Cross-sectional associations of persistent organic pollutants measured in adipose tissue and metabolic syndrome in clinically diagnosed middle-aged adults.

INTRODUCTION: Although often overlooked in clinical settings, accumulation of persistent organic pollutants (POPs) in visceral adipose tissue (VAT) is thought to be a relevant risk factor for metabolic syndrome (MetS). METHODS: One hundred and seventeen patients undergoing non-oncological surgery were randomly recruited and classified as MetS + if presented 3 out of the 5 MetS components: waist circumference (WC), systolic and diastolic blood pressure (SBP and DBP, respectively), serum glucose, insulin, triglycerides (TG) and high-density lipoprotein (HDL) cholesterol levels, according International Diabetes Federation (IDF) criteria. Seventeen organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were measured in adipose tissue samples. Linear, logistic and weighted quantile sum (WQS) regression models, adjusted for age and sex, were performed. RESULTS: One third of the participants were males (36.8%) with a median age of 44 years, showing clinical evidences of MetS (35.0%). Adjusted linear regression models showed that WC correlated positively with all OCP concentrations. Higher fasting serum glucose levels were related to higher HCB and γ-HCH concentrations. The remaining OCPs and PCBs were not associated with this MetS component. HCB was inversely associated with HDL cholesterol levels, while PCB-180 was positively associated. HCB and γ-HCH concentrations were also positively correlated with DBP and SBP levels. PCB-138 was also positively associated with SBP. Adjusted logistic models revealed that exposure to HCB and γ-HCH were associated with increased odds of MetS [ORs (95%CI) 1.53 (1.22-1.92) and 1.39 (1.10-1.76) respectively; p < 0.01]. No associations were observed for the remaining POPs. WQS models showed a positive and significant mixture effect of POPs on the odds of MetS (exp [beta] = 2.34; p < 0.001), with γ-HCH (52.9%), o,p'-DDT (26.9%) and HCB (19.7%) driving the association. CONCLUSIONS: Our findings support that POPs accumulated in VAT, specifically HCB and (gamma)-HCH, are associated with both isolated components and clinically diagnosed SMT.

Expression Profiles of Genes Related to Development and Progression of Endometriosis and Their Association with Paraben and Benzophenone Exposure.

Increasing evidence has been published over recent years on the implication of endocrine-disrupting chemicals (EDCs), including parabens and benzophenones in the pathogenesis and pathophysiology of endometriosis. However, to the best of our knowledge, no study has been published on the ways in which exposure to EDCs might affect cell-signaling pathways related to endometriosis. We aimed to describe the endometriotic tissue expression profile of a panel of 23 genes related to crucial cell-signaling pathways for the development and progression of endometriosis (cell adhesion, invasion/migration, inflammation, angiogenesis, and cell proliferation/hormone stimulation) and explore its relationship with the exposure of patients to parabens (PBs) and benzophenones (BPs). This cross-sectional study included a subsample of 33 women with endometriosis from the EndEA study, measuring their endometriotic tissue expressions of 23 genes, while urinary concentrations of methyl-, ethyl-, propyl-, butyl-paraben, benzophenone-1, benzophenone-3, and 4-hydroxybenzophenone were determined in 22 women. Spearman's correlations test and linear and logistic regression analyses were performed. The expression of 52.2% of studied genes was observed in >75% of endometriotic tissue samples and the expression of 17.4% (n = 4) of them in 50-75%. Exposure to certain PB and BP congeners was positively associated with the expression of key genes for the development and proliferation of endometriosis. Genes related to the development and progression of endometriosis were expressed in most endometriotic tissue samples studied, suggesting that exposure of women to PBs and BPs may be associated with the altered expression profile of genes related to cellular pathways involved in the development of endometriosis.

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

Aim: The aim of this study was to explore associations of urinary concentrations of bisphenols A (BPA), S (BPS), and F (BPF) and of thiobarbituric acid reactive substances (TBARS) with the risk of endometriosis in women of childbearing age. Methods: This case-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 1.0-2.3] and Σbisphenols [OR 1.5; 95%CI 0.9-2.3] but was not associated with the presence of BPS and BPF. Classification of the women by tertiles of exposure revealed statistically significant associations between endometriosis risk and the second tertile of exposure to BPA [OR 3.7; 95%CI 1.3-10.3] and Σbisphenols [OR 5.4; 95%CI 1.9-15.6]. In addition, TBARS concentrations showed a close-to-significant relationship with increased endometriosis risk [OR 1.6; 95%CI 1.0-2.8], and classification by TBARS concentration tertile revealed that the association between endometriosis risk and concentrations of BPA [OR 2.0; 95%CI 1.0-4.1] and Σbisphenols [OR 2.2; 95%CI 1.0-4.6] was only statistically significant for women in the highest TBARS tertile (>4.23 µM). 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.

