Thyroid cancer and endocrine disruptive chemicals: a case-control study on per-fluoroalkyl substances and other persistent organic pollutants.

Objective: The aim was to evaluate the possible association between some endocrine disruptive chemicals and thyroid cancer (TC) in an Italian case-control cohort. Methods: We enrolled 112 TC patients and 112 sex- and age-matched controls without known thyroid diseases. Per- and poly-fluoroalkyl substances (PFAS), poly-chlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (4,4'-DDT and 4,4'-DDE) were measured in the serum by liquid or gas chromatography-mass spectrometry. Unconditional logistic regression, Bayesan kernel machine regression and weighted quantile sum models were used to estimate the association between TC and pollutants' levels, considered individually or as mixture. BRAFV600E mutation was assessed by standard methods. Results: The detection of perfluorodecanoic acid (PFDA) was positively correlated to TC (OR = 2.03, 95% CI: 1.10-3.75, P = 0.02), while a negative association was found with perfluorohexanesulfonic acid (PFHxS) levels (OR = 0.63, 95% CI: 0.41-0.98, P = 0.04). Moreover, perfluorononanoic acid (PFNA) was positively associated with the presence of thyroiditis, while PFHxS and perfluorooctane sulfonic acid (PFOS) with higher levels of presurgical thyroid-stimulating hormone (TSH). PFHxS, PFOS, PFNA, and PFDA were correlated with less aggressive TC, while poly-chlorinated biphenyls (PCB-105 and PCB-118) with larger and more aggressive tumors. Statistical models showed a negative association between pollutants' mixture and TC. BRAF V600E mutations were associated with PCB-153, PCB-138, and PCB-180. Conclusion: Our study suggests, for the first time in a case-control population, that exposure to some PFAS and PCBs associates with TC and some clinical and molecular features. On the contrary, an inverse correlation was found with both PFHxS and pollutants' mixture, likely due to a potential reverse causality.

Repeated Human Exposure to Semivolatile Organic Compounds by Inhalation: Novel Protocol for a Nonrandomized Study.

BACKGROUND: Semivolatile organic compounds (SVOCs) comprise several different chemical families used mainly as additives in many everyday products. SVOCs can be released into the air as aerosols and deposit on particulate matter during use by dispersion, evaporation, or abrasion. Phthalates are SVOCs of growing concern due to their endocrine-disrupting effects. Human data on the absorption, distribution, metabolism, and excretion (ADME) of these compounds upon inhalation are almost nonexistent. OBJECTIVE: The goal of this study is to develop a method for repeated inhalation exposures to SVOCs to characterize their ADME in humans. METHODS: We will use diethylhexyl phthalate (DEHP), a major indoor air pollutant, as a model SVOC in this novel protocol. The Swiss official Commission on Ethics in Human Research, Canton de Vaud, approved the study on October 14, 2020 (project-ID 2020-01095). Participants (n=10) will be repeatedly exposed (2 short daily exposures over 4 days) to isotope-labeled DEHP (DEHP-d4) to distinguish administered exposures from background exposures. DEHP-d4 aerosols will be generated with a small, portable, aerosol-generating device. Participants will inhale DEHP-d4-containing aerosols themselves with this device at home. Air concentrations of the airborne phthalates will be less than or equal to their occupational exposure limit (OEL). DEHP-d4 and its metabolites will be quantified in urine and blood before, during, and after exposure. RESULTS: Our developed device can generate DEHP-d4 aerosols with diameters of 2.5 µm or smaller and a mean DEHP-d4 mass of 1.4 (SD 0.2) µg per puff (n=6). As of May 2023, we have enrolled 5 participants. CONCLUSIONS: The portable device can be used to generate phthalate aerosols for repeated exposure in human studies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51020.

Exposure to endocrine disrupters and cardiometabolic health effects in preschool children: Urinary parabens are associated with wider retinal venular vessels.

