Cuantificación de contaminantes con actividad disruptora endocrina en leche materna: puesta a punto de la metodología analítica y resultados preliminares

Los Disruptores Endocrinos (DEs) son sustancias exógenas que alteran una o más funciones del sistema endocrino y consecuentemente causan efectos adversos en la salud de un organismo intacto o en su progenie. . El presente trabajo se incluye en el proyecto titulado: “Disruptores endocrinos en leche materna del Banco de Leche del Complejo Hospitalario Universitario de Granada (BLCHUG)”, que abarca el estudio de compuestos orgánicos persistentes y no persistentes en muestras de leche materna, siendo los compuestos no persistentes los seleccionados para este estudio. Los contaminantes orgánicos no persistentes o “pseudopersistentes” acceden al organismo a diario y de manera cotidiana, son rápidamente excretados y contribuyen de igual manera a la dosis interna que los compuestos orgánicos persistentes. Entre los más relevantes para la salud pública se encuentran: bisfenoles (bisfenol A, F y S); parabenos (MP, EP, PP y BP); y benzofenonas (BP-1 a BP-12 y 4-OH-BP). La leche materna es el principal alimento en los bebes lactantes y, por tanto, la principal vía de exposición a DEs por vía alimentaria. En este contexto, es de crítica importancia el desarrollo de metodologías analíticas adecuadas que permitan evaluar la exposición de los bebes a diferentes DEs a través de la leche materna.Universidad de Granada. Máster Oficial en Avances en Radiología Diagnóstica y Terapéutica y Medicina Físic

Endocrine Disrupting Chemicals in Cosmetics and Personal Care Products and Risk of Endometriosis

In the last years, the variety and consumption of cosmetics and personal care products (PCPs) have greatly increased, although the long-term adverse effects to low doses of chemicals used in their production and with proven hormone-mimicking properties have been still poorly addressed. Among these endocrine disrupting chemicals (EDCs), parabens, benzophenones, bisphenols, and phthalates are the most widely found in these products. Given the estrogenic-dependent nature of the endometrium, it has been hypothesized the potential contribution of these EDCs contained in cosmetics and PCPs in the risk of endometriosis. In this book chapter, we have summarized the current evidence supporting this hypothesis, highlighting epidemiological, in vivo, and in vitro studies that have addressed the potential influence of parabens, benzophenones, bisphenols, and phthalates in the origin and progression of this chronic feminine disease

Concentrations of bisphenol A and parabens in socks for infants and young children in Spain and their hormone-like activities

Background: Little information is available on the content of bisphenol A (BPA) and other endocrine-disrupting chemicals (EDCs) such as parabens in infant textiles and clothes. Objectives: 1) To determine the concentrations of BPA and parabens in socks for infants and young children purchased in Spain, 2) to assess the (anti-)estrogenicity and (anti-)androgenicity of extracts from the socks, and 3) to estimate dermal exposure doses to these chemicals. Methods: Thirty-two pairs of socks for infants and young children (1–48 months) were purchased from 3 stores in Granada (Spain). Textile material was cut from the foot, toe, and leg of each sock (n=96 samples) for chemical analysis. Hormone-like activities were determined in foot sections (n=32 samples) by using the E-Screen assay for (anti-)estrogenicity and PALM luciferase assay for (anti-)androgenicity. Results: BPA was present in 90.6% of samples at concentrations ranging from<0.70 to 3736 ng/g. BPA levels were around 25-fold higher in socks from store 1, which had a higher cotton content compared to stores 2 and 3. Ethyl-paraben was found in 100% of samples, followed by methyl-paraben (81.0%), and propyl-paraben (43.7%). No butyl-paraben was detected in any sample. Estrogenic activity was detected in 83.3% of socks from store 1 (range=48.2–6051 pM E2eq/g) but in only three socks from stores 2 and 3. Anti-androgenic activity was detected in six of the 32 socks studied (range=94.4–2989 μM Proceq/g), all from store 1. Estimated dermal exposure to BPA was higher from socks for children aged 36–48 months (median=17.6 pg/kg/day), and dermal exposure to parabens was higher from socks for children aged 24–36 months (median=0.60 pg/kg/day). Discussion: This is the first report in Europe on the wide presence of BPA and parabens in socks marketed for infants and children. BPA appears to contribute to the hormone-like activity observed in sock extracts.This research was funded in part by grants from the European Union Commission (The European Human Biomonitoring Initiative H2020-EJP-HBM4EU), the Spanish Ministry of Health (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 III Institute of Health (ISCIII) for the predoctoral research contract (FI17/00316) granted to L.M. Iribarne-Durán, the postdoctoral research contracts granted to F. Vela-Soria (Sara Borrell- CD17/00212) and C. Freire (Miguel Servet-FEDER fund MS16/00085), and the José María Segovia de Arana contract granted to N. Olea (INT18/00060), and to the Spanish Ministry of Science, Innovation, and Universities for the Ramón y Cajal contract (RYC-2016-20155) granted to J.P. Arrebola

