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Background: Bisphenol A (BPA) is an endocrine disruptor that it is present in numerous products of daily use. The aim of this study was to assess the potential association of serum BPA concentrations and the risk of incident breast and prostate cancer in a sub-cohort of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC).Methods: We designed a case-cohort study within the EPIC-Spain cohort. Study population consisted on 4812 participants from 4 EPIC-Spain centers (547 breast cancer cases, 575 prostate cancer cases and 3690 sub-cohort participants). BPA exposure was assessed by means of chemical analyses of serum samples collected at recruitment. Borgan II weighted Cox regression was used to estimate hazard ratios.Results: Median follow-up time in our study was 16.9 years. BPA geometric mean serum values of cases and sub-cohort were 1.12 ng/ml vs 1.10 ng/ml respectively for breast cancer and 1.33 ng/ml vs 1.29 ng/ml respectively for prostate cancer. When categorizing BPA into tertiles, a 40% increase in risk of prostate cancer for tertile 1 (p = 0.022), 37% increase for tertile 2 (p = 0.034) and 31% increase for tertile 3 (p = 0.072) was observed with respect to values bellow the limit of detection. No significant association was observed between BPA levels and breast cancer risk.Conclusions: We found a similar percentage of detection of BPA among cases and sub-cohort from our population, and no association with breast cancer risk was observed. However, we found a higher risk of prostate cancer for the increase in serum BPA levels. Further investigation is needed to understand the influence of BPA in prostate cancer risk. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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 E 2 eq/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). 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. Unlabelled Image • BPA was present in 91% of socks at concentrations ranging from <0.70 to 3736 ng/g. • Ethyl-paraben was found in 100% of socks, followed by methyl- and propyl-paraben. • Around 41% of socks extracts were estrogenic and 19% were anti-androgenic. • Hormone-like activities were higher in socks with higher BPA content. • The median estimated dermal exposure dose to BPA was 19.6 pg/kg/day. [ABSTRACT FROM AUTHOR]

Childhood obesity is one of the most serious public health challenges of our times. Although an important body of experimental evidence highlights the obesogenic potential of endocrine disruptors such as bisphenol A (BPA), the epidemiological evidence remains inconclusive and limited. To assess associations between urinary BPA concentrations and several adiposity measures in peripubertal boys from the Environment and Childhood (INMA) cohort in Granada, Spain. BPA concentrations were determined in spot urine samples from 298 boys aged 9–11, and their weight, height, waist circumference, and percentage body fat mass were measured. Overweight/obesity was defined as BMI z-score ≥85th percentile and abdominal obesity as waist-to-height ratio (WHtR) ≥0.5. Associations were assessed using multivariable linear and logistic regression models. In adjusted models, each natural log-unit increase in urinary BPA concentrations was associated with higher BMI z-score (β = 0.22; 95%CI = 0.03, 0.41) and increased odds of overweight/obesity (OR = 1.46; 95%CI = 1.05, 2.05). Children with higher BPA concentrations had higher WHtR values (β = 0.007; 95%CI = −0.001, 0.015), and BPA was associated with a greater risk of abdominal obesity (OR = 1.45; 95%CI = 1.03, 2.06). No associations were found with % body fat mass. BPA may exert an obesogenic effect in peripubertal boys, potentially increasing the risk of overweight/obesity, especially abdominal obesity. However, these results should be interpreted with caution given the modest sample size and the possibilities of reverse causality and residual confounding by diet and lifestyle patterns. • We assessed associations between BPA and adiposity measures in peripubertal boys. • Urinary BPA concentrations were associated with the risk of overweight/obesity. • BPA concentrations were also associated with abdominal obesity, but not body fat mass. • BPA could exert an obesogenic effect, preferentially targeting abdominal fat. • Prepuberty constitutes a less explored critical window for BPA effects. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is one of the main ubiquitous compounds released from plastics in the environment. This compound, considered an endocrine disruptor, poses a risk to aquatic wildlife and human population, being included in multiple environmental monitoring programmes. Following the regulations restricting BPA use in the last years, BPA-like chemicals have been produced and used as BPA substitutes. However, they are not commonly included in monitoring programs yet and their presence is thus misrepresented, despite showing similar endocrine disrupting potential. In this work, an analytical method for analysing bisphenol A and five of its analogues (Bisphenol S, B, F, AF and Tetrabromobisphenol A) is described, validated for water (riverine, sea and wastewater), sediment, and biota (fish and biofilm) and applied to monitor their presence in the Ebro River Delta (NE Spain). In addition, plastic litter was also collected to evaluate their role as potential source of bisphenols. All compounds except BPF were detected in the analysed samples. Wastewater treatment plants (WWTPs) were discarded as major sources of BPs into the natural aquatic environment, as no BPs were detected in treated effluents. Indeed, the high levels of BPs in the natural environment could be related with direct discharge of raw wastewater from small rural population nucleus. The analysis of riverine plastic leachates yielded 4 out of the 6 BPs analysed, strengthening the hypothesis that plastic debris are also a source of BPs in the natural environment. Whereas Bisphenol S and BPA were detected in water and, to a limited extent, in biota, less polar analogues (mainly BPAF and TBBPA) were not found in any of the water samples. Instead, these hydrophobic BPs were found in fish tissues and biofilm, pointing out plastics and microplastics as their possible vectors. Finally, biofilm demonstrated its potential as sentinel of chemical contamination in freshwater environment. [Display omitted] • Bisphenols were studied in biotic and non-biotic fluvial compartments. • Polar bisphenols detected in all environmental compartments. • Less polar bisphenol analogues only found in fish tissues and fluvial biofilm. • Plastic litter pointed out as a source of bisphenol contamination in river. • Fluvial biofilm as a sentinel for bisphenols monitoring in the aquatic environment. [ABSTRACT FROM AUTHOR]

