The association of prenatal phthalates, organophosphorous pesticides, and organophosphate esters with early child language ability in Norway.

BACKGROUND: Prenatal exposure to phthalates, organophosphate esters, and organophosphorous pesticides have been associated with neurodevelopmental deficits including language ability, however, few studies consider the effect of exposure mixtures and the potential longitudinal detriments over time. OBJECTIVE: This study examines the influence of prenatal exposure to phthalates, organophosphate esters, and organophosphorous pesticides, on children's language ability from toddlerhood to the preschool period. METHODS: This study includes 299 mother-child dyads from Norway in the Norwegian Mother, Father and Child Cohort Study (MoBa). Prenatal exposure to chemicals were assessed at 17 weeks' gestation, and child language skills were assessed at 18 months using the Ages and Stages Questionnaire communication subscale and at preschool age using the Child Development Inventory. We ran two structural equation models to examine the simultaneous influences of chemical exposures on parent-reported and teacher-reported child language ability. RESULTS: Prenatal organophosphorous pesticides were negatively associated with preschool language ability through language ability at 18 months. Additionally, there was a negative association between low molecular weight phthalates and teacher-reported preschool language ability. There was no effect of prenatal organophosphate esters on child language ability at either 18 months or preschool age. CONCLUSIONS: This study adds to the literature on prenatal exposure to chemicals and neurodevelopment and highlights the importance of developmental pathways in early childhood.

Organophosphorus Pesticide Exposure at 17 Weeks' Gestation and Odds of Offspring Attention-Deficit/Hyperactivity Disorder Diagnosis in the Norwegian Mother, Father, and Child Cohort Study.

Prenatal organophosphorus pesticides (OPs) are ubiquitous and have been linked to adverse neurodevelopmental outcomes. However, few studies have examined prenatal OPs in relation to diagnosed attention-deficit/hyperactivity disorder (ADHD), with only two studies exploring this relationship in a population primarily exposed through diet. In this study, we used a nested case-control study to evaluate prenatal OP exposure and ADHD diagnosis in the Norwegian Mother, Father, and Child Cohort Study (MoBa). For births that occurred between 2003 and 2008, ADHD diagnoses were obtained from linkage of MoBa participants with the Norwegian Patient Registry (N = 297), and a reference population was randomly selected from the eligible population (N = 552). Maternal urine samples were collected at 17 weeks' gestation and molar sums of diethyl phosphates (ΣDEP) and dimethyl phosphates metabolites (ΣDMP) were calculated. Multivariable adjusted logistic regression models were used to estimate the association between prenatal OP metabolite exposure and child ADHD diagnosis. Additionally, multiplicative effect measure modification (EMM) by child sex was assessed. In most cases, mothers in the second and third tertiles of ΣDMP and ΣDEP exposure had slightly lower odds of having a child with ADHD, although confidence intervals were wide and included the null. EMM by child sex was not observed for either ΣDMP or ΣDEP. In summary, we did not find evidence that OPs at 17 weeks' gestation increased the odds of ADHD in this nested case-control study of ADHD in MoBa, a population primarily experiencing dietary exposure.

Prenatal Exposure to Organophosphorus Pesticides and Preschool ADHD in the Norwegian Mother, Father and Child Cohort Study.

Prenatal organophosphorus pesticide (OPP) exposure has been associated with child attention-deficit/hyperactivity disorder (ADHD) in agricultural communities and those that are exposed to residentially applied insecticides. To examine this association in populations that are exposed primarily through diet, we estimate the associations between prenatal OPP exposure and preschool ADHD in the Norwegian Mother, Father and Child Cohort Study (MoBa), and describe modification by paraoxonase 1 (PON1) gene variants. We used participants from the MoBa Preschool ADHD Sub-study (n = 259 cases) and a random sample of MoBa sub-cohort participants (n = 547) with birth years from 2004 to 2008. Prenatal urinary dialkylphosphate (DAP) metabolites (total diethylphosphate [∑DEP] and total dimethylphosphate [∑DMP]) were measured by an ultra-performance liquid chromatography-time-of-flight system and summed by molar concentration. Maternal DNA was genotyped for coding variants of PON1 (Q192R and L55M). We used a multivariable logistic regression to calculate the odds ratios (OR) and 95% confidence intervals, adjusted for maternal education, parity, income dependency, age, marital status, ADHD-like symptoms, pesticide use, produce consumption, and season. We found no associations between DAP metabolite concentrations and preschool ADHD. The adjusted ORs for exposure quartiles 2-4 relative to 1 were slightly inverse. No monotonic trends were observed, and the estimates lacked precision, likely due to the small sample size and variation in the population. We found no evidence of modification by PON1 SNP variation or child sex. Maternal urinary DAP concentrations were not associated with preschool ADHD.

