First-morning Void Research Articles

Investigation of Urinary Metabolites of Organophosphate Esters in Hanoi, Vietnam: Assessment Exposure and Estimated Daily Intake.

In recent years, organophosphate esters (OPEs) have become one of the most common additives in various consumer products worldwide, therefore the exposure and impact of OPEs on human health are drawing a lot of attention. In this study, three metabolites of OPEs including bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPhP) and diethyl phosphate (DEP) were investigated in first-morning void urine samples taken from a population (age range: 3-76years old) in Hanoi, Vietnam. The most dominant urinary OPE metabolite was DEP with the geometric mean of specific gravity adjust (SG-adjusted) concentration were 1960ngmL-1 and detected frequency (DF) of 98%. Followed by DPhP (8.01ngmL-1, DF: 100%) and BDCIPP (2.18ngmL-1, DF: 51%). The results indicated that gender and age might have associations with the OPE metabolites variation in urine samples. The levels of OPE metabolites in urine samples from females were slightly higher than in males. An increase in age seems to have an association with a decrease in DPhP levels in urine. Exposure doses of parent OPEs were evaluated from the unadjusted urinary concentration of corresponding OPE metabolite. The estimated exposure doses of triethyl phosphate (TEP) (mean: 534,000ngkg-1d-1) were significantly higher than its corresponding reference dose, suggesting the high potential risk from the current exposure doses of TEP to human health. The results of this work provided the initial information on the occurrence of three OPE metabolites in urine from Hanoi, Vietnam and estimated exposure dose of corresponding parent OPEs.

Short term temporal variability of selected organophosphate esters among healthy adults living in the National Capital Region of Canada

Organophosphate esters (OPEs) are used primarily as flame-retardants and plasticizers. OPEs are commonly detected in various environmental matrices, food and drinking water, and their metabolites are frequently found and quantified in urine. Potential adverse impacts on human health, including carcinogenicity, neurotoxicity, developmental and reproductive toxicity have been well documented. Urinary concentration of OPE metabolites can vary in the same individual, depending on the sampling time, thus introducing significant uncertainty in exposure assessment. The current study focusses on the assessment of short term temporal variability in adult men and women residing in Canada's Capital Region. Fifteen OPE metabolites were analyzed in 562 daily urine samples, collected every three days for five weeks from 11 volunteers. Sample extraction procedure was performed on an automated SPE and extracts analyzed using UPLC-MS/MS. In spot urine samples as well as first morning void (FMV), the detection frequency was greater than 50% for bis (2-chloroethyl) hydrogen phosphate (BCEP), bis (1-chloro-2-propyl) phosphate (BCIPP), bis (1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP) and bis(2,4-ditert-butylphenyl) hydrogen phosphate (B2,4DtBPP). Significant difference was observed in males and females for BCEP and BCIPP. Intra-class correlation coefficient (ICC) for creatinine corrected data for the spot urine samples ranged from 0.37 to 0.69. Good reproducibility was observed for creatinine corrected DPHP and BCIPP in both spot urine and FMV samples. More variation was observed between study participants in the spot urine samples when compared to the FMV samples. However, when considering diurnal difference there was a considerable inter-day variation in the FMV samples compared to the spot samples. The strength of the study is that the participants belonged to the same geographical location and working in the same facility, hence spatial variability did not influence the outcome of the results.

Association of urine glyphosate levels with renal injury biomarkers in children living close to major vegetable-producing regions in China

Glyphosate (GLY)-based herbicides exposure contributes to renal dysfunction in experimental conditions, but the effects on humans are rarely reported. Biomonitoring is practically relevant for evaluating the association of urine GLY levels and renal damage in children living close to vegetable-cultivating regions. In this study, we collected the first-morning void urine samples of 239 healthy children (aged 3–12, 48.12 % boys) living near major vegetable-producing regions in March–May and August 2023 in Shandong Province, China. Urine levels of GLY and kidney injury-associated biomarkers were determined using ELISA kits to assess their correlation. GLY was detected in 92.05 % of urine samples (220 out of 239 participants) and the geometric concentration (GM) was 7.429 μg/L (range: 0.625 to 38.267 μg/L). Binary logistic regression and multivariate regression analysis revealed GLY detectability and levels positively correlated with home ventilation and self-producing vegetable intake of the subjects, as well as sampling periods. Moreover, a statistically significant concentration association with urine GLY was found for kidney injury-associated biomarkers (NGAL and KIM-1) (R2 = 0.923 and 0.855, respectively). Additionally, risk assessment revealed that the maximum value of probable daily intake was 0.150 mg/kg bw/day, accounting for 30.1 % of the established Acceptable Daily Intake of GLY. This study unveils a positive correlation between continuous GLY-based herbicide exposure and renal injury biomarkers of children. A large-scale epidemiological study is warranted for comprehensively assessing the effects of GLY-based herbicides on kidney function of the entire public.

