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.

Methodological approaches for the assessment of bisphenol A exposure.

Bisphenol A (BPA) is an endocrine disruptor used in food contact materials, by the application of polycarbonate plastics and epoxy resins. The main objective of this study is to compare the estimate of daily BPA exposure at 13 years of age and in the adult Portuguese population, using different methodological approaches, and assess the associations between this exposure and sociodemographic characteristics. METHODOLOGY: Cross-sectional data of 13-years follow-up from a population-based birth cohort Generation XXI (GXXI) (n = 2804) and from the National Food, Nutrition and Physical Activity Survey (IAN-AF 2015-2016) (n = 3845, ≥18 years old) was used. Dietary information was collected through three food diaries for adolescents and two non-consecutive 24-hour-recalls for adults. To estimate the daily exposure to BPA, three methodological approaches were used. "Food groups attribution" merged the food consumption data with the concentration of BPA in food groups. "Regression tree model" and "random forest" combined food consumption information with urinary BPA, measured in a subsample of 24-hour urine (in adolescents n = 216, and in adults n = 82), both used to predict BPA exposure in the remaining sample. The fit-index of the methodologies was assessed through the root mean square error (RMSE), mean absolute error (MAE) and Spearman correlation coefficient (ρ). Associations between BPA exposure and sociodemographic variables were tested by linear regression models, adjusted for sex, age groups (in adults) and educational level. Tolerable Daily Intake (TDI) of 0.2 ng/kg body weight (bw), recently proposed by the European Food Safety Authority (EFSA), was used for the risk characterization of BPA exposure. RESULTS: The "random forest" was found as the best methodology to estimate the daily BPA exposure (adolescents: RMSE = 0.989, MAE = 0.727, ρ = 0.168; adults: RMSE = 0.193, MAE = 0.147, ρ = 0.250). The median dietary BPA exposure, calculated by "food groups attribution", was 79.1 and 46.1 ng/kg bw/day for adolescents and adults, respectively, while "random forest" estimated a BPA exposure of 26.7 and 38.0 ng/kg bw/day. 99.9% of the Portuguese population presented a daily exposure above TDI. Male adolescents, females and higher educated adults, were those more exposed to BPA. CONCLUSIONS: The estimated daily BPA exposure strongly depends on the methodological approach. Food groups attribution may overestimate the exposure while the random forest appears to be a better methodological approach to estimate BPA exposure. Nevertheless, for all methods, the Portuguese population presented an unsafe BPA exposure by largely exceeding the safe levels proposed by EFSA.

Early-Life Exposure to a Mixture of Phenols and Phthalates in Relation to Child Social Behavior: Applying an Evidence-Based Prioritization to a Cohort with Improved Exposure Assessment.

BACKGROUND: Previous studies aiming at relating exposure to phenols and phthalates with child social behavior characterized exposure using one or a few spot urine samples, resulting in substantial exposure misclassification. Moreover, early infancy exposure was rarely studied. OBJECTIVES: We aimed to examine the associations of phthalates and phenols with child social behavior in a cohort with improved exposure assessment and to a priori identify the chemicals supported by a higher weight of evidence. METHODS: Among 406 mother-child pairs from the French Assessment of Air Pollution exposure during Pregnancy and Effect on Health (SEPAGES) cohort, 25 phenols/phthalate metabolites were measured in within-subject pools of repeated urine samples collected at the second and third pregnancy trimesters (∼21 samples/trimester) and at 2 months and 1-year of age (∼7 samples/period). Social behavior was parent-reported at 3 years of age of the child using the Social Responsiveness Scale (SRS). A structured literature review of the animal and human evidence was performed to prioritize the measured phthalates/phenols based on their likelihood to affect social behavior. Both adjusted linear regression and Bayesian Weighted Quantile Sum (BWQS) regression models were fitted. False discovery rate (FDR) correction was applied only to nonprioritized chemicals. RESULTS: Prioritized compounds included bisphenol A, bisphenol S, triclosan (TCS), diethyl-hexyl phthalate (ΣDEHP), mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), and mono-benzyl phthalate (MBzP). With the exception of bisphenols, which showed a mixed pattern of positive and negative associations in pregnant mothers and neonates, few prenatal associations were observed. Most associations were observed with prioritized chemicals measured in 1-y-old infants: Each doubling in urinary TCS (ß=0.78; 95% CI: 0.00, 1.55) and MEP (ß=0.92; 95% CI: -0.11, 1.96) concentrations were associated with worse total SRS scores, whereas MnBP and ΣDEHP were associated with worse Social Awareness (ß=0.25; 95% CI: 0.01, 0.50) and Social Communication (ß=0.43; 95% CI: -0.02, 0.89) scores, respectively. BWQS also suggested worse total SRS [Beta 1=1.38; 95% credible interval (CrI): -0.18, 2.97], Social Awareness (Beta 1=0.37; 95% CrI: 0.06, 0.70), and Social Communication (Beta 1=0.91; 95% CrI: 0.31, 1.53) scores per quartile increase in the mixture of prioritized compounds assessed in 1-y-old infants. The few associations observed with nonprioritized chemicals did not remain after FDR correction, with the exception of benzophenone-3 exposure in 1-y-old infants, which was suggestively associated with worse Social Communication scores (corrected p=0.07). DISCUSSION: The literature search allowed us to adapt our statistical analysis according to the weight of evidence and create a corpus of experimental and epidemiological knowledge to better interpret our findings. Early infancy appears to be a sensitive exposure window that should be further investigated. https://doi.org/10.1289/EHP11798.