Prenatal organophosphorus pesticide exposure and executive function in preschool-aged children in the Norwegian Mother, Father and Child Cohort Study (MoBa).

INTRODUCTION: Prenatal exposure to organophosphorus pesticides (OPPs) has been associated with neurodevelopmental deficits in children, however evidence linking OPPs with specific cognitive mechanisms, such as executive function (EF), is limited. OBJECTIVE: This study aims to evaluate the association between prenatal exposure to OPPs with multiple measures of EF in preschool-aged children, while considering the role of variant alleles in OPP metabolism genes. METHODS: We included 262 children with preschool attention-deficit/hyperactivity disorder (ADHD), and 78 typically developing children, from the Preschool ADHD substudy of the Norwegian, Mother, Father, and Child Cohort Study. Participants who gave birth between 2004 and 2008 were invited to participate in an on-site clinical assessment when the child was approximately 3.5 years; measurements of EF included parent and teacher rating on Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P), and three performance-based assessments. We measured OPP metabolites in maternal urines collected at ∼17 weeks' gestation to calculate total dimethyl- (ΣDMP) and diethyl phosphate (ΣDEP) metabolite concentrations. We estimated multivariable adjusted ß's and 95% confidence intervals (CIs) corresponding to a change in z-score per unit increase in log-ΣDMP/DEP. We further characterized gene-OPP interactions for maternal variants in PON1 (Q192R, M55L), CYP1A2 (1548T > C), CYP1A1 (IntG > A) and CYP2A6 (-47A > C). RESULTS: Prenatal OPP metabolite concentrations were associated with worse parent and teacher ratings of emotional control, inhibition, and working memory. A one log-∑DMP increase was associated with poorer teacher ratings of EF on the BRIEF-P (e.g. emotional control domain: ß = 0.55, 95% CI: 0.35, 0.74), when weighted to account for sampling procedures. We found less consistent associations with performance-based EF assessments. We found some evidence of modification for PON1 Q192R and CYP2A6 -47A > C. Association with other variants were inconsistent. CONCLUSIONS: Biomarkers of prenatal OPP exposure were associated with more adverse teacher and parent ratings of EF in preschool-aged children.

Critical review of analytical methods for the determination of flame retardants in human matrices.

Human biomonitoring is a powerful approach in assessing exposure to environmental pollutants. Flame retardants (FRs) are of particular concern due to their wide distribution in the environment and adverse health effects. This article reviews studies published in 2009-2020 on the chemical analysis of FRs in a variety of human samples and discusses the characteristics of the analytical methods applied to different FR biomarkers of exposure, including polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD), novel halogenated flame retardants (NHFRs), bromophenols, incl. tetrabromobisphenol A (TBBPA), and organophosphorous flame retardants (PFRs). Among the extraction techniques, liquid-liquid extraction (LLE) and solid phase extraction (SPE) were used most frequently due to the good efficiencies in the isolation of the majority of the FR biomarkers, but with challenges for highly lipophilic FRs. Gas chromatography-mass spectrometry (GC-MS) is mainly applied in the instrumental analysis of PBDEs and most NHFRs, with recent inclusions of GC-MS/MS and high resolution MS techniques. Liquid chromatography-MS/MS is mainly applied to HBCD, bromophenols, incl. TBBPA, and PFRs (including metabolites), however, GC-based analysis following derivatization has also been used for phenolic compounds and PFR metabolites. Developments are noticed towards more universal analytical methods, which enable widening method scopes in the human biomonitoring of FRs. Challenges exist with regard to sensitivity required for the low concentrations of FRs in the general population and limited sample material for some human matrices. A strong focus on quality assurance/quality control (QA/QC) measures is required in the analysis of FR biomarkers in human samples, related to their variety of physical-chemical properties, low levels in most human samples and the risk of contamination.

