Occurrence of multiple bisphenol S analogues in children from Shantou, China.

Emerging bisphenol S analogues (BPSs) have gained their application perspectives to replace bisphenol A (BPA) and BPA analogues (BPAs). However, the extent of human exposure and potential health risk from BPSs is rarely known yet. We hypothesized that children living in Shantou, China, a well-known e-waste recycling city, may expose to emerging BPSs together with BPA and BPAs. In this study, BPA, six commonly used BPAs and 11 emerging BPSs were determined simultaneously in 240 urine samples collected from children residing in Shantou. BPA, BPS, bisphenol F, bisphenol AF and three BPSs of 2,4'-bis(hydroxyphenyl)sulfone, 4-((4-(allyloxy)phenyl)sulfonyl)phenol and diphenylsulfone (DPS) were the urinary predominant bisphenols with detection frequencies of 67-100% in the children. BPA was found at the highest median concentration (3.36 µg/g creatinine) followed by BPS (0.313) and DPS (0.187). It is interesting to find that the girls and children in the younger group (2 ≤ age < 5) had consistently higher concentrations of the seven dominant bisphenols than the boys and these of the older group (5 ≤ age ≤ 10), respectively. The children with under/overweight suffered higher burdens of bisphenol exposure based on medians of estimated daily intakes. Association analysis results indicated that the Shantou children exposed themselves to multiple BPSs along with BPA and BPAs from assumed consumer products and/or contaminated environments.

Occurrence of emerging bisphenol S analogues in urine from five occupational populations in South China.

Bisphenol S (BPS) and its 11 emerging analogues were investigated in 325 urine samples from five occupational populations in South China. Besides BPS, ten emerging BPS analogues were newly identified and detected in the urine. It should be noted that urinary concentrations of dominant BPS analogues of 2,4'-bis(hydroxyphenyl)sulfone (2,4-BPS), bis(3-allyl-4-hydroxyphenyl)sulfone (TGSA) and diphenylsulfone (DPS) were 1.1-2.3 times higher than that of BPS, with overall detection frequencies at 74-91 %. The median sum concentrations of the target 12 bisphenols (ng/mL) were found highest in urine from cashiers (1.12), followed by water plant staffs (0.994), teachers (0.552), doctors (0.408) and power plant staffs (0.333). The composition profile of the urinary dominant bisphenols was occupational-dependent, with 2,4-BPS accounting for 45-73 % in cashiers and power plant staffs, and with DPS and TGSA for 74-82 % among doctors, teachers and water plant staffs. Significant correlations were found among the most frequently detected bisphenols in cashiers, indicating their common application and emission pathways. The median exposures based on estimated daily intakes (EDIs, ng/kg bw/day) for the 12 bisphenols in cashiers and water plant staffs (31.6-35.6) were 1.8-3.4 times higher than those of teachers, doctors and power plant staffs (10.6-17.5). This is the first study to identify multiple emerging BPS analogues in urine from occupational populations, especially cashiers and water plant staffs.

Prenatal urinary concentrations of phenols and risk of preterm birth: exploring windows of vulnerability.

OBJECTIVE: To explore windows of vulnerability to prenatal urinary phenol concentrations and preterm birth. DESIGN: Prospective cohort. SETTING: A large fertility center in Boston, Massachusetts. PATIENT(S): A total of 386 mothers who sought fertility treatment and gave birth to a singleton between 2005 and 2018. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Singleton live birth with gestational age <37 completed weeks. RESULT(S): Compared with women with non-preterm births, urinary bisphenol A (BPA) concentrations were higher across gestation among women with preterm births, particularly during mid-to-late pregnancy and among those with female infants. Second trimester BPA concentrations were associated with preterm birth (Risk Ratio [RR] 1.24; 95%CI: 0.92, 1.69), which was primarily driven by female (RR 1.40; 95%CI: 1.04, 1.89) and not male (RR 0.85; 95%CI 0.50, 1.46) infants. First trimester paraben concentrations were also associated with preterm birth (RR 1.17; 95%CI: 0.94, 1.46) and similarly the association was only observed for female (RR 1.46; 95% CI: 1.10, 1.94) and not male infants (RR 0.94; 95%CIC: 0.72, 1.23). First trimester urinary bisphenol S concentrations showed a suggested risk of preterm birth (RR 1.25; 95%CI: 0.82, 1.89), although the small case numbers precluded sex-specific examination. CONCLUSION(S): We found preliminary evidence of associations between mid-to-late pregnancy BPA and early pregnancy paraben concentrations with preterm birth among those with female infants only. Preterm birth risk may be compound, sex, and window specific. Given the limited sample size of this cohort, results should be confirmed in larger studies, including fertile populations.

