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Aim: To describe the expression profile in endometriotic tissue of genes involved in four signaling pathways related to the development and progression of endometriosis (cell cycle, apoptosis, cell differentiation and lipid metabolism) and to explore its relationship with the women exposure to chemicals with hormonal activity released from cosmetics and personal care products (PCPs). Methods: This cross-sectional study, encompassed within the EndEA study, comprised a subsample of 33 women with endometriosis. Expression levels of 13 genes (BMI1, CCNB1, CDK1, BAX, BCL2L1, FOXO3, SPP1, HOXA10, PDGFRA, SOX2, APOE, PLCG1 and PLCG2) in endometriotic tissue and urinary concentrations of 4 paraben (PB) and 3 benzophenone (BP) congeners were quantified. Bivariate linear and logistic regression analyses were performed to explore the associations between exposure and gene expression levels. Results: A total of 8 out 13 genes (61.5%) were expressed in >75% of the samples. Exposure to congeners of PBs and/ or BPs was associated with the overexpression of CDK1 gene (whose protein drives cells through G2 phase and mitosis), HOXA10 and PDGFRA genes (whose proteins favor pluripotent cell differentiation to endometrial cells), and APOE (whose protein regulates the transport and metabolism of cholesterol, triglycerides and phospholipids in multiple tissues) and PLCG2 genes (whose protein creates 1D-myo-inositol 1,4,5-trisphosphate and diacylglycerol, two important second messengers). Conclusions: Our findings suggest that women exposure to cosmetic and PCP-released chemicals might be associated with the promotion of cell cycle and cell differentiation as well as with lipid metabolism disruption in endometriotic tissue, three crucial signaling pathways in the development and progression of endometriosis. However, further studies should be accomplished to confirm these preliminary data.

Background Breast milk is the main source of nutrition for infants but may be responsible for their exposure to environmental chemicals, including endocrine-disrupting chemicals. Aim To review available evidence on the presence and concentrations of bisphenols, parabens (PBs), and benzophenones (BPs) in human milk and to explore factors related to exposure levels. Methods A systematic review was carried out using Medline, Web of Science, and Scopus databases, conducting a comprehensive search of peer-reviewed original articles published during the period 2000–2020, including epidemiological and methodological studies. Inclusion criteria were met by 50 studies, which were compiled by calculating weighted detection frequencies and arithmetic mean concentrations of the chemicals. Their risk of bias was assessed using the ROBINS-I checklist. Results Among the 50 reviewed studies, concentrations of bisphenols were assessed by 37 (74.0%), PBs by 21 (42.0%), and BPs by 10 (20.0%). Weighted detection frequencies were 63.6% for bisphenol-A (BPA), 27.9–63.4% for PBs, and 39.5% for benzophenone-3 (BP-3). Weighted mean concentrations were 1.4 ng/mL for BPA, 0.2–14.2 ng/mL for PBs, and 24.4 ng/mL for BP-3. Mean concentrations ranged among studies from 0.1 to 3.9 ng/mL for BPA, 0.1 to 1063.6 ng/mL for PBs, and 0.5 to 72.4 ng/mL for BP-3. The highest concentrations of BPA and PBs were reported in samples from Asia (versus America and Europe). Higher BPA and lower methyl-paraben concentrations were observed in samples collected after 2010. Elevated concentrations of these chemicals were associated with socio-demographic and lifestyle factors in eight studies (16.0%). Two epidemiological studies showed moderate/serious risk of bias. Conclusions This systematic review contributes the first overview of the widespread presence and concentrations of bisphenols, PBs, and BPs in human breast milk, revealing geographical and temporal variations. The methodological heterogeneity of published studies underscores the need for well-conducted studies to assess the magnitude of exposure to these chemicals from human milk.