BACKGROUND AND AIM: Parabens are widely used as antimicrobial preservatives in personal care products. Studies investigating obesogenic or cardiovascular effects of parabens show discordant results, while data on preschool children are lacking. Paraben exposure during early childhood could have profound cardiometabolic effects later in life. METHODS: In this cross-sectional study paraben concentrations [methyl (MeP), ethyl (EtP), propyl (PrP), butyl (BuP)] were measured by ultra-performance liquid chromatography/tandem mass spectrometry in 300 urinary samples of 4-6-year-old children of the ENVIRONAGE birth cohort. Paraben values below the limit of quantitation (LOQ) were imputed by censored likelihood multiple imputation. The associations between log-transformed paraben values and cardiometabolic measurements (BMI z-scores, waist circumference, blood pressure and retinal microvasculature) were analyzed in multiple linear regression models with a priori selected covariates. Effect modification by sex was investigated by including interaction terms. RESULTS: Geometric means (geometric SD) of urinary MeP, EtP, and PrP levels above the LOQ were 32.60 (6.64), 1.26 (3.45), and 4.82 (4.11) µg/L, respectively. For BuP more than 96% of all measurements were below the LOQ. Regarding the microvasculature, we found direct associations between MeP and central retinal venular equivalent (ß = 1.23, p = 0.039) and PrP with the retinal tortuosity index (x103)(ß = 1.75, p = 0.0044). Furthermore, we identified inverse associations between MeP and ∑parabens with BMI z-scores (ß = -0.067, p = 0.015 and ß = -0.070, p = 0.014 respectively), and EtP with mean arterial pressure (ß = -0.69, p = 0.048). The direction of association between EtP and BMI z-scores showed evidence for sex-specific differences with a direct trend in boys (ß = 0.10, p = 0.060). CONCLUSIONS: Already at young age paraben exposure is associated with potentially adverse changes in the retinal microvasculature.

Associations between endocrine disruptor contamination and thyroid hormone homeostasis in Belgian type 1 diabetic children.

PURPOSE: Humans are daily exposed to many environmental pollutants, some of which being suspected to be thyroid disruptors. Some populations could be particularly susceptible to thyroid disruption, such like diabetics due to the well-known relation between the thyroid function and the control of carbohydrate homeostasis by pancreas. Therefore, the aim of this study was to investigate the associations between the exposure to several persistent and non-persistent chemicals and thyroid hormones levels in children with type 1 diabetes. METHODS: Blood and urine sample were collected from 54 children diagnosed for type 1 diabetes mellitus. The concentrations of 7 phthalate metabolites, 4 parabens, 7 bisphenols, benzophenone 3 and triclosan were measured in urine, while 15 organochlorine pesticides, 4 polychlorinated biphenyls (PCBs) and 7 perfluoroalkyl substances were analyzed in serum samples. In the same time, the blood levels of free thyroxine (fT4), thyroid stimulating hormone (TSH) and glycated hemoglobin (Hb1Ac) were determined. RESULTS: We highlighted positive associations between serum perfluorohexane sulfonate and urinary monoethylphthalate levels, and TSH level in blood. We also found that PCB 138 was positively associated to fT4 while urinary levels of bisphenol F were negatively correlated to this hormone. Finally, we observed positive associations between Hb1Ac levels and the contamination by PCB 153 and two urinary phthalate metabolites: mono-2-ethyl-5-hydroxyhexyl phthalate and mono-2-ethyl-5-oxoxyhexyl phthalate. CONCLUSION: Our results showed that our small cohort of children with type 1 diabetes mellitus is potentially susceptible to thyroid disruptions by some pollutants. Moreover, for these children, both di-(2-ethylhexyl) phthalate metabolites would potentially hamper the glucose homeostasis. Nevertheless, additional studies are mandatory to further explore these findings.

Human biomonitoring survey (Pb, Cd, As, Cu, Zn, Mo) for urban gardeners exposed to metal contaminated soils.

Eighty eight adult gardeners and their relatives volunteered to provide urine and blood samples for a human biomonitoring survey among users of one of the biggest allotment garden from Wallonia, showing high trace metal(oid) concentrations in soils. The purpose was to determine if environmental levels of lead (Pb), cadmium (Cd) and arsenic (As) led to concentrations of potential health concern in the study population. Blood and urine biomarkers were compared to reference and intervention cut-off values selected from the literature. The study population exhibited (i) moderately high blood lead levels with median value of 23.1 µg/L, (ii) high urinary concentrations of speciated As (inorganic arsenic and its metabolites) with a median value of 7.17 µg/g.cr., i.e. twice the median values usually observed in general populations, and (iii) very high Cd levels in urine with a median value of 1.23 µg/L, in the range of 95th-97.5th percentiles measured in general adult populations. Biomarker levels in the study population were also mostly above those measured in adults from local populations living on contaminated soils, as reported in the current literature. All biomarkers of Pb, Cd and As showed weak to strong statistically significant correlations, pointing towards a joint environmental source to these three contaminants as being at least partially responsible for the high exposure levels observed. Urine and blood biomarkers show statistically significant associations with variables related to individual characteristics (age, smoking status, …) and Pb domestic sources (Pb pipes, cosmetics, …) but involves also behavioral and consuming habits related to gardening activities on the contaminated allotment garden. At such levels, owing to co-exposure and additive effects of Cd, As and Pb regarding renal toxicity known from literature, the study strongly suggests that this population of gardeners is at risk with respect to chronic kidney diseases.

