Tinne Geens

A review of dietary and non-dietary exposure to bisphenol-A.

Due to the large number of applications of bisphenol-A (BPA), the human exposure routes are multiple. We aimed to review shortly the food and non-food sources of BPA, and to evaluate their contribution to the human exposure. Food sources discussed here include epoxy resins, polycarbonate and other applications, such as paperboard and polyvinylchloride materials. Among the non-food sources, exposures through dust, thermal paper, dental materials, and medical devices were summarized. Based on the available data for these exposure sources, it was concluded that the exposure to BPA from non-food sources is generally lower than that from exposure from food by at least one order of magnitude for most studied subgroups. The use of urinary concentrations from biomonitoring studies was evaluated and the back-calculation of BPA intake seems reliable for the overall exposure assessment. In general, the total exposure to BPA is several orders of magnitude lower than the current tolerable daily intake of 50 μg/kg bw/day. Finally, the paper concludes with some critical remarks and recommendations on future human exposure studies to BPA.

Analytical and environmental aspects of the flame retardant tetrabromobisphenol-A and its derivatives

The present article reviews the available literature on the analytical and environmental aspects of tetrabromobisphenol-A (TBBP-A), a currently intensively used brominated flame retardant (BFR). Analytical methods, including sample preparation, chromatographic separation, detection techniques, and quality control are discussed. An important recent development in the analysis of TBBP-A is the growing tendency for liquid chromatographic techniques. At the detection stage, mass-spectrometry is a well-established and reliable technology in the identification and quantification of TBBP-A. Although interlaboratory exercises for BFRs have grown in popularity in the last 10 years, only a few participating laboratories report concentrations for TBBP-A. Environmental levels of TBBP-A in abiotic and biotic matrices are low, probably due to the major use of TBBP-A as reactive FR. As a consequence, the expected human exposure is low. This is in agreement with the EU risk assessment that concluded that there is no risk for humans concerning TBBP-A exposure. Much less analytical and environmental information exists for the various groups of TBBP-A derivatives which are largely used as additive flame retardants.

Are potential sources for human exposure to bisphenol-A overlooked?

This review summarizes the numerous applications of bisphenol-A (BPA) and the potential sources for human exposure. The exposure to humans is believed to occur mainly through food contamination from polycarbonate bottles, as well as through food and beverage cans coated with epoxy resins. However, there seems to be a discrepancy between exposure assessments based on biomonitoring data and those based on food/drink concentrations. Several recent studies indicated also the importance of non-food sources. Although the main use of BPA is polymerization to polycarbonate and epoxy resins, it can also be used as an additive, from which it may be easily released. Several studies have already provided scientific evidence for the contribution of sources for dermal BPA absorption, such as thermal paper where BPA is used as an additive. Polymeric applications of BPA require further investigation regarding the amounts of BPA present, as well as the factors affecting its release and potential dermal or non-dermal exposure from these sources. It is clear that not all sources of BPA have been identified. This overview emphasizes the necessity to study also the exposure to these unexpected sources of BPA.

Assessment of human exposure to Bisphenol-A, Triclosan and Tetrabromobisphenol-A through indoor dust intake in Belgium.

Bisphenol-A (BPA), Triclosan (TCS) and Tetrabromobisphenol-A (TBBPA) are phenolic organic contaminants used in a variety of household applications. Through manufacture and usage, these contaminants can leach into the environment and can be detected in indoor dust. In this study, we determined the concentrations of BPA, TCS and TBBPA in indoor dust samples from 18 houses and 2 offices in Flanders, Belgium. The analysis was performed using solid-liquid extraction, clean-up and measurement by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Median concentrations of the 18 domestic dust samples were 1460, 220 and 10 ng g(-1) dust for BPA, TCS and TBBPA, respectively. Concentrations in offices were almost 5-10 times higher for BPA and TBBPA, while TCS concentrations were comparable at both locations. An assessment of the daily intake of these contaminants through dust was made and the contribution of dust to the total human exposure was calculated. For all three contaminants, dust seems to be a minor contributor (<10% of total exposure) to the total daily exposure. Food intake appears to be the major source of human exposure to BPA and TBBPA as dermal uptake through personal care products seems to be the major contributor for TCS.

