A novel analytical approach for the determination of ethylene-thiourea and propylene-thiourea in vegetal foodstuffs by high-performance liquid chromatography hyphenated to inductively coupled plasma-tandem mass spectrometry.

This study reports a novel analytical approach for the simultaneous determination of ethylene-thiourea (ETU) and propylene-thiourea (PTU) in fruits and vegetables by (reverse phase) high-performance liquid chromatography (HPLC) coupled to inductively coupled plasma-tandem mass spectrometry (ICP-QQQMS or ICP-MS/MS). A baseline separation of ETU and PTU was achieved in less than 5 min. A robust method validation by using the accuracy profile approach was performed by carrying out four measurement series in duplicate at six different levels over a timespan of 4 weeks (different days). The recovery factors ranged from 87 to 101% for ETU and from 98 to 99% for PTU (depending on the spiking level). The coefficient of variation in terms of repeatability (CVr) ranged from 1 to 4.7% for ETU and from 1.8 to 3.9% for PTU (depending also on the analyte level) while the coefficient of variation in terms of intermediate reproducibility (CVR) ranged from 3.4 to 10% for ETU and from 1.8 to 10.8% for PTU. The limit of quantification was 0.022 mg kg-1 (wet weight) for ETU and 0.010 mg kg-1 (ww) for PTU. This novel approach was proved to be highly robust and suitable for the determination of ETU and PTU in foodstuffs of vegetal origin.

Source apportionment and seasonal variation in particulate PAHs levels at a coastal site in Belgium.

In the present study, estimation of the atmospheric polycyclic aromatic hydrocarbons (PAHs) was done in particulate samples collected from De Haan, Belgium, during different seasons. The sampling site was situated very close to the north sea and far from the influence of local or industrial activities. The levels of PAHs depicted a distinct seasonal trend, being highest during the spring season. The observations of the study indicated a mean value of 2.6 ng m-3 for concentration of all the 16 US EPA PAHs, thus being significantly lower when compared to results of previous studies focused on other sites. The dominating PAHs species reported were naphthalene, fluoranthene, benzo[a]anthracene, chrysene, and indeno[1,2,3c,d] pyrene. Assessment of the seasonal variation of the PAH levels was also done with respect to diagnostic ratio-based source identification, analysis of back trajectories, and principle component analysis. Burning of fossil fuels was observed to be the prominent source of atmospheric PAHs in the study area. Further, lifetime cancer risk assessment was performed to assess the detrimental health impacts on humans on being exposed to atmospheric PAHs. Particulate PAHs present in the ambient air of Belgium shows no carcinogenic health impacts. However, considering the industrial expansion in the region, efforts are required to prevent the environmental contamination of PAHs. Graphical abstract.

Serum POP concentrations are highly predictive of inner blubber concentrations at two extremes of body condition in northern elephant seals.

Long-lived, upper trophic level marine mammals are vulnerable to bioaccumulation of persistent organic pollutants (POPs). Internal tissues may accumulate and mobilize POP compounds at different rates related to the body condition of the animal and the chemical characteristics of individual POP compounds; however, collection of samples from multiple tissues is a major challenge to ecotoxicology studies of free-ranging marine mammals and the ability to predict POP concentrations in one tissue from another tissue remains rare. Northern elephant seals (Mirounga angustirostris) forage on mesopelagic fish and squid for months at a time in the northeastern Pacific Ocean, interspersed with two periods of fasting on land, which results in dramatic seasonal fluctuations in body condition. Using northern elephant seals, we examined commonly studied tissues in mammalian toxicology to describe relationships and determine predictive equations among tissues for a suite of POP compounds, including ΣDDTs, ΣPCBs, Σchlordanes, and ΣPBDEs. We collected paired blubber (inner and outer) and blood serum samples from adult female and male seals in 2012 and 2013 at Año Nuevo State Reserve (California, USA). For females (N = 24), we sampled the same seals before (late in molting fast) and after (early in breeding fast) their approximately seven month foraging trip. For males, we sampled different seals before (N = 14) and after (N = 15) their approximately four month foraging trip. We observed strong relationships among tissues for many, but not all compounds. Serum POP concentrations were strong predictors of inner blubber POP concentrations for both females and males, while serum was a more consistent predictor of outer blubber for males than females. The ability to estimate POP blubber concentrations from serum, or vice versa, has the potential to enhance toxicological assessment and physiological modeling. Furthermore, predictive equations may illuminate commonalities or distinctions in bioaccumulation across marine mammal species.

