Exposure to bisphenol A in European women from 2007 to 2014 using human biomonitoring data - The European Joint Programme HBM4EU.

BACKGROUND: Bisphenol A (BPA; or 4,4'-isopropylidenediphenol) is an endocrine disrupting chemical. It was widely used in a variety of plastic-based manufactured products for several years. The European Food Safety Authority (EFSA) recently reduced the Tolerable Daily Intake (TDI) for BPA by 20,000 times due to concerns about immune-toxicity. OBJECTIVE: We used human biomonitoring (HBM) data to investigate the general level of BPA exposure from 2007 to 2014 of European women aged 18-73 years (n = 4,226) and its determinants. METHODS: Fifteen studies from 12 countries (Austria, Belgium, Denmark, France, Germany, Greece, Israel, Luxembourg, Slovenia, Spain, Sweden, and the United Kingdom) were included in the BPA Study protocol developed within the European Joint Programme HBM4EU. Seventy variables related to the BPA exposure were collected through a rigorous post-harmonization process. Linear mixed regression models were used to investigate the determinants of total urine BPA in the combined population. RESULTS: Total BPA was quantified in 85-100 % of women in 14 out of 15 contributing studies. Only the Austrian PBAT study (Western Europe), which had a limit of quantification 2.5 to 25-fold higher than the other studies (LOQ=2.5 µg/L), found total BPA in less than 5 % of the urine samples analyzed. The geometric mean (GM) of total urine BPA ranged from 0.77 to 2.47 µg/L among the contributing studies. The lowest GM of total BPA was observed in France (Western Europe) from the ELFE subset (GM=0.77 µg/L (0.98 µg/g creatinine), n = 1741), and the highest levels were found in Belgium (Western Europe) and Greece (Southern Europe), from DEMOCOPHES (GM=2.47 µg/L (2.26 µg/g creatinine), n = 129) and HELIX-RHEA (GM=2.47 µg/L (2.44 µg/g creatinine), n = 194) subsets, respectively. One hundred percent of women in 14 out of 15 data collections in this study exceeded the health-based human biomonitoring guidance value for the general population (HBM-GVGenPop) of 0.0115 µg total BPA/L urine derived from the updated EFSA's BPA TDI. Variables related to the measurement of total urine BPA and those related to the main socio-demographic characteristics (age, height, weight, education, smoking status) were collected in almost all studies, while several variables related to BPA exposure factors were not gathered in most of the original studies (consumption of beverages contained in plastic bottles, consumption of canned food or beverages, consumption of food in contact with plastic packaging, use of plastic film or plastic containers for food, having a plastic floor covering in the house, use of thermal paper…). No clear determinants of total urine BPA concentrations among European women were found. A broader range of data planned for collection in the original questionnaires of the contributing studies would have resulted in a more thorough investigation of the determinants of BPA exposure in European women. CONCLUSION: This study highlights the urgent need for action to further reduce exposure to BPA to protect the population, as is already the case in the European Union. The study also underscores the importance of pre-harmonizing HBM design and data for producing comparable data and interpretable results at a European-wide level, and to increase HBM uptake by regulatory agencies.

Urinary and Fecal Excretion of 121 Environmental Chemicals in Pet Dogs and Cats: Significance of Feces in Biomonitoring of Exposures.

Laboratory animal studies have reported the biliary excretion of chemicals following exposure. Nevertheless, feces are rarely used as a matrix in biomonitoring of chemical exposures. In this study, feces and urine from pet dogs and cats were analyzed for the presence of 45 plasticizers, 45 environmental phenols, and 31 pesticides. Thirty-two analytes were detected in ≥70% pet feces, while up to 29 analytes were frequently (≥70%) found in urine. The sum concentrations of all analytes (∑All) in pet feces were significantly higher than those measured in urine (median: 393-666 ng/g wet weight in feces vs 216-464 ng/mL in urine). Plasticizers were the dominant class of chemicals, accounting for 81-97% and 69-77% of ∑All in urine and feces, respectively. Analyte concentrations measured in paired urine and feces exhibited weak correlations. The excretion rates of the chemicals via urine and feces were calculated through a reverse dosimetry approach. Low-molecular-weight phthalates excreted predominantly in urine, whereas high-molecular-weight phthalates and several organophosphate triesters were excreted predominantly in feces. The fecal excretion rates of parabens, benzophenones, bisphenols, naphthalene, 2,4-dichloronicotinic acid, and 4-nitrophenol were similar to or higher than those of urinary excretion. Our results suggest that feces are an important matrix in biomonitoring of exposure to environmental chemicals.

Development of a robust non-targeted analysis approach for fast identification of endocrine disruptors and their metabolites in human urine for exposure assessment.