The occurrence of 50 multi-class pollutants comprising 18 polycyclic aromatic hydrocarbons (PAHs), 12 phthalate esters (PAEs), 12 organophosphorus flame retardants (OPFRs), 6 synthetic musk compounds (SMCs) and 2 bisphenols was studied in atmospheric particulate matter (PM 2.5) samples collected at an industrial area focused on automotive manufacturing located at the Southwestern Atlantic European region (Vigo city, Spain) during 1-year period. Among all quantitated pollutants in PM 2.5 samples, bisphenol A (BPA) was the most predominant with an average concentration of 6180 pg m−3, followed by PAHs comprising benzo(b+j)fluoranthene (BbF + BjF) and benzo(g,h,i)perylene (BghiP), accounting for 546 pg m−3 and 413 pg m−3 respectively. In addition, two OPFRs concerning tris(chloropropyl) phosphate (TCPP) and triphenyl phosphine oxide (TPPO) were the next following the concentration order, accounting for 411 pg m−3 and 367 pg m−3 respectively; being butyl benzyl phthalate (BBP) the most profuse PAE (56.1 pg m−3 by average). High relative standard deviations (RSDs) were observed during the whole sampling period, while statistically significant differences were only observed for PAHs concentrations during cold and warm seasons. Furthermore, some water-soluble ions and metal(oid)s were analysed in PM 2.5 samples to be used as PM source tracers, whose concentrations were quite below the target levels set in the current legislation. Data obtained from principal component analysis (PCA) and PAHs molecular indices suggested a pyrogenic and petrogenic origin for PAHs, whereas occurrence of the remaining compounds seems to be attributed to resources used in the automotive industrial activity settled in the sampling area. Moreover, although a substantial anthropogenic source to PM 2.5 in the area was observed, marine and soil resuspension contributions were also accounted. Finally, carcinogenic and non-carcinogenic risks posed by PM 2.5 -bound pollutants inhalation were assessed, being both averages within the safe level considering the whole period. [Display omitted] • Bisphenol A was the most predominant compound, with a mean value of 6180 pg m−3. • The occurrence of PM 2.5 -bound industrial chemicals was persistent all year round. • PM 2.5 sources were mainly attributed to combustion and automotive manufacturing. • Health risks posed by inhalation of PM 2.5 -bound pollutants were in the safe level. [ABSTRACT FROM AUTHOR]

Young children, whose growth and development are highly dependent on the endocrine system, are particularly vulnerable to endocrine disruptor exposure. The main objectives of this study were to measure BPA migration levels from cans, fruit juice bottles/packs, and microwave containers used for food/drinks consumed by a sample of 6- to 8-year old schoolchildren in Spain and to estimate the relationship between their resulting BPA exposure and diet quality index scores (Mediterranean Diet Score and Breakfast Quality Index). The mean BPA concentration was 11.8 ng/mL for vegetable cans, 22.1 ng/mL for pulse cans, 3.6 ng/mL for juice bottles/packs, and 1.2 ng/mL for microwave containers. Results revealed a significant association between the Mediterranean Diet Score and low BPA exposure of the children. BPA exposure below the median level was significantly associated with a higher score in both the first-grade (P = 0.030) and second-grade (p = 0.0001) groups. However, no association was found between BPA exposure and the Breakfast Quality Index. In conclusion, children with a stronger adherence to a Mediterranean-like diet appear to be less exposed to BPA migrating from food packaging and microwave containers. Further research is warranted on the inadvertent exposure of children to endocrinedisrupting chemicals from these sources. [ABSTRACT FROM AUTHOR]

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Copyright of Revista de Toxicología is the property of Asociacion Espanola de Toxicologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The occurrence and spatial distribution of alkylphenols (4- tert -octylphenol, 4- n -octylphenol, 4- n -nonylphenol, nonylphenol) and bisphenol A were examined in five estuaries along the Northwest coastal area of Spain. As far as we know, no previous works about this topic could be found in the literature. A total of 98 seawater samples were collected during May 2011–July 2012 and analyzed by a highly sensitive DLLME–LC–MS/MS methodology recently developed. Results indicated nonylphenol was the most ubiquitous compound with maximal concentration of 0.337 μg L −1 (Ría de Vigo). The environmental quality standards (EQS) established in Directive 2013/39/EU for 4- tert -octylphenol were slightly exceeded in some sampling points. Fishing harbours, water treatment plant and industrial discharges were supposed as the main sources of contamination. Low and medium ecological risk was determined in all estuaries. Possible endocrine effects on biota and population were estimated in terms of estrogenic activity and daily intake respectively, and no risk was found in any case. [ABSTRACT FROM AUTHOR]