Biomarkers, matrices and analytical methods targeting human exposure to chemicals selected for a European human biomonitoring initiative.

The major purpose of human biomonitoring is the mapping and assessment of human exposure to chemicals. The European initiative HBM4EU has prioritized seven substance groups and two metals relevant for human exposure: Phthalates and substitutes (1,2-cyclohexane dicarboxylic acid diisononyl ester, DINCH), bisphenols, per- and polyfluoroalkyl substances (PFASs), halogenated and organophosphorous flame retardants (HFRs and OPFRs), polycyclic aromatic hydrocarbons (PAHs), arylamines, cadmium and chromium. As a first step towards comparable European-wide data, the most suitable biomarkers, human matrices and analytical methods for each substance group or metal were selected from the scientific literature, based on a set of selection criteria. The biomarkers included parent compounds of PFASs and HFRs in serum, of bisphenols and arylamines in urine, metabolites of phthalates, DINCH, OPFRs and PAHs in urine as well as metals in blood and urine, with a preference to measure Cr in erythrocytes representing Cr (VI) exposure. High performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was the method of choice for bisphenols, PFASs, the HFR hexabromocyclododecane (HBCDD), phenolic HFRs as well as the metabolites of phthalates, DINCH, OPFRs and PAHs in urine. Gas chromatographic (GC) methods were selected for the remaining compounds, e.g. GC-low resolution MS with electron capture negative ionization (ECNI) for HFRs. Both GC-MS and LC-MS/MS were suitable for arylamines. New developments towards increased applications of GC-MS/MS may offer alternatives to GC-MS or LC-MS/MS approaches, e.g. for bisphenols. The metals were best determined by inductively coupled plasma (ICP)-MS, with the particular challenge of avoiding interferences in the Cd determination in urine. The evaluation process revealed research needs towards higher sensitivity and non-invasive sampling as well as a need for more stringent quality assurance/quality control applications and assessments.

Effect of Four Novel Bio-Based DES (Deep Eutectic Solvents) on Hardwood Fractionation.

Using the basic principle of construction between a hydrogen bond acceptor (HBA) and a hydrogen bond donor (HBD), four bio-based deep eutectic solvents (DESs) were prepared in a 1:2 molar ratio of HBA:HBD. 2,3-Dihydroxypropyl-1-triethylammonium chloride ([C9H22N+O2]Cl-) was synthesized from raw glycerol and used as an HBA. Lactic acid, urea, pure glycerol, and ethylene glycol were selected as HBD. Attempts to prepare DESs, using citric acid and benzoic acid as HBDs, were unsuccessful. All these DESs were characterized using FTIR and NMR techniques. Besides, physicochemical parameters such as pH, viscosity, density, and melting point were determined. The behavior of these DES to fractionate olive pomace was studied. Lignin recovery yields spanned between 27% and 39% (w/w) of the available lignin in olive pomace. The best DES, in terms of lignin yield ([C9H22N+O2]Cl- -lactic acid), was selected to perform a scale-up lignin extraction using 40 g of olive pomace. Lignin recovery on the multigram scale was similar to the mg scale (38% w/w). Similarly, for the holocellulose-rich fractions, recovery yields were 34% and 45% for mg and multi-gram scale, respectively. Finally, this DES was used to fractionate four fruit pruning samples. These results show that our novel DESs are alternative approaches to the ionic liquid:triethylammonium hydrogen sulfate and the widely used DES: choline chloride:lactic acid (1:10 molar ratio) for biomass processing.

Association between the pregnancy exposome and fetal growth.

