Pooled analysis of genotoxicity markers in relation to exposure in the Flemish Environment and Health Studies (FLEHS) between 1999 and 2018.

BACKGROUND: The Flemish Environment and Health Studies (FLEHS) are human biomonitoring surveys running in Flanders since 1999. Additionally to biomarkers of exposure, markers of genotoxicity and oxidative stress have been measured, including the alkaline comet and micronucleus assay in peripheral whole blood cells, and urinary concentrations of 8-oxo-2'-deoxyguanosine (8-oxodG). AIM: Exposure-effect associations were explored in a pooled dataset of nine different cross-sectional FLEHS surveys. Data of adolescents collected in a time frame of about 20 years (1999-2018) were compiled. The aim of the study was to examine whether increased variation in exposure, lifestyle and environmental factors would lead to more powerful and robust exposure-effect associations. MATERIALS & METHODS: The biomarkers were measured in 2283 adolescents in the age range of 14-18 years. Exposure to polycyclic aromatic hydrocarbons [1-hydroxypyrene (1-OHP)], benzene (tt'-muconic acid), metals (arsenic, cadmium, copper, nickel, thallium, lead, chromium), persistent organochlorines and phthalates were assessed in blood or urine. Furthermore, outdoor air levels of particulate matter (PM10 and PM2.5) at the residences of the youngsters were calculated. Pooled statistical analysis was done using mixed models. Study-specific differences in the genotoxicity markers and in the strength/direction of the association were accounted for. This was done by incorporating the random factor 'study' and a random study slope (if possible). The exposure markers were centered around the study-specific mean in order to correct for protocol changes over time. RESULTS: A significant association was observed for the urinary oxidative stress marker 8-oxodG, which was positively associated with 1-OHP (5% increase for doubling of 1-OHP levels, p = 0.001), and with urinary copper (26% increase for doubling of copper levels, p = 0.001), a metal involved in the Fenton reaction in biological systems. 8-oxodG was also associated with the sum of the metabolites of the phthalate di(2-ethylhexyl) phthalate (DEHP) (3% increase for doubling of the DEHP levels, p = 0.02). For those associations, data pooling increased the statistical power. However, some of the associations in the individual surveys, were not confirmed in the pooled analysis (such as comet assay and 8-oxodG vs. atmospheric PM; and 8-oxodG vs. urinary nickel). This may be due to inconsistencies in exposure-effect relations and/or variations in the pollutant mix over time and regions. CONCLUSION: Pooled analysis including a large population of 2283 Flemish adolescents showed that 8-oxodG, a marker of oxidative DNA damage is a valuable marker to assess impact of daily life pollutants, such as PAHs, Cu and the phthalate DEHP.

Implications of biological factors on accumulation of persistent organic pollutants in Antarctic notothenioid fish.

In the present study, the possible associations between selected persistent organic pollutants (POPs) and biological factors were assessed in different tissues of two Antarctic notothenioid fish: Notothenia rossii (NOR) and Trematomus newnesi (TRN) collected at Potter Cove, King George Island/Isla 25 de Mayo, South Shetland Islands. Specifically, association patterns between biological factors (body size, lipid content, body condition) and POP concentrations (polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT) and metabolites, polybrominated diphenyl ethers (PBDEs), and hexachlorocyclohexane (HCH), hexachlorobenzene (HCB), chlordanes (CHLs) and methoxylated polybrominated diphenyl ethers (MeO-PBDEs)), were explored by using two approaches: multivariate analyses (principal component analysis: PCA) and intraspecific correlations. Integrating results suggest that biological factors such as size, KI and tissue type seemed to be associated to selective accumulation of POPs for immature specimens of N. rossii, and KI and tissue type for mature specimens of T. newnesi. Each particular factor should be considered when choosing N. rossii or T. newnesi as sentinels for POPs pollution in Antarctic marine environments. Further, both nototheniids showed a selective accumulation pattern in their gonads of penta-chlorinated biphenyls (penta-CBs; 55.5 and 29ngg-1 lw for N. rossii and T. newnesi, respectively) and organochlorine pesticides such as DDTs (199 and 13.3ngg-1 lw, for N. rossii and T. newnesi respectively), and of polybrominated diphenyl ethers (PBDEs) in gills (97.2 and 22.1 for ngg-1 lw, for N. rossii and T. newnesi, respectively), highlighting the importance of these tissues in monitoring studies of pollution in fish. The current study expands the knowledge concerning the biological factors to be investigated when specific pollutants are monitored and supports the importance of tissue type for the selective accumulation of POPs in Antarctic fish. Additionally, a contribution to the scarce data on concentration of MeO-PBDEs in Antarctic marine organisms, particularly in the highly diverse perciform suborder Notothenioidei is provided.