Urinary levels of parabens, phthalate metabolites, bisphenol A and plasticizer alternatives in a Belgian population: Time trend or impact of an awareness campaign?

A human biomonitoring study was carried out in 2015 within an adult population living in Liege (Belgium). Some phthalate metabolites and parabens were measured in the urine of 252 participants, and information were collected about their food habits, life styles and home environment to identify some predictors of exposure. Concomitantly, an awareness campaign was initiated by the Provincial Authorities of Liege and spread over 2 years. Three years later (2018), 92 of the initial participants provided again urine samples, and the levels of phthalate metabolites, phthalate substitute (DINCH), parabens, bisphenol-A and bisphenol alternatives (bisphenol-S, -F, -Z, -P) were determined and compared to those obtained in 2015 to assess time trends. In 2015, methyl- and ethylparaben were the most abundant parabens (P50 = 9.12 µg/L and 1.1 µg/L respectively), while propyl- and butylparaben were sparsely detected. Except for mono-2-ethylhexyl phthalate and 6-OH-mono-propyl-heptyl phthalate, all other targeted phthalate metabolites were positively quantified in most of the urine samples (between 89 and 98%) with median concentrations ranging between 2.7 µg/L and 21.3 µg/L depending on the metabolite. The multivariate regression models highlighted some significant associations between urinary phthalate metabolite or paraben levels and age, rural or urban character of the residence place, and the use of some personal care products. However, all determination coefficients were weak meaning that the usual covariates included in the models only explained a small part of the variance. Between 2015 and 2018, levels of parabens and phthalate metabolites significantly decreased (from 1.3 to 2.5 fold) except for monoethyl phthalate which seemed to remain quite constant. Contrariwise, all bisphenol alternatives and DINCH metabolites were measured in higher concentrations in 2018 vs 2015 while BPA levels did not differ significantly. However, it was not feasible to unequivocally highlight an impact of the awareness campaign on the exposure levels of the population.

Determination of contamination levels for multiple endocrine disruptors in hair from a non-occupationally exposed population living in Liege (Belgium).

Today, the interest in hair as alternative matrix for human biomonitoring of environmental pollutants has increased, but available data on chemical levels in hair remain scarce. In this study, the measurement of 2 bisphenols (A and S), 3 parabens (methyl-, ethyl- and propylparabens) and 8 perfluroralkyl compounds (PFCs) namely perfluoroctanesulfonate (PFOS), perfluorohexanesulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluroroheptanoic acid (PFHpA), perfluoropentanoic acid (PFPeA) and perfluorohexanoic acid (PFHxA) was carried out, using a thoroughly validated UPLC-MS/MS method, in the hair from 114 adults living in Liege (Belgium) and surrounding areas. The most frequently quantified compounds in the population were: bisphenol S (97.4%, median = 31.9 pg·mg-1), methylparaben (94.7%, median = 28.9 pg·mg-1), bisphenol A (93.9%, median = 46.6 pg·mg-1), ethylparaben (66.7%, median = 5.2 pg·mg-1), propylparaben (54.8%, median = 16.4 pg·mg-1) and PFOA (46.4%, median < 0.2 pg·mg-1). The other PFCs were detected only in few samples although current exposure of the Belgian population to PFCs was previously demonstrated using blood analyses. Nonparametric statistical analyses were performed to evaluate the influence of gender, hair treatments and hair length, but no significant difference was observed. Only age was positively correlated with the propylparaben contamination. Although blood seems to remain more suitable for PFCs exposure assessment, the results of this study suggest that hair can be an appropriate matrix for biomonitoring of organic pollutants such as parabens or bisphenols.

Bio-surveillance of environmental pollutants in the population of Kinshasa, Democratic Republic of Congo (DRC): a small pilot study.