Maternal bisphenol urine concentrations, fetal growth and adverse birth outcomes: A population-based prospective cohort.

BACKGROUND: Exposure to bisphenols may affect fetal growth and development. The trimester-specific effects of bisphenols on repeated measures of fetal growth remain unknown. Our objective was to assess the associations of maternal bisphenol urine concentrations with fetal growth measures and birth outcomes and identify potential critical exposure periods. METHODS: In a population-based prospective cohort study among 1379 pregnant women, we measured maternal bisphenol A, S and F urine concentrations in the first, second and third trimester. Fetal head circumference, length and weight were measured in the second and third trimester by ultrasound and at birth. RESULTS: An interquartile range increase in maternal pregnancy-averaged bisphenol S concentrations was associated with larger fetal head circumference (difference 0.18 (95% confidence interval (CI) 0.01 to 0.34) standard deviation scores (SDS), p-value< 0.05) across pregnancy. When focusing on specific critical exposure periods, any detection of first trimester bisphenol S was associated with larger second and third trimester fetal head circumference (difference 0.15 (95% CI 0.05 to 0.26) and 0.12 (95% CI 0.02 to 0.23) SDS, respectively) and fetal weight (difference 0.12 (95% CI 0.02 to 0.22) and 0.16 (95% CI 0.06 to 0.26) SDS, respectively). The other bisphenols were not consistently associated with fetal growth outcomes. Any detection of bisphenol S and bisphenol F in first trimester was also associated with a lower risk of being born small size for gestational age (Odds Ratio 0.56 (95% CI 0.38 to 0.74) and 0.55 (95% CI 0.36 to 0.85), respectively). Bisphenols were not associated with risk of preterm birth. CONCLUSIONS: Higher maternal bisphenol S urine concentrations, especially in the first trimester, seem to be related with larger fetal head circumference, higher weight and a lower risk of being small size for gestational age at birth.

Associations Between Thyroid Hormone Levels and Urinary Concentrations of Bisphenol A, F, and S in 6-Year-old Children in Korea.

OBJECTIVES: Bisphenol A (BPA) is used in the electrical, mechanical, medical, and food industries. Previous studies have suggested that BPA is an endocrine disruptor. Regulation of BPA has led to increased use of bisphenol F (BPF) and bisphenol S (BPS). However, few studies have investigated the associations of BPF and BPS with thyroid dysfunction in children. Our study investigated the associations of prenatal BPA and early childhood BPA, BPF, and BPS exposure with thyroid function in 6-year-old children. METHODS: Prenatal BPA concentrations were measured during the second trimester of pregnancy in an established prospective birth cohort. We measured urinary BPA, BPF, and BPS concentrations and thyroid hormone levels (thyroid-stimulating hormone, total T3, and free T4) in 6-year-old children (n=574). We examined the associations between urinary bisphenol concentrations and percentage change of thyroid hormone concentrations using multivariate linear regression. We also compared thyroid hormone levels by dividing the cohort according to BPA, BPF, and BPS concentrations. RESULTS: The associations between prenatal BPA and total T3 levels were statistically significant in all models, except for girls when using a crude model. The associations between urinary BPA and BPS concentrations and levels of all thyroid hormones were not statistically significant. However, we observed that lower free T4 levels (-1.94%; 95% confidence interval, -3.82 to -0.03) were associated with higher urinary BPF concentrations in girls only. CONCLUSIONS: Our findings identified significant associations between prenatal BPA exposure and total T3 levels in all children and between BPF exposure and free T4 levels in girls only.

Exposure to bisphenols and asthma morbidity among low-income urban children with asthma.