A PUBLIC HEALTH PERSPECTIVE ON THE IMPORTANCE OF PLASMA PHENYLALANINE AND TYROSINE DETERMINATION IN RELATION TO NEWBORN SCREENING AND MONITORING OF TREATMENT IN PHENYLKETONURIA.

Newborn screening of phenylketonuria (PKU) is performed in many countries, including Romania, in addition to screening for congenital hypothyroidism. Patients affected by PKU require frequent measurements of phenylalanine (Phe) level in blood plasma. Such a determination is important not only in early diagnostic, but also in monitoring the treatment of PKU to maintain phenylalaninemia within limits that will not affect the brain. A simple, highly sensitive, accurate and rather inexpensive procedure for the simultaneous determination of Phe and Tyr plasma concentrations was previously described in this journal. The new procedure may be applied in many clinical laboratories, including those with no previous experience in diagnosis of inherited amino acid metabolic disorders. In this way the major public health problems linked to PKU not being detected in the first weeks of life (including the burden of institutionalized children with preventable mental retardation) may be avoided.

Potential impact of sitagliptin on collagen-derived dipeptides in diabetic osteoporosis.

It is known that diabetes coincides with an increased risk of osteoporosis. While a disturbed collagen metabolism is proposed as a possible cause, much remains unknown about the enzymes involved and changes in the collagen-derived dipeptides and amino acids. Therefore, we sought to study this intricate pathway and the effect of dipeptidyl peptidase 4 (DPP4) inhibitors. Control and streptozotocin-nicotinamide-induced diabetic rats were treated for 12 weeks with vehicle or sitagliptin, a DPP4 inhibitor (Con/VH, Con/SG, DM/VH and DM/SG). The activities of four key enzymes involved in collagen breakdown were determined in serum (DPP4, matrix metalloproteinase 2 and 9 and prolidase). Dipeptide (Ala-Pro, Gly-Pro, Pro-Pro and Pro-Hyp) and amino acid (Pro and Hyp) concentrations were measured by liquid chromatography coupled to mass spectrometry. We found three-fold higher MMP9 activities in DM/VH than in controls, while in DM/SG this rise was attenuated. MMP2 and prolidase did not differ in the investigated groups. Furthermore, we are the first to report on two-fold higher Ala-Pro and Pro-Pro levels in diabetes compared to controls. In contrast, Pro-Hyp concentrations were lower in diabetes (DM/VH and DM/SG). DPP4 inhibition does not seem to have a direct influence on the collagen metabolism in streptozotocin-nicotinamide-induced diabetic rats. Instead, it probably acts through its effect on osteoprotective substrates. In diabetes, increased MMP9 activities seem to favour the production of Ala-Pro and Pro-Pro containing collagen fragments. The high Pro-Hyp levels in untreated controls might have a bone-stimulating effect. Nevertheless, the biological significance of these dipeptides is not yet clear and should be further investigated.

[Novel psychoactive substances: a worldwide problem that requires an adequate approach]. / Les nouveles susbtances psychoactives: un problème mondial nècessitant une prise en charge adaptèe.

