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Altered systemic oxidative stress is a consequence of environmental exposures and diseases, among other stress factors. The extent of oxidative stress in humans is assessed through the analysis of oxidative stress biomarkers (OSBs) in biospecimens such as urine. Allantoin is an OSB, a specific product of the oxidation of uric acid, that is measurable in urine. In this study, concentrations and inter- and intraindividual variability in urinary concentrations of allantoin were determined in healthy individuals. The results were compared with those found for other OSBs of lipids, proteins, and DNA in the same set of samples. Allantoin was found in all urine samples (N = 515), at concentrations that ranged from 0.88 to 41.7 mmol mol–1 creatinine (0.90 to 112 μg mL–1 urine). The intraclass correlation coefficient (ICC) of urinary allantoin measured in samples collected longitudinally for over a month from 19 individuals (0.74 for creatinine corrected and 0.80 for volumetric concentrations) showed an excellent ...

Background Exposure to bisphenols may affect fetal growth and development. The trimester-specific effects of bisphenols on repeated measures of fetal growth remain unknown. Our objective was to assess the associations of maternal bisphenol urine concentrations with fetal growth measures and birth outcomes and identify potential critical exposure periods. Methods In a population-based prospective cohort study among 1379 pregnant women, we measured maternal bisphenol A, S and F urine concentrations in the first, second and third trimester. Fetal head circumference, length and weight were measured in the second and third trimester by ultrasound and at birth. Results An interquartile range increase in maternal pregnancy-averaged bisphenol S concentrations was associated with larger fetal head circumference (difference 0.18 (95% confidence interval (CI) 0.01 to 0.34) standard deviation scores (SDS), p-value Conclusions Higher maternal bisphenol S urine concentrations, especially in the first trimester, seem to be related with larger fetal head circumference, higher weight and a lower risk of being small size for gestational age at birth.

Importance: Exposure to phthalates may affect fetal growth, but previous studies are inconsistent and have not explored the trimester-specific effects of phthalates on repeated measures of fetal growth. Objective: To assess the associations of maternal phthalate metabolites urine concentrations with fetal growth measures and birth outcomes and identify potential windows of vulnerability to exposure. Design: Population-based prospective cohort study, the Generation R Study (2002–2006). Data analysis was performed from November 2019 to June 2020. Setting: Rotterdam, the Netherlands. Participants: 1379 pregnant women. Exposures: Maternal phthalate metabolites urine concentrations in first, second and third trimester. Main outcomes and measures: Fetal head circumference, length and weight measured in the second and third trimester by ultrasound and at birth and preterm birth and small size for gestational age at birth. Results: Higher pregnancy-averaged phthalic acid, low molecular weight phthalate (LMWP), high molecular weight phthalate (HMWP) and di-2-ethylhexylphthalate (DEHP) concentrations tended to be associated with lower fetal weight SDS across gestation. The associations of phthalic acid and LMWP with fetal weight became stronger as pregnancy progressed (differences −0.08 (95% CI −0.14 to −0.02) SDS and −0.09 (95% CI −0.16 to −0.02) SDS at 40 weeks per interquartile range increase in phthalic acid and LMWP, respectively). Higher concentrations of specific LMWP, HMWP and DEHP metabolites were also associated with smaller head circumference and lower length SDS at birth and an increased risk of preterm birth and small size for gestational age at birth (p-values < 0.05). We observed differences by timing of exposure in these associations. Conclusions and relevance: Higher maternal phthalate metabolites urine concentrations seem to be related with fetal growth restriction and preterm birth. Phthalates may have trimester specific effects on fetal growth and birth outcomes. Further studies are needed to explore the underlying mechanisms and long-term consequences.