Human breast milk is considered the optimal source of nutrition for infants. Milk from breast milk banks offers an alternative to infant formulas for vulnerable hospitalized neonates most likely to benefit from exclusive human milk feeding. However, breast milk can also be a source of exposure to environmental contaminants, including endocrine-disrupting chemicals (EDCs).To evaluate concentrations of phenolic EDCs, including bisphenols, parabens (PBs), and benzophenones (BPs), in samples from a human milk bank in Granada, Southern Spain and to explore sociodemographic, reproductive, and lifestyle factors related to their concentrations in the milk.Concentrations of three bisphenols [bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS)], four PBs [methyl- (MeP), ethyl- (EtP), propyl- (n-PrP), and butyl-paraben (n-BuP)], and six BPs [BP-1, BP-2, BP-3, BP-6, BP-8, and 4-hydroxy-BP] were determined in milk samples from 83 donors. Information on potential explanatory variables was gathered using the milk bank donor form and an ad hoc questionnaire. Multiple linear and logistic regression models were fitted.Detectable concentrations were found of at least one of the analyzed compounds in all donor breast milk samples and at least five compounds in one-fifth of them. The most frequently detected compounds were MeP (90.5%), BP-3 (75.0%), EtP (51.2%), n-PrP (46.4%), and BPA (41.7%). Median concentrations ranged between0.10 ng/mL (n-PrP, n-BuP, BP-1) and 0.59 ng/mL (BP-3). No sample contained detectable concentrations of BPF, BPS, or most BPs (BP-2, BP-6, BP-8, and 4- hydroxy-BP). Breast milk phenol concentrations were associated with parity, the utilization of deodorants, mouthwash, skin care products, and cosmetics, and the intake of nutritional supplements.Results reveal the widespread presence of BPA, PBs, and BP-3 in donor breast milk samples, highlighting the need for preventive measures to enhance the benefits of breast milk from milk banks and from breastfeeding women in general.

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.

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. Methods: This case&ndash, control study enrolled 124 women between January 2018 and July 2019: 35 women with endometriosis (cases) and 89 women without endometriosis undergoing abdominal surgery for other reasons (controls). Endometriosis was diagnosed (cases) or ruled out (controls) by laparoscopic inspection of the pelvis and the biopsy of suspected lesions (histological diagnosis). Fasting urine samples were collected before surgery to determine concentrations of BPA, BPS, BPF, and TBARS. Associations of bisphenol and TBARS concentrations with endometriosis risk were explored with multivariate logistic and linear regression analyses. 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&ndash, 2.3] and &Sigma, bisphenols [OR 1.5, 95%CI 0.9&ndash, 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&ndash, 10.3] and &Sigma, bisphenols [OR 5.4, 95%CI 1.9&ndash, 15.6]. In addition, TBARS concentrations showed a close-to-significant relationship with increased endometriosis risk [OR 1.6, 2.8], and classification by TBARS concentration tertile revealed that the association between endometriosis risk and concentrations of BPA [OR 2.0, 4.1] and &Sigma, bisphenols [OR 2.2, 4.6] was only statistically significant for women in the highest TBARS tertile (&gt, 4.23 &mu, M). 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.