A Preliminary Link between Hydroxylated Metabolites of Polychlorinated Biphenyls and Free Thyroxin in Humans.

BACKGROUND: Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (HO-PCBs) interfere with thyroid hormone action both in vitro and in vivo. However, epidemiologic studies on the link between PCB exposure and thyroid function have yielded discordant results, while very few data are available for HO-PCBs. OBJECTIVES: Our study aimed at investigating the relationship between clinically available markers of thyroid metabolism and serum levels of both PCBs and HO-PCBs. SUBJECTS AND METHODS: In a group of 180 subjects, thyroid-stimulating hormone (TSH) and free thyroxin (fT4), 29 PCBs (expressed both in lipid weight and in wet weight) and 18 HO-PCBs were measured in serum. RESULTS: In regression models, adjusted for gender, age, current smoking behavior, BMI and total lipid levels, serum levels of 3HO-PCB118 and 3HO-PCB180, and PCB95(lw), PCB99(lw) and PCB149(lw) were independent, significant predictors of fT4. A stepwise, multiple regression with gender, age, current smoking behavior, BMI and total lipid levels and all five previously identified significant compounds retained age, BMI, PCB95(lw), PCB99(lw) and 3HO-PCB180 as significant predictors of fT4. TSH levels were not predicted by serum levels of any of the PCBs or HO-PCBs. CONCLUSIONS: Our study indicates that in vivo, circulating fT4 levels can be linked to serum levels of several PCBs and hydroxylated PCB metabolites.

Endocrine-disrupting polychlorinated biphenyls in metabolically healthy and unhealthy obese subjects before and after weight loss: difference at the start but not at the finish.

BACKGROUND: A subset of obese individuals does not exhibit metabolically unfavorable features; this group is referred to as metabolically healthy obese (MHO). Serum concentrations of polychlorinated biphenyls (PCBs), which are chemicals with endocrine-disrupting properties, have been shown to be lower in MHO than in metabolically unhealthy obese (MUO). OBJECTIVE: We studied PCB serum concentrations during and after weight loss and their relation with metabolic health. DESIGN: We determined metabolic health features (weight, blood pressure, lipids, inflammation, and glucose metabolism) and serum PCB concentrations of 27 PCBs in a cohort of 184 overweight and obese subjects. Metabolic health was evaluated with the use of the criteria of the metabolic syndrome (MetS) [metabolic syndrome according to Adult Treatment Panel III criteria present (MetS+) or metabolic syndrome according to Adult Treatment Panel III criteria absent (MetS−)] or with extended criteria with inflammation and insulin resistance taken into account (MUO compared with MHO). Participants were treated with lifestyle counseling or bariatric surgery. A metabolic and toxicological re-evaluation was performed after 6 and 12 mo. RESULTS: At baseline, serum ΣPCB concentrations were significantly higher in MUO than in MHO (ΣPCBs: 138 ±105 compared with 365 ± 481 ng/g lipid weight; P = 0.01) but not in MetS+ compared with MetS− subjects. No difference was detected in the percentage increase in PCB serum concentrations in MetS+ compared with MetS− subjects (median: 58% compared with 43% and 31% compared with 69% at 6 and 12 mo, respectively). The comparison of persistent with resolved MetS and MUO did not reveal any difference in ΣPCB concentration increments (median: 49% compared with 58% at 12 mo for MUO; P > 0.05). In a regression model with age, smoking, and body mass index corrected for, PCB serum concentrations at baseline were not predictive of the persistence or resolution of a metabolically unfavorable state. CONCLUSION: Our study indicates that the increment in serum concentrations of PCBs does not differ according to metabolic health and does not seem to influence the beneficial metabolic health effects of weight loss. This study was registered at clinicaltrials.gov at NCT01778868.

Contrasted accumulation patterns of persistent organic pollutants and mercury in sympatric tropical dolphins from the south-western Indian Ocean.