BACKGROUND: Bisphenol A (BPA) has been linked with pediatric asthma development and allergic airway inflammation in animal models. Whether exposure to BPA or its structural analogs bisphenol S (BPS) and bisphenol F (BPF) is associated with asthma morbidity remains unknown. OBJECTIVE: We examined associations between bisphenols and morbidity due to pediatric asthma. METHODS: We quantified concentrations of BPA, BPS, and BPF in 660 urine samples from 148 predominantly low-income, African American children (aged 5-17 years) with established asthma. We used biobanked biospecimens and data on symptoms, health care utilization, and pulmonary function and inflammation that were collected every 3 months over the course of a year. We used generalized estimating equations to examine associations between concentrations or detection of urinary bisphenols and morbidity outcomes and assessed heterogeneity of associations by sex. RESULTS: We observed consistent positive associations between BPA exposure and measures of asthma morbidity. For example, we observed increased odds of general symptom days (adjusted odds ratio [aOR] = 1.40 [95% C = 1.02-1.92]), maximal symptom days (aOR = 1.36 [95% CI = 1.00-1.83]), and emergency department visits (aOR = 2.12 [95% CI =1.28-3.51]) per 10-fold increase in BPA concentration. We also observed evidence of sexually dimorphic effects; BPA concentrations were associated with increased odds of symptom days and health care utilization only among boys. Findings regarding BPS and BPF did not consistently point to associations with asthma symptoms or health care utilization. CONCLUSION: We found evidence to suggest that BPA exposure in a predominantly low-income, minority pediatric cohort is associated with asthma morbidity and that associations may differ by sex. Our findings support additional studies, given the high pediatric asthma burden and widespread exposure to BPA in the United States.

Quantification of bisphenols in Korean urine using online solid-phase extraction-high-performance liquid chromatography-tandem mass spectrometry.

Bisphenol A (BPA), an endocrine-disrupting chemical, has been used as a basic raw material for the production of polycarbonate plastics. As concern over the toxic effects of BPA grows, it is gradually being replaced in many consumer products with compounds such as bisphenol F (BPF) and bisphenol S (BPS). In this study, online solid-phase extraction-high-performance liquid chromatography-tandem mass spectrometry was used to analyze the urinary concentrations of BPA, BPF, and BPS in 2487 Korean urine samples collected between 2017 and 2018. The detection rates and geometric mean (GM) concentrations were as follows: BPA (82.1 %; 0.65 µg/L), BPF (11.1 %; not calculated), and BPS (63.6 %; 0.20 µg/L), respectively. The mean daily intake based on urinary BPA concentrations was 0.013 µg/kg bw/day (95th percentile, 0.089 µg/kg bw/day), which is lower than the tolerable daily intake. This is the first study observing urinary BPA, BPF, and BPS concentrations based on a nationally representative Korean population and could contribute to the evaluation of bisphenol analogue exposure levels in risk assessments.

Association between dietary contribution of ultra-processed foods and urinary concentrations of phthalates and bisphenol in a nationally representative sample of the US population aged 6 years and older.

Ultra-processed food consumption has been associated with several health outcomes such as obesity, hypertension, cardiovascular disease and cancer. The deleterious nutrient profile of these products, and the presence of food additives, neoformed contaminants and contact materials such as phthalates and bisphenol may be some of the potential pathways through which ultra-processed food influences disease outcomes. The aim of this study was to examine the association between dietary contribution of ultra-processed foods and urinary biomarker concentrations of parent compounds or their metabolites including Di(2-ethylhexyl) phthalate (ΣDEHP), Di-isononyl phthalate (ΣDiNP), Monocarboxynonyl phthalate (mCNP), Mono (3-carboxypropyl) phthalate (mCPP), Monobenzyl phthalate (mBzP), Bisphenol A (BPA), Bisphenol F (BPF) and Bisphenol S (BPS), in the US. Participants from the cross-sectional 2009-2016 National Health and Nutrition Examination Survey, aged 6+ years, with urinary measures and with one 24-hour dietary recall were included in the study. Ultra-processed foods were identified based on the NOVA classification system, a four-group food classification based on the extent and purpose of industrial food processing. Linear regression was used to compare average urinary creatinine-standardized concentrations across quintiles of energy contribution of ultra-processed foods. Models incorporated survey sample weights and were adjusted for different sociodemographic and life-style variables. Adjusted geometric means of ΣDiNP, mCNP, mCPP, mBzP and BPF increased monotonically from the lowest to the highest quintile of ultra-processed food consumption. As both phthalates/bisphenol and ultra-processed foods have been previously associated with insulin resistance, diabetes, general/abdominal obesity and hypertension, our results suggest the possibility of contact materials in ultra-processed foods as one link between ultra-processed food and these health outcomes. Future studies could confirm findings and further explore these mechanisms of action.