Comprehensive LC-MS/MS method combined with tandem hybrid hydrolysis for multiple exposure assessment of multiclass environmental pollutants.

Environmental pollutants (EPOLs), such as phthalates, volatile organic compounds, phenols, parabens, polycyclic aromatic hydrocarbons, pyrethroids, and environmental tobacco smoke, are highly heterogeneous compounds. Recently, attention has been drawn to the assessment of the combinatory effects of multiple EPs. To correlate multiple exposures with potential health implications, advanced comprehensive analytical methods covering multiclass EPOLs are essential. However, because of several technical problems associated with enzyme hydrolysis, simultaneous extraction, and multiresidue liquid chromatography-tandem mass spectrometry analysis, it is difficult to establish a comprehensive method covering a number of EPOLs in a single sample preparation and analytical run. We developed tandem hybrid hydrolysis, modified direct injection, and a comprehensive mobile phase to overcome these technical problems and established a comprehensive analytical method for simultaneous biomonitoring of multiclass EPOLs. Tandem hybrid hydrolysis using ß-glucuronidase and consecutive acid hydrolysis allowed selective hydrolysis of glucuronide- and sulfate-conjugated metabolites without phthalate degradation. The comprehensive mobile phase composed of 0.01% acetic acid and acetonitrile enabled us to simultaneously analyze 86 EPOLs, with good chromatographic behavior and ionization efficiency. Modified direct injection allowed a small amount of sample and simultaneous urinary extraction. The method was validated and applied to 39 urine samples from 19 mother-newborn pairs for multiple exposure assessment. Results showed that BP-3, a general component in sunblock products, and monoethyl phthalate, a metabolite of diethyl phthalate, exhibit a clear positive correlation between mothers and newborns. Therefore, the developed method has potential as a novel analytical tool for long-term, large-scale, and data-rich human biomonitoring of EPOLs.

A novel method for rapid and quantitative detection of bisphenol A in urine.

Bisphenol A (BPA) is classified as an endocrine disruptor (ED) and it can interact with variety of hormone receptors leading to hormonal disruption and increased risk of various adverse health effects. Reducing human exposure to BPA is one of the main challenges of public health, as it is constantly present in daily life. A low-cost and commonly applied method to enable determination of BPA in the patient's body has yet to be developed. Currently available techniques are expensive, time-consuming, and require access to highly equipped analytical chemistry laboratories. Here we describe a fast and cheap engineered lateral flow assay of our design, to detect of BPA in urine samples. The technology not only provides an opportunity to perform rapid medical diagnostics without the need for an access to the central laboratory but also a means for self-diagnosis by the patient. The addition of ß-glucuronidase improves the sensitivity of detection as it releases the free BPA from glucuronide complexes in urine. This invention may become a demonstrated analytical means for lowering human exposure to BPA and probably also to other EDs and consequently, may be useful in decrease of the risk for several lifestyle diseases.