Association of Urinary Levels of Bisphenols A, F, and S with Endometriosis Risk: Preliminary Results of the End EA Study

Aim: The aim of this study was to explore associations of urinary concentrations of bisphenols A (BPA), S (BPS), and F (BPF) and of thiobarbituric acid reactive substances (TBARS) with the risk of endometriosis in women of childbearing age. Results: After adjustment for urinary creatinine, age, BMI, parity, and residence, endometriosis risk was increased with each 1 log unit of BPA [OR 1.5; 95%CI 1.0–2.3] and Sbisphenols [OR 1.5; 95%CI 0.9–2.3] but was not associated with the presence of BPS and BPF. Classification of the women by tertiles of exposure revealed statistically significant associations between endometriosis risk and the second tertile of exposure to BPA [OR 3.7; 95%CI 1.3–10.3] and Sbisphenols [OR 5.4; 95%CI 1.9–15.6]. In addition, TBARS concentrations showed a close-to-significant relationship with increased endometriosis risk [OR 1.6; 95%CI 1.0–2.8], and classification by TBARS concentration tertile revealed that the association between endometriosis risk and concentrations of BPA [OR 2.0; 95%CI 1.0–4.1] and Sbisphenols [OR 2.2; 95%CI 1.0–4.6] was only statistically significant for women in the highest TBARS tertile (>4.23 uM). Conclusion: Exposure to bisphenols may increase the risk of endometriosis, and oxidative stress may play a crucial role in this association. Further studies are warranted to verify these findings.Instituto de Salud Carlos III: PI17/01743; Instituto de Salud Carlos III: PI16/01820; Instituto de Salud Carlos III: PI16/01812; Instituto de Salud Carlos III: PI16/01858; Instituto de Salud Carlos III: PI17/01526; Instituto de Salud Carlos III: IFI18/00052; Instituto de Salud Carlos III: FI17/00316; Instituto de Salud Carlos III: INT18/00060; European Commission: H2020-EJP-HBM4EU

Recovery of Meteorological Data for the Observatory of A Guarda, Spain

We herein describe the recovery of a series of data on temperature, humidity, precipitation, evaporation, wind, and local weather conditions from documentary sources obtained from the Jesuit observatory of A Guarda (Galicia, Spain) for the period 1881–1896. The data were digitized and made available in accessible electronic formats. Comparisons were made with present-day meteorological data obtained from two nearby stations. We further believe that the discovery of some new complementary documentary sources made during the present research could be a basis for future data recovery efforts. Among these new results, early ozone data from the period are of outstanding importance to meteorologists

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)

Bisphenol A and its analogues: A comprehensive review to identify and prioritize effect biomarkers for human biomonitoring