Due to their high trophic position and long life span, small cetaceans are considered as suitable bioindicators to monitor the presence of contaminants in marine ecosystems. Here, we document the contamination with persistent organic pollutants (POPs) and total mercury (T-Hg) of spinner (Stenella longirostris, n =21) and Indo-Pacific bottlenose dolphins (Tursiops aduncus, n=32) sampled from the coastal waters of La Réunion (south-western Indian Ocean). In addition, seven co-occurring teleost fish species were sampled and analyzed as well. Blubber samples from living dolphins and muscle from teleosts were analyzed for polychlorinated biphenyls (PCBs), DDT and metabolites (DDTs), chlordanes (CHLs), hexachlorocyclohexanes (HCHs), hexachlorobenzene (HCB), and polybrominated diphenyl ethers (PBDEs). Methoxylated PBDEs (MeO-PBDEs), reported as having a natural origin, were also analyzed. T-Hg levels were measured in blubber and skin biopsies of the two dolphin species. Stable isotopes δ(13)C and δ(15)N values were determined in skin of the dolphins and in the muscle of teleosts. For PCBs, HCHs and T-Hg, concentrations were significantly higher in T. aduncus than in S. longirostris. For other POP levels, intra-species variability was high. MeO-PBDEs were the dominant compounds (55% of the total POPs) in S. longirostris, while PCBs dominated (50% contribution) in T. aduncus. Other contaminants showed similar profiles between the two species. Given the different patterns of POPs and T-Hg contamination and the δ(15)N values observed among analyzed teleosts, dietary and foraging habitat preferences most likely explain the contrasted contaminant profiles observed in the two dolphin species. Levels of each class of contaminants were significantly higher in males than females. Despite their spatial and temporal overlap in the waters of La Réunion, S. longirostris and T. aduncus are differently exposed to contaminant accumulation.

Deep-ocean foraging northern elephant seals bioaccumulate persistent organic pollutants.

As top predators in the northeast Pacific Ocean, northern elephant seals (Mirounga angustirostris) are vulnerable to bioaccumulation of persistent organic pollutants (POPs). Our study examined a suite of POPs in blubber (inner and outer) and blood (serum) of free-ranging northern elephant seals. For adult females (N=24), we satellite tracked and sampled the same seals before and after their approximately seven month long foraging trip. For males, we sampled different adults and sub-adults before (N=14) and after (N=15) the same foraging trip. For females, we calculated blubber burdens for all compounds. The highest POP concentrations in males and females were found for ∑DDTs and ∑PCBs. In blubber and serum, males had significantly greater concentrations than females for almost all compounds. For males and females, ∑DDT and ∑PBDEs were highly correlated in blubber and serum. While ∑PCBs were highly correlated with ∑DDTs and ∑PBDEs in blubber and serum for males, ∑PCBs showed weaker correlations with both compounds in females. As females gained mass while foraging, concentrations of nearly all POPs in inner and outer blubber significantly decreased; however, the absolute burden in blubber significantly increased, indicating ingestion of contaminants while foraging. Additionally, we identified three clusters of seal foraging behavior, based on geography, diving behavior, and stable carbon and nitrogen isotopes, which corresponded with differences in ∑DDTs, ∑PBDEs, MeO-BDE 47, as well as the ratio of ∑DDTs to ∑PCBs, indicating the potential for behavior to heighten or mitigate contaminant exposure. The greatest concentrations of ∑DDTs and ∑PBDEs were observed in the cluster that foraged closer to the coast and had blood samples more enriched in (13)C. Bioaccumulation of POPs by elephant seals supports mesopelagic food webs as a sink for POPs and highlights elephant seals as a potential sentinel of contamination in deep ocean food webs.

Levels and profiles of chlorinated and brominated contaminants in Southern Hemisphere humpback whales, Megaptera novaeangliae.