BACKGROUND: Environmental pollutants are known to be ubiquitous and may present toxic effects (endocrine-disruption properties, carcinogenicity …) and represent a real threat to human health. The aim of the present pilot study was to assess the content of environmental pollutants (inorganic, persistent, and non-persistent pollutants) in biological samples (urine, serum, and whole blood), collected from volunteers in Kinshasa, capital of Democratic Republic of Congo, in order to identify pollutants of interest and to design a protocol for a larger scale study. METHODS: From randomly selected 15 volunteers living in Kinshasa, aged from 25 to 66 years, (mean age = 43.4 years), including 10 men and 5 women, urine, whole blood, and serum samples were used in this study to estimate the contents in these environmental pollutants, using inductively coupled plasma mass spectrometry, gas chromatography coupled to mass spectrometry, and liquid chromatography coupled to mass spectrometry. RESULTS: When compared to data nationally and internationally available, the preliminary outcomes of this study indicated a very high level of exposure to environmental pollutants in the population of Kinshasa, especially for heavy metals, parabens and triclosan. To a lesser extent, contamination measured for glyphosate, phthalates, organochlorine pesticides, pyrethroids and dialkylphosphate pesticides was also significant. In contrast, the investigated population of Kinshasa was found to be weakly exposed to other persistent organic pollutants like polychlorinated biphenyls, brominated flame retardants, phenolic organohalogens, and perfluoroalkyl substances. CONCLUSION: Although the biologic fluids were collected from a limited number of volunteers (n = 15), the results of the present report clearly indicate that the population of Kinshasa is not spared by the investigated environmental pollutants. Moreover, this study gives us important information to design a larger scale study protocol.

Background contamination of perfluoralkyl substances in a Belgian general population.

The few Belgian studies on the human exposure to perfluoroalkyl substances (PFASs) have until now concerned the Northern part of Belgium (Flanders), while data related to Wallonia (South region) are missing. To fill this gap, 8 perfluorinated carboxylic acids and 3 perfluorinated alkyl sulfonates were measured in the serum of 242 adults (>18 years old) recruited in 2015 and living in the Province of Liege. Some multivariate regression models were also built with the PFAS levels and the participant's answers to a questionnaire about their diet and lifestyle habits in order to identify some predictors of exposure. The results obtained showed that although PFAS levels observed in our population seemed to be similar or lower than those reported in other countries, and especially lower than in the Northern part of Belgium, half of the population showed PFOS and PFOA serum levels above the health guidance values set by the German HBM Commission. As expected, age and gender were the main covariates explaining the different PFAS serum levels between participants, while breastfeeding (for women), consumption of fish and seafood, consumption of rice, and use of nail polish seemed also to impact the PFAS body burden of our population. Nevertheless, the statistical models were poorly predictive suggesting that the main sources of exposure were not taken into account.

Assessment of children's exposure to currently used pesticides in wallonia, Belgium.

In spring 2016, a study was carried out to characterize currently used pesticide (CUP) exposure among children living in Wallonia (Belgium). Pesticides were measured in both first morning urine voids of 258 children aged from 9 to 12 years and in ambient air collected close to the children's schools. Out of the 46 pesticides measured in the air, 19 were detected with frequencies varying between 11 % and 100 %, and mean levels ranging from <0.04 to 2.37 ng/m³. Only 3 parent pesticides were found in 1-10% of the urine samples, while all the metabolites analyzed were positively detected at least once. The captan metabolite (THPI) was quantified in 23.5 % of the samples, while 3,5,6-trichloro-2-pyridinol (chlopryrifos metabolite) was detected in all urines with levels ranging from 0.36-38.96 µg/l. 3-phenoxybenzoic acid (3-PBA), trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (t-DCCA) and diethylphosphate were the most abundant pyrethroid metabolites and dialkylphosphate measured. The air inhalation was demonstrated to be a minor route of exposure for the selected CUPs. Statistical regressions highlighted predictors of exposure for some pesticides such like consumption of grey bread, presence of carpets at home or indoor use of pesticides, although no clear source was identified for most of them.

Association between mixture of persistent organic pollutants and thyroid pathologies in a Belgian population.

Previous years, the incidence of autoimmune thyroid diseases has increased worldwide. The presence of many pollutants in the environment suspected to be thyroid disruptors may have contributed to the observed increase. Unfortunately, the results from epidemiological studies assessing the association between pollution and thyroid disorders remain inconsistent, maybe due to a nearly complete neglect of the mixture effect. The blood levels of 12 brominated flame retardants, 3 polychlorinated biphenyls, 16 organochlorine pesticides, 7 perfluoroalkyl substances and 16 phenolic organohalogens were measured in 35 hypothyroid and 44 hyperthyroid volunteers and in 160 individuals from the general population designed as controls. Weighted quantile sum (WQS) regressions were performed to compute indexes representing the mixture of POPs, and we assessed the relations with thyroid disorders. Nineteen pollutants were detected in more than 40% of the individuals and were thus included in the WQS indexes. The WQS index was statistically significantly associated with an increased odds of hypothyroidism (odds ratio (OR) = 98.1; 95% CI: 5.51-1747) with the highest weights attributed to PCB 138 (w = 0.210), 3-OH-CB 180 (w = 0.197), 4-OH-CB 146 (w = 0.188), 4',4-DDE (w = 0.156) while there were no evidence of a relation with increased odds of hyperthyroidism. Given the relative low number of individuals included in the present investigation, standard WQS methodology could not be used, this study should thus be considered as a preliminary, hypothesis-generating study. Nevertheless, these results highlighted the importance of considering the potential effect of chemical mixture when studying endocrine disruptors.