Urinary heavy metals and attention-deficit/hyperactivity symptoms of preschool children: a mixed-exposure analysis

The neurotoxic effects of certain heavy metals are well established, but only a few studies have investigated the joint effect of concurrent exposure to multiple ones. The study aims to evaluate the association between mixed exposure to neurotoxic metals and the psychosocial behavior of preschool children. Using a stratified sampling strategy, we recruited participants from 105 kindergartens in 41 townships of Taiwan and excluded those with blood lead levels ≥ 3.5 µg/L. The first-morning void urines were collected and analyzed for cadmium, manganese, arsenic, chromium, lead, and nickel concentrations using inductively coupled plasma mass spectrometry. We applied the parentally reported Strengths and Difficulties Questionnaire (SDQ) and Swanson, Nolan, and Pelham IV (SNAP-IV) scales to evaluate the psychosocial behaviors. Multiple linear regressions were utilized to evaluate the associations between each heavy metal and the outcomes, while the mixed effect of concurrent exposure was estimated by using a Quantile g-computation approach. A total of 977 preschool children were included in the study, and the mean (SD) age was 5.7 (0.7) years old. In single pollutant models, we observed adverse effects of urinary manganese, nickel, arsenic, and lead on the specific subsets of SDQ. Furthermore, the combined effect of six heavy metals significantly affected the hyperactivity/inattention symptoms (beta = 0.46, 95% CI: 0.13–0.78, with all metals increased by one quartile), and chromium and lead were the two major contributors. Similar detrimental effects of urinary cadmium and lead were also observed in the SNAP-IV subsets, although the joint effect analysis was not significant. The study provided evidence that concurrent exposure to multiple heavy metals may exert increased risks of hyperactivity/inattention in children compared to single pollutant exposure. Further studies are needed to verify our findings regarding mixed exposure to multiple neurotoxic metals.

CORRELATION OF 24-HOUR URINARY PROTEIN TO SPOT URINARY PROTEIN TO CREATININE RATIO AT DIFFERENT TIMES OF THE DAY IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Spot urine protein to creatinine ratio has become a conventional measure of daily protein excretion in patients with chronic kidney disease (CKD). It is easily obtained and is reproducible. However, the values may vary with the time of the day, and collecting the first-morning void is typical. Twenty-four hours of urinary protein has been the traditional gold standard test for estimating protein excretion. This test is still carried out in centers where spot measurements are unavailable. We conducted our study to determine the correlation between 24-hour urinary protein and spot urinary protein to creatinine ratio at different times of the day (early morning, afternoon, and night). Sixty-seven patients of CKD fulfilling the inclusion criteria were asked to provide 24-hour urine samples according to standard recommendations. According to protocol, small aliquots of urine samples (5 ml each) were taken from the 24-hour sample to be processed for spot urinary protein and creatinine. Data was analyzed on SPSS version 22 and is presented as numbers, means + SD (age, spot urinary protein to creatinine ratio for morning, afternoon, and night), and frequencies (gender, type of kidney disease). Pearson's 'r' was tested for a significant correlation between 24 hours of urine protein and all different samples of spot collections. In contrast, sensitivity and specificity for spot urine protein-to-creatinine ratio predicting 24-hour protein excretion of <1, 1 – 3.5, and >3.5 g/day were determined using receiver operating characteristic curves (ROC Curves). In our cohort of patients across all stages of chronic kidney disease, we observed that there was a strong correlation between all three protein-to-creatinine ratio samples with 24 hours of urinary protein excretion; however, nighttime protein creatinine ratio showed the strongest correlation with 24 hours of urinary protein excretion (Pearson's r: 0.797). Nighttime spot urine protein to creatinine ratio sample was also found to have the highest sensitivity across all 24-hour urinary protein excretion levels.A nighttime spot urinary protein to creatinine ratio sample may reliably predict 24 hours of urinary protein excretion.