The use of new psychoactive substances (NPSI is increasing worldwide. Each year the number of NPS which are found through seizures in Belgium rises. The prevalence in the general population is unknown. In the Belgian nightlife at least 7% has already consumed an NPS at least once. NPS are alternatives for traditional illicit drugs (cannabis, cocaine, ecstasy, ...) made legal by adding a small modification within the chemical structure. But these modified substances are often more dangerous because there is little known about the acute and chronic effects, which could lead quickly to overdosing. Current legislation in Belgium uses a nominative list. However, this procedure is not suited to respond fast enough to the dynamic nature of NPS. In 2014 a new legislation based on generic classification was introduced as a solution and should be in place in 2015 in Belgium to reduce the rising number of legal drugs. An important consequence of generic classification is that certain medicines and other useful compounds will be included by this new law, which is a problem for the pharmaceutical industry and pharmacy. I cooperation with the FAGG exceptions for these substances were made.

Assessment of human exposure to indoor organic contaminants via dust ingestion in Pakistan.

UNLABELLED: Ingestion of indoor dust has been acknowledged as an important route of exposure to organic contaminants (OCs). We investigated the presence of polybrominated diphenyl ethers (PBDEs), novel brominated flame retardants (NBFRs), organophosphate flame retardants (OPFRs), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs) in indoor floor dust from rural homes (N=31) and mosques (N=12) in Gujrat, Pakistan. Low concentrations were observed for most contaminants. OPFRs were the principle contaminants, with tri-(2-butoxyethyl)-phosphate (TBEP) and tri-phenyl-phosphate (TPP) having medians of 66 and 109 ng/g, respectively. PBDEs were only minor constituents in the investigated samples, with BDE 209 (median 40 ng/g) being the most important congener. Levels and profile of ∑PBDEs, ∑NBFRs, ∑HCHs, ∑DDTs, and ∑PCBs revealed no difference (P<0.05) between samples of dust from homes and mosques, indicating similar emission sources. Exposure scenarios using 5th percentile, median, mean, and 95th percentile levels were estimated for both adult and toddlers. Typical high-end, using median levels and high dust ingestion, exposure for adults were 0.02, 0.02, 0.03, <0.01, and 0.65 ng/kg bw/day and for toddlers 0.39, 0.45, 0.69, 0.01, and 15.2 ng/kg bw/day for ∑PBDEs, ∑NBFRs, ∑OCPs, ∑PCBs, and ∑OPFRs, respectively. To the authors' knowledge, this is the first study to document the presence of indoor OCs in Pakistani dust. PRACTICAL IMPLICATIONS: This is the first report on the analysis of various contaminants in indoor dust from Pakistan. Some of these chemicals are currently being used in different consumer products. The study will help to further an understanding of the levels of different organic contaminants (OCs) in Pakistani indoor environments and will enlighten the generally ignored area of environmental pollution in Pakistan. Furthermore, studies based on animal models have shown that some of the analyzed chemicals can cause different types of chronic toxicities. However, our results showed that the levels of estimated exposure via dust ingestion for all chemicals were several orders of magnitude lower than their reference dose (RfD) values or than those reported in studies from Belgium, China, Singapore, and the UK (Ali et al., 2011a; Harrad et al., 2008; Tan et al., 2007a,b; Van den Eede et al., 2011a; Wang et al., 2010).

Internal exposure of Flemish teenagers to environmental pollutants: Results of the Flemish Environment and Health Study 2016-2020 (FLEHS IV).