Background Benzophenone (BP)-type ultraviolet (UV) light filters are chemicals frequently added to personal care products, insect repellents, sunscreens, and beverage and food packaging to diminish the harmful effects of UV sunlight on human skin or foodstuffs. BP-type UV filters have shown negative effects on male reproduction function in in vitro and animal models, but human epidemiologic studies are limited. The goal of this study was to examine associations between urinary concentrations of BP-type UV filters and semen quality and reproductive hormone levels. Methods This is a cross-sectional study with 215 young university students (18–23 years old) recruited between 2010 and 2011 in Southern Spain (Murcia Region). All men provided a urine, blood and semen sample on a single day. Urinary concentrations of 2,4-dihydroxybenzophenone (BP-1); 2,2′,4,4′-tetrahydroxybenzophenone (BP-2); 2-hydroxy-4-methoxybenzophenone (BP-3); 2,2′-dihydroxy-4-methoxybenzophenone (BP-8) and 4-hydroxybenzophenone (4OH-BP) were measured by dispersive liquid–liquid microextraction and ultra-high performance liquid chromatography with tandem mass spectrometry detection. Semen quality was evaluated by measuring volume, sperm counts, motility and morphology. Serum samples were analyzed for reproductive hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), inhibin B and estradiol (E2). Associations between urinary concentrations of BP-type UV filters and semen quality parameters and reproductive hormone levels were examined using linear regression, adjusting for potential confounders. Results Ninety-seven percent of the men had detectable urinary concentrations of at least one of the five BP-type UV filters quantified. After adjustment for important covariates (body mass index, smoking status and time of blood sample collection), there was a significant positive association between urinary BP-1 and BP-3 concentrations and serum FSH levels (β = 0.08, 95%CI: 0.009; 0.15 and β = 0.04, 95%CI: 0.0002; 0.08, respectively). Urinary BP-1 concentration was also significantly positively associated with T/E2 (β = 0.04, 95%CI: 0.002; 0.07) and negatively with inhibin b/FSH (β = −0.11, 95%CI: −0.21; −0.006) ratio. No significant associations were found between other urinary BP-type UV filters and other reproductive hormone levels or between any semen parameters and any of the urinary BP-type UV filters quantified. Conclusions Our results suggest that, in young men, urinary BP-type UV filters may be associated with a modest alteration of some reproductive hormones, but the effects we report on reproductive function are likely to be small, and of unclear clinical significance. Further research is needed to replicate these findings in other male populations.

Concerns are growing about human exposure to endocrine disrupting chemicals (EDCs), especially during developmental stages. Parabens (PBs) and ultraviolet filters (UVFs) are prevalent EDCs widely used as additives in cosmetics and personal care products (PCPs). The objective of this study was to develop a method to determine four PBs and ten UVFs in human milk using QuEChERS treatment and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS). Multivariate strategies were applied to optimize experimental parameters. Limits of quantification ranged from 0.1 to 0.2 ng mL−1 and inter-day variability (evaluated as relative standard deviation) from 6% to 13%. The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. Recovery percentages ranged from 87% to 112%. The method was satisfactorily applied to assess target compounds in human milk samples from 15 donors. This analytical procedure can provide information on newborn exposure to these EDCs.

Background Environmental factors are believed to account for a substantial burden of type 2 diabetes mellitus (T2DM). Non-persistent environmental pollutants (npEPs) are a group of widely-used chemicals identified as endocrine/metabolic disrupting chemicals and obesogens. The aim of this study was to analyse the potential associations of serum levels of three groups of npEPs with the risk of incident T2DM. Methods This is a longitudinal study within a sub-sample of Granada EPIC-Spain cohort (n = 670). We quantified serum concentrations of 7 npEPs: four parabens (Methylparaben (MP) ethylparaben (EP), propylparaben (PP) and butilparaben (BP); two benzophenones: Benzophenone 1 (BP1), Benzophenone 3 (BP3); and Bisphenol A (BPA). Exposure was assessed by means of chemical analyses of serum samples collected at recruitment, and information on potential confounders was gathered by using validated questionnaires at baseline. Follow-up was performed by review of patients’ clinical records. Cox Proportional Hazards Models were used for the statistical analyses. Results Median follow-up time was 23 years. There were 182 (27%) incident T2DM diagnoses in our sub-cohort. MP was the most frequently detected npEP, 88.42% samples above the limit of detection, and BP showed the lowest percentage of detection (19.21%). Those individuals within the fourth PP quartile (0.53–9.24 ng/ml) showed a statistically significant increased risk of T2DM (HR = 1.668 p = 0.012), while BP1 concentrations showed an inverse non-significant trend with the risk. Conclusions We evidenced a potential contribution of npEP exposure on T2DM, but no clear trend was observed. However, limitations in relation to exposure estimation might influence our findings and further research is warranted to confirm our results.

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 stopcocks, 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 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).