Exposure to some phthalate diesters and bisphenol A in the general population is a cause of increasing concern because of their potential adverse effects on the reproductive and endocrine systems and their broad presence in foodstuff and consumer products. The aims of this work are to assess patterns of exposure to phthalates and bisphenol A in a pilot sample of Spanish mothers and their children, and to provide basic information to address priorities in future Spanish surveys/research. Urinary levels of eight phthalate metabolites and bisphenol A have been measured in samples from 120 mother–child pairs in one rural and one urban location in central Spain, recruited as part of the European project DEMOCOPHES. More than 96% of the participants were exposed to all the compounds studied here with generally higher levels in children than their mothers. The sum of secondary DEHP metabolites gave a GM of 33.3 μg/g creatinine (95% CI 30.2–36.6) for mothers and 63.0 μg/g creatinine (95% CI 56.8–69.8) for children. Mono-ethyl phthalate (MEP) was the metabolite with the highest levels, with geometric means (GM) of 150.8 μg/g creatinine (95% CI 124.0–183.5) for mothers and 198.9 μg/g creatinine (95% CI 165.2–239.6) for children. Bisphenol A urinary levels were relatively low with geometric means of 2.0 μg/g (95% CI 1.6–2.4) for mothers and 2.01 μg/g (95% CI 1.7–2.4) for children. Personal care products like body lotions and fragrances showed associations with MEHP, MEP, MnBP and cx-MiNP and canteen food with MBzP and bisphenol A. Exposure of mothers and their children are correlated, except for MEP. As phthalates and bisphenol A are non-persistent chemicals, a daily, intermittent exposure of the population is taking place. [ABSTRACT FROM AUTHOR]

Highlights: [•] Concentration of plastic constituents in bottled water ranged from 0.002 to 24.2μg/L. [•] DEHP was identified in 33% of waters packaged in glass bottles with crown cap. [•] Migration of plasticizers and additives in PET bottles was very low. [•] Bisphenol A was identified in 77% of waters packaged in polycarbonate jugs. [•] Storage of bottled waters for 1year did not affect the migration rate. [ABSTRACT FROM AUTHOR]

The aims of this study are to investigate the presence of 30 substances known or thought to act as endocrine disrupting compounds in tap water from the main water supply areas for region of Madrid, to determine the total estrogenic activity of the samples analysed and to estimate the health risk for the population resulting from those compounds found at detectable concentrations. To this end, a one-off composite sampling was performed in August 2012 in which six tap water samples were collected from private residences in the drinking water supply network of the region of Madrid. A total of 14 of the 30 endocrine disruptors analysed were found at concentrations ranging from 0.3 to 165 ng/L. The organophosphorus flame retardants were detected at the highest concentrations followed by the plasticizer bisphenol A, alkylphenols, anticorrosion agents and preservatives. Tap water in the region of Madrid is contaminated with traces (ng/L) of compounds with endocrine disrupting properties. Although the concentrations of endocrine disrupting compounds obtained are too low to be able to confirm a public health risk, and no risk has been detected upon evaluation, it should be remembered that these compounds act at very low doses and that their effects may only appear in the long term. [ABSTRACT FROM AUTHOR]

Highlights: [•] An in situ bioassay evaluates relationships between EDCs and snail reproduction. [•] Reproduction endpoints and embryo development of Physella acuta were studied in three Iberian basins. [•] Eggs per clutch increase but total number of eggs decrease downstream the basins. [•] Number of juveniles at the end of the experiment was lower downstream. [•] EDC concentrations were correlated with reproduction variables. [Copyright &y& Elsevier]

Abstract: The objective of this study was to determine different brominated flame retardants (BFRs) in sewage sludge produced in 17 wastewater treatment plants (WWTPs) located in the Northeast of Spain. A total of eight polybrominated diphenyl ether (PBDE) congeners, from tri- to deca-BDEs, were analyzed. The emerging BFR compounds, hexabromobenzene (HBB), pentabromoethylbenzene (PBEB) and decabromodiphenylethane (DBDPE) were also analyzed. The instrumental methodology for the analysis was based on gas chromatography coupled to mass spectrometry with negative chemical ionization (GC-NICI-MS). Moreover, liquid cromathography-quadrupole linear ion trap mass spectrometry (LC-QqLIT-MS/MS) was applied for the determination of hexabromocyclododecanes (HBCDs), tetrabromobisphenol A (TBBPA) and their related compounds, bisphenol A (BPA), monobromobisphenol A (MonoBBPA), dibromobisphenol A (DiBBPA) and tribromobisphenol A (TriBBPA). The most abundant PBDE congener in these sewage sludge samples was BDE-209, with levels ranging from nd to 2303ng/g dw. In addition, a significant concentrations of DBDPE were also detected, nd–257ng/g dw, due to their increase production as a Deca-BDE substitute. The emerging compounds HBB and PBEB were detected in 4 WWTPs and their concentrations ranged between nd–5.71 and nd–2.33ng/g, respectively. TBBPA was detected in quantifiable levels in 15 of the 17 WWTPs analyzed, in concentration range of nd–472ng/g dw, whereas HBCDs were only found in 8 WWTPs in lower concentrations, between nd and 97.5ng/g dw. Based on the analysis of sewage sludge samples from different WWTPs and in order to evaluate the impact of these contaminants in the environment, an estimation of BFRs accumulated in the total sewage sludge produced in Catalonia was carried out, with values of 57.8kg/year, 6.76kg/year, 13.5kg/year, 1.56kg/year, 0.18kg/year and 0.02kg/year for PBDEs, DBDPE, TBBPA, HBCDs, HBB and PBEB respectively. [Copyright &y& Elsevier]