The Flemish Environment and Health Study (FLEHS) collects information on internal exposure to a broad range of environmental chemicals in the general population in Flanders, the Northern region of Belgium. The aim is to establish biomonitoring exposure distributions for the general population in support of public health and environmental policy, environmental risk assessment and risk management decisions. In 2017-2018, urine and blood samples were collected from 428 teenagers by a stratified clustered two stage randomized design. Samples were analyzed for a broad range of biomarkers related to exposure to chlorinated and newer pesticides, brominated and organophosphate flame retardants (BFR/OPFR), polychlorinated biphenyls (PCBs), bisphenols, phthalates and alternative plasticizers, per-and polyfluoroalkyl substances (PFAS), polycyclic aromatic hydrocarbons (PAHs), benzene, metals and trace elements. The geometric mean levels and percentiles of the distribution were estimated for each biomarker, for the whole study population and following stratification for sex, the household educational attainment and the residence area's urbanicity. Geometric means of biomarkers of lead, dichlorodiphenyltrichloroethane (DDT), PCBs, PAHs, regulated phthalates and bisphenol A (BPA) were lower than in the previous FLEHS cycles. Most biomarker levels were below health-based guidance values (HB-GVs). However, HB-GVs of urinary arsenic, blood lead, blood cadmium, sum of serum perfluorooctane sulfonate (PFOS) and perfluoro-1-hexanesulfonate (PFHxS) and the urinary pyrethroid metabolite (3-PBA) were exceeded in respectively 25%, 12%, 39.5%, 10% and 22% of the teenagers. These results suggest that the levels of exposure in the Flemish population to some environmental chemicals might be of concern. At the same time, we noticed that biomarkers for BPA substitutes, metabolites of OPFRs, an expanded list of PFAS, glyphosate and its metabolite could be measured in substantial proportions of participants. Interpretation of these levels in a health-risk context remains uncertain as HB-GVs are lacking. Household educational attainment and residential urbanicity were significant exposure determinants for many biomarkers and could influence specific biomarker levels up to 70% as shown by multiple regression analysis. The research consortium also took care of the broader external communication of results with participants, policy makers, professional groups and civil society organizations. Our study demonstrated that teenagers are exposed to a wide range of chemicals, it demonstrates the success of public policies to reduce exposure but also points to concern and further priorities and needs for follow up.

Environmental pollutants and type 2 diabetes: a review of mechanisms that can disrupt beta cell function.

The prevalence of diabetes mellitus is currently at epidemic proportions and it is estimated that it will increase even further over the next decades. Although genetic predisposition and lifestyle choices are commonly accepted reasons for the occurrence of type 2 diabetes, it has recently been suggested that environmental pollutants are additional risk factors for diabetes development and this review aims to give an overview of the current evidence for this. More specifically, because of the crucial role of pancreatic beta cells in the development and progression of type 2 diabetes, the present work summarises the known effects of several compounds on beta cell function with reference to mechanistic studies that have elucidated how these compounds interfere with the insulin secreting capacity of beta cells. Oestrogenic compounds, organophosphorus compounds, persistent organic pollutants and heavy metals are discussed, and a critical reflection on the relevance of the concentrations used in mechanistic studies relative to the levels found in the human population is given. It is clear that some environmental pollutants affect pancreatic beta cell function, as both epidemiological and experimental research is accumulating. This supports the need to develop a solid and structured platform to fully explore the diabetes-inducing potential of pollutants.

Analysis of the flame retardant metabolites bis(1,3-dichloro-2-propyl) phosphate (BDCPP) and diphenyl phosphate (DPP) in urine using liquid chromatography-tandem mass spectrometry.

Organophosphate triesters tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and triphenyl phosphate are widely used flame retardants (FRs) present in many products common to human environments, yet understanding of human exposure and health effects of these compounds is limited. Monitoring urinary metabolites as biomarkers of exposure can be a valuable aid for improving this understanding; however, no previously published method exists for the analysis of the primary TDCPP metabolite, bis(1,3-dichloro-2-propyl) phosphate (BDCPP), in human urine. Here, we present a method to extract the metabolites BDCPP and diphenyl phosphate (DPP) in human urine using mixed-mode anion exchange solid phase extraction and mass-labeled internal standards with analysis by atmospheric pressure chemical ionization liquid chromatography tandem mass spectrometry. The method detection limit was 8 pg mL(-1) urine for BDCPP and 204 pg mL(-1) for DPP. Recoveries of analytes spiked into urine ranged from 82 ± 10% to 91 ± 4% for BDCPP and from 72 ± 12% to 76 ± 8% for DPP. Analysis of a small number of urine samples (n=9) randomly collected from non-occupationally exposed adults revealed the presence of both BDCPP and DPP in all samples. Non-normalized urinary concentrations ranged from 46-1,662 pg BDCPP mL(-1) to 287-7,443 pg DPP mL(-1), with geometric means of 147 pg BDCPP mL(-1) and 1,074 pg DPP mL(-1). Levels of DPP were higher than those of BDCPP in 89% of samples. The presented method is simple and sufficiently sensitive to detect these FR metabolites in humans and may be applied to future studies to increase our understanding of exposure to and potential health effects from FRs.