Assessment of Bisphenol A Levels in Preschool Children: Results of a Human Biomonitoring Study in Ankara, Turkey

Objective: There is general concern regarding environmental chemical exposure and the impact it may have on human health. This is particularly important for vulnerable populations such as infants and children during critical periods of development. Bisphenol A (BPA) is an endocrine disrupting chemical used worldwide over the last 30 years in many consumer products. Evidence points to widespread human exposure to BPA. The aim of this study was to evaluate the exposure of Turkish preschool children to BPA. Methods: This study was conducted as a preliminary investigation of BPA in urine, collected from 3-6 year old children living in Ankara. After spot urine samples were taken from preschool children, free BPA, ß-D-glucuronide and total BPA were determined using high-performance liquid chromatography tandem mass spectrometry and adjusted by creatinine concentration. Results: Preschool children from Ankara (n=125; males n=70, females n=55; mean age: 4.50±1.26) were recruited. BPA was detected in 76.8% of children from Ankara city, with urinary concentrations ranging from < limit of quantification to 18.36 µg/g creatinine. Total BPA levels were not statistically different between boys (1.26 µg/g creatinine) and girls (2.24 µg/g creatinine) (p>0.05). Conclusion: This study is an important contribution to the limited information about childhood exposure to BPA. The estimated daily BPA intake in this study is substantially lower than the European Food Safety Authority derived tolerable daily intake of 4 µg/kg BW/day.

Urinary concentrations of phenols in association with biomarkers of oxidative stress in pregnancy: Assessment of effects independent of phthalates.

BACKGROUND: Maternal exposure to environmental phenols is common in pregnancy and has been linked to preterm birth, preeclampsia, and reduced fetal growth. One potential mechanism may be through increased maternal oxidative stress. OBJECTIVE: We examined the associations between a panel of 10 urinary phenols, including dichlorophenols, benzophenone-3, parabens, triclosan and triclocarban, and bisphenol-S, and two urinary oxidative stress biomarkers, 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane. All exposure and outcome biomarkers were measured at 4 time points in pregnancy. METHODS: We used repeated measures models to examine the association between repeated exposure and outcome biomarkers. Additionally, we used adaptive elastic net (AENET) to identify non-null associations accounting for the correlation structure of exposures, both for phenols and urinary phthalate metabolites that were previously associated with the oxidative stress biomarkers in our study population. RESULTS: In adjusted repeated measures models, we observed that dichlorophenols, benzophenone-3, triclosan, and some parabens were associated with increases in both oxidative stress biomarkers. The greatest effect estimates were observed for 2,5-dichlorophenol; an interquartile range (IQR) increase in this compound was associated with a 15.2% (95% confidence interval [CI] = 11.0, 19.6) increase in 8-OHdG and a 16.7% (95% CI = 9.66, 24.2) increase in 8-isoprostane. Bisphenol-S detection was associated with a clear increase in 8-isoprostane (18.5%, 95% CI = 7.68, 30.5) but a more modest increase in 8-OHdG (6.18%, 95% CI = -0.27, 13.1). However, AENET models did not consistently select any of the phenols as predictors of 8-OHdG or 8-isoprostane when phthalate metabolites were included in the model. CONCLUSION: Overall, urinary phenols were associated with increases in biomarkers of oxidative stress in pregnancy but either to a lesser extent, or due to correlation with, urinary phthalate metabolites.

Trends and disparities in urinary BPA concentrations among U.S. emerging adults.