Exposure to Bisphenol A and Its Analogs among Thai School-Age Children.

Bisphenol F (BPF) and bisphenol S (BPS) have become popular substitutes for bisphenol A (BPA) in the plastic industry due to concerns over BPA's adverse effects. However, there is limited information on children's exposure to these chemicals. This study aims to assess the extent of BPA, BPF, and BPS exposure and determine factors that influence such exposure. A group of Thai children (age 6-13 years, N = 358) were recruited between October 2019 and 2020. Two first-morning voids were collected one week apart. Demographic and exposure-related information was gathered. Urinary concentrations of bisphenols were analyzed by liquid chromatography and tandem mass spectrometry. Correlation between bisphenol concentrations with age, body weight, and sources of bisphenol exposure, was determined using generalized estimating equations with linear model. BPA, BPF, and BPS were detected at 79.6%, 31.0%, and 16.8%, with geometric mean (GM) concentrations of 1.41, 0.013, and 0.014 ng/mL, respectively. Younger children aged <10 years exhibited 1.3-1.6 times higher GM levels of all bisphenols compared to older children. Exposure to food stored in plastic containers was associated with higher levels of BPF and BPS. In conclusion, BPA was the most frequently detected bisphenol in urine samples from Thai children, followed by BPF and BPS.

Isolation and Identification of S. aureus in Urinary Tract Infection

Urinary Tract Infection (UTI) defines a condition in which the urinary tract is infected with a pathogen causing inflammation which is a common, distressing, and occasionally life-threatening condition. Staphylococcus aureus is frequently isolated from urine samples obtained from long-term care patients. The significance of staphylococcal bacteriuria is uncertain. We hypothesized that S. aureus is a urinary pathogen and that colonized urine could be a source of future staphylococcal infection. Methods: This study focused on the frequency of S. aureus and its antibiotic susceptibility in different gender in the Derna District. A total of 200 UTI cases were reviewed in this study from Augustus 2022 to October 2022. Midstream specimens of urine, preferably of the first-morning void were collected from known UTI patients. Cultural and biochemical characterization of S. aureus Results: During this study period 200 samples were received, and from these samples, 170 bacterial isolates were obtained. Out of 170 isolates 160 were identified as S.aureus. Out of this predominant numbers were that of S.aureus 160 (94%), followed by other bacterial isolated 10 (6%). Also, it is shown that the highest number of S. aureus isolated were from married females (57.3%) followed by a male (42.7%). And it is showing 69.3% sensitivity toward Ciprofloxacin. Followed by Teicoplanin which shows 25.3% sensitivity, piperacillin, and Ofloxacin showed the lowest sensitivity. Thus our study showed that there were statistically significant differences between the isolated S. aureus and age, gender, and marital status. We concluded that ciprofloxacin is a better antibiotic used for S. aureus.

Urine Dipstick Analysis on Automated Platforms: Is a Reliable Screening Tool for Proteinuria? An Experience from Umberto I Hospital in Rome.