Polychlorinated biphenyl and organochlorine pesticide contamination signatures in deep-sea fish from the Mediterranean Sea.

Polychlorinated biphenyl (PCB) and OCP concentrations were determined in the livers of two deep-sea fish species, roughsnout grenadier and hollowsnout grenadier, from the Adriatic Sea. In both species, contaminant concentrations were in the following order: PCBs>DDTs>>HCB. Contaminant load was higher in roughsnout grenadier (PCB: 12,327ngg(-1); DDTs: 5357ngg(-1); HCB: 13.1ngg(-1)) than in hollowsnout grenadier (PCB: 1234ngg(-1); DDTs: 763ngg(-1); HCB 6.3ngg(-1)). PCB patterns were dominated by higher chlorinated congeners (hexa-CBs: 50.3-52.1%, hepta-CBs: 29.6-35.5%, penta-CBs: 8.0-11.1% and octa-CBs :5.2-5.4%). PCBs 138, 153 180 and 187 were the most abundant. Regarding the DDT pattern, p,p'-DDE was prevalent in both species (roughsnout grenadier: 99.7%, hollowsnout grenadier: 90%), suggesting no recent DDT input. In both species, the total 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalent (TEQ) concentrations (roughsnout grenadier: mean 43.77pg/g, hollowsnout grenadier: mean 20.49pg/g), calculated from non- and mono-ortho PCBs, reached those encountered in marine organisms at higher levels in the trophic chain.

Internal exposure to pollutants measured in blood and urine of Flemish adolescents in function of area of residence.

The Centre for Environment and Health in Flanders, the Northern part of Belgium, started a biomonitoring program on adolescents in 2003. 1679 adolescents residing in nine areas with different patterns of pollution participated in the study. Possible confounding effects of lifestyle and personal characteristics were taken into account. The geometric mean levels of cadmium and lead in whole blood amounted to 0.36 and 21.7 microg l(-1), those of PCBs, DDE and HCB in serum to 68, 94 and 20.9 ng g(-1) fat, and those of 1-hydroxypyrene and t,t'-muconic acid in urine to 88 ng g(-1) creatinine and 72 microg g(-1) creatinine. Significant regional differences in internal lead, cadmium, PCBs, DDE and HCB exposure were observed in function of area of residence, even after adjustment for age, sex, smoking (and body mass index for the chlorinated compounds). Compared to a reference mean, internal exposure was significantly higher in one or more of the areas: Cd and Pb in the Antwerp agglomeration, Cd in the Antwerp harbour, PCBs in the Ghent agglomeration, PCBs, DDE and HCB in the Ghent harbour, Cd, PCBs, DDE and HCB in the rural area, DDE in Olen and in the Albert canal areas. Adolescents living in an area with intensive fruit cultivation (showing overall the lowest values) and, surprisingly, in areas around household waste incinerators (average of six areas), had no significantly increased internal exposures. Subjects from separate areas around waste incinerators showed significant differences in body load of various environmental contaminants.

Evaluation of the usefulness of bird feathers as a non-destructive biomonitoring tool for organic pollutants: a comparative and meta-analytical approach.