Background and aims: Fetal exposure to endocrine disruptors such as phthalates and bisphenols may lead to developmental metabolic adaptations. We examined associations of maternal phthalate and bisphenol urine concentrations during pregnancy with lipids, insulin, and glucose concentrations at school age. Methods: In a population-based, prospective cohort study among 757 mother–child pairs, we measured maternal phthalate and bisphenol urine concentrations in first, second and third trimester of pregnancy. We measured non-fasting lipids, glucose and insulin blood concentrations of their children at a mean age of 9.7 (standard deviation 0.2) years. Analyses were performed for boys and girls separately. Results: An interquartile range (IQR) higher natural log transformed third trimester maternal urine phthalic acid concentration was associated with a 0.20 (95% confidence interval (CI) 0.07–0.34) standard deviation score (SDS) higher triglycerides concentration among boys. Maternal bisphenol urine concentrations were not associated with non-fasting lipid concentrations during childhood. An IQR higher natural log transformed second trimester maternal high molecular weight phthalates (HMWP) and di-2-ethylhexylphthalate (DEHP) urine concentration were associated with a 0.19 (95% CI 0.31–0.07) respectively 0.18 (95% CI 0.31–0.06) SDS lower glucose concentration among boys. An IQR higher natural log transformed third trimester maternal bisphenol F urine concentration was associated with a 0.22 (95% CI 0.35–0.09) SDS lower non-fasting insulin concentration among boys. Conclusions: Our results suggest potential persisting sex specific effects of fetal exposure to phthalates and bisphenols on childhood lipid concentrations and glucose metabolism. Future studies are needed for replication and exploring underlying mechanisms.

Background Exposure to bisphenols and phthalates might influence bone health. We hypothesized that exposure to bisphenols and phthalates during fetal life has persistent effects on bone development. Objectives To analyze the associations of fetal exposure to bisphenols and phthalates with bone health in school-aged children. Methods Among 1,362 mother-child pairs participating in a population-based cohort study, we measured maternal urinary concentrations of bisphenols and phthalates at first, second and third trimester with high performance liquid chromatography electrospray ionization-tandem mass spectrometry. Total body bone mineral density (BMD) and bone area (BA) were measured using dual-energy X-ray absorptiometry (DXA) at 6 and 10 years, and were both used to calculate bone mineral content (BMC) and area-adjusted BMC (aBMC, a measure of volumetric BMD). Results Maternal bisphenol concentrations were not associated with childhood bone measures at 6 years. After adjustment for covariates and multiple testing correction, an interquartile range increase in maternal first trimester bisphenol S (BPS) concentrations was associated with lower BMD and aBMC at 10 years (−6.08 (95% confidence interval (CI), −9.97 to −2.19) mg/cm2 and -0.12 (95% CI, −0.20 to −0.04) g). Maternal third trimester low molecular weight (LMW) phthalate concentrations were associated with higher aBMC at 6 years whereas, maternal third trimester di-n-octylphthalate (DNOP) concentrations were associated with lower aBMC at 10 years. However, these associations did not remain statistically significant after multiple testing correction. Discussion Maternal first trimester BPS concentrations are associated with lower BMD and aBMC in school-aged children. These findings should be considered as hypothesis generating and need further replication and exploration of potential underlying mechanisms.

Human exposure to neonicotinoid insecticides (hereafter “neonics”) is a concern. Spot urine samples have been widely used in the assessment of exposure to neonics. Urinary concentrations, however, can vary greatly over time due to variable exposure, potentially leading to exposure misclassification. In this study, within- and between-individual variability of urinary concentrations of 13 neonics and their metabolites collected consecutively for up to 44 days from 19 individuals were examined. We also measured seven oxidative stress biomarkers (OSBs) in repeated urine samples to elucidate their relationship with neonic exposure by mixed regression models. Intraclass correlation coefficients (ICCs, a ratio of between-individual variance to total variance) were used to assess the reproducibility of neonic/metabolite concentrations. Sensitivity and specificity were used to evaluate how well spot urine samples determined an individual’s average exposure over 44 days. A fair to good reproducibility was observed for N-desmethyl-acetamiprid (ICC = 0.42), whereas thiamethoxam, imidacloprid, clothianidin, imidaclothiz, 6-chloronicotinic acid, and sulfoxaflor showed poor reproducibility (ICC = 0.02–0.37). Use of single-spot urine samples to classify high (top 33%) exposure showed higher specificities (0.68–0.92) than sensitivities (0.32–0.88). The minimum number of specimens (k) required to estimate participant-specific mean for neonic exposures within 20% of the “true” values ranged from 16 to 172. Significant positive correlations were found between some of neonic and OSB concentrations. The high variability found in the urinary concentrations of most neonics/metabolites suggests that a single measurement can result in exposure misclassification. Keywords: Exposure, Neonicotinoid, Insecticide, Urine, Oxidative stress, ICC