Urinalysis is commonly used as a screening tool for kidney disease. In many cases, the dipstick urine assay includes the assessment of albumin/protein and creatinine; consequently, the value of their ratio is available on the urine section report. Identification of albuminuria/proteinuria at early stages is an important issue to prevent or at least delay the onset of chronic kidney disease (CKD), kidney failure, and the progression of cardiovascular damage linked to the kidney's loss of function. Sensitive and specific diagnostic methods are required for the assessment of such an important biomarker: urine albumin, creatinine, and their ratio (ACR) measured with quantitative assays are considered the gold standard. Routine dipstick methods (more rapid and at a lower cost) are intended for wide population screening. The aim of our study was to verify the reliability of an automated urinalysis dipstick method by comparing the results with the quantitative test of creatinine and albumin performed on a clinical chemistry platform. The first-morning voids of 249 patients who arrived from different departments were analyzed in the Central Laboratory of the University Hospital Policlinico Umberto I in Rome. We found a good correlation between the two assays, even though we observed that the dipstick assessment tends to overestimate the ACR's value, disclosing a higher number of false positives if compared to the reference method. As an important novelty in this study, we analyzed our data considering age (starting from pediatric to geriatric patients) and sex as variables for a sub-stratification of the participants. Our results show that positive values need to be confirmed with quantitative methods, especially in women and younger people, and that from samples that resulted as diluted at the dipstick assay, the ACR's values can be obtained if they are reanalyzed with quantitative assays. Moreover, patients with microalbuminuria (ACR 30-300 mg/g) or severe albumin urinary excretion (ACR > 300 mg/g) should be reanalyzed using quantitative methods to obtain a more reliable calculation of the ACR.

Are human exposure assessment the same for non-persistent organic chemicals? -from the lens of urinary variability and predictability

Assessment of human exposure to mixtures of non-persistent chemicals from food matrices and consumer products requires accurate characterization and estimation of their preceding exposure levels, and assessment sampling approaches for these varying chemicals remain disputable. Here, we used high-throughput targeted method to quantify urinary concentrations of 59 most common non-persistent chemicals (6 parabens, 14 bisphenols, 1 triclosan, 7 benzophenones, 2 dichlorophenols, 13 phthalate metabolites and 16 antioxidants) in 158 consecutive spot samples from 11 participants over three consecutive days, 33 samples of which were first morning voids (FMVs). We found 49 chemicals with detection frequencies over 70 % in all urine samples. Principal component analyses showed greater inter-person variations than each person's inter-day variations. Intraclass correlation coefficient (ICC) to assess the reproducibility of targeted chemicals demonstrated that regardless of sampling approaches, dichlorophenols, most parabens, benzophenones and triclosan showed moderate to high reproducibility (0.445 < ICC < 0.969), with relatively high predictive power of FMVs for 24-h collections. Notably, most phthalates, bisphenols and antioxidants showed low ICC values. Together, our work demonstrates that FMV samples may be adequate for assessing human exposure to parabens, benzophenones, triclosan and dichlorophenols, whereas multiple consecutive urine collections may be advantageous for evaluating exposure to most phthalates, bisphenols and antioxidants.

Urinary biomonitoring of glyphosate exposure among male farmers and non-farmers in the Biomarkers of Exposure and Effect in Agriculture (BEEA) study

BACKGROUND AND AIM: Glyphosate is the most widely applied herbicide worldwide. Despite potential health effects of glyphosate, biomonitoring data of glyphosate exposure in agriculture and other settings are limited. We measured urinary glyphosate concentrations and assessed their determinants among male farmers and non-farmers from Iowa and North Carolina in the BEEA study. METHODS: Based on questionnaire-assessed pesticide exposure histories, we selected four groups of BEEA participants: recently exposed farmers with occupational glyphosate use in the last 7 days (n=98), farmers with high cumulative lifetime days of glyphosate use (&amp;#x3e;80th percentile) but no use in the last 7 days (n=70), farmers with minimal lifetime glyphosate use (n=100), and non-farmers with no occupational pesticide exposure (n=100). We quantified glyphosate in first-morning void urine samples using ion chromatography isotope-dilution tandem mass spectrometry. We estimated geometric mean urinary glyphosate concentrations across groups and evaluated associations with potential determinants using linear regression. RESULTS: Glyphosate was detected in urine of most recently (91%), high-lifetime (93%), and low-lifetime (88%) exposed farmers, as well as non-farmers (81%); geometric mean concentrations were 0.86, 0.58, 0.44, and 0.37 µg/L, respectively. Compared to non-farmers, urinary glyphosate concentrations were significantly elevated among recently exposed farmers (P&amp;#x3c;0.0001), particularly those who used glyphosate within 1 day of urine collection [age- and creatinine-adjusted geometric mean ratio (GMR)=6.4, 95% confidence interval (CI)=4.3-9.3] and those not wearing gloves during glyphosate application (GMR=2.6, 95% CI=2.0-3.4). CONCLUSIONS: Preliminary results suggest that a high proportion of both farming and non-farming populations may be exposed to glyphosate. Substantial exposure contrast between those with and without recent occupational glyphosate use was detectable in urine. Given the short elimination half-life of glyphosate, the exposure differences between groups may be even greater than those reflected by measured urine concentrations. Continued biomonitoring of glyphosate in various settings is warranted. KEYWORDS: Glyphosate, exposure assessment, pesticide biomonitoring