In this study, we investigated whether bird feathers can be used as a non-destructive biomonitor for organic pollutants. We analysed the outermost tail feathers of 8 terrestrial and aquatic bird species from Belgium (8 species, n=108) for polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and organochlorine pesticides (OCPs). Every compound class could be quantified in one single tail feather of the birds under study (sum PCBs ranging from 5.5 to 510 ng/g feather, sum PBDEs from 0.33 to 53 ng/g feather, sum DDTs from 1.5 to 730 ng/g feather), except for PBDEs in feathers of the common moorhen (Gallinula chloropus). Further, we calculated Pearson correlations between concentrations of organic pollutants in feathers and concentrations in corresponding muscle or liver tissue from the birds. Correlations were found significant in half of the cases of the terrestrial species, but were found not significant for the aquatic species, with the exception of a significant correlation of sum PCBs in the common moorhen. Only for the common buzzard (Buteo buteo) (n=43) all correlations were found significant (0.32

Is external contamination with organic pollutants important for concentrations measured in bird feathers?

Although there is increasing evidence that bird feathers can be used as a non-destructive biomonitoring tool for organic pollutants [such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and p,p'-dichlorodiphenyl-trichloroethane and metabolites (DDTs)], the importance of external contamination of these organic pollutants onto the feathers has not been considered. Here we examine to which extent external contamination of organic pollutants occurs onto the feathers of a predatory bird. We have analysed primary wing feathers of 16 common buzzards (Buteo buteo) collected in Belgium. In order to study differences in external contamination within and among wing feathers, the vane and the shaft of each feather were separated and were analysed in parallel, pooled for the three inner and the three outer primary wing feathers. Most organic pollutants could be measured in these pooled samples of both the vane and the shaft. Concentrations of hexachlorobenzene (HCB), DDTs, PCBs and PBDEs were significantly higher in the vane compared to the shaft. The profiles of PCBs and PBDEs in the shaft closely resembled the profiles in liver and muscle tissue, in contrast with the profile of the vane. The PBDE congeners 47, 99 and 153 had a similar contribution in shafts of primary feathers of common buzzards. Although these results suggest that external contamination could be important on the vane, no differences in the profile of PBDEs or PCBs were found between the inner and outer (more exposed) primary feathers. Furthermore, correlation coefficients with internal tissues were not univocally distinct between the shaft and the vane. Therefore our results indicate that the higher concentrations found in the vane in comparison to the shaft do not originate from external contamination via the air, but that other factors such as structure and chemical properties of the feathers may be of importance. The lack of significant external contamination onto the feather surface is an additional asset for the use of feathers as a non-destructive biomonitor for organic pollutants.

Experimental evaluation of the usefulness of feathers as a non-destructive biomonitor for polychlorinated biphenyls (PCBs) using silastic implants as a novel method of exposure.

Risk assessment of pollutants requires both monitoring studies in the field and experimental exposure studies. In this study, we evaluated silastic implants as an alternative method of exposure for use in toxicological studies and at the same time evaluated the usefulness of feathers as a non-destructive biomonitor for PCBs. European starlings (Sturnus vulgaris) were exposed to different doses (including a control group) of environmentally relevant concentrations of PCB 153 during a 15-week period using silastic implants with both ends/only one end sealed. After implantation, there was a rapid and significant increase in PCB 153 blood concentration in the exposed groups. The significant differences in blood concentrations among the treatment groups show that silastic implants are useful as a method of exposure. Moreover, the ratio between the tissue concentrations of two treatment groups reflected the difference in implantation doses between these groups. There was also a clear difference in tissue concentrations among the treatment groups, although we could not test this statistically due to the small sample sizes. The slow release kinetics for a prolonged period and the relatively stable blood concentrations during the 15-week period render silastic tubes very interesting to study the effects of chronic exposure to pollutants. Our results also revealed that sealing both ends of the implant instead of only one did not significantly affect the exposure. There were strong, significant positive correlations between the blood and the tissues, which confirm the use of blood to monitor PCBs. To evaluate the usefulness of feathers as a non-destructive biomonitor for PCBs, we plucked the original and newly grown wing and tail feathers. We observed strong, significant positive correlations between the concentrations in the newly grown feathers and concentrations in the muscle, liver, brain and blood. PCB 153 concentrations in the newly grown feathers differed among the treatment groups. To our knowledge, our results provide the first experimental evidence that feathers are useful as a non-destructive biomonitoring tool for PCBs.