Metabolomic perturbation precedes glycolytic dysfunction and procreates hyperglycemia in a rat model due to bisphenol S exposure.

Previous studies highlighted bisphenol S (BPS), an industrial chemical responsible for harmful effects comparable to its congener substance bisphenol A (BPA). Accounted for various adversities to biological functions, it could alter the expression of endogenous metabolites in many metabolic processes. The study was aimed to investigate the altered metabolites in hyperglycemic condition triggered by sub-chronic exposure of BPS in serum and urine samples of Wistar rats. Invaded effects of hyperglycemia due to BPS exposure on Wistar rats were investigated by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Metabolomic profiling of serum and urinary metabolites was done by gas chromatography-mass spectrometry (GC-MS) analysis. The metabolomics data were represented by one way ANOVA, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) along with the mapping of perturbed metabolic pathways. The OGTT and ITT showed increased levels of glucose in treated animals with median and high doses, indicating the manifestation of hyperglycemia. The metabolomic profiling of serum and urine revealed BPS could cause consequential metabolomic perturbation mainly of amino acids, sugars, and organic acids. Furthermore, the extrapolation of Kyoto Encyclopedia of Genes and Genomes (KEGG) based systematic analysis helped to monitor the altered pathways, including amino acids, glycolysis, pyruvate metabolism, etc., which were provoked due to BPS exposure. The overview of the perturbed metabolite profiling in rats promisingly showed early diagnostic markers of hyperglycemic condition triggered due to the BPS exposure. Findings from this study will be helpful towards the exploration of mechanistic insights of several disturbed pathways.

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.

Association of urinary levels of bisphenols F and S used as bisphenol A substitutes with asthma and hay fever outcomes.

BACKGROUND: Bisphenols F (BPF) and S (BPS) are bisphenol A (BPA) analogs used as substitutes in consumer products. Despite previous reports of BPA's association with asthma, no studies have examined its structural analogs in relation to asthma and allergy outcomes. OBJECTIVE: To examine the association of urinary BPF, BPS, and BPA with asthma and hay fever in a US representative sample. METHODS: We analyzed data from 3,538 participants aged 12 years or older in the 2013-2016 National Health and Nutrition Examination Survey (NHANES). Children aged 6-11 years (N = 738), who did not have all covariate data available, were analyzed separately. Covariate-adjusted logistic regression was used to assess the association of the exposures with the outcomes. RESULTS: BPF, BPS, and BPA were detected in 57.1%, 88.4%, and 94.8% of the urine samples, respectively. Urinary BPF detection was positively associated with current asthma (odds ratio [OR]: 1.54, 95% confidence interval [CI]: 1.16-2.04) and hay fever (OR: 1.66, 95% CI: 1.12-2.46). Urinary BPS was associated with increased odds of current asthma in men (OR: 1.64, 95% CI: 1.13-2.40) and urinary BPA was associated with increased odds of asthma without hay fever in children aged 6-11 years (OR: 2.65, 95% CI: 1.05-6.68). CONCLUSION: Our nationally-representative findings document that BPF and BPS exposure is common in the US and that exposure to these BPA analogs is associated with asthma and/or hay fever. Our results suggest that BPF and BPS may not be safe alternatives to BPA; however, prospective studies should be conducted to confirm these results.

Changes in urinary excretion of phthalates, phthalate substitutes, bisphenols and other polychlorinated and phenolic substances in young Danish men; 2009-2017.