The study documents the levels and profiles of selected contaminants [polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs) and methoxylated PBDEs (MeO-PBDEs)] in blubber biopsy samples collected from humpback whales (Megaptera novaeangliae) in Antarctic Peninsula waters. In addition, we investigated year-to-year and sex-related differences in the bioaccumulation patterns. Except for hexachlorobenzene (HCB), whose concentrations were in the same range as those found in whales from the Northern Hemisphere, levels of all other compounds were lower in Southern Hemisphere whales compared to literature data on animals from the Arctic and subarctic region. The mean contribution to the sum of all anthropogenic organohalogen compounds (ΣOHC) decreased in the following order ΣPCBs (44%)>HCB (31%)>ΣDDXs (13%)>ΣCHLs (4.6%)>ΣHCHs (4.4%)>ΣPBDEs (0.9%). The predominant compounds within each chemical class were: PCBs 153, 149, 101 and 138; p,p'-DDE; γ-HCH; trans-nonachlor; PBDEs 99 and 47. The most dominant MeO-PBDE congener was 6-MeO-BDE 47. As samples were collected during three consecutive summer seasons, year-to-year trends could be assessed indicating a significant decrease from 2000 to 2003 for ΣCHL levels. Higher ΣPBDE concentrations and higher values of the ΣPBDE / ΣMeO-PBDE ratio, as well as higher ratios between the two MeO-BDEs (2'-MeO-BDE 68/6-MeO-BDE 47) were found in females compared to males. Higher ΣMeO-PBDE concentrations and higher values of the ratios between the lower chlorinated and the higher chlorinated PCBs were found in males than in females. In addition, five out of six significant differences found through discriminant function analysis were gender-related. The literature reports both feeding in mid- to low-latitudes and sex-related differences in migration patterns for humpback whales from the Southern Hemisphere, indicating that the hypothesis of dietary differences between males and females cannot be excluded. Nevertheless, additional studies are required for further investigation of this hypothesis.

Daily intake of bisphenol A and triclosan and their association with anthropometric data, thyroid hormones and weight loss in overweight and obese individuals.

Bisphenol A (BPA) and triclosan (TCS) were determined in urine of Belgian overweight and obese (n=151) and lean (n=43) individuals. After the first urine collection (0M), obese patients started a diet program or have undergone bariatric surgery. Hereafter, three additional urine samples from obese patients were collected after 3 (3M), 6 (6M) and 12 (12M) months. Both compounds were detected in >99% of the samples. BPA had median concentrations of 1.7 and 1.2ng/mL in obese and lean groups, respectively, while TCS had median concentrations of 1.5 and 0.9ng/mL in the obese and lean groups, respectively. The obese group had higher urinary concentrations (ng/mL) of BPA (p<0.5), while no significant differences were found for TCS between the obese and lean groups. No time trends between the different collection moments were observed. The BPA concentrations in the obese group were negatively associated with age, while no gender difference or relationship with body mass index was observed. For TCS, no relationships with gender, BMI, or age were found. The temporal variability of BPA and TCS was assessed with calculation of the intraclass correlation coefficient, Spearman rank correlation coefficients, and surrogate category analysis. We observed evidence that single spot urine samples might be predictive of exposure over a longer period of time. Dietary intakes of BPA and TCS did not differ significantly among the time points considered after obese individuals started losing weight (6 and 12months). Multiple linear regression analyses after adjusting for age and weight loss revealed negative associations between urinary TCS and serum FT4 in the 0M and 3M female obese individuals and positive associations between urinary BPA and serum TSH in the lean group.

Urinary phthalate metabolites are associated with insulin resistance in obese subjects.

Phthalates are potentially involved in the development of type 2 diabetes mellitus. In a cohort of 123 obese subjects, 10 phthalate metabolites were analyzed. An oral glucose tolerance test was performed and various estimates of insulin resistance and beta-cell function were calculated. After adjustment for age, physical activity level, smoking behavior, medication use and body mass index, several phthalate metabolites were linked to markers of glucose tolerance and insulin resistance.

Bioaccumulation of hydroxylated polychlorinated biphenyls and pentachlorophenol in the serum of northern elephant seal pups (Mirounga angustirostris).

Northern elephant seals (NES) (Mirounga angustirostris) from the Año Nuevo State Reserve (CA, USA) were sampled at 1-, 4-, 7- and 10-week post-weaning. Concentrations of hydroxylated polychlorinated biphenyls (HO-PCBs) and their parent PCBs were measured in the serum of each individual. The ΣHO-PCB concentrations in the serum increased significantly between early and late fast (from 282 ± 20 to 529 ± 31 pg/mL). This increase might result from a mobilisation of HO-PCBs transferred from the mother during gestation and/or lactation and stored in the pup's liver. Food deprivation has been shown to exacerbate biotransformation capacities in mammals, birds and fish. The HO-penta-CBs was the predominant homologue group, followed by HO-hexa-CBs and HO-hepta-CBs. No preferential pathway for the metabolism of HO-PCBs (HO-direct insertion or NIH-shift of a chlorine atom) could be evidenced. The concentrations of pentachlorophenol (PCP) in the serum of weaned NES increased from 103 ± 7 pg/mL at early fast to 246 ± 41 pg/mL at late fast, which is within the range of PCP concentrations usually encountered in marine mammals.