BACKGROUND: Emerging adulthood (ages 18-25 years) is a key turning point in the life course characterized by particularly poor eating behaviors (e.g., low in fruits and vegetables, and high in fast food) and weight gain. Emerging adults are also prime consumers of personal care and other consumer products that may result in differential exposures to environmental contaminants, such as Bisphenol A (BPA), compared to adults aged 26+ years. This is of concern given BPA has been associated with adverse health outcomes such as obesity, metabolic disorders, miscarriage, infertility and breast cancer. However, no research has examined exposure to BPA among emerging adults. OBJECTIVE: To assess trends of exposure to urinary BPA among a representative sample of emerging adults compared to adults aged 26+ years. Secondarily, we aimed to identify differential associations between BPA concentrations and sociodemographic characteristics and BMI by age group. METHODS: This study uses National Health and Examination Surveys (NHANES) over 2003-2014 to test differences in BPA concentrations comparing emerging adults to adults aged 26+ years. Generalized linear models predicting log BPA by age group and sex, race/ethnicity, education, income, and food security status, and generalized linear models predicting BMI by log BPA, both age group and age as a continuous variable, sex, race/ethnicity, education, income, and food security status were conducted. Interactions with age group (i.e., age group x sex) were examined for the mutually adjusted models. All models controlled for survey year, month, and time of day, and were run with, and without, an adjustment for urinary creatinine. RESULTS: In models adjusted, and not adjusted, for urinary creatinine, emerging adults had a higher log BPA concentration than adults aged 26+ years (ß=0.153, p=0.004; ß=0.544, p<0.001), and a significantly steeper decline in BPA concentration between 2003-2004 and 2013-2014 than adults aged 26+ years (ß=-0.051, p=0.002; ß=-0.071, p=0.001). Males' log BPA concentration were lower than that for females when urinary creatinine was included in the model, and higher when urinary creatinine was excluded from the model (ß=-0.188, p<0.001; ß=0.203, p<0.001). Higher income was significantly associated with lower log BPA concentration (ß=-0.220, p<0.001; ß=-0.166, p<0.001). A significant interaction between emerging adult age group and food security status was observed, which was associated with higher BPA exposures. Log BPA concentration was associated with BMI only when urinary creatinine was excluded from the models (urinary creatinine included: ß=0.031, p=0.747; ß=0.022, p=0.815, urinary creatinine excluded: ß=0.528, p<0.001; ß=0.552, p<0.001). CONCLUSION: Findings indicate that emerging adults had higher BPA exposures than adults aged 26+ years in 2003-2004, and that emerging adults' exposure level has decreased faster than that of adults aged 26+ years. There were suggestions that the BPA concentration of emerging adults in 2013-2014 was lower than that for adults aged 26+ years, and that BPA exposure is associated with higher BMI. Our results highlight the need for additional research to identify the sources and routes of exposure to BPA and BPA replacements among emerging adults and to better characterize the variability in exposure. Intervention studies are needed to assist emerging adults in limiting their exposure to BPA, and potentially also the BPA alternatives.

Urinary bisphenol A (BPA) concentrations and exposure predictors among pregnant women in the Laizhou Wan Birth Cohort (LWBC), China.

Although BPA use is widespread and often detectable in humans, little is known about its exposure levels and potential exposure predictors in pregnant women in China. We investigated the BPA exposure levels in pregnant women and its health implications and potential exposure predictors. Urinary BPA levels were measured for 506 pregnant women in northern China. Hazard quotients (HQs) based on estimated daily intakes (EDIs) were conducted. Sociodemographic characteristics and food consumption during pregnancy were collected and seasons of sample collection were recorded. The detection rate of urinary BPA was 86.6% and the median concentrations were 0.48 µg/L (1.05 µg/g creatinine). The EDI (median = 0.008 µg/kg bw/day) was much lower than the recommended tolerable daily doses and the HQ (median = 0.002) much lower than 1. The urine collected in summer had significantly higher BPA levels than that collected in other seasons (ß = 0.225; 95% CI - 0.008, 0.458; p = 0.03). Women "always consuming shellfish" had significantly higher BPA levels than those "seldom consuming shellfish" (ß = 0.341; 95% CI 0.022, 0.66; p = 0.04). The study found a wide exposure to BPA among pregnant women in this region, which might be associated with seasonal variation and shellfish consumption. Although the HQs suggested no obvious risk, further attention to the comprehensive exposure and potential determinants should be paid in view of its endocrine-disrupting potential.

Urinary phthalate metabolite and bisphenol A levels in the Korean adult population in association with sociodemographic and behavioral characteristics: Korean National Environmental Health Survey (KoNEHS) 2012-2014.