Exposure to organophosphorus compounds of Japanese children and the indoor air quality in their residences

Several organophosphorus compounds such as organophosphate pesticides (OPPs) and trialkylphosphates (TAPs) are suspected to inhibit cholinesterase activities, to affect endocrine systems or to possibly be carcinogenic. To evaluate their adverse effects on health with chronic exposure in the general population, especially in children, we measured the household exposure to OPPs and TAPs by Japanese children via all exposure pathways and the contribution of indoor air quality. First-morning void urine was collected from subjects aged 6 to 15 years (n = 132), and airborne organophosphorus compounds were sampled in the subject's bedroom for 24 h. Airborne levels of nine OPPs and three TAPs and their urinary metabolites were determined.No significant correlations were detected for any compounds between their airborne concentrations and the urinary excretion amounts of their corresponding metabolites. The estimated daily intakes were as follows (median, μg/kg b.w./d): chlorpyrifos, 0.042; diazinon, 0.067; tri-n-butylphosphate, 0.094. The 95th percentiles of the intakes for fenthion, fenitrothion and the above three compounds did not exceed their reference limit values, although one subject had a daily intake of tri-n-butylphosphate that was about twice its reference limit value. The concentration levels of the urinary metabolite of tri-n-butylphosphate in our subjects tended to be higher than those for children in many other countries. The fractions of the amounts absorbed by inhalation to the amounts absorbed via all of the exposure pathways was only 2.3 % (median) for tri-n-butylphosphate.Inhalation did not seem to contribute very much as an absorption pathway of the organophosphorus compounds in these Japanese children while they were at home. The exposure amounts of OPPs were not suggested to be high enough to adversely affect the health of these children at present on the basis of their daily intakes compared to their reference limit values.

Long-term stability of several endocrine disruptors in the first morning urine samples and their associations with lifestyle characteristics

Parabens, triclosan (TCS), bisphenols, benzophenones, and phthalates are typical endocrine disruptors (EDs) with short half-lives in the human body. The concentration levels of those EDs in a spot urine sample are frequently used in exposure assessment studies, and the reproducibility of urinary levels of these nonpersistent EDs should be considered. In the present study, we consecutively collected 45-day first morning void (FMV) urine samples, as well as daily questionnaires, in six recruited participants and measured the urinary concentrations of six parabens, TCS, nine bisphenols, five benzophenones, and ten phthalate metabolites by using high-performance liquid chromatography-tandem mass spectrometry. MeP, EtP, PrP, TCS, BPA, BPS, BPF, and most phthalate metabolites were frequently detected (over 62 % of samples). The intraclass correlation coefficients (ICCs) for ED concentrations in FMV urine samples ranged from fair to excellent for MeP (0.683), EtP (0.702), BPA (0.505), BPS (0.908), BPF (0.887), BP-3 (0.712), mMP (0.661), mEP (0.523), mBP (0.500), miBP (0.724), mBzP (0.961) and all metabolites of DEHP (0.867–0.957), whereas they were low for PrP (0.321) and TCS (0.306). After creatinine adjustment, the values of ICCs for most target EDs were increased with mild to significant improvement. The stability of ED concentrations was affected by daily diet (MeP, TCS, BPA, mMP, miBP, mBP and mBzP), food containers (PrP and mECPP), use of personal care products (HMWP metabolites), pharmaceuticals (EtP) and recorded activities (BPS, mEHP, mBzP, mEHHP and mEOHP), as confirmed by a general linear mixed model. Furthermore, extending the FMV sampling period improved the probability of acceptable reproducibility (ICCs > 0.40) of MeP, EtP, BP-3 and mEP concentrations. For BPS, BPF and HMWP metabolite concentrations showed high probabilities (>80 %) of acceptable reproducibility in the last three days, and the increasing sample size slowly improved the ability to discriminate the subjects. The results were exactly the opposite for BPA concentrations.