Aim To evaluate concentrations of parabens (PBs) and benzophenones (BzPs) in menstrual blood and explore related sociodemographic/lifestyle factors, and to compare between menstrual and peripheral blood concentrations in a subset of samples. Material and methods Concentrations of 4 PBs [methyl- (MeP), ethyl- (EtP), propyl- (PrP) and butyl-paraben (BuP)] and 6 BzPs [BzP-1, BzP-2, BzP-3, BzP-6, BzP-8 and 4-OH-BzP] were determined in menstrual blood from 57 women and in both menstrual and peripheral blood samples from 12 women, all healthy Spanish women of reproductive age. Socio-demographic characteristics and lifestyle habits [diet and use of cosmetics and personal care products (PCPs)] were gathered using an online questionnaire. Spearman correlation analysis was performed to examine the relationship between menstrual and peripheral blood concentrations, while multivariable linear regression was used to identify potential explanatory variables for menstrual PB and BzP concentrations. Results Globally, all menstrual blood samples had detectable levels of ≥3 compounds, and 52.6% of the samples contained ≥6 compounds. MeP, PrP, and BzP-3 were the most frequently detected compounds (detection frequencies >90.0%), with median concentrations of 1.41, 0.63, and 1.70 ng/mL of menstrual blood, respectively. Age, the use of PCPs, and consumption of some food items (meat, pasta, cheese, or dairy products) were related to the menstrual blood concentrations of some PBs/BzPs. Serum:menstrual blood ratios of PBs/BzPs ranged from 1.7 to 3.6, with no inter-matrix correlations. Conclusions This study reveals, to our knowledge for the first time, the widespread presence of several PBs and BzPs in intimate contact with gynecological tissues, although their concentrations in menstrual blood were not correlated with those in peripheral blood from the same women. These results shed light on the information provided by the menstrual blood as a potential matrix for characterizing exposure to PBs and BzPs, whose consequences for women's reproductive health need to be addressed.

Bisphenol A (BPA) is considered an endocrine disruptor and it is present in numerous products of daily use. The aim of this study was to analyze serum BPA concentrations in a subcohort of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC), as well as to identify potential predictors of the exposure. The population consisted on 3553 subjects from 4 EPIC-Spain centres and BPA levels were measured in serum samples by UHPLC-MS/MS. Almost 70% of the participants showed detectable BPA values (>0.2 ng/ml), with a geometric mean of 1.19 ng/ml (95% CI: 1.12–1.25). By sex, detectable percentages were similar (p = 0.56) but with higher serum levels in men (1.27 vs 1.11 ng/ml, p = 0.01). Based on the adjusted regression models, a 50 g/day increase in the consumption of added fats and oils were associated with 43% lower BPA serum levels, while sugar and confectionary was associated with 25% higher levels of serum BPA. We evidenced differential exposure levels by province, sex and age, but not by anthropometric or lifestyle characteristics. Further investigation is needed to understand the influence of diet in BPA exposure.

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, 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.

To explore the relationship of urinary concentrations of different congeners of benzophenones and parabens with the utilization of cosmetics and personal care products (PCPs) and their impact on the risk of endometriosis, and to evaluate the influence of oxidative stress on associations found.This case-control study comprised a subsample of 124 women (35 cases; 89 controls). Endometriosis was confirmed (cases) or ruled out (controls) by laparoscopy, with visual inspection of the pelvis and biopsy of suspected lesions (histological diagnosis). Urinary concentrations of benzophenone-1 (BP-1), benzophenone-3 (BP-3), 4-hydroxibenzophenone (4-OH-BP), methyl- (MeP), ethyl- (EtP), propyl- (PrP), and butyl-paraben (BuP), and biomarkers of oxidative stress [lipid peroxidation (TBARS) and total antioxidant power (TAP)] were quantified. Information was gathered on the frequency of use of cosmetics and PCPs. Associations between the frequency of cosmetics/PCP use, urinary concentrations of benzophenones and parabens, oxidative stress, and endometriosis risk were explored in logistic and linear multivariable regression analyses.The frequency of utilization of certain cosmetics and PCPs was significantly associated with urinary concentrations of benzophenones and parabens. After adjustment for potential confounders, the risk of endometriosis was increased in women in the second versus first terciles of MeP (OR = 5.63; p-value0.001), BP-1 (OR = 5.12; p-value = 0.011), BP-3 (OR = 4.98; p-value = 0.008), and ƩBPs (OR = 3.34; p-value = 0.032). A close-to-significant relationship was observed between TBARS concentrations and increased endometriosis risk (OR = 1.60, p-value = 0.070) and an inverse association between TAP concentrations and this risk (OR = 0.15; p-value = 0.048). Oxidative stress results did not modify associations observed between benzophenone/paraben exposure and endometriosis risk.Our findings indicate that the frequency of cosmetics and PCP utilization is a strong predictor of exposure to certain benzophenone and paraben congeners. These compounds may increase the risk of endometriosis in an oxidative stress-independent manner. Further studies are warranted to corroborate these findings.