BACKDGROUND: Phthalates and bisphenol A (BPA) have been used in a variety of consumer products and are detected widely in both humans and the environment. Demographic and socio-economic characteristics that affect exposure to these chemicals have been investigated among several general populations; however, nationally-representative population-based studies are limited to Canada, Germany, and the USA. Moreover, relatively little is known about the socio-demographic characteristics that influence exposure to these chemicals among nationally representative populations of Asia. METHODS: Data are obtained from the Korean National Environmental Health Survey (2012-2014). In total, 6,478 adults (aged 19 and older) were recruited and sampled for urinary levels of major phthalate metabolites and bisphenol A. In addition, demographic and socio-economic parameters were determined from questionnaire data and the characteristics associated with urinary concentrations of the target chemicals were assessed. RESULTS: Urinary levels of bis(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) metabolites of Korean adults were generally higher, but those of mono-benzyl phthalate (MBzP) were lower, and BPA were similar or higher than those reported from national biomonitoring programs in the United States and Canada. Similar to other nationally representative populations, females and older adults showed higher creatinine-adjusted phthalate metabolite and BPA levels among the Korean population. Meanwhile, monthly household income and education were negatively associated with urinary phthalate metabolites. Among personal care products, nail polish use was positively associated with both phthalate metabolites and BPA concentrations in urine. CONCLUSION: Our observations based on a nationally representative population of Korea show that socio-demographic determinants for these urinary chemicals vary by country, and should be considered for developing appropriate mitigation measures and policies.

Simultaneous assessment of phenolic metabolites in human urine for a specific biomonitoring of exposure to organophosphate and carbamate pesticides.

Organophosphate pesticides (OPP) and carbamates are still counted among the most prominent agents used for crops protection. Up to date the determination of dialkylphosphates and their thio derivatives in urine is established for the OPP biomonitoring. However, this approach does not provide information on the exposure to specific OPP agents. A lot of OPP as well as some carbamates also provide specific urinary biomarkers indeed. Analytical methods for the determination of phenolic metabolites of OPP and carbamates have already been established by different working groups. However, these approaches only acquire one or few analytes. Therefore, we developed an analytical procedure which enables the simultaneous assessment of a wide spectrum of phenolic metabolites of OPP, carbamates and other pesticides in human urine using GC-MS/MS. The method includes enzymatic hydrolysis, solid phase extraction, derivatization, and subsequent GC-MS/MS analysis. The method showed detection limits between 0.1 and 0.4 µg/l. Variation coefficients ranged from 1 to 9 % for precision in series and 1 % to 13 % for inter-day precision. Furthermore, recovery rates between 87 and 117 % were determined. Compared with other published analytical procedures, the present method enables the simultaneous monitoring of a much broader spectrum of pesticides and biocides whose structures contain aryl moieties with competitive or improved analytical reliability. Furthermore, the suitability of the developed procedure was verified through the successful application to urine samples of pesticide exposed humans.

Bisphenol and phthalate concentrations and its determinants among pregnant women in a population-based cohort in the Netherlands, 2004-5.

BACKGROUND: Exposure to bisphenols and phthalates in pregnancy may lead to adverse health effects in women themselves and their offspring. OBJECTIVE: To describe first trimester bisphenol and phthalate urine concentrations, including bisphenol and phthalate replacements, and determine nutritional, socio-demographic and lifestyle related determinants. METHODS: In a population-based prospective cohort of 1396 mothers, we measured first trimester bisphenol, phthalate and creatinine urine concentrations (samples collected in 2004-2005, median gestational age 12.9 weeks [inter-quartile range (IQR) 12.1-14.4]). We examined associations of potential determinants with log-transformed bisphenol and phthalate concentrations. Outcomes were back-transformed. Nutritional analyses were performed in a subgroup of 642 Dutch participants only, as the Food Frequency Questionnaire was aimed at Dutch food patterns. RESULTS: Bisphenol A, bisphenol S, and bisphenol F were detected in 79.2%, 67.8% and 40.2% of the population, respectively. Mono-n-butylphthalate, mono-(2-ethyl-5-hydroxyhexyl)phthalate and monobenzylphthalate were detected in > 90% of the population. Nutritional intake was not associated with bisphenol and phthalate concentrations after correction for multiple testing was applied. Obesity was associated with higher high-molecular-weight phthalate concentrations and the lack of folic acid supplement use with higher di-n-octylphthalate concentrations (respective mean differences were 46.73nmol/l [95% CI 14.56-93.72] and 1.03nmol/l [0.31-2.06]). CONCLUSION: Bisphenol S and F exposure was highly prevalent in pregnant women in the Netherlands as early as 2004-5. Although associations of dietary and other key factors with bisphenol and phthalate concentrations were limited, adverse lifestyle factors including obesity and the lack of folic acid supplement use seem to be associated with higher phthalate concentrations in pregnant women. The major limitation was the availability of only one urine sample per participant. However, since phthalates are reported to be quite stable over time, results concerning determinants of phthalate concentrations are expected to be robust.