First Void Urinary Calcium for Tracking Bone Loss and Kidney Stone Risk in Space.

INTRODUCTION: Microgravity exposure unloads the skeleton. This increases urinary calcium excretion, which reflects both increased bone loss and kidney stone formation risk. We studied the probability that first morning void (FMV) urinary calcium (Uca) measurements would capture the highest Uca concentration in a day.METHODS: For 8 wk, three men and three women collected void-by-void 24-h urine samples weekly. Uca concentration was analyzed using a calcein-based system. Uca concentrations were ranked among all samples from each person. FMV and non-FMV (nFMV) Uca concentrations were compared with a Mann Whitney U-test. The probability that an FMV would capture the highest Uca concentration in a day was assessed.RESULTS: Among 377 voids collected, 46 were FMV and 331 were nFMV. Among all samples, the Uca concentration for FMV was significantly higher than nFMV (P < 0.0001). Out of the 46 FMVs, 24 were highest in Uca concentration for the corresponding 24-h period, giving a 52.2% probability that any given FMV would capture the highest Uca concentration in a day. The probability of measuring the highest Uca concentration from at least 1 d increased to 77.1%, and 89.1% when two or three FMVs were collected respectively.DISCUSSION: Acquiring 2-3 repeated FMVs provides a high likelihood of capturing the highest Uca from a day. This suggests repeated first morning void Uca concentrations could assess the risk of bone loss and kidney stone formation, which may provide ability for real-time implementation of countermeasure programs to prevent bone and renal complications in prolonged spaceflight.Thamer S, Buckey JC. First void urinary calcium for tracking bone loss and kidney stone risk in space. Aerosp Med Hum Perform. 2022; 93(7):546-550.

Association between urine 6-sulfatoxy-melatonin level and intravesical Bacillus Calmette-Guerin treatment-induced sleep quality deterioration in patients with non-muscle invasive bladder cancer.

The level of 6-sulfatoxy-melatonin (SaMT), a metabolite of melatonin, in first-void morning urine reflects blood melatonin levels from the previous night. We investigated the association between urine SaMT and sleep quality deterioration in patients with non-muscle invasive bladder cancer (NMIBC) treated with intravesical Bacillus Calmette-Guerin induction therapy (iBCG). We enrolled 51 patients who received iBCG once weekly for 6 or 8weeks. Patient-reported outcomes were assessed with questionnaires including the International Prostate Symptom Score (IPSS) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQC30). Questionnaires were completed before (baseline), during, at completion, and 1 and 3months after iBCG. Melatonin and SaMT levels at baseline were measured in serum and first-void morningurine samples, respectively. Based on changes in the QLQC30 insomnia subscale, 28 (55%) patients experienced sleep quality deterioration (deterioration group). Urine SaMT values in the deterioration group were lower than those in the non-deterioration group (P = 0.0015; 7.5 vs 15.4ng/mg creatinine, respectively). Nocturia scores in the non-deterioration group decreased over time, while those of the deterioration group remained high after completion of iBCG. A binary logistic regression analysis revealed that low urine SaMT levels (≤ 9.6 ng/mg creatinine), high IPSS nocturia scores at baseline, and high IPSS storage subscores at baseline were associated with BCG-induced sleep quality deterioration. This study confirmed the association among urine SaMT levels, nocturia, and sleep disturbance in patients with NMIBC who receive iBCG. We should be aware of treatment-induced impairments to aid in appropriate decision-making.