Endocrine disrupting chemicals are of concern because of possible human health effects, thus they are frequently included in biomonitoring studies. Current analytical methods are focused on known chemicals and are incapable of identifying or quantifying other unknown chemicals and their metabolites. Non-targeted analysis (NTA) methods are advantageous since they allow for broad chemical screening, which provides a more comprehensive characterization of human chemical exposure, and can allow elucidation of metabolic pathways for unknown chemicals. There are still many challenges associated with NTA, which can impact the results obtained. The chemical space, i.e., the group of known and possible compounds within the scope of the method, must clearly be defined based on the sample preparation, as this is critical in identifying chemicals with confidence. Data acquisition modes and mobile phase additives used with liquid chromatography coupled to high-resolution mass-spectrometry can affect the chemicals ionized and structural identification based on the spectral quality. In this study, a sample preparation method was developed using a novel clean-up approach with CarbonS cartridges, for endocrine-disrupting chemicals in urine, including new bisphenol A analogues and benzophenone-based UV filters, like methyl bis (4-hydroxyphenyl acetate). The study showed that data dependent acquisition (DDA) had a lower identification rate (40%) at low spiking levels, i.e., 1 ng/mL, compared to data independent acquisition (DIA) (57%), when Compound Discoverer was used. In DDA, more compounds were identified using Compound Discoverer, with an identification rate of 95% when ammonium acetate was compared to acetic acid (82%) as a mobile phase additive. TraceFinder software had an identification rate of 53% at 1 ng/mL spiking level using the DDA data, compared to 40% using the DIA data. Using the developed method, 2,4 bisphenol F was identified for the first time in urine samples. The results show how NTA can provide human exposure information for risk assessment and regulatory action but standardized reporting of procedures is needed to ensure study results are reproducible and accurate. His Majesty the King in Right of Canada, as represented by the Minister of Health, 2024.

Association of prenatal exposure to phthalates and synthetic phenols with pubertal development in three European cohorts.

BACKGROUND: There is limited epidemiological evidence on the association of prenatal exposure to phthalates and synthetic phenols with altered pubertal timing. OBJECTIVE: To examine the association of prenatal exposure to phthalates, bisphenol A (BPA), parabens, benzophenone 3 (BP-3), and triclosan (TCS) with pubertal development in girls and boys from three European cohorts. METHODS: Urinary metabolites of six different phthalate diesters (DEP, DiBP, DnBP, BBzP, DEHP, and DiNP), BPA, methyl- (MePB), ethyl- (EtPB), propyl- (PrPB), and butyl-paraben (BuPB), BP-3, and TCS were quantified in one or two (1st and 3rd trimester) urine samples collected during pregnancy (1999-2008) from mothers in three birth cohorts: INMA (Spain), EDEN (France), and MoBa (Norway). Pubertal development of their children was assessed at a single visit at age 7-12 years (579 girls, 644 boys) using the parent-reported Pubertal Development Scale (PDS). Mixed-effect Poisson and g-computation and Bayesian Kernel Machine Regression (BKMR) were employed to examine associations of individual and combined prenatal chemical exposure, respectively, with the probability of overall pubertal onset, adrenarche, and gonadarche (stage 2+) in girls and boys. Effect modification by child body mass index (BMI) was also assessed. RESULTS: Maternal concentrations of the molar sum of DEHP and of DiNP metabolites were associated with a slightly higher probability of having started puberty in boys (relative risk, RR [95% CI] = 1.13 [0.98-1.30] and 1.20 [1.06-1.34], respectively, for a two-fold increase in concentrations), with a stronger association for DiNP in boys with overweight or obesity. In contrast, BPA, BuPB, EtPB, and PrPB were associated with a lower probability of pubertal onset, adrenarche, and/or gonadarche in all boys (e.g. overall puberty, BPA: RR [95% CI] = 0.93 [0.85-1.01] and BuPB: 0.95 [0.90-1.00], respectively), and the association with BPA was stronger in boys with underweight/normal weight. In girls, MEHP and BPA were associated with delayed gonadarche in those with underweight/normal weight (RR [95% CI] = 0.86 [0.77-0.95] and 0.90 [0.84-0.97], respectively). Most of these associations were trimester specific. However, the chemical mixture was not associated with any pubertal outcome in boys or girls. CONCLUSIONS: Prenatal exposure to certain phthalates and synthetic phenols such as BPA may impact the pubertal development of boys, and weight status may modify this effect. BPA may also alter the pubertal development of girls.

Prenatal exposure to environmental phenols and fetal growth across pregnancy in the LIFECODES fetal growth study.