During the past two decades human exposure to bisphenol A (BPA) and phthalates such as di-iso-butyl phthalate (DiBP), di-n-butyl phthalate (DnBP), butylbenzyl phthalate (BBzP) and di-(2-ethyl-hexyl) phthalate (DEHP) has received substantial interest due to widespread population exposures and potential endocrine disrupting effects. Therefore, these chemicals have gradually been restricted and phased out through legislation. However, humans are still exposed to a wide range of other less studied phthalates, phthalate substitutes and BPA analogues as well as other polychlorinated and phenolic substances. In this study, we investigated human exposure to these chemicals over the past decade. Three hundred urine samples collected in 2009, 2013 and 2017 (100 samples each year) from young Danish men of the general population, participating in a large on-going cross-sectional study, were selected for the present time trend study. The urinary concentration of metabolites of 15 phthalates, di-2-ethylhexyl terephthalate (DEHTP) and di-iso-nonyl-cyclohexane-1,2-dicarboxylate (DINCH), seven bisphenols including BPA, bisphenol S (BPS) and bisphenol F (BPF), as well as triclosan, triclocarban, benzophenone-3, three chlorophenols and two phenylphenols were analyzed by two new sensitive LC-MS/MS methods developed and validated for the present study. A significant decrease in urinary concentrations over time was observed for the majority of the chemicals. Median concentrations of BPA and the metabolites of DiBP, DnBP, BBzP and DEHP were more than halved from 2009 to 2017. Similar decreases were observed for triclosan and the chloro- and phenylphenols. In contrast, metabolites of the two phthalate substitutes DEHTP and DINCH increased more than 20 and 2 times, respectively. The potential BPA substitutes; BPS and BPF also increased, but only slightly. Despite these new exposure patterns, the exposure to the old well-known chemicals, such as DiBP, DnBP, BBzP, DEHP and BPA was still higher in 2017 compared to the exposure level of the new substitutes such as DEHTP, DINCH, BPS and BPF. A significant decrease in internal exposure to most of the common phthalates and BPA over the past decade was observed, reflecting market changes and regulatory measures implemented in EU. Despite increasing exposures to some of the known phthalate substitutes and BPA analogues, the total amount of each measured chemical group (original and substitute analytes combined) was lower in the more recently collected samples. This indicates only partial direct substitution or substitution by chemicals not covered in this approach, or a general decline in the exposure to these chemical/product groups over the last decade.

Evidence of sulfur mustard exposure in victims of chemical terrorism by detection of urinary ß-lyase metabolites.

Background: Sulfur mustard (SM) is a vesicant chemical warfare agent. Ocular, dermal, and respiratory systems are the primary targets of SM exposure. The aims of this study were to perform a quantitative analysis of ß-lyase metabolites of SM as 1,1'-sulfonylbis[2-(methylthio) ethane] (SBMTE) in urine samples of chemical casualties and to investigate the relationship between the measured SBMTE levels and the severity of characteristic symptoms of SM poisoning.Methods: A bioanalytical method which is based on titanium (III) chloride reduction of ß-lyase metabolites was employed to analyze urine samples of individuals (n = 13, collected 30 h after SM exposure) using gas chromatography-tandem mass spectrometry.Results: Various levels of SBMTE were measured in urine samples of seven individuals, confirming SM exposure for each. There was a correlation observed between measured levels of SBMTE in human urine samples and severity of clinical findings including ocular, respiratory, and cutaneous lesions of SM.Discussion: In combination with clinical examination, measurement of SBMTE levels in human urine could be used as a prognostic factor for clinical outcomes in victims of SM exposure. This bioanalytical verification is also important for the documentation of alleged use of SM.Conclusion: SBMTE is an unambiguous biomarker of potential SM poisoning as it does not exist in urine samples of an unexposed population. Quantitation of urinary SBMTE concentrations in victims of SM could be used in order to enable improved interpretation of clinical findings.

The EuroMix human biomonitoring study: Source-to-dose modeling of cumulative and aggregate exposure for the bisphenols BPA, BPS, and BPF and comparison with measured urinary levels.

