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.

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.

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.

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.

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.

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.

Exposure to free and conjugated forms of bisphenol A and triclosan among pregnant women in the MIREC cohort.

BACKGROUND: Bisphenol A (BPA) and triclosan (TCS) are two nonpersistent chemicals that have been frequently measured in spot urine samples from the general population but less so in pregnant women; however, data are limited on the free (bioactive) and conjugated forms of these phenols. OBJECTIVES: The Maternal-Infant Research on Environmental Chemicals (MIREC) Study addressed these data gaps by utilizing stored maternal urine samples from a large multicenter cohort study of Canadian pregnant women. METHODS: Concentrations of free and conjugated forms of BPA and TCS were measured in about 1,890 first-trimester urine samples by ultra performance liquid chromatography-tandem mass spectrometry using isotope dilution. RESULTS: The glucuronides of BPA and TCS were the predominant forms of these chemicals measured (detected in 95% and 99% of samples, respectively), whereas the free forms were detected in 43% and 80% of samples, respectively. The geometric mean urinary concentrations for glucuronides of BPA and TCS were 0.80 µg/L (95% CI: 0.75, 0.85) and 12.30 µg/L (95% CI: 11.08, 13.65), respectively. Significant predictors of BPA included maternal age < 25 vs. ≥ 35 years, current smoking, low vs. high household income, and low vs. high education. For TCS, urinary concentrations were significantly higher in women ≥ 25 years of age, never vs. current smokers, and women with high household income and high education. CONCLUSIONS: The results from this study represent the largest national-level data on urinary concentrations of free and conjugated forms of BPA and TCS in pregnant women and suggest that maternal characteristics predicting elevated urinary concentrations of these phenols largely act in opposite directions.

Sex differences in the association of urinary bisphenol-A concentration with selected indices of glucose homeostasis among U.S. adults.

PURPOSE: Emerging evidence suggests that exposure to endocrine disruptors may initiate or exacerbate adiposity and associated health problems. This study examined sex differences in the association of urinary level of bisphenol-A (BPA) with selected indices of glucose homeostasis among U.S. adults. METHODS: Data analyses were performed using a sample of 1586 participants from the 2005 to 2008 National Health and Nutrition Examination Surveys. BPA level and the ratio of BPA-to-creatinine level were defined as log-transformed variables and in quartiles. Selected indices of glucose homeostasis were defined using fasting glucose and insulin data. Multivariate linear and logistic regression models for the hypothesized relationships were constructed after controlling for age, sex, race, education, marital status, smoking status, physical activity, total dietary intake, and urinary creatinine concentration. RESULTS: Taking the first quartile as a referent, the third quartile of BPA level was positively associated with log-transformed level of insulin and ß-cell function (homeostasis model assessment for ß-cell function) as well as insulin resistance (log-transformed homeostasis model assessment for insulin resistance; homeostasis model assessment for insulin resistance ≥2.5), with significant BPA-by-sex interaction; these associations were stronger among males than among females. Irrespective of sex, the ratio of BPA-to-creatinine level was not predictive of indices of glucose homeostasis. CONCLUSIONS: A complex association may exist between BPA and hyperinsulinemia among adult U.S. men. Prospective cohort studies are needed to further elucidate endocrine disruptors as determinants of adiposity-related disturbances.

Associations between socioeconomic status and environmental toxicant concentrations in adults in the USA: NHANES 2001-2010.

Low level chronic exposure to toxicants is associated with a range of adverse health effects. Understanding the various factors that influence the chemical burden of an individual is of critical importance to public health strategies. We investigated the relationships between socioeconomic status (SES) and bio-monitored chemical concentration in five cross-sectional waves of the U.S. National Health and Nutrition Examination Survey (NHANES). We utilised adjusted linear regression models to investigate the association between 179 toxicants and the poverty income ratio (PIR) for five NHANES waves. We then selected a subset of chemicals associated with PIR in 3 or more NHANES waves and investigated potential mediating factors using structural equation modelling. PIR was associated with 18 chemicals in 3 or more NHANES waves. Higher SES individuals had higher burdens of serum and urinary mercury, arsenic, caesium, thallium, perfluorooctanoic acid, perfluorononanoic acid, mono(carboxyoctyl) phthalate and benzophenone-3. Inverse associations were noted between PIR and serum and urinary lead and cadmium, antimony, bisphenol A and three phthalates (mono-benzyl, mono-isobutyl, mono-n-butyl). Key mediators included fish and shellfish consumption for the PIR, mercury, arsenic, thallium and perfluorononanoic acid associations. Sunscreen use was an important mediator in the benzophenone-3/PIR relationship. The association between PIR and cadmium or lead was partially mediated by smoking, occupation and diet. These results provide a comprehensive analysis of exposure patterns as a function of socioeconomic status in US adults, providing important information to guide future public health remediation measures to decrease toxicant and disease burdens within society.

Dietary and sociodemographic determinants of bisphenol A urine concentrations in pregnant women and children.