INTRODUCTION: Environmental phenols are endocrine disrupting chemicals hypothesized to affect early life development. Previous research examining the effects of phenols on fetal growth has focused primarily on associations with measures of size at delivery. Few have included ultrasound measures to examine growth across pregnancy. OBJECTIVE: Investigate associations between prenatal exposure to phenols and ultrasound and delivery measures of fetal growth. METHODS: Using the LIFECODES Fetal Growth Study (n = 900), a case-cohort including 248 small-for-gestational-age, 240 large-for-gestational age, and 412 appropriate-for-gestational-age births, we estimated prenatal exposure to 12 phenols using three urine samples collected during pregnancy (median 10, 24, and 35 weeks gestation). We abstracted ultrasound and delivery measures of fetal growth from medical records. We estimated associations between pregnancy-average phenol biomarker concentrations and repeated ultrasound measures of fetal growth using linear mixed effects models and associations with birthweight using linear regression models. We also used logistic regression models to estimate associations with having a small- or large-for-gestational birth. RESULTS: We observed positive associations between 2,4-dichlorophenol, benzophenone-3, and triclosan (TCS) and multiple ultrasound measures of fetal growth. For example, TCS was associated with a 0.09 (95 % CI: 0.01, 0.18) higher estimated fetal weight z-score longitudinally across pregnancy. This effect size corresponds to a 21 g increase in estimated fetal weight at 30 weeks gestation. Associations with delivery measures of growth were attenuated, but TCS remained positively associated with birthweight z-scores (mean difference: 0.13, 95 % CI: 0.02, 0.25). Conversely, methylparaben was associated with higher odds of a small-for-gestational age birth (odds ratio: 1.45, 95 % CI: 1.06, 1.98). DISCUSSION: We observed associations between some biomarkers of phenol exposure and ultrasound measures of fetal growth, though associations at the time of delivery were attenuated. These findings are consistent with hypotheses that phenols have the potential to affect growth during the prenatal period.

Associations between urinary level of bisphenol A, phthalates, 8-iso-prostaglandin-F2α, and emotional and behavioral problems among Chinese adolescents.

BACKGROUND: Emotional and behavioral problems (EBPs) of adolescents is a worldwide public health problem. Bisphenol A (BPA) and phthalate (PAEs) are prevalent and potentially toxic to human health. Therefore, this study aimed to investigate the associations between urinary level of BPA, PAEs, 8-iso-prostaglandin-F2α (8-iso-PGF2α), and EBPs. METHODS: A total of 865 Chinese adolescents were included in this study and EBPs was assessed using the Strengths and Difficulties Questionnaire (SDQ). Urinary concentrations of BPA and seven PAEs metabolites in adolescents were determined by high performance liquid chromatography-tandem mass spectrometry. Urinary 8-iso-PGF2α concentration was detected by enzyme-linked immunosorbent assay (ELISA). Spearman rank correlation analysis, multivariate logistic regression analysis, restricted cubic spline functions were used to explore the relationship between the levels of BPA, PAEs, 8-iso-PGF2α and EBPs. RESULTS: BPA and PAEs metabolites were positively associated with EBPs in Chinese adolescents. And the 8-iso-PGF2α was significantly non-linearly correlated with emotional symptoms, conduct problems, peer problems and total difficulties. Furthermore, 8-iso-PGF2α may partially mediate the association between BPA and PAEs exposure and EBPs. LIMITATIONS: This study was a cross-sectional study, the cause-effect relationship between BPA, PAEs exposure and EBPs could not be determined. A single spot urine sample for BPA and PAEs exposure characterization maybe could not represent their long-term exposure level. CONCLUSIONS: High exposure of BPA and PAEs are associated with EBPs, which may be partly mediated by oxidative stress among adolescents. The results of this study could provide certain ideas for subsequent related research.

Evaluation of Exposure to Bisphenol Analogs through Canned and Ready-to-Eat Meal Consumption and Their Possible Effects on Blood Pressure and Heart Rate.

Bisphenols are endocrine-disrupting chemicals used in plastics and resins for food packaging. This study aimed to evaluate the exposure to bisphenol A (BPA), bisphenol S (BPS), and bisphenol F (BPF) associated with the consumption of fresh, canned, and ready-to-eat meals and determine the effects of bisphenols on blood pressure and heart rate. Forty-eight healthy young adults were recruited for this study, and they were divided into the following three groups: fresh, canned, and ready-to-eat meal groups. Urine samples were collected 2, 4, and 6 h after meal consumption, and blood pressure and heart rate were measured. The consumption of ready-to-eat meals significantly increased urine BPA concentrations compared with canned and fresh meal consumption. No significant difference in BPS and BPF concentrations was observed between the groups. The consumption of ready-to-eat meals was associated with a significant increase in systolic blood pressure and pulse pressure and a marked decrease in diastolic blood pressure and heart rate. No significant differences were noted in blood pressure and heart rate with canned and fresh meal consumption. It can be concluded that total BPA concentration in consumed ready-to-eat meals is high. High BPA intake causes increase in urinary BPA concentrations, which may, in turn, lead to changes in some cardiovascular parameters.

Association of urinary bisphenol A with hyperlipidemia and all-cause mortality: NHANES 2003-2016.