During the last decade the safety of bisphenol A (BPA) monomer in polycarbonate baby bottles has drawn the attention of both the public and the scientific community. This paper presents the results of BPA migration from polycarbonate baby bottles bought in the Spanish market, into simulant B (3% acetic acid), 50% ethanol and into real food (reconstituted infant formula). Furthermore, it was also the objective of this study to assess the suitability of 50% ethanol as a simulant for infant formula. BPA was analysed by a multi-analyte liquid chromatography method with fluorescence detection and mass spectrometry confirmation. The method was in-house validated and accredited by the national accreditation body. The validation results for this analyte in the previous mentioned matrices were: LOD = 0.004–0.007 mg kg–1; LOQ (validated) = 0.03 mg kg–1; RSD% = 3.4–5.8; and recovery = 106.6–118.2%. A collection of 72 different baby bottle samples from 12 different brands were analysed. Baby bottle material was identified by FTIR. The migration test conditions used were those recommended for baby bottles in the Guidelines on testing conditions for articles in contact with foodstuffs (with a focus on kitchenware), prepared by the European network of laboratories for food-contact materials. In most of the migration assays the results were below the LOD. In four of the commercial brands there was detectable migration into the simulant 50% ethanol and BPA was detected in only two samples of infant formula (0.01 mg kg–1). Migration results obtained were in compliance with European Union regulations. [ABSTRACT FROM AUTHOR]

Abstract: Background: Phthalate and phenol exposure is prevalent among the general population and of potential concern for pregnant women and children because of their suspected susceptibility to endocrine effects. Objectives: To evaluate the extent of exposure to several phthalates and phenols in a sample of Spanish pregnant women – according to their individual characteristics (age, social class, education, and body mass index) – and children who participated in the INMA — Infancia y Medio Ambiente (Environment and Childhood) project. Methods: One spot urine sample was taken during the third trimester of pregnancy from 120 pregnant women and from 30 4-year old children belonging to 5 Spanish birth cohorts, and analyzed for 11 phthalate metabolites and 9 phenols. Results: Three metabolites of di(2-ethylhexyl) phthalate, mono-2-ethyl-5-carboxypentyl phthalate, mono-2-ethyl-5-hydroxyhexyl phthalate, and mono-2-ethyl-5-oxohexyl phthalate; two metabolites of dibutyl phthalates, mono-isobutyl phthalate and mono-n-butyl phthalate; monoethyl phthalate (MEP), the main metabolite of diethyl phthalate; and two phenols, methyl paraben (M-PB) and 2,5-dichlorophenol were detected in the urine samples of all women. The highest urinary concentrations were for MEP and M-PB. Urinary concentrations of all phthalate metabolites and of 2,4-dichlorophenol, 2,5-dichlorophenol, and bisphenol A were lower in the pregnant women than in the children. Among women, a positive relationship with social class and education was shown for most of the phthalate metabolites and phenols. Almost all phthalate metabolites varied by region even after adjusting for social class and education. Conclusions: Phthalate and phenol exposures are prevalent in a group of pregnant women and young children, two susceptible populations, and these exposures might be positively related to social class. [Copyright &y& Elsevier]

Abstract: The group of compounds commonly called endocrine disruptors covers a wide range of synthetic and natural substances able to alter the normal hormone function of wildlife and humans, consequently causing adverse health effects. Bisphenol A (BPA) and its chlorinated derivatives are some of these compounds. In this work, we propose a new liquid chromatography–tandem mass spectrometry (LC–MS/MS) method to determine these compounds in human placental tissue samples. The method involves an extraction phase of the extracts from the samples using ethyl acetate, followed by a clean-up phase by centrifugation prior to their quantification by LC–MS/MS using an atmospheric pressure chemical ionization (APCI) interface in the negative mode. Deuterated Bisphenol A (BPA-d16) was used as internal standard. Found detection limits (DL) ranged from 0.2 to 0.6ngg−1 and quantification limits (QL) from 0.5 to 2.0ngg−1 for Bisphenol A and its chlorinated derivatives, while inter- and intra-day variability was under 8.1%. The method was validated using standard addition calibration and a spike recovery assay. Recovery rates for spiked samples ranged from 97% to 105%. This method was satisfactorily applied to the determination of BPA and its chlorinated derivatives in 49 placental tissue samples collected from women who live in the province of Granada (Spain). [ABSTRACT FROM AUTHOR]