Simple and fast method for the measurement of legacy and novel brominated flame retardants in human serum.

Recent and reliable human biomonitoring data on brominated flame retardants (BFRs), either legacy or new BFRs, are still needed to assess human exposure. The aim of this work was therefore to develop and validate an accurate, fast and user-friendly analytical strategy for the determination of 15 legacy and novel BFRs in human serum namely 8 polybrominated diphenylethers (BDE-28, -47, -99, -100, -153, -154, -183, and -209), 1 hexabromobiphenyl (PBB-153), and 6 novel BFRs (pentabromotoluene, hexabromobenzene, pentabromoethylbenzene, 2-ethylhexy-2,3,4,5-tetrabromobenzoate, 1,2-bis(2,4,6-tribromophenoxy)ethane, and decabromodiphenylethane). This analytical procedure consisted in a simple liquid-liquid extraction followed by elution on a PHREE cartridge avoiding further laborious purification steps. The final determination was performed by gas chromatography coupled to mass spectrometry in electron capture negative ionization mode (GC-ECNI-MS). The 15 m long RTX-1614 allowed the simultaneous measurement of the 15 BFRs including low and high brominated species within a single injection on a single column. Except for 2-ethylhexy-2,3,4,5-tetrabromobenzoate (EHTBB) which showed very high response variations resulting in poor linearity, trueness and precision, and decabromodiphenylethane for which very low sensitivity was achieved, the 13 other BFRs passed the validation process with recoveries varying between 56 and 82%, and limits of quantification (LOQs) ranging from 2.5 to 6.0 pg/ml (34.5 pg/ml for BDE-209). Within the validated range of concentrations, the relative bias from the introduced levels were below 20% while the intra and inter precisions were maintained below 15%. The reliability of the technique was confirmed by successfully analyzing interlaboratory test materials (AMAP ring test for POPs in human serum).

Association between organohalogenated pollutants in cord blood and thyroid function in newborns and mothers from Belgian population.

The last decades have seen the increasing prevalence of thyroid disorders. These augmentations could be the consequence of the increasing contamination of the environment by chemicals that may disrupt the thyroid function. Indeed, in vitro studies have shown that many chemicals contaminating our environment and highlighted in human serum, are able to interfere with the thyroid function. Given the crucial importance of thyroid hormones on neurodevelopment in fetus and newborns, the influence of these pollutants on newborn thyroid homeostasis is a major health concern. Unfortunately, the overall evidence for a deleterious influence of environmental pollutants on thyroid remains poorly studied. Therefore, we assessed the contamination by polychlorinated biphenyls (PCBs), organochlorine pesticides and perfluorinated compounds (PFC) in 221 cord blood samples collected in Belgium between 2013 and 2016. Our results showed that compared to previous studies performed on newborns recruited in Belgium during the two last decades, the present pollutant contamination is declining. Multivariate statistical analyses pointed out a decrease of thyroid stimulating hormone (TSH) level in male newborns with detectable level of 4,4'- dichlorodiphenyldichloroethylene (4,4'-DDE) in comparison with those with no detectable level (p = 0.025). We also highlighted a negative association between perfluorononanoic acid (PFNA) concentration and TSH in male newborns (p = 0.018). Logistic regression showed increased odds ratio for presentation of hypothyroid in mother for each one unit augmentation of log natural concentration of PFOA (OR = 2.30, [1.18-4.5]) and PFOS (OR = 2.03 [1.08-3.83]). Our findings showed that the residual contamination by PFCs and organochlorine pollutants in cord blood are correlated with thyroid hormone in the newborns and the risk of hypothyroid in mothers.

The current environmental levels of endocrine disruptors (mercury, cadmium, organochlorine pesticides and PCBs) in a Belgian adult population and their predictors of exposure.