BACKGROUND: The connection between urinary bisphenol A (BPA) and hyperlipidemia is still unclear, and few studies have evaluated whether urinary BPA affects mortality among individuals with hyperlipidemia. Therefore, we aimed to investigate the link between urinary BPA and hyperlipidemia and assess the impact of urinary BPA on mortality risk in subjects with hyperlipidemia. METHODS: We analyzed data of the National Health and Nutrition Examination Survey from 2003 to 2016. Multivariable logistic analysis was performed to examine the relationship between urinary BPA and hyperlipidemia. Cox regression analysis was carried out to investigate the relationship between urinary BPA and all-cause mortality in subjects with hyperlipidemia. RESULTS: This study included 8,983 participants, of whom 6,317 (70.3%) were diagnosed with hyperlipidemia. The results showed that urinary BPA was higher in participants with hyperlipidemia group than those without hyperlipidemia (3.87 ± 0.32 vs. 2.98 ± 0.14, P = 0.01). Urinary BPA levels were analyzed in tertiles. Compared with tertile 1 of BPA (reference), the odds ratio (95% confidence interval) of hyperlipidemia related to tertile 3 of BPA was 1.28 (1.11-1.48). The hazard ratio for all-cause death associated with the highest versus lowest tertile of urinary BPA was 1.20 (95% confidence interval: 1.01-1.44; P = 0.04) among participants with hyperlipidemia. CONCLUSIONS: The study indicated a positive relationship between urinary BPA and the risk of hyperlipidemia. Urinary BPA was associated with a significantly higher risk of all-cause mortality in adults with hyperlipidemia.

High Levels of BPA and BPF Exposure during Pregnancy Are Associated with Lower Birth Weight in Shenyang in Northeast China.

Animal studies indicate that bisphenol A (BPA) has obesogenic effects. Recent experiments reported similar endocrine-disrupting effects of bisphenol F (BPF) and bisphenol S (BPS), which are substitutes of BPA. The aim of this study was to investigate the exposure levels of these bisphenols in pregnant women and their effects on the physical development of infants aged 0-12 months. This study recruited pregnant women who gave birth at a hospital between February 2019 and September 2020. Urine samples from these pregnant women in the third trimester of pregnancy were detected by using ultrahigh-performance liquid chromatography-triple quadruple mass spectrometry. Follow-ups at 6 and 12 months of age were conducted by telephone by pediatricians using a structured questionnaire. Multiple linear regressions were used to determine the associations between bisphenol concentrations and infant weight. A total of 113 mother-child pairs had complete questionnaires and urine samples as well as data on newborns aged 6 months and 12 months. The detection rates of urinary BPA, BPF, and BPS in pregnant women were 100, 62.83, and 46.02%, respectively. Their median levels are 5.84, 0.54, and 0.07 µg/L, respectively. Increased urinary BPA and BPF concentrations during pregnancy were significantly associated with lower birth weight (standardized regression coefficients [ß] = -0.081 kg, 95% confidence interval [CI]: -0.134 to -0.027; ß = -0.049 kg, 95% CI: -0.097 to -0.001). In addition, urinary BPA and BPF concentrations during pregnancy were positively associated with weight growth rate from 0 to 6 months (ß = 0.035 kg/mouth, 95% CI: 0.00-0.064; ß = 0.028 kg/mouth, 95% CI: 0.006-0.050), especially in female infants (ß = 0.054 kg/mouth, 95% CI: 0.015-0.093; ß = 0.035 kg/mouth, 95% CI: 0.005-0.065). Therefore, maternal BPA and BPF levels during pregnancy were negatively correlated with birth weight and positively correlated with the growth rate of infant weight at 0-6 months of age, especially in female infants.

Association of exposure to a mixture of phenols, parabens, and phthalates with altered serum thyroid hormone levels and the roles of iodine status and thyroid autoantibody status: A study among American adults.

BACKGROUND: Toxicological and epidemiological studies have shown that environmental endocrine disruptors interfere with hormonal homeostasis. However, there is limited research on the effects of mixed exposure to nonpersistent endocrine disruptors on thyroid hormones and the factors (e.g., presence status of thyroid autoantibodies or nutritional status of organismal iodine) that may influence this association. METHODS: Data were collected from the National Health and Nutrition Examination Survey (NHANES) 2007-2008 and 2011-2012. Relationships between single pollutants and thyroid hormone and thyroid autoantibody levels were assessed using generalized linear (GLM) and restricted cubic spline (RCS) regression models. Weighted quantile sum regression (WQS), group-weighted quantile sum regression (GWQS), quantile-based g-computation (qgcomp), and adaptive elasticity network (AENET) were applied to assess the mixed exposure effect. Next, subgroup analyses were performed on the basis of the urinary iodine concentration or thyroid autoantibody status to assess the modifying role of urinary iodine and thyroid autoantibodies. RESULTS: A total of 2385 study participants were included in this study. Both the single-pollutant model and the multipollutant mixed model revealed that parabens and bis(2-ethylhexyl) phthalate (DEHP) metabolites were significantly and negatively associated with serum thyroxine (T4) levels. However, no associations were found between the target pollutants and thyroid autoantibodies (thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb)). In addition, this study revealed that urinary iodine or thyroid autoantibody status altered the associations of some of the target pollutants with thyroid hormones. WQS and qgcomp analyses, revealed that the associations of mixed pollutants with hormones differed depending on the urinary iodine or antibody status, especially T4 and thyroid-stimulating hormone (TSH). CONCLUSION: Significant associations were found between phenols, parabens, and phthalates and serum thyroid hormone levels, with parabens and DEHP metabolites playing major roles. Urinary iodine and thyroid autoantibody status act as modifiers between environmental endocrine-disrupting pollutants and thyroid hormones.