Levels and profile of several classes of organic contaminants in matched indoor dust and serum samples from occupational settings of Pakistan.

Dust ingestion is an important route of human exposure to organic contaminants, especially for flame retardants (FRs) in occupational settings. Several classes of organic contaminants were analyzed in matched dust and serum samples from academics and workers in electronics and clothing stores of Faisalabad, Pakistan. The concentrations of contaminants varied in dust as follow: organophosphate FRs (∑PFRs) > novel brominated FRs (∑NBFRs) > polybrominated diphenyl ethers (∑PBDEs) > organochlorine pesticides (∑OCPs) > polychlorinated biphenyls (∑PCBs), while, in serum, concentration varied: ∑OCPs > bromophenols (∑BPs) > ∑PCBs > ∑HO-PCBs ≈ ∑PBDEs. Two NBFRs, namely 1,2-bis(2,4,6-tribromophenoxy)-ethane (BTBPE) and bis(2-ethylhexyl) tetrabromophthalate (TBPH), were detected in <10% of the serum samples. p,p'-DDE was the major contaminant in serum contributing to ∼75% of the total contaminant burden. Levels of Penta-BDE congeners in serum and dust were significantly correlated (r = 0.64, p < 0.01) for the academics, suggesting dust ingestion as an important determinant for their serum levels.

Exposure to persistent organic pollutants: relationship with abnormal glucose metabolism and visceral adiposity.

OBJECTIVE: The contribution of persistent organic pollutants (POPs) to the pandemic of type 2 diabetes mellitus and obesity has been assumed but remains speculative. Our study aimed at investigating the relationship of POP levels with detailed markers of glucose metabolism and body composition. RESEARCH DESIGN AND METHODS: Glucose tolerance was determined in a group of normal-weight and obese individuals. Fat distribution was assessed with abdominal computed tomography (CT) scanning, determining subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). Selected POPs (28 polychlorinated biphenyls [PCBs] and the pesticide p,p'-dichlorodiphenyldichloroethylene [p,p'-DDE]) were measured in serum. In a subset of obese individuals undergoing bariatric surgery, POPs were also measured in adipose tissue. RESULTS: Among obese participants, serum and adipose tissue levels of POPs were significantly correlated to glucose levels during an oral glucose tolerance test. Logistic regression using a model including age, age(2), sex, family history of diabetes, BMI, CT-VAT, smoking behavior, physical activity level score, and a POP level identified serum levels of PCB153, the sum of PCBs and p,p'-DDE as significant predictors of abnormal glucose tolerance (odds ratio 4.6, 4.8, and 3.4, respectively; P < 0.05). Adipose tissue levels of p,p'-DDE were also significant predictors (odds ratio 81.6; P < 0.05). Serum levels of PCBs were inversely related to BMI, while serum and adipose tissue levels of all POPs were positively related to the CT-VAT/SAT ratio, suggesting an important role for the visceral fat compartment in POP dynamics. CONCLUSIONS: Our findings further sustain the theory that exposure to environmentally relevant levels of POPs may exert both a diabetogenic and obesogenic effect.

Methods, fluxes and sources of gas phase alkyl nitrates in the coastal air.

The daily and seasonal atmospheric concentrations, deposition fluxes and emission sources of a few C3-C9 gaseous alkyl nitrates (ANs) at the Belgian coast (De Haan) on the Southern North Sea were determined. An adapted sampler design for low- and high-volume air-sampling, optimized sample extraction and clean-up, as well as identification and quantification of ANs in air samples by means of gas chromatography mass spectrometry, are reported. The total concentrations of ANs ranged from 0.03 to 85 pptv and consisted primarily of the nitro-butane and nitro-pentane isomers. Air mass backward trajectories were calculated by the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model to determine the influence of main air masses on AN levels in the air. The shorter chain ANs have been the most abundant in the Atlantic/Channel/UK air masses, while longer chain ANs prevailed in continental air. The overall mean N fluxes of the ANs were slightly higher for summer than those for winter-spring, although their contributions to the total nitrogen flux were low. High correlations between AN and HNO2 levels were observed during winter/spring. During summer, the shorter chain ANs correlated well with precipitation. Source apportionment by means of principal component analysis indicated that most of the gas phase ANs could be attributed to traffic/combustion, secondary photochemical formation and biomass burning, although marine sources may also have been present and a contributing factor.