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

BACKGROUND: Little information is available on the content of bisphenol A (BPA) and other endocrine-disrupting chemicals (EDCs) such as parabens in infant textiles and clothes. OBJECTIVES: 1) To determine the concentrations of BPA and parabens in socks for infants and young children purchased in Spain, 2) to assess the (anti-)estrogenicity and (anti-)androgenicity of extracts from the socks, and 3) to estimate dermal exposure doses to these chemicals. METHODS: Thirty-two pairs of socks for infants and young children (1-48 months) were purchased from 3 stores in Granada (Spain). Textile material was cut from the foot, toe, and leg of each sock (n = 96 samples) for chemical analysis. Hormone-like activities were determined in foot sections (n = 32 samples) by using the E-Screen assay for (anti-)estrogenicity and PALM luciferase assay for (anti-)androgenicity. RESULTS: BPA was present in 90.6% of samples at concentrations ranging from <0.70 to 3736 ng/g. BPA levels were around 25-fold higher in socks from store 1, which had a higher cotton content compared to stores 2 and 3. Ethyl-paraben was found in 100% of samples, followed by methyl-paraben (81.0%), and propyl-paraben (43.7%). No butyl-paraben was detected in any sample. Estrogenic activity was detected in 83.3% of socks from store 1 (range = 48.2-6051 pM E2eq/g) but in only three socks from stores 2 and 3. Anti-androgenic activity was detected in six of the 32 socks studied (range = 94.4-2989 µM Proceq/g), all from store 1. Estimated dermal exposure to BPA was higher from socks for children aged 36-48 months (median = 17.6 pg/kg/day), and dermal exposure to parabens was higher from socks for children aged 24-36 months (median = 0.60 pg/kg/day). DISCUSSION: This is the first report in Europe on the wide presence of BPA and parabens in socks marketed for infants and children. BPA appears to contribute to the hormone-like activity observed in sock extracts.

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

BACKGROUND: Newborns in neonatal intensive care units (NICUs) are in contact with a variety of medical products whose production might include synthetic 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 products 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), and butylparaben (BuP)] and using the E-Screen and PALM-luciferase assays to measure the in 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 leaching methodologies. RESULTS: BPA was found in three-fifths and PBs in four-fifths of tested NICU items, and ∼25% and ∼10% of extracts evidenced estrogenic and anti-androgenic activity, respectively. The highest BPA content was found in the three-way stopcock (>7.000 ng/g), followed by patterned transparent film dressing, gastro-duodenal feeding tubes, sterile gloves, single-lumen umbilical catheters, and intravenous (IV) infusion extension sets (concentrations ranged from 100 to 700 ng/g BPA). A total PB concentration (∑PBs) >100 ng/g was observed in several items, including light therapy protection glasses, patterned transparent film dressing, winged IV catheters, IV infusion extension sets, and textile tape. The highest estrogenic activity [>450 pM estradiol equivalent (E2eq)] was found in small dummy nipples, three-way stopcocks, and patterned transparent film dressing and the highest anti-androgenic activity [>5 mM procymidone equivalent units per gram (Proceq/g)] in small dummy nipples and three-way stopcocks. DISCUSSION: According to these findings, neonates might be exposed to multiple sources of BPA and PBs in NICUs via inhalation, dermal, oral, and IV/parenteral routes. There is a need to address the future health implications for these extremely vulnerable patients and to adopt precautionary preventive measures as a matter of urgency. https://doi.org/10.1289/EHP5564.

Urinary concentrations of parabens and reproductive parameters in young men.

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.

Urinary concentrations of benzophenone-type ultra violet light filters and reproductive parameters in young men.

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 (ß = 0.08, 95%CI: 0.009; 0.15 and ß = 0.04, 95%CI: 0.0002; 0.08, respectively). Urinary BP-1 concentration was also significantly positively associated with T/E2 (ß = 0.04, 95%CI: 0.002; 0.07) and negatively with inhibin b/FSH (ß = -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.