BACKGROUND: Several environmental contaminants were shown to possibly influence fetal growth, generally from single exposure family studies, which are prone to publication bias and confounding by co-exposures. The exposome paradigm offers perspectives to avoid selective reporting of findings and to control for confounding by co-exposures. We aimed to characterize associations of fetal growth with the pregnancy chemical and external exposomes. METHODS: Within the Human Early-Life Exposome project, 131 prenatal exposures were assessed using biomarkers and environmental models in 1287 mother-child pairs from six European cohorts. We investigated their associations with fetal growth using a deletion-substitution-addition (DSA) algorithm considering all exposures simultaneously, and an exposome-wide association study (ExWAS) considering each exposure independently. We corrected for exposure measurement error and tested for exposure-exposure and sex-exposure interactions. RESULTS: The DSA model identified lead blood level, which was associated with a 97 g birth weight decrease for each doubling in lead concentration. No exposure passed the multiple testing-corrected significance threshold of ExWAS; without multiple testing correction, this model was in favour of negative associations of lead, fine particulate matter concentration and absorbance with birth weight, and of a positive sex-specific association of parabens with birth weight in boys. No two-way interaction between exposure variables was identified. CONCLUSIONS: This first large-scale exposome study of fetal growth simultaneously considered >100 environmental exposures. Compared with single exposure studies, our approach allowed making all tests (usually reported in successive publications) explicit. Lead exposure is still a health concern in Europe and parabens health effects warrant further investigation.

Early-Life Environmental Exposures and Blood Pressure in Children.

BACKGROUND: Growing evidence exists about the fetal and environmental origins of hypertension, but mainly limited to single-exposure studies. The exposome has been proposed as a more holistic approach by studying many exposures simultaneously. OBJECTIVES: This study aims to evaluate the association between a wide range of prenatal and postnatal exposures and blood pressure (BP) in children. METHODS: Systolic and diastolic BP were measured among 1,277 children from the European HELIX (Human Early-Life Exposome) cohort aged 6 to 11 years. Prenatal (n = 89) and postnatal (n = 128) exposures include air pollution, built environment, meteorology, natural spaces, traffic, noise, chemicals, and lifestyles. Two methods adjusted for confounders were applied: an exposome-wide association study considering the exposures independently, and the deletion-substitution-addition algorithm considering all the exposures simultaneously. RESULTS: Decreases in systolic BP were observed with facility density (ß change for an interquartile-range increase in exposure: -1.7 mm Hg [95% confidence interval (CI): -2.5 to -0.8 mm Hg]), maternal concentrations of polychlorinated biphenyl 118 (-1.4 mm Hg [95% CI: -2.6 to -0.2 mm Hg]) and child concentrations of dichlorodiphenyldichloroethylene (DDE: -1.6 mm Hg [95% CI: -2.4 to -0.7 mm Hg]), hexachlorobenzene (-1.5 mm Hg [95% CI: -2.4 to -0.6 mm Hg]), and mono-benzyl phthalate (-0.7 mm Hg [95% CI: -1.3 to -0.1 mm Hg]), whereas increases in systolic BP were observed with outdoor temperature during pregnancy (1.6 mm Hg [95% CI: 0.2 to 2.9 mm Hg]), high fish intake during pregnancy (2.0 mm Hg [95% CI: 0.4 to 3.5 mm Hg]), maternal cotinine concentrations (1.2 mm Hg [95% CI: -0.3 to 2.8 mm Hg]), and child perfluorooctanoate concentrations (0.9 mm Hg [95% CI: 0.1 to 1.6 mm Hg]). Decreases in diastolic BP were observed with outdoor temperature at examination (-1.4 mm Hg [95% CI: -2.3 to -0.5 mm Hg]) and child DDE concentrations (-1.1 mm Hg [95% CI: -1.9 to -0.3 mm Hg]), whereas increases in diastolic BP were observed with maternal bisphenol-A concentrations (0.7 mm Hg [95% CI: 0.1 to 1.4 mm Hg]), high fish intake during pregnancy (1.2 mm Hg [95% CI: -0.2 to 2.7 mm Hg]), and child copper concentrations (0.9 mm Hg [95% CI: 0.3 to 1.6 mm Hg]). CONCLUSIONS: This study suggests that early-life exposure to several chemicals, as well as built environment and meteorological factors, may affect BP in children.

Concentrations of selected chemicals in indoor air from Norwegian homes and schools.

