our aim was to assess the content of bisphenol A (BPA) and parabens (PBs) and the hormone-like activities of a subset of medical prod-ucts commonly used in NICUs in prolonged intimate contact with NICU newborns.METHODS:Fifty-two NICU items were analyzed, determining the concentrations of BPA and PBs [methyl- (MeP), ethyl- (EtP), propyl- (PrP), andbutylparaben (BuP)] and using the E-Screen and PALM-luciferase assays to measure thein vitro(anti-)estrogenic and (anti-)androgenic activity,respectively, of the extracts. Items found to have elevated BPA/PB content or hormone-like activities were further extracted using leachingmethodologies.RESULTS:BPA was found in three-fifths and PBs in four-fifths of tested NICU items, and∼25%and∼10%of extracts evidenced estrogenic andanti-androgenic activity, respectively. The highest BPA content was found in the three-way stopcock (>7:000 ng=g), followed by patterned transpar-entfilm dressing, gastro-duodenal feeding tubes, sterile gloves, single-lumen umbilical catheters, and intravenous (IV) infusion extension sets (con-centrations ranged from 100 to 700 ng=g BPA). A total PB concentration (PPBs) >100 ng=g was observed in several items, including light therapyprotection glasses, patterned transparentfilm dressing, winged IV catheters, IV infusion extension sets, and textile tape. The highest estrogenic activ-ity [>450 pM estradiol equivalent (E2eq)] was found in small dummy nipples, three-way stopcocks, and patterned transparentfilm dressing and thehighest anti-androgenic activity [>5 mM procymidone equivalent units per gram (Proceq=g)] in small dummy nipples and three-way stopcocksThis research was funded in part by grants from the European Union Commission (The European Human Biomonitoring Initiative H2020-EJP-HBM4EU), the Spanish Ministry of Economy and Competitiveness, Institute of Health Carlos III - FEDER (PI16/01820, PI16/01812, PI16/01858, PI17/01743, and PI17/01526), the Andalusia Regional Government (PI-0538-2017), and the Spanish Consortium for Research on Epidemiology and Public Health(CIBERESP). The authors are also grateful to the Carlos IIIInstitute of Health (ISCIII) for the predoctoral research contract(FI17/00316) granted to L.M.I.-D., the postdoctoral researchcontract granted to C.F. (Miguel Servet-FEDER fund MS16/00085), and the José María Segovia de Arana contract granted to N.O. (INT18/00060)

Characterization of Indoor Extremely Low Frequency and Low Frequency Electromagnetic Fields in the INMA-Granada Cohort

Objective: To characterize the exposure to electric fields and magnetic fields of non-ionizing radiation in the electromagnetic spectrum (15 Hz to 100 kHz) in the dwellings of children from the Spanish Environment and Childhood-“INMA” population-based birth cohort. Methodology: The study sample was drawn from the INMA-Granada cohort. Out of 300 boys participating in the 9–10 year follow-up, 123 families agreed to the exposure assessment at home and completed a specific ad hoc questionnaire gathering information on sources of non-ionizing radiation electric and magnetic fields inside the homes and on patterns of use. Long-term indoor measurements were carried out in the living room and bedroom. Results: Survey data showed a low exposure in the children's homes according to reference levels of the International Commission on Non-Ionizing Radiation Protection but with large differences among homes in mean and maximum values. Daytime electrostatic and magnetic fields were below the quantification limit in 78.6% (92 dwellings) and 92.3% (108 dwellings) of houses, with an arithmetic mean value (± standard deviation) of 7.31±9.32 V/m and 162.30±91.16 nT, respectively. Mean magnetic field values were 1.6 lower during the night than the day. Nocturnal electrostatic values were not measured. Exposure levels were influenced by the area of residence (higher values in urban/semi-urban versus rural areas), type of dwelling, age of dwelling, floor of the dwelling, and season. Conclusion: Given the greater sensitivity to extremely low-frequency electromagnetic fields of children and following the precautionary principle, preventive measures are warranted to reduce their exposure.This work was supported by the Spanish Ministry of Health (CIBERESP and FIS PI11/0610) and the Andalusia Regional Government, Council of Innovation, Science and Enterprise (Excellence Project P09-CTS-5488) and Council of Health (SAS PI-0675-2010)

The Rise and Fall of "Respectable" Spanish Liberalism, 1808-1923: An Explanatory Framework

The article focuses on the reasons behind both the consolidation of what I have termed “respectable” liberalism between the 1830s and the 1840s and its subsequent decline and fall between 1900 and 1923. In understanding both processes I study the links established between “respectable” liberals and propertied elites, the monarchy, and the Church. In the first phase these links served to consolidate the liberal polity. However, they also meant that many tenets of liberal ideology were compromised. Free elections were undermined by the operation of caciquismo, monarchs established a powerful position, and despite the Church hierarchy working with liberalism, the doctrine espoused by much of the Church was still shaped by the Counter-Reformation. Hence, “respectable” liberalism failed to achieve a popular social base. And the liberal order was increasingly denigrated as part of the corrupt “oligarchy” that ruled Spain. Worse still, between 1916 and 1923 the Church, monarch, and the propertied elite increasingly abandoned the liberal Monarchist Restoration. Hence when General Primo de Rivera launched his coup the rug was pulled from under the liberals’ feet and there was no one to cushion the fall