Obesity and persistent organic pollutants : possible obesogenic effect of organochlorine pesticides and polychlorinated biphenyls

Persistent organic pollutants (POPs) are endocrine‐disrupting chemicals associated with the development of the metabolic syndrome and type 2 diabetes. In humans, little is known about their role in the potential origin of obesity. This study aims to assess the associations between serum levels of POPs and the prevalence of obesity in a cohort of obese and lean adult men and women. POP serum samples were investigated cross‐sectionally in 98 obese and 47 lean participants, aged ≥18 years. Serum samples were analyzed for the presence of polychlorinated biphenyl (PCB) congeners 153, 138, 180, and 170 and for the organochlorine pesticides, dichloro‐diphenyl‐dichloroethylene (pp‐DDE), and β‐hexachlorocyclohexane (βHCH). We established a significant negative correlation between BMI, waist, fat mass percentage, total and subcutaneous abdominal adipose tissue, and serum levels of PCB 153, 180, 170, and the sumPCBs. For βHCH, we demonstrated a positive correlation with BMI, waist, fat mass percentage, and total and subcutaneous abdominal adipose tissue. PCBs 180, 170, and the sum of PCBs correlated significantly negative with homeostasis model assessment for insulin resistance (HOMAIR). βHCH correlated significantly positively with HOMAIR. A strong correlation was established between all POP serum levels and age. We established a positive relationship between high serum levels of βHCH and BMI and HOMAIR, whereas serum PCB levels were inversely correlated with BMI and HOMAIR. Combined, these results suggest that the diabetogenic effect of low‐dose exposure to POPs might be more complicated than a simple obesogenic effect.

Distribution of bisphenol-A, triclosan and n-nonylphenol in human adipose tissue, liver and brain

In this study, an analytical method was optimized for the determination of bisphenol-A (BPA), triclosan (TCS) and 4-n-nonylphenol (4n-NP), environmental contaminants with potential endocrine disruptive activities, in human tissues. The method consisted of a liquid extraction step, derivatization with pentafluorobenzoylchloride followed by a clean-up on acidified silica and detection with gas chromatography coupled with mass spectrometry (GC-ECNI/MS). Recoveries ranged between 92% and 102% with a precision below 5%. Limits of quantification ranged between 0.3-0.4 ng g(-1), 0.045-0.06 ng g(-1) and 0.003-0.004 ng g(-1) for BPA, TCS and 4n-NP in different tissues, respectively. The method was applied for the determination of BPA, TCS and 4n-NP in paired adipose tissue, liver and brain samples from 11 individuals. BPA could be detected in almost all tissues, with the highest concentrations found in adipose tissue (mean 3.78 ng g(-1)), followed by liver (1.48 ng g(-1)) and brain (0.91 ng g(-1)). TCS showed the highest concentrations in liver (3.14 ng g(-1)), followed by adipose tissue (0.61 ng g(-1)), while it could be detected in only one brain sample. Levels of 4n-NP were much lower, mostly undetected, and therefore 4n-NP is considered of minor importance for human exposure. Despite the measurable concentrations in adipose tissue, these compounds seem to have a low bioaccumulation potential. The reported concentrations of free BPA in the various tissues are slight disagreement with pharmacokinetic models in humans and rats and therefore the possibility of external contamination with BPA during sample collection/storage cannot be ruled out.

Intake of bisphenol A from canned beverages and foods on the Belgian market

Bisphenol A (BPA), a contaminant which may be present in the coating of cans, was determined in 45 canned beverages and 21 canned food items from the Belgian market. Beverages had an average BPA concentration of 1.0 ng/ml, while canned foods had a higher average concentration of 40.3 ng/g. The amount of BPA present in food items was dependent on the type of can and sterilisation conditions rather than the type of food. For example, BPA was not detected in non-canned beverages (<0.02 ng/ml), while non-canned food items had a very low average concentration of 0.46 ng/g. Using detailed information from the Belgian food consumption survey, the BPA intake of adults through canned foods and beverages was estimated to be 1.05 µg/day or 0.015 µg/kg body weight/day (assuming an average adult weight of 70 kg). Intake assessments, based on urinary metabolite concentrations from the literature, resulted in slightly higher BPA intakes (range 0.028–0.059 µg/kg body weight/day). This suggests that sources other than canned foods and beverages contribute to BPA exposure in humans.

Sensitive and selective method for the determination of bisphenol-A and triclosan in serum and urine as pentafluorobenzoate-derivatives using GC-ECNI/MS.