Both building materials and consumer products have been identified as possible sources for potentially hazardous substances like phthalates, polychlorinated biphenyls (PCBs), organophosphorous flame retardants (OPFRs), polybrominated diphenyl ethers (PBDEs) and short chain chlorinated paraffins (SCCPs) in indoor air. Thus, indoor air has been suggested to contribute significantly to human exposure to these chemicals. There is lack of data on the occurrence of several of the aforementioned chemicals in indoor air. Therefore, indoor air (gas and particulate phase) was collected from 48 households and 6 classrooms in two counties in Norway. In both the households and schools, median levels of low molecular weight phthalates (785 ng/m3), OPFRs (55 ng/m3) and SCCPs (128 ng/m3) were up to 1000 times higher than the levels of PCBs (829 pg/m3) and PBDEs (167 pg/m3). Median concentrations of dimethyl phthalate (DMP), diethyl phthalate (DEP), di-isobutyl phthalate (DiBP) and SCCPs were 3-6 times higher in households compared to schools. The levels of OPFRs, PCBs and PBDEs were similar in households and schools. In univariate analysis, the indoor concentrations of different environmental chemicals were significantly affected by location of households (OPFRs), airing of living room (some PCBs and PBDEs), presence of upholstered chair/couch (OPFRs), pet animal hold (some PBDEs) and presence of electrical heaters (selected PCBs and PBDEs). Significant correlations were also detected for the total size of households with OPFRs, frequency of vacuuming the living room with selected PCBs and PBDEs, frequency of washing the living room with selected PCBs and the total number of TVs in the households with selected phthalates and SCCPs. Finally, intake estimates indicated that indoor air contributed more or equally to low molecular weight phthalates and SCCPs exposure compared to food consumption, whereas the contribution from indoor air was smaller than the dietary intake for the other groups of chemicals.

Concentrations of brominated and phosphorous flame retardants in Finnish house dust and insights into children's exposure.

Brominated and phosphorous flame retardants (BFRs, PFRs) are added to household and consumer products to reduce their flammability. Some FRs are persistent in the environment and may have adverse health effects. As exposure indoors contributes significantly to total exposure, we wanted to estimate the exposure of children (3 years of age) through dust ingestion, inhalation, and dermal absorption. We measured 17 BFRs and 10 PFRs in indoor dust, predicted their respective concentrations in the indoor air and assessed children's exposure. Among the BFRs, decabromodiphenyl ether (BDE-209) had highest median level in the dust (411 ng/g) followed by decabromodiphenyl ethane (DBDPE, 119 ng/g) and bis-ethylhexyl tetrabromophthalate (BEH-TEBP, 106 ng/g). Among the PFRs, trisbutoxyethyl phosphate (TBOEP) had the highest concentration (11100 ng/g) followed by tris(2-chloroisopropyl) phosphate (TCIPP, 1870 ng/g) and triphenyl phosphate (TPHP, 773 ng/g). FR concentration in air predicted from dust concentrations were within the interquartile range of experimental data for 10/13 of BFRs and 4/8 of PFRs compared. Dust ingestion was the major route of exposure (75-99%) for higher molecular weight BFRs, TBOEP and phenyl based PFRs (73-77%). Inhalation was important for volatile BFRs like pentabromobenzene (PBB 71%) and pentabromotoluene (PBT 52%) and dermal exposure for volatile chlorinated PFRs (TCEP 84%, TCIPP 77%). Margins of Exposure (MoE) were calculated as the ratio of total exposure to oral Reference Dose (RfD). MoEs were lowest for TCEP (220), TBOEP (240) and TCIPP (830), and > 1000 for all other FRs. These MoEs imply no risk for Finnish children by the studied FRs.

Early-life exposome and lung function in children in Europe: an analysis of data from the longitudinal, population-based HELIX cohort.