Variability in urinary concentrations of primary aromatic amines

Despite their known carcinogenic potential, primary aromatic amines (AAs) continue to be used in various consumer products. Human exposure to AAs is a subject of current concern. Although urinary measurements are used in the assessment of exposure, little is known about within- and between-individual temporal variability in urinary concentrations of AAs. In this study, we determined the concentrations of 30 AAs, nicotine and cotinine in 213 first morning void (FMV) urine samples collected longitudinally for over a five-week period from 15 participants residing in the Albany area of New York State, USA. Eight AAs, namely, aniline, 2-naphthylamine (2-NA), p-cresidine (p-CD), p-toluidine (p-TD), o/m-toluidine (o/m-TD), 4-chloroaniline (4-CA), 4,4′-methylenedi-o-toluidine (4,4’-MDA), and 2,6-dimethylaniline (2,6-DMA) were found in urine at a detection frequency (DF) in the range of 68–100%. Aniline and 2,6-DMA were the predominant compounds found at median concentrations of 6.0 and 3.81 ng/mL, respectively. Intraclass correlation coefficients (ICCs) of all urinary AA concentrations, except for 4-CA, showed moderate to poor predictability (ICC values ranged 0.248–0.697). Gender and ethnicity-related variations in ∑8AA concentrations were significant. Spearman's correlations among AA concentrations suggested that the sources of exposure were not related to tobacco smoke. No significant correlations existed between AAs concentrations and oxidative stress biomarkers (OSBs). The estimated daily intakes of AAs calculated based on urinary concentrations were several orders of magnitude below the tolerable daily intakes.

Within- and between-person variability of urinary phthalate metabolites and bisphenol analogues over seven days: Considerations of biomonitoring study design

Urine was used as a part of a human biomonitoring study based on the excretion kinetics of less-persistent contaminants, such as phthalates and bisphenol A (BPA). Despite the advantages of being non-invasive and easy to collect, urine can show a large variability of concentrations of phthalate metabolites and BPA within a person depending on sampling time. Therefore, it is essential to assess the variability of urinary concentrations for comprehensive sampling design in the context of exposure and risk assessments. In this study, 18 phthalate metabolites and eight BPs were measured in all spot urine (n = 401) collected from 12 participants for seven consecutive days to evaluate within- and between-person variabilities. The intraclass correlation coefficients (ICCs) for all spot urines were poor for monomethyl phthalate (ICC: 0.002) and BPA (0.121) but were moderate for monoethyl phthalate (0.514) and monobenzyl phthalate (0.462). Based on the results of di (2-ethylhexyl) phthalate (DEHP) metabolites, the half-life and differences in metabolic capability seem to affect the ICCs. Urinary mono (2-ethylhexyl) phthalate (MEHP), a primary metabolite of DEHP, was suggested as a short-term exposure marker of DEHP in our study. Creatinine- and specific gravity-adjusted concentrations of phthalate metabolites and BPs resulted in increased ICCs, implying requirements for randomly collected spot urine. Most analytes in the first morning voids (FMVs) were correlated significantly with those in the daily composites, suggesting the feasibility of FMVs to estimate the daily exposure dose. This study facilitates a more comprehensive sampling design and data interpretation strategy for human biomonitoring studies.

Variability of Urinary Concentrations of Phenols, Parabens, and Triclocarban during Pregnancy in First Morning Voids and Pooled Samples.

Urinary concentrations of phenols, parabens, and triclocarban have been extensively used as biomarkers of exposure. However, because these compounds are quickly metabolized and excreted in urine, characterizing participants' long-term average exposure from a few spot samples is challenging. To examine the variability of urinary concentrations of these compounds during pregnancy, we quantified four phenols, four parabens, and triclocarban in 357 first morning voids (FMVs) and 203 pooled samples collected during the second and third trimesters of 173 pregnancies. We computed intraclass correlation coefficients (ICCs) by the sample type (FMV and pool) across two trimesters and by the number of composite samples in pools, ranging from 2 to 4, within the same trimester. Among the three compounds detected in more than 50% of the samples, the ICCs across two trimesters were higher in pools (0.29-0.68) than in FMVs (0.17-0.52) and the highest ICC within the same trimester was observed when pooling either two or three composites. Methyl paraben and propyl paraben primarily exposed via cosmetic use had approximately 2-3 times higher ICCs than bisphenol A primarily exposed via diet. Our findings support that within-subject pooling of biospecimens can increase the reproducibility of pregnant women's exposure to these compounds and thus could potentially minimize exposure misclassification.