A human biomonitoring study was carried out measuring the levels of endocrine disruptors in 252 participants (18-76 years old) recruited between February and May 2015 from the general population of Liege Province (Belgium). In this study, we reported the recent levels of cadmium and mercury in urine, some organochlorine pesticides and polychlorinated biphenyls (PCBs) in serum, and their relations to demographic characteristics, lifestyle behaviors and dietary habits. The median urinary levels of mercury and cadmium were 0.81µg/l and <0.5µg/l respectively. The mercury levels were higher in participants having at least 3 dental amalgams, and consuming sea fish more than once a week. Although our mercury levels in most participants were lower than some health-based guidelines, they were higher than in our neighboring countries where ban or restrictions on the dental amalgams use were implemented. Urinary cadmium levels in current smokers were significantly higher than former or never smokers, as well as non-smokers for passively exposed vs non-exposed ones. Median PCB-153 and -180 serum levels were 53.8 and 41.1ng/g lipid respectively, but PCB-138 was below the limit of quantification of 0.15µg/l in 49% of the samples. Among the organochlorine pesticides, 4,4'-dichlorodiphenyldichloroethylene (4,4'-DDE), beta-hexachlorohexane and hexachlorobenzene were positively detected respectively in 48%, 49% and 37% of the serum samples. Eventhough, a dramatic decrease in organochlorines levels was observed, at least 1 pesticide or PCB was detected in 96% of our population, and more than 50% of our samples were contaminated by 4 or more organochlorines. Age, body mass index, and breastfeeding duration were the most predictive determinants of pesticide or PCB serum concentrations, but not dietary habits.

Determination of phenolic organohalogens in human serum from a Belgian population and assessment of parameters affecting the human contamination.

Many in vitro or in vivo studies highlighted the potential deleterious effects of phenolic organohalogenated compounds (POHs) on the health, particularly on the thyroid system homeostasis, however few large scale human epidemiological studies have been carried out, especially in Europe. Further studies monitoring the human contamination by POHs, the sources of exposure and the influence of these compounds on thyroid health are still needed. Therefore we determined the concentrations of 16 POHs (pentachlorophenol (PCP), tetrabromobisphenol A (TBBPA), 4 bromophenols (BPs), 3 hydroxy-polybromodiphenylethers (OH-PBDEs) and 7 hydroxy-polychlorobiphenyls (OH-PCBs)) in serum from 274 people aged from 18 to 76years old living in Liege (Belgium) and the surrounding area. A questionnaire about their alimentary habits, life style and home environment was also administered to the volunteers. The predominant compound measured in the population was PCP (median concentration of 593.0pgmL-1). 4-OH-CB 107, 4-OH-CB 146 and 4-OH-CB 187 were detected in all samples and contributed for 75% of the sum of OH-PCBs (ΣOH-PCBs). The median measured in our population for ΣOH-PCBs was 143.7pgmL-1. TBBPA and 2,4,6-tribromophenol were detected in 31% and 63.8% of the samples respectively while the detection frequency observed for the other BPs and the OH-PBDEs was close to zero. We computed multivariate regression models in order to assess the influence of demographic and lifestyle parameters on the PCP and ΣOH-PCBs contamination levels. Significant correlation was found between the PCP concentration and sex, smoker status, sea fish consumption and level of education, although the model seemed to be a poor (R2=0.14) predictor of the PCP concentration. The model computed for ΣOH-PCBs was more explanatory (R2=0.61) and involved age, BMI and sea fish consumption. Finally, we assessed the parameters affecting the ΣOH-PCBs/ΣPCBs ratio. The model proposed involved age, BMI, smoker status and parent PCB level, and explained 41% of the variability of the ΣOH-PCBs/ΣPCBs ratio.

Biocompatibility of polymer-infiltrated-ceramic-network (PICN) materials with Human Gingival Keratinocytes (HGKs).