BACKGROUND: Several single-exposure studies have documented possible effects of environmental factors on lung function, but none has relied on an exposome approach. We aimed to evaluate the association between a broad range of prenatal and postnatal lifestyle and environmental exposures and lung function in children. METHODS: In this analysis, we used data from 1033 mother-child pairs from the European Human Early-Life Exposome (HELIX) cohort (consisting of six existing longitudinal birth cohorts in France, Greece, Lithuania, Norway, Spain, and the UK of children born between 2003 and 2009) for whom a valid spirometry test was recorded for the child. 85 prenatal and 125 postnatal exposures relating to outdoor, indoor, chemical, and lifestyle factors were assessed, and lung function was measured by spirometry in children at age 6-12 years. Two agnostic linear regression methods, a deletion-substitution-addition (DSA) algorithm considering all exposures simultaneously, and an exposome-wide association study (ExWAS) considering exposures independently, were applied to test the association with forced expiratory volume in 1 s percent predicted values (FEV1%). We tested for two-way interaction between exposures and corrected for confounding by co-exposures. FINDINGS: In the 1033 children (median age 8·1 years, IQR 6·5-9·0), mean FEV1% was 98·8% (SD 13·2). In the ExWAS, prenatal perfluorononanoate (p=0·034) and perfluorooctanoate (p=0·030) exposures were associated with lower FEV1%, and inverse distance to nearest road during pregnancy (p=0·030) was associated with higher FEV1%. Nine postnatal exposures were associated with lower FEV1%: copper (p=0·041), ethyl-paraben (p=0·029), five phthalate metabolites (mono-2-ethyl 5-carboxypentyl phthalate [p=0·016], mono-2-ethyl-5-hydroxyhexyl phthalate [p=0·023], mono-2-ethyl-5-oxohexyl phthalate [p=0·0085], mono-4-methyl-7-oxooctyl phthalate [p=0·040], and the sum of di-ethylhexyl phthalate metabolites [p=0·014]), house crowding (p=0·015), and facility density around schools (p=0·027). However, no exposure passed the significance threshold when corrected for multiple testing in ExWAS, and none was selected with the DSA algorithm, including when testing for exposure interactions. INTERPRETATION: Our systematic exposome approach identified several environmental exposures, mainly chemicals, that might be associated with lung function. Reducing exposure to these ubiquitous chemicals could help to prevent the development of chronic respiratory disease. FUNDING: European Community's Seventh Framework Programme (HELIX project).

In-utero and childhood chemical exposome in six European mother-child cohorts.

BACKGROUND: Harmonized data describing simultaneous exposure to a large number of environmental contaminants in-utero and during childhood is currently very limited. OBJECTIVES: To characterize concentrations of a large number of environmental contaminants in pregnant women from Europe and their children, based on chemical analysis of biological samples from mother-child pairs. METHODS: We relied on the Early-Life Exposome project, HELIX, a collaborative project across six established population-based birth cohort studies in Europe. In 1301 subjects, biomarkers of exposure to 45 contaminants (i.e. organochlorine compounds, polybrominated diphenyl ethers, per- and polyfluoroalkyl substances, toxic and essential elements, phthalate metabolites, environmental phenols, organophosphate pesticide metabolites and cotinine) were measured in biological samples from children (6-12 years) and their mothers during pregnancy, using highly sensitive biomonitoring methods. RESULTS: Most of the exposure biomarkers had high detection frequencies in mothers (35 out of 45 biomarkers with >90% detected) and children (33 out of 45 biomarkers with >90% detected). Concentrations were significantly different between cohorts for all compounds, and were generally higher in maternal compared to children samples. For most of the persistent compounds the correlations between maternal and child concentrations were moderate to high (Spearman Rho > 0.35), while for most non-persistent compounds correlations were considerably lower (Spearman Rho < 0.15). For mercury, PFOS and PFOA a considerable proportion of the samples of both mothers and their children exceeded the HBM I value established by The Human Biomonitoring Commission of the German Federal Environment Agency. DISCUSSION: Although not based on a representative sample, our study suggests that children across Europe are exposed to a wide range of environmental contaminants in fetal life and childhood including many with potential adverse effects. For values exceeding the HBM I value identification of specific sources of exposure and reducing exposure in an adequate way is recommended. Considerable variability in this "chemical exposome" was seen between cohorts, showing that place of residence is a strong determinant of one's personal exposome. This extensive dataset comprising >100,000 concentrations of environmental contaminants in mother-child pairs forms a unique possibility for conducting epidemiological studies using an exposome approach.

Levels, variability and determinants of environmental phenols in pairs of Norwegian mothers and children.