BACKGROUND: Bisphenol A (BPA) and, with increasing occurrence, its analogs bisphenol S (BPS) and bisphenol F (BPF) are applied in many consumer products, leading to humans being exposed from a vast number of sources and via several routes. Estrogenic and anti-androgenic effects are exerted by the chemical BPA, and also by its analogs. Therefore, realistic exposure assessments are needed for assessing risks related to cumulative exposure. OBJECTIVES: Biomonitoring for BPA, BPS, and BPF was conducted in a human study embedded in the EU project EuroMix and the measured urinary concentrations were compared to source-to-dose calculations for source allocation and plausibility test of the model. METHODS: For two 24-hour study periods separated by 2-3 weeks, 144 adult volunteers in Norway kept detailed diaries on food consumption, personal care product (PCP) use, and thermal paper (TP) handling. Concurrently, 24 h urine was collected and urinary levels of BPA, BPS, and BPF were analyzed using ultra-high performance liquid chromatography and tandem mass spectrometry (UPLC-MS-MS). In line with the information obtained from the first study day, bisphenol exposure from food, PCPs, TP, and dust was modeled primarily individual-based with probabilistic models. Estimates for BP excretion over 24 h were obtained with the models and compared to measured amounts. RESULTS: Modeled aggregate internal exposures covered the full range of measured urinary amounts for all BP analogs. In general, individual-based medians of modeled BPA exposures were in good agreement with the measurements, but individual-specific correlation was lacking. Modeled exposures mostly underestimated BPS and BPF levels in participants with positive measurements (53% and 8%), except for the P95 values of modeled BPS exposure that were higher than measured amounts if TP was handled. Most likely, diet and TP were the sources contributing the most to BP exposure in this study. Urinary measurements did not reveal a significant correlation between the amounts of canned food consumed, the number of PCPs used, or the number of TP handling events and levels of BPA, BPS, or BPF. CONCLUSIONS: The good agreement between the ranges of modeled BPA exposure and measured BPA amounts indicates that available concentrations, especially from the main exposure source food, mirror the exposure situation realistically, and suggests that the exposure model considers the relevant exposure sources. The lack of individual-specific correlations means that the individual measured amounts and modeled exposures did not vary in parallel, e.g. due to mismatch of BP concentrations in food, TP, and other sources, or delayed internal exposure. The underestimation of modeled BPS and BPF exposure suggests that not all relevant sources were included in the respective exposure models. This could be due to a lack of input data, e.g. for food items, or due to an increased replacement of BPA with structural analogs compared to the used concentration and occurrence data.

Association of urinary bisphenols and triclosan with thyroid function during early pregnancy.

BACKGROUND: Bisphenols and triclosan are considered as potential thyroid disruptors. While mild alterations in maternal thyroid function can result in adverse pregnancy and child developmental outcomes, there is still uncertainty whether bisphenols or triclosan can interfere with thyroid function during pregnancy. OBJECTIVES: We aimed to investigate the association of urinary bisphenol A (BPA), bisphenol S (BPS), bisphenol F (BPF) and triclosan with early pregnancy thyroid function. METHODS: This study was embedded in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study (SELMA), a population-based prospective pregnancy cohort. In total, 1996 participants were included in the current study. Maternal urinary concentrations of three bisphenols and triclosan, collected at median (95% range) 10 (6-14) weeks of pregnancy as well as serum concentrations of thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), and total triiodothyronine (TT3) were measured. RESULTS: Higher BPA levels were associated with lower TT4 concentrations (non-monotonic, P = 0.03), a lower FT4/FT3 ratio (ß [SE] -0.02 [0.01], P = 0.03) and a lower TT4/TT3 ratio (ß [SE] -0.73 [0.27], P = 0.008). Higher BPF levels were associated with a higher FT3 (ß [SE] 0.01 [0.007], P = 0.04). There were no associations between other bisphenols or triclosan and absolute TSH, (F)T4 or (F)T3 concentrations. The association of BPA with thyroid function differed with gestational age. The negative association of BPA with FT4/FT3 and TT4/TT3 ratios was only apparent in early but not late gestation (P for interaction: 0.003, 0.008, respectively). CONCLUSION: These human data during pregnancy substantiate experimental findings suggesting that BPA could potentially affect thyroid function and deiodinase activities in early gestation.