OBJECTIVE: Biocompatibility of polymer-infiltrated-ceramic-network (PICN) materials, a new class of CAD-CAM composites, is poorly explored in the literature, in particular, no data are available regarding Human Gingival Keratinocytes (HGK). The first objective of this study was to evaluate the in vitro biocompatibility of PICNs with HGKs in comparison with other materials typically used for implant prostheses. The second objective was to correlate results with PICN monomer release and indirect cytotoxicity. METHODS: HGK attachment, proliferation and spreading on PICN, grade V titanium (Ti), yttrium zirconia (Zi), lithium disilicate glass-ceramic (eM) and polytetrafluoroethylene (negative control) discs were evaluated using a specific insert-based culture system. For PICN and eM samples, monomer release in the culture medium was quantified by high performance liquid chromatography and indirect cytotoxicity tests were performed. RESULTS: Ti and Zi exhibited the best results regarding HGK viability, number and coverage. eM showed inferior results while PICN showed statistically similar results to eM but also to Ti regarding cell number and to Ti and Zi regarding cell viability. No monomer release from PICN discs was found, nor indirect cytotoxicity, as for eM. SIGNIFICANCE: The results confirmed the excellent behavior of Ti and Zi with gingival cells. Even if polymer based, PICN materials exhibited intermediate results between Ti-Zi and eM. These promising results could notably be explained by PICN high temperature-high pressure (HT-HP) innovative polymerization mode, as confirmed by the absence of monomer release and indirect cytotoxicity.

Validation of a novel and rapid method for the simultaneous determination of some phenolic organohalogens in human serum by GC-MS.

Over the last decades, more and more studies focused on the impact of endocrine disruptors on the environment and human health. Among them, phenolic organohalogens (POHs) are a particular concern because of their structural resemblance with natural hormones. There are different methods that are known to quantify these compounds in human serum, however, the current extraction techniques are long, fastidious and using harmfull chemicals such as diazomethane and sulfuric acid. Consequently, we developed an alternative, sensitive and faster method to simultaneously quantify pentachlorophenol (PCP), tetrabromobisphenol A (TBBPA), 4 bromophenols, 7 hydroxypolychlorinated biphenyls (OH-PCBs) and 3 hydroxy-polybrominated diphenyl ether (OH-PBDEs) in human serum sample. The clean-up and the enrichment of the sample were performed in a single extraction step using strong anion-exchange solid phase cartridge. After a rapid liquid-liquid extraction step to remove acidic traces, the extract was derivatized using trimethylsilyldiazomethane (TMSD) and finally analyzed by a gas-chromatograph coupled with an electron negative capture chemical ionization source combined with a triple quadrupole mass spectrometer (GC-ENCI-MS) operating in single ion monitoring. The whole procedure was validated according to the total error approach. The inter and intra assay precision were demonstrated to be lower than 20% and the relative bias to be lower than 15% in the dosing range of concentrations. The limit of quantification (LOQ) ranged from 2pgmL-1 and 5pgmL-1, except for the PCP (44.6pgmL-1) and for the 2,4,6-tribromophenol (49.6pgmL-1). Finally, the method was successfully applied to measure the POH background contamination in serum samples collected from 20 Belgian blood donors recruited in CHU Mont-Godinne (Namur, Belgium) aged between 21 and 69 years old.

Measurement of emerging dechloranes in human serum using modulated gas chromatography coupled to electron capture negative ionization time-of-flight mass spectrometry.

RATIONALE: Quite recently, the presence of significant amounts of several emerging Dechlorane (Dec) flame retardants (FRs) was reported in environmental and biota samples, principally from Canada and China, but also from Europe. Several molecules were identified, e.g. Dec 602, 603, 604, Dechlorane Plus (DP), and Chlordene Plus (CP). Gas chromatography (GC) coupled to electron ionization (EI) high-resolution mass spectrometry (HRMS) is typically used for their measurement in various matrices based on hexachlorocyclopentadiene (HCCPD) fragment ions at m/z 271.8102/273.8072. METHODS: We investigated the use of GC with cryogenic zone compression and electron capture negative ionization time-of-flight mass spectrometry (CZC-GC/ECNI-TOFMS) to measure Dechlorane compounds at low levels in human serum. The TOFMS instrument provided a resolving power of 5000 (FWHM) with an acquisition rate of 25 Hz and was equipped with a specific low thermal emission filament, which allowed it to perform reproducibly in ECNI mode at ion source temperatures as low as 140°C, thus yielding a signal for the molecular ion cluster. RESULTS: The method provided comparable sensitivity to the GC/EI-SectorHRMS technique used in selected ion monitoring (SIM) mode, and specificity for the target Dechlorane compounds. The method was applied on human serum samples and quantification was performed for Dec 602, Dec 603, and CP, ranging from 0.1 to 10 ng/g lipid weight levels. The main drawbacks of the method are the high instrument detection limits (IDLs) obtained for DP and Dec 604. The method would benefit from even softer ionization and better ion transmission. CONCLUSIONS: The main advantages of the present method are the selectivity, as detection is based on the molecular ion signal, and the use of good mass accuracy combined with isotopic distribution calculation for molecular formulae investigation of halogenated compounds. This methodology should facilitate the monitoring of emerging Dechlorane contaminants in future studies, and possibly extend the scope to untargeted emerging analogues. Copyright © 2016 John Wiley & Sons, Ltd.