BACKGROUND: Exposure to environmental phenols including parabens, bisphenols (BPs), oxybenzone/benzophenone-3 (BP-3) and triclosan (TCS) is ubiquitous. Due to evidence of their estrogenic activity, they have been considered as chemicals of concern. The exposure of the Norwegian population to these compounds is presently unknown. AIMS: To measure urinary levels of twelve different environmental phenols including four emerging bisphenols: S, F, B and AF (abbreviated as BPS, BPF, BPB and BPAF, respectively) in a healthy Norwegian population. We have calculated short-term variability, estimated daily intakes and investigated important determinants of exposure. METHODS: Urine samples were collected from mothers (n = 48) and their children (n = 56) during spring/summer 2012 in two counties in Norway. RESULTS: Six environmental phenols namely methyl, ethyl and propyl paraben, BPA, BP-3 and TCS were detected in almost 100% of the urine samples. Among the emerging bisphenols, BPS was detected most frequently in the urine samples (42-48%) followed by BPF (4-15%). Parabens were positively and significantly correlated to each other in both mothers and children. Levels of parabens and BP-3 were higher in mothers compared to children. All mothers and children had lower estimated daily intakes (back calculated from the urinary concentrations) of parabens and BPA than the respective acceptable and tolerable daily intakes (ADIs and TDIs) established by the European Food Safety Authority (EFSA). Observed intraclass correlation coefficients (ICCs) indicated moderate to high reliability of spot urine measurements for all the environmental phenols (ICCs: 0.70-0.97). Use of hair products, deodorants, face and hand creams were significantly associated with higher urinary levels of parabens. CONCLUSIONS: Occurrence of environmental phenols in healthy Norwegian women and children is abundant. Among emerging bisphenols, there is widespread exposure to BPS. A single spot urine sample can be used for estimating short-term exposures of environmental phenols. Urinary levels of parabens were associated with use of PCPs.

Phthalate metabolites in Norwegian mothers and children: Levels, diurnal variation and use of personal care products.

Exposure to phthalates has been associated with reproductive and developmental toxicity. Data on levels of these compounds in the Norwegian population is limited. In this study, urine samples were collected from 48 mothers and their children in two counties in Norway. Eleven different phthalate metabolites originating from six commonly used phthalates in consumer products were determined. Concentrations of phthalate metabolites were significantly higher in children compared to mothers except for mono-ethyl phthalate (MEP). The mothers provided several urine samples during 24hours (h) and diurnal variation showed that the concentrations in the morning urine samples (24-8h) were significantly higher than at other time-periods for most of the phthalate metabolites. Intraclass correlation coefficients (ICCs) for 24-hour time-period were in the range of 0.49-0.81. These moderate to high ICCs indicate that one spot urine sample can be used to estimate the exposure to phthalates. Since a significant effect of time of day was observed, it is still advisable to standardize the collection time point to reduce the variation. For the mothers, the use of personal care products (PCPs) were less associated with morning urine samples than early day (8-12h) and evening (16-24h) urine samples. The use of perfume and hair products were positively associated with the urinary concentrations of low molecular weight phthalates. Use of shower soap and shampoo were positively associated with urinary concentration of di(2-ethylhexyl) phthalate (DEHP) metabolites. For children, face cream use was positively associated with phthalate metabolites in the morning samples, and hand soap use was negatively associated with concentration of urinary DEHP metabolites in afternoon/evening samples. Since different PCPs were associated with the urinary phthalate metabolites in different time-periods during a day, more than one spot urine sample might be required to study associations between urinary phthalate metabolites and the use of PCPs.

Exposure to organophosphorus pesticides in Norwegian mothers and their children: Diurnal variability in concentrations of their biomarkers and associations with food consumption.

Several studies have suggested that exposure to organophosphorus (OP) pesticides is detrimental for health, and in particular for children where moderate doses may have a negative impact on the neurodevelopment. This study surveys levels of the 6 non-specific urinary metabolites (dialkyl phosphates (DAPs)) of OP pesticides in Norwegian mothers (n=48) and their children (n=54), and examines the diurnal variation in concentrations as well as associations with consumption of specific food products. The highest median concentration measured in urine was found for dimethyl thiophosphate (5.3 and 5.5ng/mLSG; specific gravity corrected) for both children and mothers, respectively, followed by diethyl phosphate (3.8 and 5.3ng/mLSG, respectively). The intra-class correlation coefficients of DAPs among mothers were moderate (0.49-0.68), and consumption of fruit explained between 8% and 55% of the variations in the mothers' and their children's urinary DAP concentrations.

Molecular Basis for the Recognition of Higher Fullerenes into Ureidopyrimidinone-Cyclotriveratrylene Self-Assembled Capsules.