The development and validation of an analytical method is presented for the determination of bisphenol-A (BPA) and triclosan (TCS), two ubiquitous contaminants, in serum and urine. The glucuronidated metabolites were first turned into their free forms to determine total BPA and TCS. The determination consisted of a solid-phase extraction on Oasis HLB cartridges followed by an extractive derivatization with pentafluorobenzoylchloride. The extract was then purified on 10% (w/w) acidified silica and analyzed by gas chromatography-mass spectrometry in electron-capture negative ionization mode. Monitored ions were m/z 616 and 406 for BPA and m/z 482 and 287 for TCS, respectively. Limits of quantification were 0.5 ng/mL in serum and 0.2 ng/mL in urine for BPA and 0.1 ng/mL in serum and 0.05 ng/mL in urine for TCS. Method recoveries were between 76 and 110%, while repeatability was below 20%. The method was applied on 20 serum and 20 urine samples. The detection frequency in serum was 10% and 55% for BPA and TCS, respectively. BPA and TCS could be detected in all urine samples with median concentrations of 1.25 ng BPA/mL (range 0.58-5.20 ng/mL) and 1.71 ng TCS/mL (0.18-672 ng/mL).

Phthalate metabolites in obese individuals undergoing weight loss: Urinary levels and estimation of the phthalates daily intake.

Human exposure to chemicals commonly encountered in our environment, like phthalates, is routinely assessed through urinary measurement of their metabolites. A particular attention is given to the specific population groups, such as obese, for which the dietary intake of environmental chemicals is higher. To evaluate the exposure to phthalates, nine phthalate metabolites (PMs) were analyzed in urine collected from obese individuals and a control population. Obese individuals lost weight through either bariatric surgery or a conservative weight loss program with dietary and lifestyle counseling. Urine samples were also collected from the obese individuals after 3, 6 and 12months of weight loss. Individual daily intakes of the corresponding phthalate diesters were estimated based on the urinary PM concentrations. A high variability was recorded for the levels of each PM in both obese and control urine samples showing the exposure to high levels of PMs in specific subgroups. The most important PM metabolite as percentage contribution to the total PM levels was mono-ethyl phthalate followed by the metabolites of di-butyl phthalate and di 2-ethyl-hexyl phthalate (DEHP). No differences in the PM levels and profiles between obese entering the program and controls were observed. Although paralleled by a significant decrease of their weight, an increase in the urinary PM levels after 3 to 6months loss was seen. Constant figures for the estimated phthalates daily intake were observed over the studied period, suggesting that besides food consumption, other human exposure sources to phthalates (e.g. air, dust) might be also important. The weight loss treatment method followed by obese individuals influenced the correlations between PM levels, suggesting a change of the intake sources with time. Except for few gender differences recorded between the urinary DEHP metabolites correlations, no other differences were observed for the urinary PM levels as a function of age, body mass index or waist circumference. Linear regression analysis showed almost no significance of the relationship between measured urinary PMs and serum free thyroxine, thyroid-stimulating hormone (TSH) for all obese individuals participating to the study, while for the control samples, several PMs were significantly associated with the serum TSH levels.

Biomarkers of human exposure to personal care products: Results from the Flemish Environment and Health Study (FLEHS 2007–2011)

Personal care products (PCPs), such as soaps, perfumes, cosmetics, lotions, etc., contain a variety of chemicals that have been described as potentially hormone disrupting chemicals. Therefore, it is important to assess the internal exposure of these chemicals in humans. Within the 2nd Flemish Environment and Health Study (FLEHS II, 2007-2011), the human exposure to three classes of pollutants that are present in a wide variety of PCPs--i.e. polycyclic musks (galaxolide, HHCB and tonalide, AHTN in blood), parabens (urinary para-hydroxybenzoic acid, HBA) and triclosan (urinary TCS)--was assessed in 210 Flemish adolescents (14-15 years) and in 204 adults (20-40 years) randomly selected from the general population according to a stratified two stage clustered study design. The aim of this study was to define average levels of exposure in the general Flemish population and to identify determinants of exposure. Average levels (GM (95% CI)) in the Flemish adolescents were 0.717 (0.682-0.753) μg/L for blood HHCB; 0.118 (0.108-0.128) μg/L for blood AHTN; 1022 (723-1436) μg/L for urinary HBA and 2.19 (1.64-2.92) μg/L for urinary TCS. In the adults, levels of HBA were on average 634 (471-970) μg/L. Inter-individual variability was small for HHCB and AHTN, intermediate for HBA, and large for TCS. All biomarkers were positively associated with the use of PCPs. Additionally, levels of HHCB and AHTN increased with higher educational level of the adolescents. Both in adults and adolescents, urinary HBA levels were negatively correlated with BMI. We define here Flemish exposure values for biomarkers of PCPs, which can serve as baseline exposure levels to identify exposure trends in future biomonitoring campaigns.