Temporal variability of urinary concentrations of phthalate metabolites, parabens and benzophenone-3 in a Belgian adult population.

In the present study, we investigated the temporal within-person variability of the exposure biomarker for phthalates, parabens and benzophenone-3 (BP3) in 32 Belgian adults, each providing 11 urine spots during 4 months. We calculated the intraclass coefficient correlation (ICC), the sensitivity and the specificity to assess the temporal reproducibility and to investigate the predictive ability of the spot measurements for these classes of chemicals. Additionally, we explored the temporal variability of the estimation of the cumulative risk of exposure to phthalates (hazard index; HI). We observed fair ICC ranging from 0.55 to 0.68 for parabens, monoethyl phthalate (MEP), mono-iso-butyl phthalate (MiBP) and BP3, but lower ICC, from 0.20 to 0.49, for monobenzyl phthalate (MBzP), mono-n-butyl phthalate (MnBP), mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxo-hexyl phthalate (5-oxo-MEHP) and mono-2-ethyl-5-hydroxy-hexyl phthalate (5-OH-MEHP). The ICC estimated for HI (0.49) reflected a moderate reproducibility. The measurements in spot samples were moderate to good predictor of the 4-month level of exposure for parabens, MEP, MnBP, MiBP, BP3 and HI (sensitivity ranging from 0.67 to 0.77), but lower predictor for MEHP, 5-oxo-MEHP, 5-OH-MEHP and MBzP (sensitivity ranging from 0.58 to 0.63). The sensitivity could be increased when several spot urinary levels were averaged to predict the long-term level of exposure. Globally, our results indicate that a single spot measurement seems to correctly represent the long-term exposure for parabens, BP3, MEP, MiBP and HI. Additional spot samples seemed to be needed for the proper exposure assessment of the other target compounds.

Fish consumption patterns and hair mercury levels in children and their mothers in 17 EU countries.

The toxicity of methylmercury (MeHg) in humans is well established and the main source of exposure is via the consumption of large marine fish and mammals. Of particular concern are the potential neurodevelopmental effects of early life exposure to low-levels of MeHg. Therefore, it is important that pregnant women, children and women of childbearing age are, as far as possible, protected from MeHg exposure. Within the European project DEMOCOPHES, we have analyzed mercury (Hg) in hair in 1799 mother-child pairs from 17 European countries using a strictly harmonized protocol for mercury analysis. Parallel, harmonized questionnaires on dietary habits provided information on consumption patterns of fish and marine products. After hierarchical cluster analysis of consumption habits of the mother-child pairs, the DEMOCOPHES cohort can be classified into two branches of approximately similar size: one with high fish consumption (H) and another with low consumption (L). All countries have representatives in both branches, but Belgium, Denmark, Spain, Portugal and Sweden have twice as many or more mother-child pairs in H than in L. For Switzerland, Czech Republic, Hungary, Poland, Romania, Slovenia and Slovakia the situation is the opposite, with more representatives in L than H. There is a strong correlation (r=0.72) in hair mercury concentration between the mother and child in the same family, which indicates that they have a similar exposure situation. The clustering of mother-child pairs on basis of their fish consumption revealed some interesting patterns. One is that for the same sea fish consumption, other food items of marine origin, like seafood products or shellfish, contribute significantly to the mercury levels in hair. We conclude that additional studies are needed to assess and quantify exposure to mercury from seafood products, in particular. The cluster analysis also showed that 95% of mothers who consume once per week fish only, and no other marine products, have mercury levels 0.55 µg/g. Thus, the 95th percentile of the distribution in this group is only around half the US-EPA recommended threshold of 1 µg/g mercury in hair. Consumption of freshwater fish played a minor role in contributing to mercury exposure in the studied cohort. The DEMOCOPHES data shows that there are significant differences in MeHg exposure across the EU and that exposure is highly correlated with consumption of fish and marine products. Fish and marine products are key components of a healthy human diet and are important both traditionally and culturally in many parts of Europe. Therefore, the communication of the potential risks of mercury exposure needs to be carefully balanced to take into account traditional and cultural values as well as the potential health benefits from fish consumption. European harmonized human biomonitoring programs provide an additional dimension to national HMB programs and can assist national authorities to tailor mitigation and adaptation strategies (dietary advice, risk communication, etc.) to their country's specific requirements.