Diurnal variability in urinary volatile organic compound metabolites and its association with oxidative stress biomarkers

Volatile organic compounds (VOCs) are ubiquitous environmental pollutants that are associated with birth defects, leukemia, neurocognitive deficits, reproductive impairment and cancer in humans exposed to these compounds. Exposure to VOCs can be assessed by measuring their metabolites in urine. Little is known, however, about the temporal variability in urinary VOC metabolite (VOCM) concentrations within- and between-individuals. In this study, we determined the variability in the concentrations of 38 VOCMs in urine samples collected from 19 healthy individuals across a period of 44 days. We also measured seven biomarkers of oxidative stress (lipid, protein and DNA damage) in urine to assess the relationship of VOC exposure to oxidative stress. Seventeen VOCMs had detection frequencies (DFs) of >60% in urine, and we limited further data analysis to those compounds. The creatinine-adjusted geometric mean concentrations of VOCMs ranged from 2.70 μg/g to 327 μg/g in spot and 2.60 μg/g to 551 μg/g in first morning void (FMV) urine samples. Calculation of the intra-class correlation coefficients (ICCs) for 17 VOCM concentrations to assess their predictability and repeatability in urinary measurements showed ranges of 0.080–0.425 in spot and 0.050–0.749 in FMV urine samples, revealing notable within-individual variability. Our results suggest that taking only single measurements of VOCM concentrations in urine in epidemiological investigations may lead to exposure misclassification. In addition, VOCM concentrations were significantly and positively correlated with oxidative stress biomarkers. This study thus provides important information for formulating sampling strategies in the biomonitoring of VOC exposure in human populations.

Glyphosate and aminomethylphosphonic acid (AMPA) in urine of children and adolescents in Germany - Human biomonitoring results of the German Environmental Survey 2014-2017 (GerES V).

Since the 1970s, glyphosate has become the most used herbicide of the world. The general population is ubiquitously exposed to glyphosate. Its long-term toxicity, carcinogenic potential and other health effects are controversially discussed. Even though the possible health impacts of glyphosate are of global concern, no population-wide monitoring of glyphosate was done yet. This study presents the worldwide first population-representative data on glyphosate and its metabolite aminomethylphosphonic acid (AMPA) for children and adolescents. 2144 first-morning void urine samples of 3-17-year-old children and adolescents living in Germany were analysed for concentrations of glyphosate and AMPA in the German Environmental Survey for Children and Adolescents 2014-2017 (GerESV). In 52 % of the samples (46 % for AMPA) the urinary glyphosate concentrations were above the limit of quantification of 0.1µg/L. The geometric mean concentrations were 0.107µg/L (0.090µg/gcreatinine) for glyphosate and 0.100µg/L (0.085µg/gcreatinine) for AMPA. No clear association between exposure to glyphosate or AMPA and vegetarian diet or consumption of cereals, pulses, or vegetables could be identified. The low quantification rate and the 95th percentiles for glyphosate and AMPA of around 0.5µg/L demonstrate an overall low exposure of the young population in Germany.

Prenatal phthalate exposure and early childhood wheeze in the SELMA study.

Prenatal maternal phthalate exposure has been associated with wheeze and asthma in children, but results are inconclusive. Previous studies typically assessed exposure in late pregnancy, included only a small number of old phthalates, and assessed outcomes in children aged 5 years or older. We explored associations between 1st trimester prenatal maternal exposure to a wider range of phthalates and wheeze in early childhood. First trimester concentrations of 14 metabolites from 8 phthalates and one alternative plasticizer were quantified in first-morning void urine from 1148 mothers in the Swedish SELMA study. Associations between log-transformed metabolite concentrations and parental reported ever wheeze among 24-month-old children were investigated with logistic regression models adjusted for parental asthma/rhinitis, sex of child, maternal education, smoking, and creatinine. Metabolites of replacement phthalates di-iso-decyl phthalate (DiDP) and di-2-propylheptyl phthalate (DPHP) were associated with increased risk for wheeze (aOR 1.47, 95% CI 1.08-2.01 and aOR 1.49, 95% CI 1.04-2.15, respectively). The associations with DiDP and DPHP were stronger among children whose parents did not have asthma or rhinitis. In this group, wheeze was also associated with metabolites of butyl-benzyl phthalate (BBzP) and di-iso-nonyl phthalate (DiNP). Maternal phthalate exposure during early pregnancy may be a risk factor for wheeze in early childhood, especially among children whose parents do not have asthma or rhinitis symptoms.