Exposure assessment to bisphenol A (BPA) in Portuguese children by human biomonitoring.

Exposure to bisphenol A (BPA) is known to be widespread and available data suggests that BPA can act as an endocrine disruptor. Diet is generally regarded as the dominant BPA exposure source, namely through leaching to food from packaging materials. The aim of this study was to evaluate the exposure of 110 Portuguese children (4-18 years old), divided in two groups: the regular diet group (n = 43) comprised healthy normal weight/underweight children with no dietary control; the healthy diet group (n = 67) comprised children diagnosed for obesity/overweight (without other known associated diseases) that were set on a healthy diet for weight control. First morning urine samples were collected and total urinary BPA was analyzed after enzymatic hydrolysis via on-line HPLC-MS/MS with isotope dilution quantification. Virtually, all the children were exposed to BPA, with 91% of the samples above the LOQ (limit of quantification) of 0.1 µg/L. The median (95th percentile) urinary BPA levels for non-normalized and creatinine-corrected values were 1.89 µg/L (16.0) and 1.92 µg/g creatinine (14.4), respectively. BPA levels in the regular diet group were higher than in the healthy diet group, but differences were not significant. Calculated daily BPA intakes, however, were significantly higher in children of the regular diet group than in children of healthy diet group. Median (95th percentile) daily intakes amounted to 41.6 (467) ng/kg body weight/day in the regular diet group, and 23.2 (197) ng/kg body weight/day in the healthy diet group. Multiple logistic regression analysis revealed that children in the healthy diet group had 33% lower intakes than children in the regular diet group (OR 0.67; 95% CI 0.51-0.89). For both groups, however, urinary BPA levels and daily BPA intakes were within the range reported for other children's populations and were well below health guidance values such as the European Food Safety Authority (EFSA) temporary tolerable daily intake (t-TDI) of 4 µg/kg body weight/day. In addition, lower daily BPA intakes were more likely linked with the inherent dietary approach rather than with high BMI or obesity.

Processing 'Ataulfo' Mango into Juice Preserves the Bioavailability and Antioxidant Capacity of Its Phenolic Compounds.

The health-promoting effects of phenolic compounds depend on their bioaccessibility from the food matrix and their consequent bioavailability. We carried out a randomized crossover pilot clinical trial to evaluate the matrix effect (raw flesh and juice) of 'Ataulfo' mango on the bioavailability of its phenolic compounds. Twelve healthy male subjects consumed a dose of mango flesh or juice. Blood was collected for six hours after consumption, and urine for 24 h. Plasma and urine phenolics were analyzed by electrochemical detection coupled to high performance liquid chromatography (HPLC-ECD). Five compounds were identified and quantified in plasma. Six phenolic compounds, plus a microbial metabolite (pyrogallol) were quantified in urine, suggesting colonic metabolism. The maximum plasma concentration (Cmax) occurred 2-4 h after consumption; excretion rates were maximum at 8-24 h. Mango flesh contributed to greater protocatechuic acid absorption (49%), mango juice contributed to higher chlorogenic acid absorption (62%). Our data suggests that the bioavailability and antioxidant capacity of mango phenolics is preserved, and may be increased when the flesh is processed into juice.

Worldwide human daily intakes of bisphenol A (BPA) estimated from global urinary concentration data (2000-2016) and its risk analysis.

To evaluate BPA's potential risk to health, it is important to know human daily intake. This study describes a simple but effective method to estimate the levels of human BPA intake among four different populations based on urinary concentration data. Nationally, of the 30 countries examined, the top ten countries for adult intake were Italy, Sweden, Denmark, France, Cyprus, Australia, Israel, Ghana, Jamaica, and Belgium. When the urinary excretion sample size was large enough and over 1000, it was found that the national estimated BPA daily intakes in the child group among countries, showed a good linear relationship with those of their corresponding adult group. Except the infant group with limited data, the global estimated BPA daily intakes for children and pregnant women were 2 and 1.4 times that of the adult group. Although the national and global estimated BPA daily intakes were generally below the temporary tolerable daily intake (tTDI) recommended by the European Food Safety Authority (EFSA), but some normal individuals' daily intakes exceeded the tTDI.