Fetal exposure to phthalates and bisphenols might have long-lasting effects on growth and fat development. Not much is known about the effects on general and organ fat development in childhood. We assessed the associations of fetal exposure to phthalates and bisphenols with general and organ fat measures in school-aged children.In a population-based, prospective cohort study among 1128 mother-child pairs, we measured maternal urinary phthalate metabolites and bisphenol concentrations in first, second, and third trimester. Offspring body mass index, fat mass index by dual-energy X-ray absorptiometry, and visceral and pericardial fat indices and liver fat fraction were measured by magnetic resonance imaging at 10 years.After adjustment for confounders and correction for multiple testing, an interquartile range increase in first trimester phthalic acid concentrations remained associated with a 0.14 (95% confidence interval: 0.05, 0.22) standard deviation score increase in pericardial fat index. We also observed tendencies for associations of higher maternal low molecular weight phthalate urinary concentrations in second trimester with childhood pericardial fat index, but these were not significant after adjustment for multiple testing. High molecular weight phthalate, di-2-ethylhexyl phthalate, and di-n-octyl phthalate concentrations were not associated with childhood outcomes. Maternal urinary bisphenol concentrations were not associated with childhood adiposity.Maternal first trimester phthalic acid concentrations are associated with increased childhood pericardial fat index at 10 years of age, whereas maternal bisphenol concentrations are not associated with childhood adiposity. We did not find significant sex-specific effects. These findings should be considered as hypothesis generating and need further replication and identification of underlying mechanisms.

Exposure of humans to pesticides is widespread. Measurement of urinary levels of pesticides and their metabolites is often used in the assessment of body burdens and exposure doses to these chemicals. An understanding of temporal variability in urinary levels of pesticides within individuals is critical for accurate exposure assessment. We examined within- and between-individual variability in concentrations of nine organophosphate and pyrethroid insecticides as well as two phenoxy herbicides in urine collected consecutively for up to 44 days from 19 individuals. Seven oxidative stress biomarkers also were measured in urine samples to elucidate their relationship with pesticide exposure. Intraclass correlation coefficients (ICCs) were calculated to assess reproducibility in urinary pesticide concentrations from repeated measures. Sensitivity and specificity analyses were performed to evaluate the suitability of spot urine to characterize average exposures. Data analysis was further limited to seven pesticides and their metabolites, which had a detection frequency of >60%. Poor reproducibility was found for the seven pesticides and their metabolites in both spot (ICCs ≤0.24) and first-morning-void (FMV) samples (ICCs

Objectives: Fetal exposure to phthalates and bisphenols may lead to vascular developmental adaptations, which program later cardiovascular disease. We examined the associations of fetal exposure to phthalates and bisphenols with childhood blood pressure. Methods: In a population-based, prospective cohort study among 1,064 mother-child pairs, we measured maternal urine phthalate and bisphenol concentrations in first, second and third trimester of pregnancy. We measured childhood blood pressure at the mean age of 9.7 years (standard deviation 0.2 years) old. Analyses were performed for the total group, and for boys and girls separately. Results: Maternal urine phthalate concentrations were not associated with childhood blood pressure among boys. Higher third trimester maternal urine concentrations of high molecular weight phthalates (HMWP), di-2-ehtylhexylphthalate (DEHP) and di-n-octylphthalate (DNOP) were associated with lower systolic and diastolic blood pressure among girls (p-values

Oxidative stress in humans is affected by the health and nutritional status as well as exposure to external environmental factors. To evaluate the effects of external factors, an assessment of baseline levels as well as diurnal variations in oxidative stress status of healthy individuals is needed. In this study, we examined intra- and inter-individual variability of oxidative stress biomarkers (OSBs) of lipids (malondialdehyde [MDA] and four F2-isoprostane isomers, namely, 8-isoprostaglandinF2α [8-PGF2α], 11β-prostaglandinF2α [11-PGF2α], 15(R)-prostaglandinF2α [15-PGF2α], and 8-iso,15(R)-prostaglandinF2α [8,15-PGF2α]); proteins (o,o′-dityrosine [diY]); and DNA (8-hydroxy-2′-deoxyguanosine [8-OHdG]) in urine from healthy individuals. The significance of creatinine correction, which is typically used to account for urinary dilution, on OSB concentrations was evaluated. Analysis of 515 urine samples, collected longitudinally from 19 healthy individuals daily for over a month, showed inter-individual coefficient of variation (CV) in concentrations from 112% for MDA to 272% for 15-PGF2α. Intra-individual CV in concentrations ranged from 29% for 8-OHdG to 149% for 15-PGF2α. MDA was the most abundant OSB found in urine. The intra- and inter-individual variability in F2-isoprostane concentrations were higher than the values calculated for diY, 8-OHdG, and MDA. All seven OSB concentrations were significantly correlated with each other and with creatinine. Creatinine normalization of OSB concentrations improved predictability in OSB concentrations over time. Our results suggest that 8-OHdG, showing the highest ICC (0.96), yielded more reproducible measurements with a low CV, and is the most suitable biomarker of OSB in spot urine samples. The measured concentrations and diurnal variability in urinary OSB levels in healthy individuals reported in this study are useful as a benchmark for future toxicological and epidemiological studies. Keywords: Biomarker, Oxidative stress, Urine, Variability, 8-hydroxy-2′-deoxyguanosine, Isoprostane, ICC

Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers in consumer products, which contributes to widespread exposure of humans. OPE diester metabolites in urine have been used as biomarkers of human exposure to these chemicals. Little is known, however, about occurrence and temporal variability in urinary concentrations of OPE metabolites in humans. In this study, 11 OPE metabolites were measured in 213 urine samples collected from 19 volunteers from Albany, New York, United States, at 3-day intervals for five weeks to investigate temporal variability in urinary concentrations. Diphenyl phosphate (DPHP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were the major OPE metabolites, detected in all urine samples at specific gravity (SG)-adjusted concentrations (geometric mean, GM) of 1060 and 414 pg/mL and creatinine (Cr)-adjusted concentration (GM) of 404 and 156 ng/g, respectively. Inter-day variability in urinary OPE metabolite concentrations in 19 individuals was evaluated by intraclass correlation coefficients (ICCs). The inter-day variability in Cr-adjusted OPE metabolite concentrations (ICC: 0.31–0.67) was lower than those of SG-adjusted (ICC: 0.19–0.71) and unadjusted urinary concentrations (ICC: 0.24–0.74). BDCIPP (ICC: 0.68) and bis(2-chloroethyl) phosphate (BCEP) (ICC: 0.67) concentrations showed a moderate-to-high reliability over the sampling period, whereas the other nine OPE metabolites exhibited a moderate reliability (ICC: 0.31–0.55). Urine samples were further stratified by gender, age, ethnicity, and body mass index (BMI). The concentrations of BDCIPP and DPHP were significantly lower in males with normal BMI (BMI: 18.5–25 kg/m2) than in females and other BMI categories (p

In this work, a method based on selective pressurised liquid extraction followed by microextraction by packed sorbents (MEPS) for the determination of brominated diphenyl ethers (BDEs) in sewage sludge is presented. The factors affecting the MEPS procedure were optimised. Acetone:water (25:75) sPLE extracts were drawn-ejected 10 times through C18 cartridges at 5 μL s(-1). The cartridge was dried five times with 250 μL of air and the BDEs were eluted at 25 μL s(-1) with 100 μL of n-hexane that were directly injected at 13 μL s(-1) in the GC-MSMS system. Under these conditions, there were no carry-over effects. The method was characterised in terms of limits of detection, repeatability, intermediate precision and accuracy. The use of MEPS for the determination of BDEs in sewage sludge means an improvement of the limits of detection due to the preconcentration and clean-up performed before the injection of the whole elute in the PTV injector. The GC-MSMS LODs (25 pg mL(-1)) were improved with MEPS to less than 3 pg mL(-1). RSD less than 7% and recovery values from 92% to 102% were shown. Finally, the method was applied to the sPLE extract analyses of sewage sludge from several wastewater treatment plants in La Rioja. To our knowledge, this is the first time that the MEPS technique has been applied to the analysis of BDEs, and the first time that it has been used for the analysis of extracts from a solid sample.

This study presents a focused ultrasound solid-liquid extraction (FUSLE) and gas chromatography tandem mass spectrometry method for the determination of brominated diphenyl ethers (BDEs), from mono- to hexa-congeners, in indoor dust. This approach provided a simple, fast, and economical method. After the solvent extraction selection, the FUSLE conditions were studied using a central composite design. Finally, the number of extraction cycles was studied. The selected conditions were 8 mL of 3:1 n-hexane-acetone mixture as extraction solvent, at a power of 65% for 20 s. The proposed method allowed accurate determination of BDEs, with recovery values around 100% and detection limits between 0.05 and 0.8 ng g(-1). It also has advantages over other existing methods in terms of simplicity, analysis time, and solvent consumption. The analysis of several indoor dust samples showed high concentration values of BDEs 47, 99, 100, 153, and 154 in some of the samples, moreover, BDEs 47 and 99 were found in all samples.