Exposure to endocrine disrupting chemicals including phthalates, phenols, and parabens in infancy: Associations with neurodevelopmental outcomes in the MARBLES study.

BACKGROUND: Endocrine disrupting chemicals (EDCs) are widely used compounds with the potential to affect child neurodevelopmental outcomes including autism spectrum disorders (ASD). We aimed to examine the urinary concentrations of biomarkers of EDCs, including phthalates, phenols, and parabens, and investigate whether exposure during early infancy was associated with increased risk of later ASD or other non-typical development (Non-TD) or adverse cognitive development. METHODS: This analysis included infants from the Markers of Autism Risks in Babies-Learning Early Signs (MARBLES) study, a high-risk ASD cohort (n = 148; corresponding to 188 urine samples). Thirty-two EDC biomarkers were quantified in urine among infants 3 and/or 6 months of age. Trends in EDC biomarker concentrations were calculated using least square geometric means. At 36 months of age, children were clinically classified as having ASD (n = 36), nontypical development (Non-TD; n = 18), or typical development (TD; n = 81) through a clinical evaluation. Trinomial logistic regression analysis was used to test the associations between biomarkers with ASD, or Non-TD, as compared to children with TD. In single analyte analysis, generalized estimating equations were used to investigate the association between each EDC biomarkers and longitudinal changes in cognitive development using the Mullen Scales of Early Learning (MSEL) over the four assessment time points (6, 12, 24, and 36 months of age). Additionally, quantile g-computation was used to test for a mixture effect. RESULTS: EDC biomarker concentrations generally decreased over the study period, except for mono-2-ethyl-5-carboxypentyl terephthalate. Overall, EDC biomarkers at 3 and/or 6 months of age were not associated with an increased risk of ASD or Non-TD, and a few showed significant inverse associations. However, when assessing longitudinal changes in MSEL scores over the four assessment time points, elevated monoethyl phthalate (MEP) was significantly associated with reduced scores in the composite score (ß = -0.16, 95% CI: 0.31, -0.02) and subscales of fine motor skills (ß = -0.09, 95%CI: 0.17, 0.00), and visual reception (ß = -0.11, 95% CI: 0.23, 0.01). Additionally, the sum of metabolites of di (2-ethylhexyl) terephthalate (Æ©DEHTP) was associated with poorer visual reception (ß = -0.09, 95% CI: 0.16, -0.02), and decreased composite scores (ß = -0.11, 95% CI: 0.21, -0.01). Mixtures analyses using quantile g-computation analysis did not show a significant association between mixtures of EDC biomarkers and MSEL subscales or composite scores. CONCLUSION: These findings highlight the potential importance of infant exposures on cognitive development. Future research can help further investigate whether early infant exposures are associated with longer-term deficits and place special attention on EDCs with increasing temporal trends and whether they may adversely affect neurodevelopment.

Determination of the urinary concentrations of six bisphenols in public servants by online solid-phase extraction-liquid chromatography tandem mass spectrometry.

Bisphenols are widely used as monomers and additives in plastic production. Thus, bisphenol A (BPA) and its most prominent substitutes have been detected in many environmental and human samples. This study proposes an online solid-phase extraction analytical methodology coupled to liquid chromatography with tandem mass spectrometry for the determination of six bisphenols (BPA and bisphenols F (BPF), S (BPS), AF (BPAF), B (BPB), and E (BPE)) in urine samples as an efficient and automated methodology. The method was developed and validated for all bisphenols with good recoveries (92-112%) and repeatability (RSD ≤ 10%) despite the variable matrix effects, except BPAF (which would require a dedicated internal standard), achieving method quantification limits in the 0.05-2.2 ng mL-1 range. The methodology was subsequently applied to 435 urine samples from a non-occupational exposure population (civil servants for the regional government) from Santiago de Compostela (Galicia, Spain). Only BPA, BPF, and BPS were positively detected; the last two presented higher detection frequencies than BPA. When the urinary concentrations are extrapolated to human intake and compared to the European Food Safety Agency (EFSA) tolerable daily intake (TDI) of 2 × 10-4 µg kg-1 day-1 (TDI), all BPA positively identified samples would surpass this threshold. Although no TDI exists currently for the other two identified bisphenols, it is evident that human exposure to bisphenols should be limited. Finally, the results stratification by gender revealed higher levels of exposure to BPF in the women group.

Recent use of consumer and personal care products and exposures to select endocrine disrupting chemicals among urban children with asthma.