Urinary bisphenol S concentrations: Potential predictors of and associations with semen quality parameters among men attending a fertility center.

BACKGROUND: Bisphenol S (BPS) was introduced in the market as a potentially safer alternative to bisphenol A (BPA). However, there are limited studies on health effects of BPS and no epidemiologic studies on its relationship with male reproductive health outcomes, specifically semen quality. OBJECTIVE: To investigate predictors of urinary BPS concentrations and its association with semen parameters among men attending a fertility center. METHODS: This cross-sectional analysis included 158 men of couples seeking fertility treatment (2011-2017) contributing 338 paired semen and urine samples. At the time of sample collection, men completed a questionnaire on self-reported use of household products and food intake within the previous 24 h. Urinary concentrations of BPA, BPS and bisphenol F were quantified using isotope-dilution tandem mass spectrometry. Semen samples were analyzed following WHO guidelines. Multivariable mixed models were used to investigate predictors of urinary BPS concentrations and to evaluate associations between urinary BPS concentrations and semen parameters, using random intercept to account for correlation in outcomes across multiple observations per man and adjusting for abstinence time, specific gravity, age, body mass index (BMI), year of sample collection and BPA concentrations. Analyses were also stratified by BMI (≥25 vs <25 kg/m2). RESULTS: Median (IQR) urinary BPS concentration was 0.30 (0.20, 0.90) µg/L, and 76% of samples had detectable (>0.1 µg/L) concentrations. Self-reported fabric softener and paint/solvent use as well as intake of beef and cheese within 24 h before urine collection were positively associated with BPS concentrations. Men with higher BPS concentrations also had significantly higher BMI. Lower semen parameters were found among men with detectable BPS concentrations, compared to men with non-detectable BPS [2.66 vs. 2.91 mL for volume (p = 0.03), 30.7 vs. 38.3 mil/mL for concentration (p = 0.03), 76.8 vs. 90.0 mil for total count (p = 0.09), 43.7 vs. 47.0% for motility (p = 0.06), and 5.42 vs. 6.77% for morphologically normal sperm (p = 0.24)]. Some associations of BPS with lower semen parameters were only found among men with a BMI ≥ 25 kg/m2. CONCLUSIONS: We identified dietary and lifestyle factors associated with BPS exposure, suggesting potential avenues for reducing exposures. We also observed negative associations between BPS and semen parameters, especially among overweight and obese men.

Bisphenol A and bisphenol S exposures during pregnancy and gestational age - A longitudinal study in China.

Bisphenol A (BPA) and its substitute bisphenol S (BPS) are endocrine-disrupting chemicals and metabolized rapidly in human body. BPA exposure in late pregnancy has been suggested to be associated with preterm birth (PTB), but the associations of trimester BPA and BPS exposures with gestational age have been rarely studied. We aimed to examine maternal urinary BPA and BPS levels longitudinally measured across pregnancy in relation to gestational age and PTB. A prenatal cohort study was conducted between 2014 and 2015 in Wuhan, China. Maternal urinary BPA and BPS concentrations were measured in a complete series of urine samples collected in the 1st, 2nd and 3rd trimesters from 850 pregnant women and corrected by specific gravity. In comparison with the lowest tertile of maternal urinary BPA, higher levels of averaged BPA concentration across pregnancy was associated with a 1.97-day decrease in gestation (95% CI: 3.25, -0.68) and an adjusted odds ratio of 3.19 (95% CI: 1.00, 10.45) for PTB. Higher BPA concentrations in three trimesters were also negatively associated with gestational age and positively correlated with PTB. In contrast, only a positive association of third-trimester BPS with gestational age was found, but the significant association disappeared in the adjusted models. Both maternal trimester and averaged BPA exposure across pregnancy were significantly associated with shortened gestation and increased risk of PTB. However, the results showed little evidence of a relationship between BPS and PTB.

Analysis of four parabens and bisphenols A, F, S in urine, using dilute and shoot and liquid chromatography coupled to mass spectrometry.