A fast, simple, and easily automated method for the determination of two insecticides, diazinon and deltamethrin, and two fungicides, iprodione and prochloraz, in mushroom cultivation compost samples, based on selective pressurised liquid extraction (SPLE) and gas chromatography coupled to tandem mass spectrometry, is presented. The proposed method integrates extraction and clean-up processes in one single step, by adding a clean-up sorbent into the extraction cell. SPLE variables were thoroughly studied by experimental design. First, different clean-up sorbents and extraction solvents were screened at two temperature levels using a multifactor design; resulting Florisil and 1 : 1 acetone-dichloromethane the best combination. Then, temperature, extraction time, and sample-sorbent mass ratio were optimized by a central composite design. Best recoveries were obtained with a 0.4 sample-sorbent ratio, at 105°C and a 2 min extraction time. The SPLE method was characterized in terms of recovery (with values ranging from 81 to 103%), repeatability and intermediate precision (showing relative standard deviations less than 12% in most cases), and sensitivity (providing detection limits between 0.1 and 6 ng mL–1). However, in spite of the clean-up process a matrix effect was observed and therefore standard addition calibration was recommended.

A method to determine caffeoylquinic acids (CQAs) in three sources (herbal extract, feed additive and finished feed) using for the first time focused ultrasound solid–liquid extraction (FUSLE) followed by ultra-high performance liquid chromatography (UPLC) coupled to quadrupole-time of flight mass spectrometry is presented. Pressurized liquid extraction (PLE) was also tested as extraction technique but it was discarded because cynarin was not stable under temperature values used in PLE. The separation of the CQAs isomers was carried out in only seven minutes. FUSLE variables such as extraction solvent, power and time were optimized by a central composite design. Under optimal conditions, FUSLE extraction was performed with 8 mL of an 83:17 methanol–water mixture for 30 s at a power of 60%. Only two extraction steps were found necessary to recover analytes quantitatively. Sensitivity, linearity, accuracy and precision were established. Matrix effect was studied for each type of sample. It was not detected for mono-CQAs, whereas the cynarin signal was strongly decreased due to ionization suppression in presence of matrix components; so the quantification by standard addition was mandatory for the determination of di-caffeoylquinic acids. Finally, the method was applied to the analysis of herbal extracts, feed additives and finished feed. In all samples, chlorogenic acid was the predominant CQA, followed by criptochlorogenic acid, neochlorogenic acid and cynarin. The method allows an efficient determination of chlorogenic acid with good recovery rates. Therefore, it may be used for screening of raw material and for process and quality control in feed manufacture.

A method for the determination of perfluorocarboxylic acids (PFCAs) and perfluorooctanesulfonic acid (PFOS) in sewage sludge based on focused ultrasound solid-liquid extraction (FUSLE) and reverse-phase ultra-performance liquid chromatography (UPLC) coupled to quadrupole-time of flight mass spectrometry (QTOFMS) has been developed. FUSLE is a fast, low-cost and efficient extraction technique based on the application of high power focused ultrasonic waves using a micro-tip immersed directly in the extraction mixture. For the method development, the extraction solvent was studied and afterwards the factors affecting the extraction efficiency were optimised by means of a central composite design. Optimal FUSLE conditions were: 8 mL of acetonitrile as extraction solvent and an ultrasonic irradiation power of 65% for only 20 s. Two extraction cycles were enough for the quantitative extraction of PFCs from sewage sludge. Limits of detection below 0.2 ng g-1 (dry sewage sludge), relative standard deviation values less than 8% and recovery values between 69 and 104% were found for the target analytes. Finally, the method was applied to the analysis of sewage sludge samples from several wastewater treatment plants of La Rioja. © 2013 Elsevier B.V. All rights reserved.

Additional file 1: Supplemental Material Bisphenols. Tables containing additional subscriptive data and results of sensitivity analysis.

Additional file 1: Supplemental Material Bisphenols. Tables containing additional subscriptive data and results of sensitivity analysis.