Background The prevalence of arterial hypertension (AHT), a well-known risk factor for cardiovascular disease, has considerably increased over last decades. Non-persistent environmental pollutants (npEPs) are a group of ubiquitous chemicals, widely used in consumer products such as food packaging and cosmetics, which have been identified as endocrine disrupting chemicals and obesogens. The aim of this study was to assess the potential associations of serum levels of three groups of npEPs with the risk of incident AHT. Methods Cohort study within a sub-cohort of Granada EPIC-Spain center (n = 670). We quantified serum concentrations of three groups of npEPs, i.e., bisphenol A (BPA), four parabens: methylparaben (MP), ethylparaben (EP), propylparaben (PP) and butylparaben (BP), and two benzophenones: benzophenone 1 (BP1), benzophenone 3 (BP3), in samples collected at recruitment. Statistical analyses were performed by means of Cox Proportional Hazard Models. Results Median follow-up time was 23 years. BPA and MP were found in >80% of the study population. Individuals within the 4th PP quartile (0.53–9.24 ng/ml) showed a statistically significant increased risk of AHT (HR = 1.40, p = 0.015). No associations were found for the rest of pollutants. Conclusions Overall, we evidenced no associations of most npEPs with AHT risk, with the exception of an increased risk in the highest PP percentiles. Considering the limitations of using one spot serum sample for exposure characterization, further research on the potential contribution of npEPs on the development of AHT risk is warranted.

Benzophenones and parabens are synthetic chemicals used in many personal care products, foods and pharmaceuticals. Benzophenones are used to protect the skin and materials from the adverse effects of UV-radiation, and parabens are used as preservatives. Despite their widespread occurrence and proven endocrine disrupting activity, relatively little is known about human exposure to these compounds. In the present work, an analytical method based on sample treatment using dispersive liquid-liquid microextraction (DLLME) for the extraction of six benzophenones (benzophenone-1, -2, -3, -6, -8 and 4-hydroxybenzophenone) and four parabens (methyl-, ethyl-, propyl- and butyl- paraben) from human menstrual blood samples, followed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, is proposed and validated. The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. The limits of detection ranged from 0.1 to 0.3ngmL-1, with recoveries of 93.8% to 108.9%, and precision (evaluated as relative standard deviation) lower than 14% for all selected compounds. This method was successfully applied for the determination of the target compounds in 25 samples of human menstrual blood. Methylparaben and benzophenone-3 were the most frequently detected compounds (96%).

