Obesity or diet? Levels and determinants of phthalate body burden – A case study on Portuguese children

In this study we analyzed one of the most comprehensive sets of 21 urinary phthalate metabolites representing exposure to 11 parent phthalates (DEP, DMP, DiBP, DnBP, BBzP, DEHP, DiNP, DiDP, DCHP, DnPeP, DnOP) in first morning urine samples of 112 Portuguese children (4-18 years) sampled in 2014/15. The study population consisted of two groups: group 1 with normal weight/underweight children (N = 43) following their regular diet and group 2 with obese/overweight children (N = 69) following a healthy diet (with nutritional counselling). Most of the metabolites were above the limits quantification (81-100%) except for MCHP, MnPEP and MnOP. Metabolite levels were generally comparable to other recent child and general populations sampled worldwide, confirming the steady decline in exposures to most phthalates. Compared to Portuguese children sampled in 2011/2012, median urinary metabolite levels decreased by approximately 50% for DEHP, DnBP, DiBP and BBzP. Risk assessments for individual phthalates and the sum of the anti-androgenic phthalates did not indicate to attributable health risks, also at the upper percentiles of exposure. In the healthy diet group the median concentration of the DEHP metabolites was significant lower, while all phthalate metabolites except MEP tended to be lower compared to the regular diet group. Multiple log-linear regression analyses revealed significantly lower daily intakes (DIs) for all phthalates in the healthy diet group compared to the regular diet group (geometric mean ratios (gMR) between 0.510-0.618; p ≤ 0.05), except for DEP (gMR: 0.811; p = 0.273). The same analyses with the continuous variable body mass index instead of the diet groups also showed effects on the DIs (gMRs between 0.926-0.951; p ≤ 0.05), however much smaller than the effects of the diet. The results indicate that obese children following a healthy diet composed of fresh and less packaged/processed food can considerably reduce their intake for most phthalates and can have lower phthalate intakes than regular weight/regular diet children.Luísa Correia-Sá is grateful to Fundação para a Ciência e a Tecnologia (FCT) by the grant (SFRH/BD/87019/2012), financed by POCH, subsidized by Fundo Social Europeu and Ministério da Ciência, Tecnologia e Ensino Superior. The authors are thankful to the project Qualidade e Segurança Alimentar – uma abordagem (nano)tecnológica, reference NORTE-01-0145-FEDER-000011.info:eu-repo/semantics/publishedVersio

Time course of phthalate cumulative risks to male developmental health over a 27-year period: Biomonitoring samples of the German Environmental Specimen Bank

In several human biomonitoring surveys, changes in the usage patterns of phthalates have come to light, but their influence on the risks associated with combined exposures is insufficiently understood. Based on the largest study to date, the 27-year survey of urinary phthalate metabolite levels in 24-hour urine samples from the German Environmental Specimen Bank, we present a deep analysis of changing phthalate exposures on mixture risks. This analysis adopts the Hazard Index (HI) approach based on the five phthalates DBP, DIBP, BBP, DEHP and DINP. Calculations of the hazard index for each study participant included updated phthalate reference doses for anti-androgenicity (RfDAAs) that take account of new evidence of phthalates’ developmental toxicity. The Maximum Cumulative Ratio (MCR) approach was used to establish whether a subject’s combined exposure was dominated by one phthalate or was influenced by several phthalates simultaneously. Generally, over the years there was a shift towards lower HIs and higher MCRs, reflecting an increased complexity of the combined exposures. The decade from 1988 to about 1999 was characterised by rather high HIs of between 3 and 7 (95th percentile) which were driven by exposure to DBP and DEHP, often exceeding their single acceptable exposures. Traditional single phthalate risk assessments would have underestimated these risks by up to 50%. From 2006 onwards, no study participant experienced exposures above acceptable levels for a single phthalate, but combined exposures were still in excess of HI = 1. From 2011 onwards most individuals stayed below HI = 1. In interpreting these results, we caution against the use of HI = 1 as an acceptable limit and develop proposals for improved and more realistic mixture risk assessments that take account of co-exposures to other anti-androgenic substances also capable of disrupting the male reproductive system. From this perspective, we regard HIs between 0.1 and 0.2 as more appropriate for evaluating combined phthalate exposures. Assessed against lowered HIs of 0.1 – 0.2, the combined phthalate exposures of most study participants exceeded acceptable levels in all study years, including 2015. Continued monitoring efforts for phthalate combinations are required to provide the basis for appropriate risk management measures.Federal Ministry for the Environment, Nature Conservation, and Nuclear Safety (BMU), Germany; Horizon 2020 research and innovation programm

Exposure assessment to bisphenol A (BPA) in Portuguese children by human biomonitoring