Accumulation, tissue-specific distribution and debromination of decabromodiphenyl ether (BDE 209) in European starlings (Sturnus vulgaris).

In this study we investigated the accumulation, tissue-specific distribution and possible debromination of BDE 209 in a terrestrial songbird species, the European starling, using silastic implants as a method of exposure. BDE 209 accumulated in the blood of the exposed starlings to a mean peak concentration of 16+/-4.1 ng/ml on day 10. After this peak, there was a decline to 3.3+/-0.4 ng/ml blood at the end of the exposure period of 76 days, which suggests elimination of BDE 209. In the exposed group, the muscle concentrations (461 ng/g lipid weight [lw], 430 ng/g lw) were about twofold those in liver (269 ng/g lw, 237 ng/g lw). In addition to BDE 209, other PBDE congeners, particularly octa- and nonaBDEs, were also present in the muscle and liver, suggesting bioformation from BDE 209. To our knowledge, these results are the first indications for the debromination of BDE 209 in birds.

Brominated flame retardants and organochlorine pollutants in aquatic and terrestrial predatory birds of Belgium: levels, patterns, tissue distribution and condition factors.

Liver and muscle samples from 7 species of aquatic and terrestrial predatory birds from Flanders (Belgium) were analysed for polychlorinated biphenyls (PCBs), polybrominated diphenylethers (PBDEs) and organochlorine pesticides (OCPs). PCBs were the predominant compounds in our samples, which showed highest concentrations in the liver of barn owl (Tyto alba) and sparrowhawk (Accipiter nisus) (up to 1000 microg/g lipid weight). PBDEs could be determined in most samples at lower concentrations than PCBs (up to 64 microg/g lipid in sparrowhawk liver). Sparrowhawks had the highest levels of hexachlorobenzene, DDTs and PBDEs. In contrast, kestrels (Falco tinnunculus) had relatively low levels of most measured organochlorines. BDE 47 was the most abundant congener in heron (Ardea cinerea) and grebe (Podiceps cristatus), while BDE 47, 99 and 153 were equally important in the terrestrial species. BDE 183 and BDE 209 were only measured in the terrestrial birds. These results indicate that terrestrial birds may be more exposed to higher brominated BDE congeners than aquatic species.

Within- and among-clutch variation of organohalogenated contaminants in eggs of great tits (Parus major).

In this study we investigated the variation of organohalogenated compounds, such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs), within and among clutches of a small insectivorous songbird, the great tit (Parus major), and determined whether egg laying order affects the concentrations of these compounds. PCBs were the major organohalogenated contaminants in the eggs of great tits (mean 4778 ng/g lipid weight), while PBDEs (mean 204 ng/g lipid weight) and DDTs (mean 601 ng/g lipid weight) were found at much lower concentrations. Within-clutch variability of PCBs, PBDEs, and DDTs residues in the egg samples was small (7%, 3%, and 22%, respectively) compared to among-clutch variability (93%, 97%, and 78%, respectively). The small within-clutch variability may be in part related to the small home range of great tits and low spatial heterogeneity of the contaminants. We found no laying order effects on the concentrations of PCBs, PBDEs, and DDTs. Our results show that random egg samples of great tits are suitable as a biomonitoring tool for contamination with persistent organohalogenated pollutants in terrestrial environments.

Circulating phthalates during critical illness in children are associated with long-term attention deficit: a study of a development and a validation cohort.