Abstract: A simple and fast capillary chromatographic method has been developed to identify and quantify organic pollutants at sub-ppb levels in real water samples. The major groups of pesticides (organic halogens, organic phosphorous, and organic nitrogen compounds), some hydrocarbons (polycyclic aromatic hydrocarbons), phthalates and some phenols such as phenol and bisphenol A (endocrine disruptors) were included in this study. The procedure was based on coupling, in-tube solid-phase microextraction (IT-SPME) by using a conventional GC capillary column (95% methyl–5% phenyl substituted backbone, 80cm×0.32mm i.d., 3μm film thickness) in the injection valve to capillary liquid chromatography with diode array detection. A comparative study between the IT-SPME manifold and a column-switching device using a C18 column (35mm×0.5mm i.d., 5μm particle size) has been performed. The IT-SPME procedure was optimal, it allows reaching limits of detection (LODs) between 0.008 and 0.2μg/L. No matrix effect was found and recoveries between 70 and 116% were obtained. The precision of the method was good, and the achieved intra- and inter-day variation coefficients were between 2 and 30%. This procedure has been applied to the screening analysis of 28 compounds in whole waters from several points of the Mediterranean coast (Valencia Community, Spain). [Copyright &y& Elsevier]

Abstract: Bisphenol-A (BPA), material for polycarbonate and epoxy resin synthesis, has been detected in canned food, among other food containers. In mammal studies, BPA transferred from mother to fetus, caused abnormality of reproductive organs, and advanced female puberty. BPA from canned food and microwave containers was analyzed using high performance liquid chromatography and gas chromatography-mass spectrometry. Population was cohort of mother–son pairs established at Granada University Hospital. Frequency of food consumption (including canned food) was studied with a semi-quantitative questionnaire. The most frequently consumed products were fish and juice cans, consumed 1–3 times/week by 34.7% and 22.3% of the study population, respectively. The women made little use of polymer microwave containers, 52.8% never using them and 45.9% using them <3 times/month. Estimated mean (standard deviation) intake of BPA was 1.1(0.839) microgram/day. No relationship was found between BPA exposure and maternal socio-demographic variables or newborn characteristics. This study offers the first estimate of BPA dietary intake by pregnant women in Southern Spain. The consumption of canned foods and drinks by these women means that their exposure was lower than EFSA estimates for the European population. Nevertheless it remains of concern, given the proven undesirable effects of low-level exposure and higher susceptibility of pregnant women. [Copyright &y& Elsevier]

Background: Bisphenol A (BPA) is one of the most common endocrine disruptor compounds in our environment, promoting a xenoestrogenic state. Numerous studies have shown a relationship between exposure to BPA and male infertility problems. Spermatic DNA integrity is a critical factor for the correct transmission of paternal genetic material to the embryo. However, only a very few studies have investigated the association between urinary BPA concentrations and human sperm DNA fragmentation (SDF)., Method: Cross-sectional study conducted with 158 healthy university students (18-23 years), recruited between 2010 and 2011 in the Region of Murcia (Spain). The subjects provided urine and semen samples on a single day. Urinary BPA concentrations were measured by dispersive liquid-liquid microextraction and ultrahigh performance liquid chromatography with tandem mass spectrometry detection, and SDF analysed using the Sperm Chromatin Dispersion test. Statistical analyses were made using linear regression adjusting for potential covariates and confounding factors., Results: No association was found between urinary BPA concentrations and SDF index in the total group. However, in the subgroup of men with SDF index> 30%, significant positive associations across quartiles (p-trend=0.02) and as a continuous BPA levels were observed (β = 0.055, 95%, CI: 0.002; 0.108)., Conclusion: Our results show that, within the subgroup of men with relatively high SDF index, the higher the concentration of BPA the greater the SDF index. Nonetheless, more studies are required to confirm these results and draw conclusions in other male populations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cardiovascular disease, particularly ischemic heart disease (IHD), is the leading cause of mortality worldwide. Bisphenol A (BPA) is considered an endocrine disruptor and obesogen, present in numerous products of daily use. The aim of this study was to assess the potential association of serum BPA concentrations and the risk of incident IHD in a sub-cohort of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC). We designed a case-cohort study within the EPIC-Spain cohort. The population consisted of 4636 participants from 4 EPIC-Spain centers (946 IHD cases and 3690 sub-cohort participants). BPA exposure was assessed by means of chemical analyses of serum samples collected at recruitment. Follow-up was performed by linking with national and regional databases and reviewing patients' clinical records. Cox Proportional Hazards Models were used for the statistical analyses. Median follow-up time was 16 years and 70% of the participants showed detectable BPA values (>0.2 ng/ml). Geometric mean (GM) values of cases and sub-cohort were 1.22 ng/ml vs 1.19 ng/ml respectively (p = 0.90). Cox regression models showed no significant association of BPA serum levels and IHD, acute myocardial infarction or angina pectoris risk. We evidenced a similar percentage of detection of BPA among cases and sub-cohort participants from our population, and no clear association with IHD risk was observed. However, further investigation is needed to understand the influence of BPA on IHD risk. • BPA concentrations were quantified in serum from 946 adults with ischemic heart disease. • There was a higher proportion of overweight and obesity in cases than in the sub-cohort. • BPA serum concentration was higher in cases than in participants of the sub-cohort. • We observed no increased risk on IHD with BPA exposure. [ABSTRACT FROM AUTHOR]