BACKGROUND: Emerging studies suggest that endocrine disrupting chemicals (EDCs) in personal care and other consumer products are linked with various adverse health effects, including respiratory and reproductive effects. Despite Black persons using more personal care products than other demographic groups and having a high asthma burden, little is known regarding their consumer product use patterns and associated EDC exposures. OBJECTIVE: To examine the association between recent exposure to select EDCs with specific consumer products and behaviors in a cohort of 110 predominantly Black children with asthma, ages 8-17 years, living in Baltimore City, Maryland. METHODS: We quantified concentrations of bisphenol A (BPA), bisphenol S (BPS), bisphenol F, two dichlorophenols, four parabens, triclosan, benzophenone-3, and triclocarban in spot urine samples. Questionnaires were used to capture recent (last 24-h) consumer product use and behaviors. Associations between EDCs and consumer product uses/behaviors were assessed using multivariable linear regression, adjusting for age, gender, race/ethnicity, and caregiver income level. Effect estimates were expressed as geometric mean ratios of biomarker concentrations of product-users vs non-users. RESULTS: Increased concentrations to select EDCs were associated with recent use of air freshener (ratios; BPA: 1.9, 95%CI 1.4-2; BPS 1.7, 95%CI 1-2.97; propyl paraben: 3.0, 95%CI 1.6-5.6), scented candles (methyl paraben: 2.6, 95%CI 1.1-6.1), and scented carpet powder (2,5-dichlorophenol: 2.8, 95%CI 1.2-6.3). Additionally, consuming canned food was associated with some increased biomarker concentrations (ratios: BPA: 1.7, 95%CI 1.2-2.4; BPS: 2.1, 95% CI: 1.2-3.6). SIGNIFICANCE: These findings add to the body of evidence suggesting that recent use of select consumer products in Black children contributes to exposure of chemicals of concern and could potentially inform exposure mitigation interventions. Findings have broad potential health implications for pediatric populations and Black children who may face exposure and health disparities. IMPACT: Little is known about how children's personal care product use and consumer behaviors affect their exposures to endocrine disrupting chemicals (EDCs). This is particularly true for Black children who often experience a disparate exposure burden to many EDCs. This is a significant knowledge gap among children that are uniquely vulnerable to EDCs as they undergo critical windows of growth and development. Our findings show associations between consumer products and EDC exposures in predominantly Black children in low-income settings. Identifying EDC exposure determinants has broad health implications as many of these chemicals have been associated with adverse health risks.

Environmental and occupational exposure to bisphenol compounds in Finland.

The aim of the study was to assess non-occupational and occupational exposure to bisphenol compounds in Finland. The participants were 151 non-occupationally exposed volunteers and 15 potentially exposed employees of a sewage-pipe relining company and a floor-coating company. The following chemicals were measured in the urine samples: bisphenol A (BPA), bisphenol F (BPF), bisphenol A diglycidyl ether (BADGE), bisphenol F diglycidyl ether (BFDGE), and the metabolites of the latter two [bisphenol A (2,3-dihydroxypropyl) glycidyl ether (BADGE·H2O), bisphenol A bis(2,3-dihydroxypropyl) ether (BADGE·2 H2O), bisphenol A (3-chloro-2-hydroxypropyl) (2,3-dihydroxypropyl) ether (BADGE·HCl·H2O), bisphenol A (3-chloro-2-hydroxypropyl) glycidyl ether (BADGE·HCl), and bisphenol A bis(3-chloro-2-hydroxypropyl) ether (BADGE·2HCl) and bisphenol F bis(2,3-dihydroxypropyl) ether (BFDGE·2 H2O), and bisphenol F bis(3-chloro-2-hydroxypropyl) ether (BFDGE·2HCl)]. BADGE and BFDGE were also measured in breathing zone air samples and hand-wipe samples of the sewage-pipe relining and floor-coating workers. Non-occupational exposure to BPA has decreased in Finland. The BPF level of the non-occupationally exposed was higher than the respective levels reported in the recent literature. BPA and BPF concentrations in the workers' urine samples were in the same range as those in the corresponding concentrations of the non-occupationally exposed population. Higher concentrations of BADGE and BFDGE metabolites were found in some of the workers' urine samples. Elevated urine concentrations were also observed in the samples collected the next morning. Some of the urinary BADGE and BFDGE metabolite results correlated with the hand-wipe results. The results show that occupational exposure to BADGE and BFDGE may occur in sewage-pipe relining and floor-coating work. They also indicate that dermal contamination plays a role in total exposure. Although the measured urinary levels indicate that the absorption of these bisphenol compounds are unlikely to pose a systemic health risk, the risk of dermal sensitization remains.

Determination of nine bisphenol analogues in human urine by high-throughput solid-phase extraction and ultra-high performance liquid chromatography-tandem mass spectrometry analysis.