Mobilisation of lipophilic pollutants from blubber in northern elephant seal pups (Mirounga angustirostris) during the post-weaning fast.

Northern elephant seals (NES) (Mirounga angustirostris) from the Año Nuevo State Reserve (CA, USA) were longitudinally sampled during the post-weaning fast in order to study the mobilisation and redistribution of various classes of persistent organic pollutants (POPs), such as polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (p,p'-DDE) and hexachlorobenzene (HCB) between blubber and blood. Inner and outer blubber layers were analysed separately. Organohalogenated compounds were detected in all blubber samples in the decreasing order of their concentrations: p,p'-DDE > PCBs ⪢ HCB > PBDEs. The concentrations of all studied compounds were homogeneously distributed in the blubber layer at early fast, since the concentrations of POPs were statistically not different in the inner and outer layers. With the progression of the fast, the concentrations of PBDEs, PCBs and p,p'-DDE increased more sharply in inner blubber than in outer blubber. As a result, their levels became significantly higher in inner blubber as compared to outer blubber at late fast. The rise of pollutant concentrations in blubber might result from a less efficient mobilisation than triglycerides and/or a reuptake by adipocytes of some of the pollutants released into the circulation. The mobilisation of pollutants from blubber was higher at late fast. An increase of pollutant concentrations was observed in serum between early and late fast. Lower halogenated congeners (i.e. tetra-CBs) were present in higher proportions in serum, whereas the higher halogenated congeners (i.e. hepta-CBs) were mainly found in the inner and outer blubber layers. The transfer ratios of both PBDEs and PCBs from inner blubber to serum decreased with the number of chlorine and bromine atoms. In addition, the distribution of both types of compounds between serum and blubber was strongly influenced by their lipophilic character (logKow values), with more lipophilic compounds being less efficiently released from blubber to serum.

Downsides of the recycling process: harmful organic chemicals in children's toys.

Most of the materials used in consumer goods contain a number of additives which are meant to improve key properties like plasticity or flame resistance. At the end-of-life of the product, many polymeric materials are recycled and the additives they contain, such as flame retardants (FRs) and plasticizers, are transferred to the newly manufactured goods. We have investigated the occurrence and profiles of FRs, such as polybrominated diphenyl ethers (PBDEs) and phosphate FR (PFRs) and of plasticisers, such as phthalate esters, in 106 toys samples. Low levels and detection frequencies of components of the technical Penta-BDE and Deca-BDE mixtures were found, with BDE 209 being the dominant PBDE in all samples (maximum value was 0.14mg/g or 0.014%). The levels of PFRs and phthalates were up to 10,000 times higher than those of the PBDEs, with triphenyl phosphate and diethylhexyl phthalate being the major representatives of these classes. Maximum values were 1.3 and 6.9%, respectively. The detection frequencies were up to 50% for PFRs and 98% for phthalates. All but one of the toys produced after the REACH regulation went into force complied with its provisions. The samples were grouped according to relevant selection criteria to assess the risk for children of different age groups. Using models in the literature, exposure to these chemicals was tentatively assessed. It is clear that at the levels found in the investigated toys, these additives do not contribute to the intended characteristics of the materials, but in some cases may pose a health hazard to the children. Most likely, recycled materials are an important source of these additives in toys and therefore, their (re)use in products for children should be subject to stricter restrictions.

Expression of obesity markers and Persistent Organic Pollutants levels in adipose tissue of obese patients: reinforcing the obesogen hypothesis?