Obesogenic endocrine-disrupting chemicals, such as bisphenol A (BPA) and its analogue bisphenol S (BPS), seem to play an important role in the development of obesity, although contradictory results have been reported. The aim of the present study was to conduct a gender analysis of the factors associated with exposure to dietary bisphenols in 585 Spanish adolescents. Dietary BPA and BPS exposure was assessed using a food frequency questionnaire. Foods and macronutrients accounting for more than 95% of energy intake were selected for analysis. Stepwise regression was used to estimate the foods that most contributed to dietary bisphenol exposure in the sample. Gender-related factors associated with greater dietary bisphenol exposure were evaluated using multivariate logistic regression models. Canned tuna was the main dietary source of BPA and BPS in both adolescent boys and girls. Overweight/obese girls showed a higher risk of high dietary exposure to BPA (odds ratio (OR): 3.38, 95% confidence interval (CI): 1.25-9.07) and total bisphenols (OR: 2.81, 95% CI: 1.03-7.67) in comparison with girls with a BMI lower than 25 kg/m 2 . Present results indicate a positive association of dietary exposure to both total bisphenols and BPA with being overweight/obese in adolescent girls.

This study was aimed at reconstructing the exposure to bisphenol (BPA) of 60 pregnant women from the EXHES-Spain cohort. A biomonitoring study was conducted by determining BPA levels in urine samples over the three trimesters of pregnancy. Moreover, the correlations between BPA levels and the role of different potential exposure sources, with special emphasis on the dietary intake, were also studied. Urine samples were subjected to dispersive liquid-liquid microextraction and the subsequent analysis via gas chromatography-mass spectrometry. BPA was detected in 76% of the urine samples. A significant decrease of urinary BPA levels was observed along pregnancy, as mean concentrations of creatinine-adjusted BPA were 4.64, 4.84 and 2.51 μg/g in the first, second and third trimester, respectively. This decrease was essentially associated with changes in the dietary habits of the pregnant women, including a lower intake of canned food and drinks. However, the potential role of other pregnancy-related biochemical or physiological factors should not be disregarded. Very interestingly, significant differences in urine BPA levels were found according to the fruit consumption pattern, as women who ate more citrus fruits showed lower BPA concentrations in urine. The reconstructed exposure to BPA was estimated in 0.072, 0.069 and 0.038 μg BPA/kg of body weight/day in the first, second and third trimesters, respectively. These values are far below the temporary tolerable daily intake (t-TDI) established by the EFSA., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Developmental exposure to bisphenol A (BPA) and other phenolic endocrine disrupting chemicals (EDCs) may affect child neurodevelopment, but data on the effects of prenatal exposure to phenols on cognitive function remain sparse. Our aim was to examine the association of placental concentrations of several phenolic EDCs, including BPA, parabens (PBs), and benzophenones (BzPs), with cognitive development in preschool children from the Environment and Childhood (INMA) Project in Spain. Concentrations of BPA, four PBs (methylparaben [MePB], ethylparaben [EtPB], propylparaben [PrPB], and butylparaben [BuPB]), and six BzPs (BzP-1, BzP-2, BzP-3, BzP-6, BzP-8, and 4-hydroxybenzophenone [4-OH-BzP]) were measured in 490 placenta samples randomly selected from five INMA cohorts collected between 2000 and 2008. Neuropsychological assessment of cognitive and motor function was performed with the McCarthy Scales of Children's Abilities (MSCA) at the age of 4-5 years. Associations were assessed in a sub-sample of 191 mother-child pairs using linear and logistic regression models adjusted for confounding factors. PB compounds were detected in more than 71% of placentas, BPA in 62%, 4-OH-BzP in 50%, and the remaining BzPs in <9% of the samples. Because of the low detection frequency of BzP compounds, only 4-OH-BzP was included in the exposure-outcome analyses. After adjustment for confounders, BPA was associated with greater odds of scoring lower (below the 20th percentile) in the verbal (third vs. first exposure tertile: odds ratio [OR] = 2.78, 95% confidence interval [CI] = 1.00; 5.81, p-trend = 0.05) and gross motor (detected vs. undetected: OR = 1.75, 95%CI = 1.06; 9.29) areas, and these associations were only significant for boys. Regarding PB compounds, PrPB was associated with lower scores in memory (detected vs. undetected: β = -4.96, 95%CI = -9.54; -0.31), span memory (OR = 2.50, 95%CI = 0.95; 6.92 and 2.71, 95%CI = 0.97; 6.64, respectively for second and third tertiles, p-trend = 0.03), and motor function (β = -5.15, 95%CI = -9.26; -0.01 for third vs. first exposure tertile, p-trend = 0.04). EtPB and total PBs concentrations in the second tertile were also associated with poorer visual function of posterior cortex and worse quantitative performance, respectively, but linear trends were not statistically significant. The associations of BPA and PrPB with poorer verbal, memory, and motor skills are novel observations that warrant further attention. Larger prospective studies are required to confirm whether prenatal exposure to BPA and other phenolic EDCs is associated with impaired cognitive development. [ABSTRACT FROM AUTHOR]