This study was conceived as a first step to evaluate the suitability of adipose tissue cadmium (Cd) concentrations as a biomarker for the assessment of long-term exposure. Specifically, the aim of this work was to explore the socio-demographic, dietary, and lifestyle determinants of adipose tissue Cd concentrations. The study population is a subsample of GraMo cohort. Adipose tissue samples were intraoperatively collected from 226 adult volunteers recruited in two public hospitals from Granada, Spain. Cd concentrations in adipose tissue were analyzed by High-Resolution Inductively Coupled Plasma Mass Spectrometry (HR-ICP-MS). Data on socio-demographic characteristics, lifestyle, diet and health status were collected by face-to-face interviews. Predictors of Cd concentrations were assessed by multivariable linear regression with a stepwise variable selection. We found detectable levels of Cd in the adipose tissue of all the study participants, with a mean concentration (±standard deviation) of 12.66 ± 18.91 μg/kg. Smoking habit at recruitment was associated with increased adipose tissue Cd concentrations (β for smokers = 0.669 p 0.001; β for former smokers = 0.502, p 0.001; reference = non-smokers). Age was positively associated with Cd concentrations (β = 0.014, p 0.001), and men showed lower concentrations than women (β = -0.424, p 0.001). Obesity, measured as Body Mass Index (BMI), showed an inverse association with Cd concentrations (β = -0.038, p 0.001). Egg consumption ≥2 portions/week (β = 0.241, p = 0.025) was positively associated with Cd concentrations. Perceived exposure to paints was also positively associated with Cd concentrations. The observed associations with age, smoking habit, BMI, and egg and meat consumption did not substantially change after sex/gender stratification. Our results are consistent with currently-known Cd sources and suggest other potential pathways, which might be population-specific. As a whole, our findings underline the potential relevance of adipose tissue as a biological matrix for exposure characterization to Cd, as well as for the assessment of long-term clinical implications of the exposure, particularly in obesity-related diseases.

The aim of this study was to assess differences between two biological matrices (serum and breast adipose tissue) in the evaluation of persistent organic pollutant (POP) exposure in breast cancer patients. The study population consisted of 103 women undergoing surgery for newly diagnosed breast carcinoma in a public hospital in Granada, Southern Spain. Independent variables were gathered from questionnaires and clinical records. POP concentrations were quantified in breast adipose tissue and serum samples. Spearman correlation tests were performed between pairs of POP concentrations and stepwise multivariable linear regression analyses were conducted to assess predictors of concentrations in the two matrices. p,p'- Dichlorodiphenyldichloroethylene (p,p'-DDE) showed the the highest median concentration in both matrices (194.34 and 173.84 ng/g lipid in adipose tissue and serum, respectively). Median wet-basis adipose tissue:serum ratios ranged from 109.34 to 651.62, while lipid-basis ratios ranged from 0.88 to 4.34. In general, we found significant positive correlation coefficients between pairs of POPs in adipose tissue and in serum, which were always higher in adipose tissue. We found positive and statistically significant correlations between serum and adipose tissue concentrations of p,p'-DDE and hexachlorobenzene (HCB) but not of polychlorinated biphenyls (PCBs). Age was positively associated with most POPs in adipose tissue and serum, while the body mass index was positively associated with adipose tissue HCB concentrations and negatively associated with serum PCB-153 and PCB-138 concentrations. Recent weight loss was inversely associated with POP residues in adipose tissue and positively associated with POP residues in serum. Serum HCB and PCB-180 concentrations were lower in patients who had received preoperative chemotherapy. According to our results, serum and adipose tissue POP concentrations in breast cancer patients may be differentially affected by external predictors. Taken together, these findings indicate the need to take account of the individual POP(s) under study and the biological matrix used when relating internal POP exposure to breast cancer disease and to make a careful selection of covariates for adjusting the model.