INTRODUCTION: Persistent Organic Pollutants (POPs) accumulate in adipose tissue and some are described to possess endocrine disrupting capacities. Therefore, it is important to evaluate their effects on key endocrine pathways in adipose tissue (AT), to further evaluate their potential role in metabolic pathologies such as obesity. OBJECTIVES: THE AIM IS TWOFOLD: (i) evaluate gene expression levels of obesity marker genes, i.e. the adipokines leptin (LEP), adiponectin (ADIPOQ) and Tumor Necrosis Factor α (TNFα) and the nuclear receptor, Peroxisome Proliferator Activated Receptor γ (PPARγ) in paired subcutaneous (SAT) and visceral (VAT) AT of obese subjects (n = 50) and to relate these values to serum concentrations of LEP and ADIPOQ (ii) evaluate the association of expression levels of marker genes in AT and serum with POP concentrations in AT. RESULTS AND CONCLUSIONS: Leptin and adiponectin levels in serum were positively correlated to respectively expression levels of leptin in SAT and adiponectin in VAT. Our study shows more significant correlations between gene expression of obesity marker genes and POP concentrations in VAT compared to SAT. Since VAT is more important than SAT in pathologies associated with obesity, this suggests that POPs are able to influence the association between obesity and the development of associated pathologies. Moreover, this finding reveals the importance of VAT when investigating the obesogen hypothesis. Concerning PPARγ expression in VAT, negative correlations with polychlorinated biphenyls (PCBs) concentrations were found in non T2D patients. LEP serum concentrations correlated with several PCBs in women whereas in men no correlations were found. This strengthens the potential importance of gender differences in obesity and within the obesogen hypothesis.

Dynamics of organohalogenated contaminants in human serum from obese individuals during one year of weight loss treatment.

We investigated the dynamics of several organohalogenated contaminants (OHCs) and their metabolites in an obese population during weight loss. Serum samples from obese individuals were taken before patients lost weight and after three, six, and twelve months. Samples were also collected from a matched lean control population. Analyzed OHCs were polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (HO-PCBs), pentachlorophenol (PCP), polybrominated diphenyl ethers, and organochlorine pesticides (OCPs). Significantly lower concentrations of major PCBs, their metabolites, and PCP were measured in obese individuals at the initial moment of their enrolling in the project. While dilution differences might be responsible for the lower concentrations in the neutral OHCs, we suggest that a lower CYP-mediated metabolic activity can partially explain the data for the HO-PCBs. Additionally, lower chlorinated substituted PCBs had a higher percentage contribution to the sum PCBs in obese individuals, while higher chlorinated PCBs had a higher contribution for the controls. Increasing serum levels for all OHCs were observed during weight loss. The release from adipose tissue seemed dependent on the octanol-water partition coefficient, since OHCs with higher log Kow values displayed a higher release in serum. This also influenced the HO-PCBs profile after weight loss with lower chlorinated HO-PCBs increasingly gaining importance. Although weight loss is beneficial, it also influences the release of OHCs from adipose tissue and their metabolism. Therefore, the increase in the levels of compounds with endocrine effects might be of concern.

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.

Organohalogenated contaminants in domestic cats' plasma in relation to spontaneous acromegaly and type 2 diabetes mellitus: a clue for endocrine disruption in humans?

It was recently hypothesized that pets may serve as sentinels to explore human exposure to organohalogenated chemicals (OHCs) via indoor environments and adverse health effects. The current study investigates OHCs contamination in domestic cats suffering from diabetes mellitus (DM), particularly DM induced by acromegaly and a form of DM akin to human type 2 DM (T2DM). Plasma from three groups of domestic cats was analyzed: acromegaly induced DM, T2DM and age matched control cats without DM. Analytes targeted included organochlorine pesticides, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs), together with their hydroxylated (HO-) metabolites. Similar PCB profiles were measured in cat plasma compared to humans, while the PBDE profile (dominated by BDE-99 (48%-55%) and BDE-47 (19%-25%)), the PCB and PBDE metabolite profiles were different in cat plasma than found in humans. Significantly higher OHC concentrations were recorded in plasma of acromegalic cats compared to the other two groups. Group differences in the PCBs/HO-PCBs ratios suggest that acromegalic cats have a lower capacity to metabolize persistent OHCs, like PCBs, than diabetic cats or cats without an endocrinopathy. As pituitary tumorigenesis in animals can be induced by estrogens, and PCBs may act as xenoestrogens, further investigation into whether there could be a causative link with the induction of feline acromegaly is warranted. Interestingly, BDE-47/BDE-99 ratios in cats were similar to the ratios in house dust. The results of this study suggest that domestic cats may represent a good model to assess human exposure to chemicals present in indoor dust.