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. • Almost 70% of the population had detectable serum levels of BPA, which are similar to other populations. • Geographical differences were observed in serum BPA levels across studied provinces. • Women showed in average 26% lower BPA serum concentrations than men. • Intake of sugar and confectionery was positively associated with serum BPA levels. • Intake of vegetable oils was inversely associated with serum BPA levels. [ABSTRACT FROM AUTHOR]

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. • We analyzed phenols, parabens and oxidative stress in adipose tissue. • BP-3 was associated with enhanced GPx activity and decreased GSH levels. • BPA was associated with lower GRd activity and increased GSSG. • MeP was associated with lower GRd, HO-1, SOD, and TBARS. • These pollutants might act as a tissue-specific source of free radicals. [ABSTRACT FROM AUTHOR]

One of the major challenges currently faced is to develop systematic ways of addressing chemical mixtures in environmental assessment. With this purpose, a simple, rapid, and sensitive method for the detection and quantification of a mixture of relevant contaminants in molluscs has been developed. The method is based on QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) and Ultra-High Performance Liquid Chromatography-High Resolution Mass Spectrometry (UHPLC-HRMS). It includes a mixture of 23 compounds formed by pesticides, endocrine disruptors and pharmaceuticals (metolachlor, simazine, desethylatrazine, atrazine, thiabendazole, diazinon, malathion, bentazone, MCPA, propanil, acetamiprid, imidacloprid, caffeine, bisphenol A, triclosan, triclocarban, methylparaben, ethylparaben, propylparaben, 1H-benzotriazole, sulfamethoxazole, venlafaxine and carbamazepine). The method was developed and validated in 4 different types of shellfish of high commercial interest such as mussel (Mytilus galloprovincialis), oyster (Crassostrea gigas), cockle (Cerastoderma edule) and razor shell (Solen marginatus). The mean percentage of recoveries obtained for all the compounds in each mollusc type (intra-specie) ranged from 96% to 107% showing the good performance of the method developed. The relative standard deviation was under 10% for the intra-day and 17% inter-day analyses. Method detection limits and method quantification limits were below 10 ng/g dry weight for all the species and compounds targeted. Finally, the method was applied to aquaculture samples, oysters and cockles, from Ebro Delta (Spain), after some episodes of mortality occurred in 2017. A high level of bisphenol A was detected in C. edule which may explain the mortality suffered by this organism. C. gigas presented low levels of metolachlor, bentazone, acetamiprid, and methylparaben. Image 1 • Simultaneous determination of a mixture of relevant contaminants in molluscs. • The method includes pesticides, endocrine disruptors and pharmaceuticals. • Simple, rapid and sensitive. • Developed and validated in 4 different types of shellfish of high commercial interest. • Applied to aquaculture samples from Ebro Delta, Spain. [ABSTRACT FROM AUTHOR]