Urinary concentrations of non-persistent environmental pollutants (npEPs) are widely assessed in biomonitoring studies under the assumption that they are metabolised and eliminated in urine. However, some of these chemicals are moderately lipophilic, and their presence in other biological matrices should also be evaluated to estimate mid/long-term exposure to npEPs and its impact on human health. The present study aims to explore concentrations and potential determinants of npEPs in adipose tissue from a hospital-based adult cohort (GraMo cohort, Southern Spain). Concentrations of bisphenol-A (BPA), benzophenone-3 (BP-3), triclosan (TCS), three chlorophenols (2,4-DCP, 2,5-DCP and 2,4,5-TCP) and two phenylphenols (2-PP and 4-PP), triclocarban (TCCB) and parabens [methyl- (MeP), ethyl- (EtP), propyl- (n-PrP and i-PrP), butyl- (n-BuP and i-BuP) and benzyl-paraben (BzP)] were analysed in adipose tissue samples from a subcohort of 144 participants. Spearman correlation tests were performed, followed by stepwise multivariable linear regression analyses to assess determinants of the exposure. Detection frequencies and median concentrations were: BPA (86.8%, 0.54 ng/g tissue), BP-3 (79.2%, 0.60 ng/g tissue), TCS (45.8%,LOD), 2-PP (18.8%,LOD), MeP (100.0%, 0.40 ng/g tissue), EtP (20.1%,LOD) and n-PrP (54.2%, 0.06 ng/g tissue). The remaining npEPs were detected in10% of the samples. BPA, MeP, EtP and n-PrP levels were significantly and positively correlated, while BP-3 showed a positive correlation with TCS and 2-PP. Older participants showed higher concentrations of TCS and MeP, while BMI was inversely associated with most of the analysed compounds and perceived recent weight loss was inversely associated with 2-PP. Female participants and residents of rural areas had increased BP-3 concentrations. npEP concentrations were positively associated with the consumption of fatty food but negatively associated with the consumption of vegetables and fruit. This study reveals the widespread presence of numerous npEPs in adipose tissue from adults in southern Spain, suggesting a generalized distribution of these environmental compounds in fatty tissues. In these adults, many of the determinants of npEP concentrations in adipose tissue were similar to those of more lipophilic and persistent compounds.

Parabens are a group of alkyl esters of p-hydroxybenzoic acid that are commonly added to personal care products, cosmetics, pharmaceuticals and beverage and food processing as antimicrobial preservatives. Parabens have been reported to show estrogenic effects and affect male reproduction function in animal models, but human epidemiologic studies are still scarce. The objective of this study was to examine associations between urinary concentrations of parabens and semen quality and reproductive hormone levels. This was a cross-sectional study with 215 young university students (18-23years old) recruited between 2010 and 2011 in Southern Spain (Murcia Region). All men provided a urine, blood and semen sample on a single day. Urinary paraben concentrations (methylparaben, ethylparaben, propylparaben and butylparaben) were measured by dispersive liquid-liquid microextraction and ultra-high performance liquid chromatography with tandem mass spectrometry detection. Semen quality was evaluated by measuring volume, sperm concentration, total sperm count (TSC), motility and morphology following WHO guidelines. Serum samples were analyzed for reproductive hormones, including follicle-stimulating hormone, luteinizing hormone, testosterone, inhibin B and estradiol using immunoassays. Associations between urinary concentrations of parabens and semen quality parameters and reproductive hormone levels were examined using linear regression, adjusting for potential covariates. Ninety-four percent of the men had detectable urinary concentrations of parabens. After taking into account important covariates, urinary concentrations of parabens or their molar sum were not significantly associated with any semen parameters or any of the reproductive hormone levels. Relative to men in the lowest quartile of sum of urinary paraben concentrations, the adjusted difference (95% CI) of TSC (millions) for men in the 2nd, 3rd, and 4th quartiles were 4.1% (-37.1;45.3), -1.6% (-41.9;38.8), and -9.8% (-52.5;32.8), respectively (P-trend=0.55). Our results suggest that, in young men, urinary parabens may not adversely impact reproductive function, but further research is warranted to confirm these findings in other male populations.

Aim: Human populations are widely exposed to numerous so-called endocrine-disrupting chemicals, exogenous compounds able to interfere with the endocrine system. This exposure has been associated with several health disorders. New analytical procedures are needed for biomonitoring these xenobiotics in human matrices. A quick and inexpensive methodological procedure, based on sample treatment by dispersive liquid–liquid microextraction, is proposed for the determination of bisphenols, parabens and benzophenones in samples. Results: LOQs ranged from 0.4 to 0.7 ng ml-1 and RSDs from 4.3 to 14.8%. Conclusion: This methodology was satisfactorily applied in the simultaneous determination of a wide range of endocrine-disrupting chemicals in human milk samples and is suitable for application in biomonitoring studies.