Fullerenes C60 , C70 , and C84 may be readily encaged within a hydrogen-bonded dimeric capsule, based on two concave cyclotriveratrylene (CTV) scaffolds, each containing three self-complementary 2-ureido-4-[1H]-pyrimidinone (UPy) subunits. NMR spectroscopy and circular dichroism studies, complemented by dispersion-corrected DFT calculations, are reported with the aim of characterizing such capsule-fullerene complexes both structurally and energetically. Six fullerenes are considered: in agreement with experiments, calculations find that encapsulation is most favorable for C84 (on a par with C90 ), and follows the trend C60

Development of an ion-pair liquid chromatography-high resolution mass spectrometry method for determination of organophosphate pesticide metabolites in large-scale biomonitoring studies.

Organophosphate based pesticides are widely used in the agricultural sector, and exposure to these chemicals is common for the general population. Pesticides are toxic due to the inhibition of acetylcholinesterases, and the potential for adverse health effects have been investigated in past and recent studies. Human biomonitoring of organophosphate pesticide exposure is carried out through the determination of the metabolites in urine (dialkylphosphates, DAPs). Hereby we present a new method for determination of the 6 non-specific metabolites dimethyl phosphate (DMP), diethyl phosphate (DEP), dimethyl thiophosphate (DMTP), diethyl thiophosphate (DETP), dimethyl dithiophosphate (DMDTP), and diethyl dithiophosphate (DEDTP) in urine based on off-line solid phase extraction (anion exchange, 96-well plates) followed by ion-pair ultra-performance liquid chromatography time-of-flight mass spectrometry. Recoveries and accuracies in control urine spiked at 5ng/mL ranged from 48% to109% and from 91% to 115%, respectively. The method limits of detection for the DAPs were 1.2ng/mL for DMP, 0.38ng/mL for DEP, 0.20ng/mL for DMTP, 0.33ng/mL for DETP, 0.64ng/mL for DMDTP, and 0.15ng/mL for DEDTP. The method was applied to samples from a Norwegian mother/child study group (n=48/56) and the DAPs detection frequencies in urine from mothers and children were about: 40% for DMP, 95% for DEP, 96% for DMTP, 50% for DETP, 15% for DMDTP, and 1% for DEDTP. In both mothers and children, the most abundant DAPs were DMTP (median 2.4/5.2ng/mL) and DEP (median 2.6/3.4ng/mL) followed by DMP (median 1.5/2.1ng/mL). The SG corrected concentrations of DEP and DETP in mothers were statistically higher than in children (p-value<0.05; Mann-Whitney test) which might suggest a higher exposure to pesticides in these mothers, or significant differences in toxicokinetics between adults and children. The method was proven robust and suitable for large-scale biomonitoring studies.

Persistent and emerging pollutants in the blood of German adults: Occurrence of dechloranes, polychlorinated naphthalenes, and siloxanes.

Human biomonitoring is a valid method to determine exposure, identify time trends, and monitor the effects of restrictions and measures. To characterize the recent exposure of Germans to persistent or emerging substances, we analyzed 4 dechloranes, 33 polychlorinated naphthalenes (PCNs), and 3 cyclic volatile methyl siloxanes (cVMS) in 42 plasma samples. The samples were collected from blood donors on a random selection. The median values of both Dechlorane Plus (DDC-CO) isomers were 1.23ng/gl.w. for anti- and 0.77ng/gl.w. for syn-DDC-CO. The two other dechloranes were found at lower levels. The median level of ∑-PCNs was 575pg/gl.w. (range: 101-1406pg/gl.w.). On average, the levels of PCNs in plasma were dominated by the congeners CN73, CN66/67, and CN51, which were responsible for approximately 71% of the total amount of PCNs. The cVMS octa-, deca-, and dodecamethylcyclotetrasiloxane could be determined in only some samples, with maximum values of 0.73, 0.48, and 0.79µg/l, respectively. Regarding dechloranes, our results are similar to those from other western countries but slightly lower than results from China. The levels of PCNs in German blood are similar to those observed in the U.S.A., but considerably lower than those reported for Korea. Using a preliminary TEF (toxic equivalency factor), the mean TEQ of the 9 quantifiable PCNs in Germany was low (0.36pg TEQ/gl.w.). The PCN levels in our study group are lower compared to previous studies.