Bisphenol A (BPA) exposure during early life may have endocrine-disrupting effects, but the dietary and sociodemographic predictors of BPA exposure during pregnancy and childhood remain unclear. Our aim was to evaluate the correlations between, and sociodemographic and dietary predictors of, serial urinary BPA concentrations measured during pregnancy and childhood in a Spanish birth cohort study. BPA was measured in two spot urine samples collected from 479 women during the first and third trimester of pregnancy and in one urine sample from their 4-year old children (n=130). Average dietary intakes were reported in food frequency questionnaires during the first and third pregnancy trimester and at age 4years. Multivariate mixed models and linear regression models were used to estimate associations between sociodemographic and dietary factors and BPA concentrations. A small, but statistically significant correlation was found between serial maternal BPA concentrations measured during pregnancy (r=0.17). Pregnant women who were younger, less-educated, smoked, and who were exposed to second-hand tobacco smoke (SHS) had higher BPA concentrations than others. BPA concentrations were also higher in children exposed to SHS. High consumption of canned fish during pregnancy was associated with 21% [GM ratio=1.21; 95%CI 1.02, 1.44] and 25% [GM ratio=1.25; 95%CI 1.05, 1.49] higher urinary BPA concentrations in the first and third pregnancy trimester, respectively, compared to the lowest consumption group. This study suggests that canned fish may be a major source of BPA during pregnancy in Spain, a country of high canned fish consumption. Further evaluation of specific BPA exposure sources in the sociodemographic group of younger women who smoke, are exposed to SHS, and have a low educational level is needed. Studies identifying sources of exposure would benefit from repeat BPA measurements and questionnaires specifically focused on dietary and packaging sources.

Rapid and sensitive analysis of phthalate metabolites, bisphenol A, and endogenous steroid hormones in human urine by mixed-mode solid-phase extraction, dansylation, and ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry.

Steroid hormone levels in human urine are convenient and sensitive indicators for the impact of phthalates and/or bisphenol A (BPA) exposure on the human steroid hormone endocrine system. In this study, a rapid and sensitive method for determination of 14 phthalate metabolites, BPA, and ten endogenous steroid hormones in urine was developed and validated on the basis of ultra-performance liquid chromatography coupled with electrospray ionization triple quadrupole mass spectrometry. The optimized mixed-mode solid phase-extraction separated the weakly acidic or neutral BPA and steroid hormones from acidic phthalate metabolites in urine: the former were determined in positive ion mode with a methanol/water mobile phase containing 10 mM ammonium formate; the latter were determined in negative ion mode with a acetonitrile/water mobile phase containing 0.1 % acetic acid, which significantly alleviated matrix effects for the analysis of BPA and steroid hormones. Dansylation of estrogens and BPA realized simultaneous and sensitive analysis of the endogenous steroid hormones and BPA in a single chromatographic run. The limits of detection were less than 0.84 ng/mL for phthalate metabolites and less than 0.22 ng/mL for endogenous steroid hormones and BPA. This proposed method had satisfactory precision and accuracy, and was successfully applied to the analyses of human urine samples. This method could be valuable when investigating the associations among endocrine-disrupting chemicals, endogenous steroid hormones, and relevant adverse outcomes in epidemiological studies.

Enantioselective separation and determination of adrafinil and modafinil on Chiralcel OJ-H column in rat serum and urine using solid-phase extraction followed by HPLC.

A simple and rapid normal-phase HPLC method for enantiospecific separation of a psychostimulant, adrafinil (ADL), and its metabolite modafinil (MDL) in rat serum and urine was developed. The separation was accomplished on a normal-phase polysaccharide stationary phase Chiralcel OJ-H using n-hexane-ethanol (62:38 v/v) as a mobile phase at a flow rate of 1.0 mL/min. Detection was carried out at 225 nm using a photo diode array (PDA) detector. The elution order of the enantiomers was determined by a polarimeter connected in series with the PDA. ADL and its metabolite were recovered from rat serum and urine by solid phase extraction using Oasis HLB cartridges and the mean recoveries were >or=80%. The enantiomers were eluted within 15 min without any interference from endogenous substances. The calibration curves were linear (r(2) > 0.998) in the concentration range of 1.20-500 microg/mL for ADL and MDL. The assay was specific, accurate, precise and reproducible (intra- and inter-day precisions RSDs <7.2%). ADL in rat serum was stable over three freeze-thaw cycles at ambient temperature for 4 h. The method was successfully applied to pharmacokinetic studies of adrafinil after an oral administration to rats.

Positive- and negative-ion mass spectrometry of diphenylmethane antihistaminics and their analogues and rapid clean-up of them from biological samples.

Positive-ion electron impact (PIEI), positive-ion chemical ionization (PICI) and negative-ion chemical ionization (NICI) mass spectra are presented for 15 compounds of diphenylmethane antihistaminics and their analogues, and each fragmentation pathway was analyzed. In the PIEI mode, molecular peaks were very small or missing for most compounds. Peaks at m/z 58, due to a dimethylaminomethyl group liberated, constituted base peaks in five compounds. Peaks at m/z 165 and/or 167, due to diaromatic rings plus a methyl group, appeared in most compounds. In the PICI mode, peaks due to M+H and M+C2H5 appeared in all compounds. Peaks due to diaromatic rings plus a methyl or ethyl group constituted base peaks in five compounds, which had an ether bond in their structures. In the NICI mode, anions at m/z M-H appeared in most compounds. Peaks at m/z 35 were observed for compounds having a chlorine group in their structures. Detection limits for total ion monitoring of these compounds were 20-50 ng on column in the PIEI mode, 100-200 ng in the PICI mode and 500-1000 ng in the NICI mode. A rapid and simple clean-up procedure of these drugs with use of Sep-Pak C18 cartridges is also presented. The drugs could be detected by gas chromatography with DB-1 and DB-17 capillary columns with satisfactory separation from impurities in their underivatized forms. The recovery of the drugs, which had been added to whole blood and urine, was more than 60% except for meclizine.