Human biomonitoring (HBM) studies have demonstrated widespread and daily exposure to bisphenol A (BPA). Moreover, BPA structural analogues (e.g. BPS, BPF, BPAF), used as BPA replacements, are being increasingly detected in human biological matrices. BPA and some of its analogues are classified as endocrine disruptors suspected of contributing to adverse health outcomes such as altered reproduction and neurodevelopment, obesity, and metabolic disorders among other developmental and chronic impairments. One of the aims of the H2020 European Human Biomonitoring Initiative (HBM4EU) is the implementation of effect biomarkers at large scales in future HBM studies in a systematic and standardized way, in order to complement exposure data with mechanistically-based biomarkers of early adverse effects. This review aimed to identify and prioritize existing biomarkers of effect for BPA, as well as to provide relevant mechanistic and adverse outcome pathway (AOP) information in order to cover knowledge gaps and better interpret effect biomarker data. A comprehensive literature search was performed in PubMed to identify all the epidemiologic studies published in the last 10 years addressing the potential relationship between bisphenols exposure and alterations in biological parameters. A total of 5716 references were screened, out of which, 119 full-text articles were analyzed and tabulated in detail. This work provides first an overview of all epigenetics, gene transcription, oxidative stress, reproductive, glucocorticoid and thyroid hormones, metabolic and allergy/immune biomarkers previously studied. Then, promising effect biomarkers related to altered neurodevelopmental and reproductive outcomes including brainderived neurotrophic factor (BDNF), kisspeptin (KiSS), and gene expression of nuclear receptors are prioritized, providing mechanistic insights based on in vitro, animal studies and AOP information. Finally, the potential of omics technologies for biomarker discovery and its implications for risk assessment are discussed. To the best of our knowledge, this is the first effort to comprehensively identify bisphenol-related biomarkers of effect for HBM purposes.European Union Commission H2020-EJP-HBM4EU 733032HBM4EU Initiativ

Caracterización de la exposición a disruptores endocrinos no persistentes en madres lactantes y neonatos ingresados en la UCIN

En conjunto, los resultados obtenidos en esta tesis doctoral ponen de manifiesto la necesidad de abordar las implicaciones a corto, medio y largo plazo, de la exposición a DEs no persistentes sobre la salud de los recién nacidos, especialmente de aquellos extremadamente vulnerables. Además, requiere de la necesidad de adoptar medidas preventivas con carácter urgente.Tesis Univ. Granada.Instituto de Salud Carlos III (código de expediente: PI16/01820)Horizon 2020 #733032Instituto de Salud Carlos III (código de expediente: FI17/00316)Instituto de Salud Carlos III (código de expediente: MV/19/00053

Human Exposure to Bisphenols, Parabens, and Benzophenones, and Its Relationship with the Inflammatory Response: A Systematic Review

Bisphenols, parabens (PBs), and benzophenones (BPs) are widely used environmental chemicals that have been linked to several adverse health effects due to their endocrine disrupting properties. However, the cellular pathways through which these chemicals lead to adverse outcomes in humans are still unclear, suggesting some evidence that inflammation might play a key role. Thus, the aim of this study was to summarize the current evidence on the relationship between human exposure to these chemicals and levels of inflammatory biomarkers. A systematic review of peer-reviewed original research studies published up to February 2023 was conducted using the MEDLINE, Web of Science, and Scopus databases. A total of 20 articles met the inclusion/exclusion criteria. Most of the reviewed studies reported significant associations between any of the selected chemicals (mainly bisphenol A) and some pro-inflammatory biomarkers (including C-reactive protein and interleukin 6, among others). Taken together, this systematic review has identified consistent positive associations between human exposure to some chemicals and levels of pro-inflammatory biomarkers, with very few studies exploring the associations between PBs and/or BPs and inflammation. Therefore, a larger number of studies are required to get a better understanding on the mechanisms of action underlying bisphenols, PBs, and BPs and the critical role that inflammation could play