A comprehensive study on packaging used in commercially available milk products from Spanish markets has been presented. Concentrations of four phthalates, seven parabens and BPA were determined in forty-two milk products. Eleven brands and five types of packaging (metallic aluminium bag, carton, high-density polyethylene, metal pail and polyethylene terephthalate) were included in the study. BPA showed the lowest concentrations (8.3 pg/g f.w.), far below those of phthalates (6431 pg/g f.w.) and parabens (6234 pg/g f.w.). Metallic aluminium bags were the least migrating packaging (considering plasticisers and monomers) followed by HDPE bottles, in the case of phthalates. Parabens showed their highest concentrations for fresh-milk samples. Levels found were far below the specific migration limits established by the EU and the cumulative hazard index was lower than 1, indicating that adverse health effects were not expected. In general, the results found in Spanish samples were lower than those reported in other countries., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Population is continuously exposed to endocrine disrupting compounds present in everyday products such as parabens, bisphenol A (BPA), and perfluoroalkyl compounds (PFCs). The aims of this study were, first, to evaluate human exposure to three parabens (methylparaben (MeP), ethylparaben (EtP) and propylparaben (PrP)), BPA and six PFCs (perfluorobutanoic acid, perfluoropentanoic acid, perfluorohexanoic acid, perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS)) through the analysis of hair samples from children, women and men and, then, to evaluate possible relationships between pollutant concentration in hair and age, gender, smoking and dyeing habits or hair colour. Hair samples were collected from 42 volunteers from Seville (Spain) (10 children, 16 women and 16 men). Six of the monitored pollutants (MeP, EtP, PrP, BPA, PFHpA and PFOS) were detected in at least 76% of the samples analysed. The highest concentrations and frequency of detection (100% of the samples) corresponded to MeP and PrP (up to 14,187 and 9009 ng/g, respectively). BPA was found in 83% of the samples at concentrations in the range from 24 to 1427 ng/g whereas PFCs were detected at concentrations in the range from 0.6 to 15.5 ng/g, being PFHpA and PFOS the ones most frequently detected (86% and 76%, respectively). Concentrations of BPA and parabens in adults were statistically higher than those in children. The results of this study reveal the suitability of hair for biomonitoring endocrine disrupting compounds of high concern (PFCs, parabens and BPA) to which population is internally or/and externally but continuously exposed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Bisphenol A (BPA) is a pervasive environmental toxicant with known reproductive effects on sperm parameters and hormone levels. Several observational studies have investigated the associations between BPA exposure and male reproductive function, but findings are inconsistent. The objective of this study was to assess the associations between urinary BPA concentrations and semen quality and reproductive hormone levels in a cross-sectional study with 215 healthy young university students (18-23 years old), investigated between 2010 and 2011 in Southern Spain (Murcia Region). All subjects provided urine, blood serum and semen samples on a single day. Urinary BPA concentrations 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, concentration, motility, morphology and total sperm count (TSC). Serum samples were analyzed for reproductive hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, inhibin B and estradiol. Relationships between urinary BPA concentrations and semen quality parameters and reproductive hormone levels were examined using linear regression, adjusting for potential confounders and covariates. Ninety-five percent of the men had detectable urinary BPA concentrations with unadjusted median (5th-95th) of 2.8 (0.16-11.5) ng/mL. After adjustment for important covariates, there was a significant positive association between urinary BPA concentrations and serum LH levels (β = 0.07, 95%CI: 0.02;0.12, p-value < 0.01). Urinary BPA concentration was also significantly and inversely associated with sperm concentration (β = - 0.04, 95%CI: - 0.07;- 0.02, p-value < 0.01) and TSC (β = - 0.05, 95%CI: - 0.08;- 0.02, p-value < 0.01). No significant associations were found between BPA and other semen parameters or reproductive hormone levels. Our results support the hypothesis that BPA exposure may be associated with a reduction in Leydig cell capacity (increased LH levels) and decreased sperm counts in young men., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The occurrence, distribution and bioaccumulation of five endocrine disrupting compounds (4-tert-octylphenol, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol and bisphenol A) in water, sediment and biota (Corbicula fluminea) collected along the Minho River estuary (NW Iberian Peninsula) were examined. Samples were collected in two campaigns (May and November, 2012) and analyzed by different extraction procedures followed by liquid chromatography tandem mass spectrometry determination. The presence of linear isomers (4-n-octylphenol and 4-n-nonylphenol) was scarcely observed whereas branched isomers (4-tert-octylphenol and nonylphenol) were measured in almost all samples. Wastewater treatment plant effluents and nautical, fishing and agricultural activities are considered the primary source of pollution of the river by alkylphenols. The presence of bisphenol A in the river could be mainly associated to punctual sources of contamination from industrial discharges. A decrease in the total concentration of phenolic compounds in water was observed from spring to autumn (from 0.888 μg L(-1) in May to 0.05 μg L(-1) in November), while similar values were shown in C. fluminea samples from the two campaigns (1388 and 1228 ng g(-1) dw in spring and autumn, respectively). In sediments, the total concentration of the target compounds varied between 13 and 4536 ng g(-1) dw (average of 1041 ng g(-1) dw). Sediment-water partition coefficient (Kd), bioaccumulation factor (BAF) and biota-sediment accumulation factor (BSAF) were estimated and highest values were obtained for nonylphenol. Calculated risk quotients showed low and moderate risk for the aquatic environment from the presence of the target compounds at all sampling points. The estimation of the daily intake of the studied compounds via water and biota ingestion indicated no risk for human health., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Abstract: Urdaibai was declared a Biosphere’s Reserve by UNESCO in 1984. Because we observed a high prevalence of hermaphroditism in mussels sampled in Urdaibai in March 2004, we started the present research work in order to determine the presence of endocrine disruptors (EDs) in sediments and to study possible EDs effects on mussels and oysters using gonad index and vitellogenin (VTG)-like protein levels as biomarkers. Samples were collected at five localities in April 2007 and 2008, and in October 2007. Estrogenic hormones were not detected in sediments and levels of bisphenol A and organotin compounds were very low. Alkylphenols were found at moderate levels and showed a time-dependent decrease. Phthalates were found at levels up to 8000ng/g. High prevalence of oocyte atresia and necrosis occurred in mussels sampled in April. Retarded gametogenesis was observed in an oyster population from a shipyard. Hermaphrodites or alterations in VTG-like protein levels were not found but the high prevalence of histopathological alterations in oocytes is of concern. [ABSTRACT FROM AUTHOR]