A new strategy for the analysis of 4 parabens (methylparaben, ethyl paraben, propyl paraben and butyl paraben) and 3 bisphenols (A, F and S) in human urine has been developed. Dilute and shoot and liquid chromatography coupled to mass spectrometry (LC-MS/MS) determination was employed. Procedural matched calibration, certified materials and spiked samples were used for validation. The obtained recoveries varied between 85 and 104% with a precision lower than 20% for all analytes. The LOQ was 0.20 ng mL for all analytes. Negative atmospheric pressure chemical ionization in the selected reaction monitoring mode was used for MS detection. The proposed method was successfully applied for the determination of these compounds in 15 human urine samples from lactating women from the Valencian region (Spain). Methyl paraben (MP) and Bisphenol A (BPA) presented high detection frequency (93% for MP and 80% for BPA), BPS and BPF presented a detection frequency of 33 and 26% respectively. Methyl paraben was detected in a concentration range of 0.2-2952 ng mL-1, 0.2-12 ng mL-1 for bisphenol A, 0.5-39 ng mL-1 for BPF and 0.5-8.5 ng mL-1 for BPS.

Comparison of Bisphenol A and Bisphenol S Percutaneous Absorption and Biotransformation.

BACKGROUND: Bisphenol S (BPS) has been widely substituted for bisphenol A (BPA) on thermal papers, but little is known about its skin absorption. OBJECTIVES: We compared the percutaneous absorption and biotransformation of BPS and BPA in vitro and in a controlled human trial. METHODS: Absorption and biotransformation of BPS and BPA were monitored across reconstructed human epidermis at two environmentally relevant doses over 25 h. In the human trial, five male participants handled thermal receipts containing BPS and washed their hands after 2 h. Urine (0-48 h) and serum (0-7.5h) were analyzed for target bisphenols, and one participant repeated the experiment with extended monitoring. BPS data were compared with published data for isotope-labeled BPA ([Formula: see text]) in the same participants. RESULTS: At doses of 1.5 and [Formula: see text] applied to reconstructed human epidermis, the permeability coefficient of BPS (0.009 and [Formula: see text], respectively) was significantly lower than for BPA (0.036 and [Formula: see text], respectively), and metabolism of both bisphenols was negligible. In participants handling thermal receipts, the quantities of BPS and [Formula: see text] on hands was significantly correlated with maximum urinary event flux ([Formula: see text]), but the slope was lower for BPS than BPA ([Formula: see text] and 1.1, respectively). As a proportion of total urinary bisphenol, free BPS [[Formula: see text]: [Formula: see text]] was higher than for free BPA ([Formula: see text]). Postexposure maximum urinary BPS concentrations (0.93 to [Formula: see text]; [Formula: see text]) were in the 93-98th percentile range of BPS in background Canadians ([Formula: see text]; [Formula: see text]). CONCLUSION: Both the in vitro and human studies suggested lower percutaneous absorption of BPS compared with BPA, but a lower biotransformation efficiency of BPS should also be considered in its evaluation as a BPA substitute. https://doi.org/10.1289/EHP5044.

Urinary levels, composition profile and cumulative risk of bisphenols in preschool-aged children from Nanjing suburb, China.

Due to the extensive use in consumer products, the bisphenols (BPs) pollution in the environments has aggravated and people are frequently exposed to BPs. In this research, four BPs, i.e., bisphenol A (BPA), bisphenol F (BPF), bisphenol S (BPS) and bisphenol AF (BPAF), were determined in urine samples collected from Gaochun District preschool-age children and the concentrations, distribution profiles, potential sources and cumulative risk assessment of the target compounds were studied. Total concentrations of 4 BPs ranged from 2 to 3113.1 ng/L, with the average concentration of 648.6 ng/L. BPA was the predominant congener (accounting for 94%), followed by BPS. Correlation analysis indicated a negative relationship between BPA and BPAF (R = -0.273, p < 0.05). The estimated daily intakes suggested that young females were more sensitive to BPs. Moreover, the cumulative risk for hazard quotient (HQ) of BPA has been evaluated and the results showed that no high risk had occurred. It provided basic information on the occurrence and human exposure to urinary BPs of preschool aged children from Gaochun District.