Concentrations of perfluoroalkyl substances in donor breast milk in Southern Spain and their potential determinants

This research would not have been achieved without the selfless collaboration of the donors who took part in the study. The authors gratefully acknowledge editorial assistance from Richard Davies and the support of the "UNETE research unit" of the Centro de Investigacion Biomedica (University of Granada). This research was funded in part by grants from the European Union Commission (The European Human Biomonitoring Initiative H2020-EJP-HBM4EU), Biomedical Research Networking Center-CIBER de Epidemiologia y Salud Publica (CIBERESP), and the Carlos III Institute of Health (ISCIII) (PI16/01820, PI16/01812, PI16/01858, PI17/01743, and PI17/01526). The authors are also grateful to the ISCIII and the "Fondo Europeo de Desarrollo Regional" (ISCIII/FEDER) for the predoctoral research contract granted to L.M. Iribarne-Duran (FI17/00316), the Sara Borrell postdoctoral research contract granted to F. Vela-Soria (grant no. CD17/00212), the Jose Maria Segovia de Arana contract granted to N. Olea (INT18/00060) and the Miguel Servet Type I Program granted to C. Freire (grant no. MS16/00085). This paper is part of the PhD thesis developed by Laura Serrano in the context of the "Clinical Medicine and Public Health Program" of the University of Granada. The funders had no role in the study design, data collection or analysis, decision to publish, or preparation of the manuscript. Funding for open access charge: University of Granada/CBUA.Background: Breast milk is considered to offer the best nutrition to infants; however, it may be a source of exposure to environmental chemicals such as perfluoroalkyl compounds (PFAS) for breastfeeding infants. PFAS are a complex group of synthetic chemicals whose high stability has led to their ubiquitous contamination of the environment. Objective: To assess the concentrations and profiles of PFAS in breast milk from donors to a human milk bank and explore factors potentially related to this exposure. Methods: Pooled milk samples were collected from 82 donors to the Human Milk Bank of the Virgen de las Nieves University Hospital (Granada, Spain). Ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) was applied to determine milk concentrations of 11 PFAS, including long-chain and short-chain compounds. A questionnaire was used to collect information on donors’ socio-demographic characteristics, lifestyle, diet, and use of personal care products (PCPs). Factors related to individual and total PFAS concentrations were evaluated by multivariate regression analysis. Results: PFAS were detected in 24–100% of breast milk samples. PFHpA was detected in 100% of samples, followed by PFOA (84%), PFNA (71%), PFHxA (66%), and PFTrDA (62%). Perfluorooctane sulfonate (PFOS) was detected in only 34% of donors. The median concentrations ranged from <0.66 ng/dL (perfluorohexane sulfonic acid [PFHxS]) to 19.39 ng/L (PFHpA). The median of the sum of PFAS concentrations was 87.67 ng/L and was higher for short-chain than long-chain PFAS. Factors most frequently associated with increased PFAS concentrations included intake of creatin animal food items and use of PCPs such as skin care and makeup products. Conclusions: Several PFAS, including short-chain compounds, are detected in pooled donor milk samples. Breast milk may be an important pathway for the PFAS exposure of breastfed infants, including preterm infants in NICUs. Despite the reduced sample size, these data suggest that various lifestyle factors influence PFAS concentrations, highlighting the use of PCPs."UNETE research unit" of the Centro de Investigacion Biomedica (University of Granada)European Union Commission (The European Human Biomonitoring Initiative H2020-EJP-HBM4EU)Biomedical Research Networking Center-CIBER de Epidemiologia y Salud Publica (CIBERESP)Instituto de Salud Carlos III PI16/01820 PI16/01812 PI16/01858 PI17/01743 PI17/01526 FI17/00316 CD17/00212 INT18/00060 MS16/00085"Fondo Europeo de Desarrollo Regional" (ISCIII/FEDER) FI17/00316 CD17/00212 INT18/00060 MS16/00085University of Granada/CBU