PURPOSE: Environmental phthalate exposure has been associated with attention deficit disorders in children. We hypothesized that in children treated in the pediatric intensive care unit (PICU), circulating phthalates leaching from indwelling medical devices contribute to their long-term attention deficit. METHODS: Circulating plasma concentrations of di(2-ethylhexyl)phthalate (DEHP) metabolites were quantified in 100 healthy children and 449 children who had been treated in PICU and were neurocognitively tested 4 years later. In a development patient cohort (N = 228), a multivariable bootstrap study identified stable thresholds of exposure to circulating DEHP metabolites above which there was an independent association with worse neurocognitive outcome. Subsequently, in a second patient cohort (N = 221), the observed independent associations were validated. RESULTS: Plasma concentrations of DEHP metabolites, which were virtually undetectable [0.029 (0.027-0.031) µmol/l] in healthy children, were 4.41 (3.76-5.06) µmol/l in critically ill children upon PICU admission (P < 0.001). Plasma DEHP metabolite concentrations decreased rapidly but remained 18 times higher until PICU discharge (P < 0.001). After adjusting for baseline risk factors and duration of PICU stay, and further for PICU complications and treatments, exceeding the potentially harmful threshold for exposure to circulating DEHP metabolites was independently associated with the attention deficit (all P ≤ 0.008) and impaired motor coordination (all P ≤ 0.02). The association with the attention deficit was confirmed in the validation cohort (all P ≤ 0.01). This phthalate exposure effect explained half of the attention deficit in post-PICU patients. CONCLUSIONS: Iatrogenic exposure to DEHP metabolites during intensive care was independently and robustly associated with the important attention deficit observed in children 4 years after critical illness. Clinicaltrials.gov identifier: NCT00214916.

A comparison between wastewater-based drug data and an illicit drug use survey in a selected community.

BACKGROUND: Estimations of drug use are mostly based on population surveys that can suffer from response biases. The current study evaluates using wastewater-based epidemiology (WBE) for assessing illicit drug use by comparing wastewater data with that from a population survey. METHODS: Introductory letters (29,083) were sent to inhabitants of Lier, Belgium, asking them to participate in an online survey study. Participants were asked to indicate their drug use in the past week for a 12-week period (September-November 2014). Concomitant wastewater samples were collected from the associated wastewater treatment plant in four bi-weekly periods. Samples were analyzed using solid-phase extraction and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). RESULTS: On average, 263 (1%) inhabitants filled out the questionnaire each week. According to the survey results, cannabis was the most used drug, followed by amphetamine, cocaine and methylenedioxymethamphetamine (MDMA). Wastewater data corroborated these results. Cocaine, amphetamine and MDMA showed a significant difference between days of the week. The four sampling periods differed significantly from each other for cocaine, amphetamine and methadone. CONCLUSION: Observed drug consumption patterns from survey and wastewater data match national and international data. Wastewater analyses confirm that WBE can be reliably used to confirm patterns and trends in drug use. Future studies should focus on identifying the most opportune sampling period giving the most reliable estimates of drug use and use smaller, contained communities such as festivals or prisons if methodology allows.

Investigation of agreement between wastewater-based epidemiology and survey data on alcohol and nicotine use in a community.

BACKGROUND/AIMS: Alcohol and nicotine are the two most used substances world-wide and associated with increased burden of disease. Since surveys on substance use may be difficult due to response biases, wastewater-based epidemiology (WBE) was developed as a more objective measure of nicotine and alcohol use. This study compares estimates of nicotine and alcohol use from a wastewater sampling campaign in a medium-sized Belgian city with a concurrently executed population survey. METHODS: 29,083 letters about participation in an online survey study on weekly alcohol and tobacco use were sent to the inhabitants of Lier, Belgium. Wastewater samples were collected from the associated treatment plant in four bi-weekly periods. Samples were analyzed using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Ethylsulfate was used as alcohol biomarker and cotinine and trans-3'-hydroxycotinine as nicotine biomarker. RESULTS: 263 (1%) surveys were filled out on average per week. According to survey data, alcohol and nicotine were used less than in the rest of Belgium and this was matched by the wastewater data. Nicotine use, but not alcohol use, showed a significant variation over the sampling periods. Both nicotine and alcohol showed increase use during the weekend while only alcohol showed a different use pattern throughout the week. CONCLUSION: No correlation between WBE and survey data could be demonstrated, possibly due to small sample sizes. However, this study shows that weekly trends in alcohol and nicotine use can be quickly detected from wastewater analysis and the occurrence of major events such as festivals can be identified.