Absorption, Metabolism and Excretion of Cranberry (Poly)phenols in Humans: A Dose Response Study and Assessment of Inter-Individual Variability.

The beneficial health effects of cranberries have been attributed to their (poly)phenol content. Recent studies have investigated the absorption, metabolism and excretion of cranberry (poly)phenols; however, little is known about whether they follow a dose response in vivo at different levels of intake. An acute double-blind randomized controlled trial in 10 healthy men with cranberry juices containing 409, 787, 1238, 1534 and 1910 mg total (poly)phenols was performed. Blood and urine were analyzed by UPLC-Q-TOF-MS. Sixty metabolites were identified in plasma and urine including cinnamic acids, dihydrocinnamic, flavonols, benzoic acids, phenylacetic acids, benzaldehydes, valerolactones, hippuric acids, catechols, and pyrogallols. Total plasma, but not excreted urinary (poly)phenol metabolites, exhibited a linear dose response (r² = 0.74, p < 0.05), driven by caffeic acid 4-O-ß-d-glucuronide, quercetin-3-O-ß-d-glucuronide, ferulic acid 4-O-ß-d-glucuronide, 2,5-dihydroxybenzoic acid, 2,4-dihydroxybenzoic acid, ferulic acid, caffeic acid 3-O-ß-d-glucuronide, sinapic acid, ferulic acid 4-O-sulfate, 3-hydroxybenzoic acid, syringic acid, vanillic acid-4-O-sulfate, (4R)-5-(3'-hydroxyphenyl)-γ-valerolactone-4'-O-sulfate, 4-methylgallic acid-3-O-sulfate, and isoferulic acid 3-O-sulfate (all r² ≥ 0.89, p < 0.05). Inter-individual variability of the plasma metabolite concentration was broad and dependent on the metabolite. Herein, we show that specific plasma (poly)phenol metabolites are linearly related to the amount of (poly)phenols consumed in cranberry juice. The large inter-individual variation in metabolite profile may be due to variations in the gut microbiome.

Probabilistic integrated risk assessment of human exposure risk to environmental bisphenol A pollution sources.

Environmental bisphenol A (BPA) exposure has been linked to a variety of adverse health effects such as developmental and reproductive issues. However, establishing a clear association between BPA and the likelihood of human health is complex yet fundamentally uncertain. The purpose of this study was to assess the potential exposure risks from environmental BPA among Chinese population based on five human health outcomes, namely immune response, uterotrophic assay, cardiovascular disease (CVD), diabetes, and behavior change. We addressed these health concerns by using a stochastic integrated risk assessment approach. The BPA dose-dependent likelihood of effects was reconstructed by a series of Hill models based on animal models or epidemiological data. We developed a physiologically based pharmacokinetic (PBPK) model that allows estimation of urinary BPA concentration from external exposures. Here we showed that the daily average exposure concentrations of BPA and urinary BPA estimates were consistent with the published data. We found that BPA exposures were less likely to pose significant risks for infants (0-1 year) and adults (male and female >20 years) with <10(-6)-fold increase in uterus weight and immune response outcomes, respectively. Moreover, our results indicated that there was 50 % risk probability that the response outcomes of CVD, diabetes, and behavior change with or without skin absorption would increase 10(-4)-10(-2)-fold. We conclude that our approach provides a powerful tool for tracking and managing human long-term BPA susceptibility in relation to multiple exposure pathways, and for informing the public of the negligible magnitude of environmental BPA pollution impacts on human health.

Risk assessment based on urinary bisphenol A levels in the general Korean population.