Bisphenol analogues (BPs) are a class of typical environmental endocrine-disrupting chemicals (EDCs). This study aimed to establish a highly sensitive and high-throughput method utilizing 96-well solid-phase extraction (96-well SPE) in conjunction with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) employing multiple reaction monitoring (MRM), information-dependent acquisition (IDA), and enhanced product ion (EPI) scan modes for the identification and quantitative analysis of nine BPs in human urine. Urine samples were initially thawed to room temperature, followed by digestion using ß-glucuronidase in an ammonium acetate buffer solution at 37 °C overnight. Subsequently, they were purified using 96-well SPE and finally analyzed by UHPLC-MS/MS. The limits of detection (LOD) for the nine BPs ranged from 0.05 µg∙kg-1 to 0.3 µg kg-1. Average recoveries fell within the range of 92.8 % to 111.7 %. Moreover, both the intra-day and inter-day precisions were satisfactory, with relative standard deviations (RSDs) ranging from 2.2 % to 6.7 % and 3.5 % to 6.3 %, respectively. The targets in the samples exhibited a perfect match, with a purity fit value exceeding 70 % from the self-built library. The analytical method developed in this study demonstrates high accuracy and sensitivity. In addition, the MRM-IDA-EPI mode can effectively identifies the target BPs and prevents false positive detection of analytes in the urine.

Maternal pre-pregnancy BMI influences the associations between bisphenol and phthalate exposures and maternal weight changes and fat accumulation.

BACKGROUND: Bisphenols and phthalates are two classes of endocrine-disrupting chemicals (EDCs) thought to influence weight and adiposity. Limited research has investigated their influence on maternal weight changes, and no prior work has examined maternal fat mass. We examined the associations between exposure to these chemicals during pregnancy and multiple maternal weight and fat mass outcomes. METHODS: This study included a sample of 318 women enrolled in a Canadian prospective pregnancy cohort. Second trimester urinary concentrations of 2 bisphenols and 12 phthalate metabolites were quantified. Self-reported and measured maternal weights and measured skinfold thicknesses were used to calculate gestational weight gain, 3-months and 3- to 5-years postpartum weight retention, late pregnancy fat mass gain, total postpartum fat mass loss, and late postpartum fat mass retention. Adjusted robust regressions examined associations between chemicals and outcomes in the entire study population and sub-groups stratified by pre-pregnancy body mass index (BMI). Bayesian kernel machine regression examined chemical mixture effects. RESULTS: Among women with underweight or normal pre-pregnancy BMIs, MBzP was negatively associated with weight retention at 3- to 5-years postpartum (B = -0.04, 95%CI: -0.07, -0.01). Among women with overweight or obese pre-pregnancy BMIs, MEHP and MMP were positively associated with weight retention at 3-months and 3- to 5-years postpartum, respectively (B's = 0.12 to 0.63, 95%CIs: 0.02, 1.07). DEHP metabolites and MCNP were positively associated with late pregnancy fat mass gain and late postpartum fat mass retention (B's = 0.04 to 0.18, 95%CIs: 0.001, 0.32). Further, the mixture of EDCs was positively associated with late pregnancy fat mass gain. CONCLUSION: In this cohort, pre-pregnancy BMI was a key determinant of the associations between second trimester exposure to bisphenols and phthalates and maternal weight changes and fat accumulation. Investigations of underlying physiological mechanisms, windows of susceptibility, and impacts on maternal and infant health are needed.

The relationship between bisphenol A and phthalates with precocious puberty in Vietnamese children.

OBJECTIVES: This study is aimed to explore the correlation between bisphenol A (BPA) and phthalates, including diethylhexylphthalate (DEHP) and dibutylphthalate (DBP), and precocious puberty (PP). METHODS: A case-control study was conducted in Ho Chi Minh City, Vietnam, from November 2021 to April 2022, involving 250 children, with 124 of them diagnosed with PP and 126 serving as controls. We assessed the levels of urinary BPA, DEHP, and DBP in all participants and examined their association with the risk of PP. RESULTS: BPA was detected in 11.3 % of PP cases but was not found in any individuals in the control group (p<0.001). Diethylhexylphthalate metabolite (MEHP) was not detected in any of the samples. Positive urinary results for dibutylphthalate metabolite (MBP) were observed in 8.1 % of PP cases and 2.4 % in the control group, with an odds ratio of 3.6 (95 % confidence interval: 0.97-13.4, p=0.03). CONCLUSIONS: The PP group exhibited a higher prevalence of positive urinary BPA and DBP levels compared to the control group.

Prenatal and childhood exposure to bisphenols and bone mineral density in 7-year-old children from the Odense Child Cohort.