Exposure to bisphenol A (BPA) is known to be widespread and available data suggests that BPA can act as an endocrine disruptor. Diet is generally regarded as the dominant BPA exposure source, namely through leaching to food from packaging materials. The aim of this study was to evaluate the exposure of 110 Portuguese children (4-18 years old), divided in two groups: the regular diet group (n = 43) comprised healthy normal weight/underweight children with no dietary control; the healthy diet group (n = 67) comprised children diagnosed for obesity/overweight (without other known associated diseases) that were set on a healthy diet for weight control. First morning urine samples were collected and total urinary BPA was analyzed after enzymatic hydrolysis via on-line HPLC-MS/MS with isotope dilution quantification. Virtually, all the children were exposed to BPA, with 91% of the samples above the LOQ (limit of quantification) of 0.1 μg/L. The median (95th percentile) urinary BPA levels for non-normalized and creatinine-corrected values were 1.89 μg/L (16.0) and 1.92 μg/g creatinine (14.4), respectively. BPA levels in the regular diet group were higher than in the healthy diet group, but differences were not significant. Calculated daily BPA intakes, however, were significantly higher in children of the regular diet group than in children of healthy diet group. Median (95th percentile) daily intakes amounted to 41.6 (467) ng/kg body weight/day in the regular diet group, and 23.2 (197) ng/kg body weight/day in the healthy diet group. Multiple logistic regression analysis revealed that children in the healthy diet group had 33% lower intakes than children in the regular diet group (OR 0.67; 95% CI 0.51-0.89). For both groups, however, urinary BPA levels and daily BPA intakes were within the range reported for other children's populations and were well below health guidance values such as the European Food Safety Authority (EFSA) temporary tolerable daily intake (t-TDI) of 4 μg/kg body weight/day. In addition, lower daily BPA intakes were more likely linked with the inherent dietary approach rather than with high BMI or obesity.info:eu-repo/semantics/publishedVersio

Carbohydrate Intake in the Etiology of Crohn's Disease and Ulcerative Colitis

Background: Diet may have a role in the etiology of inflammatory bowel disease. In previous studies, the associations between increased intakes of carbohydrates, sugar, starch, and inflammatory bowel disease are inconsistent. However, few prospective studies have investigated the associations between these macronutrients and incident Crohn's disease (CD) or ulcerative colitis (UC). Methods: A total of 401,326 men and women were recruited between 1991 and 1998. At recruitment, dietary intakes of carbohydrate, sugar, and starch were measured using validated food frequency questionnaires. The cohort was monitored identifying participants who developed incident CD or UC. Cases were matched with 4 controls, and odds ratios were calculated for quintiles of total carbohydrate, sugar, and starch intakes adjusted for total energy intake, body mass index, and smoking. Results: One hundred ten participants developed CD, and 244 participants developed UC during follow-up. The adjusted odds ratio for the highest versus the lowest quintiles of total carbohydrate intake for CD was 0.87, 95% CI = 0.24 to 3.12 and for UC 1.46, 95% CI = 0.62 to 3.46, with no significant trends across quintiles for either (CD, Ptrend = 0.70; UC, Ptrend = 0.41). Similarly, no associations were observed with intakes of total sugar (CD, Ptrend = 0.50; UC, Ptrend = 0.71) or starch (CD, Ptrend = 0.69; UC, Ptrend = 0.17). Conclusions: The lack of associations with these nutrients is in agreement with many case–control studies that have not identified associations with CD or UC. As there is biological plausibility for how specific carbohydrates could have an etiological role in inflammatory bowel disease, future epidemiological work should assess individual carbohydrates, although there does not seem to be a macronutrient effect

Rational design and direct fabrication of multi-walled hollow electrospun fibers with controllable structure and surface properties

Multi-walled hollow fibers with a novel architecture are fabricated through utilizing a direct,one-step tri-axial electrospinning process with a manufacturing methodology which does not require any post-treatments for the removal of core material for creating hollowness in the fiber structure. The hydrophilicity of both inner and outer layers’ solution needs to be dissimilar and carefully controlled for creating a two-walled/layered hollow fiber tructure with a sharp interface. To this end, Hansen solubility parameters are used as n index of layer solution affinity hence allowing for control of diffusion across the layers and the surface porosity whereby an ideal multi-walled hollow electrospun fiber is shown to be producible by tri-axial electrospinning process. Multi-walled hollow electrospun fibers with different inner and outer diameters and different surface morphology are successfully produced by using dissimilar material combinations for inner and outer layers (i.e., hydrophobic polymers as outer layer and hydrophilic polymer as inner layer). Upon using different material combinations for inner and outer layers, it is shown that one may control both the outer and inner diameters of the fiber. The inner layer not only acts as a barrier and thus provides an ease in the encapsulation of functional core materials of interest with different viscosities but also adds stiffness to the fiber. The structure and the surface morphology of fibers are controlled by changing applied voltage, polymer types, polymer concentration, and the evaporation rate of solvents. It is demonstrated that if the vapor pressure of the solvent for a given outer layer polymer is low, the fiber diameter decreases down to 100 nm whereas solvents with higher vapor pressure result in fibers with the outer diameter of up to 1 μm. The influence of electric field strength on the shape of Taylor cone is also monitored during the production process and the manufactured fibers are structurally investigated by relevant surface characterization techniques