Bisphenol A (BPA) is a high-volume industrial chemical used in the global production of polycarbonate plastics and epoxy resins, which are used in food and drink containers, such as tableware (plates and mugs). Due to its broad applications, BPA has been detected in human blood, urine and breast milk as well as environmental substances, including water, indoor and outdoor air, and dust. Indeed, exposure to high concentrations of BPA can result in a variety of harmful effects, including reproductive toxicity, through a mechanism of endocrine disruption. Our comparison of reported BPA urinary concentrations among different countries revealed that exposures in Korea may be higher than those in other Asian countries and North America, but lower than or similar to those in European countries. The current study included a total of 2044 eligible subjects of all ages. The subjects were evenly divided between males and females (48.58% and 51.42%, respectively). The geometric mean (GM) of pre-adjusted (adjusted) urinary BPA concentrations was 1.83µg/L (2.01µg/g creatinine) for subjects of all ages, and there was no statistically difference in BPA concentrations between males (1.90µg/L, 1.87µg/g creatinine) and females (1.76µg/L, 2.16µg/g creatinine). Multiple regression analysis revealed only one positive association between creatinine pre-adjusted urinary BPA concentration and age (ß=-0.0868, p<0.001). The 95th percentile levels of 24-hour recall (HR), food frequency questionnaires (FFQ) and estimated daily intake (EDI) through urinary BPA concentrations were 0.14, 0.13, and 0.22µg/kg bw/day, respectively. According to the Ministry of Food and Drug Safety (MFDS), a tolerable daily intake (tDI) of 20µg/kg bw/day was established for BPA from the available toxicological data. Recently, the European Food Safety Authority (EFSA) established a temporary TDI of 4µg/kg bw/day based on current toxicological data. By comparing these TDIs with subjects' exposure, we conclude that there are no health concerns for any age group as a result of current levels of dietary exposure to BPA.

Bisphenol A and child and youth behaviour: Canadian Health Measures Survey 2007 to 2011.

BACKGROUND: Bisphenol A (BPA) is a synthetic industrial chemical commonly used in consumer products. Results from the Canadian Heath Measures Survey (CHMS) indicate that more than 90% of children and youth aged 6 to 19 have detectable levels of urinary BPA. Childhood concentration levels of BPA have been linked with negative behavioural outcomes. DATA AND METHODS: The data are from the first two cycles (2007 to 2009 and 2009 to 2011) of the CHMS, which collected biomonitoring indicators via spot blood and urine samples. Behavioural outcomes--hyperactivity/inattention, emotional symptoms, conduct problems, peer problems, and prosocial behavior--were assessed with Goodman's Strengths and Difficulties Questionnaire. Geometric mean urinary BPA concentration was examined overall and by demographic and socioeconomic correlates. Six multiple logistic regression analyses were conducted to investigate associations between childhood BPA concentrations and risk status for each outcome. RESULTS: Children aged 6 to 8 had higher BPA concentrations than did older children and youth. Concentrations were significantly higher among children and youth exposed to second-hand smoke every day or almost every day and those in low or lower-middle income households. Higher BPA concentrations were associated with increased odds of hyperactivity among girls and lower prosocial behaviour among boys. INTERPRETATION: These findings suggest an association between urinary BPA concentration and children's behavioural outcomes.

Exposure assessment of adult intake of bisphenol A (BPA) with emphasis on canned food dietary exposures.

Bisphenol A (BPA) is a high-volume, synthetic compound found in epoxy resins and plastics used in food packaging. Food is believed to be a major source of BPA intake. In this study, we measured the concentration of BPA in convenience samplings of foodstuffs purchased in Dallas, Texas. Sampling entailed collection of 204 samples of fresh, frozen, and canned foods in two rounds in 2010. BPA was positive in 73% of the canned food samples, while it was found in only 7% of non-canned foods at low concentrations. The results of this food sampling program were used to calculate adult dietary intakes of BPA. A pathway approach combined food intakes, a "canned fraction" parameter which described what portion of total intake of that food came from canned products, and measured food concentrations. Dietary intakes were calculated as 12.6 ng/kg-day, of which 12.4 ng/kg-day was from canned foods. Canned vegetable intakes alone were 11.9 ng/kg-day. This dietary intake was compared to total intakes of BPA estimated from urine measurements of the National Health and Nutrition Examination Survey (NHANES). Total adult central tendency intakes ranged from 30 to 70 ng/kg-day for NHANES cycles between 2005 and 2010. Three possibilities were explored to explain the difference between these two approaches for intake estimation. Not all foods which may have been canned, particularly canned beverages such as soft drinks, were sampled in our food sampling program. Second, non-food pathways of exposure may be important for adults, including thermal paper exposures, and dust and air exposures. Finally, our canned food concentrations may not be adequately representative of canned foods in the United States; they were found to be generally lower compared to canned food concentrations measured in six other worldwide food surveys including three in North America. Our finding that canned food concentrations greatly exceeded non-canned concentrations was consistent with other studies, and underscores the importance of canned foods in the overall exposure of adults of BPA.