BACKGROUND: Bisphenol A (BPA) is a well-known endocrine disrupter used in several consumer products. Restricted use of BPA has led to increased use of bisphenol F (BPF) and bisphenol S (BPS). While previous studies found no associations between prenatal BPA and BPF exposure and bone mineral density (BMD), two recent cohort studies found that prenatal BPS exposure was negatively associated with bone mineral density in the offspring. AIM: To determine possible associations between maternal and child urinary bisphenol concentrations, BMD and bone mineral content (BMC) in 7-year-old healthy children. METHODS: Pregnant women were recruited in 2010-2012 to participate in the Odense Child Cohort (OCC), Denmark. Maternal urine samples were collected in gestational week 28 and urinary BPA concentration was measured by isotope diluted LC-MS/MS. The children delivered a urine sample at age 7 years in which BPA, BPF and BPS were measured by an extended LS-MS/MS method based on the original method. At age 7 years DXA scans were performed and BMC and Z-score for BMD calculated. Associations between osmolality adjusted urinary maternal BPA and child BPA, BPF and BPS concentrations and BMC and BMD Z-score were examined by multiple linear regression analysis adjusted for potential confounders. Additionally, a combined effect of the bisphenols were evaluated by including the sum of child urinary BPA, BPF and BPS concentrations in the statistical analyses. RESULTS: A total of 546 mothers and 453 children aged 7 years participated. BPA was detected in 84% and 96% of the maternal and child urine samples, respectively. We found no significant association between maternal urinary BPA concentration during pregnancy and BMC and BMD Z-score in 7-year-old children. In addition, no association between current bisphenol exposure in tertiles and bone density was found, interestingly, current BPA and summed bisphenol exposure in the highest 10% was associated with lower BMD Z-score at age 7-years, statistically significant for boys. CONCLUSION: In these low exposed children we found no association between prenatal or current bisphenol exposure in tertiles and BMD in healthy children, however, the highest 10% exposed children had lower BMD, significant for boys, suggesting a negative impact with high bisphenol exposure. The short half-lives of bisphenols and the cross-sectional nature of the child exposure prompt more longitudinal studies to further clarify this topic.

[Determination of six bisphenols in human urine by ultra-high performance liquid chromatography-tandem mass spectrometry].

OBJECTIVE: To develop and validate a solid phase extraction-ultra-high performance liquid chromatography-tandem mass spectrometry method for the determination of six bisphenols(bisphenol S, bisphenol F, bisphenol A, 2, 2'-methylenediphenol, bisphenol AF, bisphenol AP) in urine. METHODS: After enzymolysis of urine sample, the target substances were quickly purified and extracted by WAX solid phase extraction column. On ACQUITY BEH C_(18) column(2.1 mm×100 mm, 1.7 µm), the mobile phase of water and methanol was used to separate. Finally, multi-reaction detection was carried out under electrospray negative ion scanning, and quantification was carried out by internal standard method. RESULTS: The correlation coefficients(r) of the target compounds were all more than 0.998 in the range of 0.1-50.0 ng/mL, the linearity was good, and the detection limits were all lower than 0.1 ng/mL. The recoveries of the three standard concentrations(0.5, 5.0 and 50.0 ng/mL) were all between 80% and 120%, and the relative standard deviation was less than 20%(n=5). The standard reference material was detected and the concentration was within the reference range. CONCLUSION: This method can be used to detect six bisphenols in urine quickly and accurately, is suitable for the trace analysis of bisphenol compounds in human urine.

Exposure characteristics and cumulative risk assessment of bisphenol A and its substitutes: the Taiwan environmental survey for toxicants 2013.

Introduction: Ever since the use of bisphenol A (BPA) has been restricted, concerns have been raised regarding the use of its substitutes, such as bisphenol S (BPS) and bisphenol F (BPF). Meanwhile, the EU European Food Safety Authority (EFSA) issued the new tolerable daily intake (TDI) after the latest re-risk assessment for BPA, which enforced the need for cumulative risk assessment in the population. This study was conducted to identify BPA and its substitute's exposure characteristics of the general Taiwanese population and estimate the cumulative risk of bisphenol exposure. Methods: Urine samples (N = 366 [adult, 271; minor, 95]) were collected from individuals who participated in the Taiwan Environmental Survey for Toxicants 2013. The samples were analyzed for BPA, BPS, and BPF through ultraperformance liquid chromatography-tandem mass spectrometry. Daily intake (DI) levels were calculated for each bisphenol. Hazard quotients (HQs) were calculated with the consideration of tolerable DI and a reference dose. Additionally, hazard index (HI; sum of HQs for each bisphenol) values were calculated. Results: Our study found that the median level of BPA was significantly higher in adults (9.63 µg/g creatinine) than in minors (6.63 µg/g creatinine) (p < 0.001). The DI of BPS was higher in female (0.69 ng/kg/day) than in male (0.49 ng/kg/day); however, the DIs of BPF and BPS were higher in boys (1.15 and 0.26 ng/kg/day, respectively) than in girls (0.57 and 0.20 ng/kg/day, respectively). Most HI values exceeded 1 (99% of the participants) after EFSA re-establish the TDI of BPA. Discussion: Our study revealed that the exposure profiles and risk of BPA and its substitute in Taiwanese varied by age and sex. Additionally, the exposure risk of BPA was deemed unacceptable in Taiwan according to new EFSA regulations, and food contamination could be the possible source of exposure. We suggest that the risk of exposure to BPA and its substitutes in most human biomonitoring studies should be reassessed based on new scientific evidence.