Month of birth, vitamin D and risk of immune mediated disease: a case control study

ABSTRACT: BACKGROUND: A season of birth effect in immune-mediated diseases (ID) such as multiple sclerosis and type 1 diabetes has been consistently reported. We aimed to investigate whether season of birth influences the risk of rheumatoid arthritis, Crohn's disease, ulcerative colitis and systemic lupus erythematosus in addition to multiple sclerosis, and to explore the correlation between the risk of ID and predicted ultraviolet B (UVB) light exposure and vitamin D status during gestation. METHODS: The monthly distribution of births of patients with ID from the UK (n = 115,172) was compared to that of the general population using the Cosinor test. Predicted UVB radiation and vitamin D status in different time windows during pregnancy were calculated for each month of birth and correlated with risk of ID using the Spearman's correlation coefficient. RESULTS: The distributions of ID births significantly differed from that of the general population (P = 5e-12) with a peak in April (odds ratio = 1.045, 95% confidence interval = 1.024, 1.067, P <0.0001) and a trough in October (odds ratio = 0.945, 95% confidence interval = 0.925, 0.966, P <0.0001). Stratification by disease subtype showed seasonality in all ID but Crohn's disease. The risk of ID was inversely correlated with predicted second trimester UVB exposure (Spearman's rho = -0.49, P = 0.00005) and third trimester vitamin D status (Spearman's rho = -0.44, P = 0.0003). CONCLUSIONS: The risk of different ID in the UK is significantly influenced by the season of birth, suggesting the presence of a shared seasonal risk factor or factors predisposing to ID. Gestational UVB and vitamin D exposure may be implicated in the aetiology of ID

Pre-pubertal exposure with phthalates and bisphenol A and pubertal development.

Epidemiological studies indicate associations between childhood exposure with phthalates and bisphenol A (BPA) and the pubertal development. We examined associations between the pre-pubertal phthalate and BPA body burden and the longitudinally assessed sexual maturation of eight- to thirteen-year-old children.We started with eight- to ten-year-old children in the baseline study and quantified phthalate metabolites and BPA in 472 urine samples (250 boys; 222 girls; mean age: 8.8 years). Associations between the pubertal development, assessed in three annual follow-up studies by Puberty Development scale questionnaires (PD scales), and the chemical exposure from the baseline visit were longitudinally analyzed with generalized estimation equations.The number of children with both chemical measures and PD scores (calculated from the PD scales) was 408. In the third follow-up, 49% of the girls and 18% of the boys had reached mid-puberty. For girls, we observed a delayed pubertal development with the di-hexyl-ethyl phthalate (DEHP) metabolites (β: -0.16 to -0.23; p ≤ 0.05 or p ≤ 0.1), mono-n-butyl phthalate (β: -0.15; 95% CI: -0.31; 0.01), mono-benzyl phthalate (β: -0.11; 95% CI: -0,24; -0,01), and mono-ethyl phthalate (MEP) (β: -0.15; 95% CI: -0.28; -0.01). In addition, significant non-linear associations of the DEHP metabolites and BPA with the PD scores were found, when their quadratic effects were included in the GEE models. In boys, no consistent relationships between the PD scores and the chemicals were detected except of an accelerated development with the ∑DEHP metabolites (β: 0.16; 95% CI: -0.02; -0.34).We found indications that pre-pubertal exposures with phthalates and BPA were associated with pubertal timing in children, particularly in girls. For boys, associations were inconsistent, and not necessarily in line with the known anti-androgenicity of some phthalates during prenatal exposure

Characteristics of the study population and the phthalate metabolite and BPA concentrations in urine.

<p>Characteristics of the study population and the phthalate metabolite and BPA concentrations in urine.</p

Multinomial GEE analyses of the PD scores with phthalate metabolites and BPA concentrations (ln- μg/l) in boys (N = 210).

<p>Multinomial GEE analyses of the PD scores with phthalate metabolites and BPA concentrations (ln- μg/l) in boys (N = 210).</p