A large-scale nationwide study of urinary phenols in the Chinese population.

Bisphenol A (BPA), tetrabromobisphenol A (TBBPA), and their substitutes are commonly used in everyday products. However, large-scale internal exposure levels of them in China, the factors influencing on them, and the associated health risks were not systematically investigated still. In the present study, there were 1157 morning urine samples collected from residents of 26 provincial capitals in China for the measurement of BPA and seven bisphenol analogues, as well as TBBPA and its substitutes, i.e., tetrachlorobisphenol A and 4,4'-sulphonylbis(2,6-dibromophenol). The concentrations of Σ8bisphenols and Σ3TBBPAs ranged from

Absorption, metabolism and excretion of once-weekly somapacitan, a long-acting growth hormone derivative, after single subcutaneous dosing in human subjects.

Somapacitan is a reversible albumin-binding growth hormone (GH) derivative in clinical development for once-weekly administration in patients with adult GH deficiency (AGHD) and children with GH deficiency (GHD). To date, the use of somapacitan in AGHD or severe AGHD has been approved in the USA and Japan, respectively. This study (ClinicalTrials.gov, NCT02962440) investigated the absorption, metabolism and excretion, as well as the pharmacokinetics (PK), of tritium-labelled somapacitan ([3H]-somapacitan). Seven healthy males received a single subcutaneous dose of 6 mg somapacitan containing [3H]-somapacitan 20 MBq. Blood, serum, plasma, urine, faeces, and expired air were collected for radioactivity assessment. Metabolites were identified and quantified in plasma and urine collected. The PK of plasma components were determined, and the radioactive peaks of the most abundant plasma metabolites and urine metabolites were selected for analysis. Twenty-eight days after dosing, 94.0% of the administered dose was recovered as [3H]-somapacitan-related material, most of which was excreted in urine (80.9%); 12.9% was excreted in faeces, and an insignificant amount (0.2%) was exhaled in expired air. PK properties of [3H]-somapacitan-related material appeared to be consistent across plasma, serum and blood. Three abundant plasma metabolites (P1, M1 and M1B) and two abundant urine metabolites (M4 and M5) were identified. The total exposure of intact somapacitan accounted for 59% of the total exposure of all somapacitan-related material, P1 accounted for 21% and M1 plus M1B accounted for 12%. M4 and M5 were the most abundant urine metabolites and accounted for 37% and 8% of the dosed [3H]-somapacitan radioactivity, respectively. No intact somapacitan was found in excreta. Two subjects had six adverse events (AEs); all were mild in severity and unlikely to be related to trial product. The majority of dosed [3H]-somapacitan (94%) was recovered as excreted metabolites. Urine was the major route for excretion of somapacitan metabolites, followed by faeces, and exhalation in expired air was negligible. The low molecular weights of identified urine metabolites demonstrate that somapacitan was extensively degraded to small residual fragments that were excreted (fully biodegradable). The extensive metabolic degradation and full elimination of metabolites in excreta were the major clearance pathways of somapacitan and the key elements in its biological fate. A single dose of 6 mg somapacitan (containing [3H]-somapacitan) in healthy male subjects was well tolerated with no unexpected safety issues identified.

[Association of Urinary Phenol Concentration and Blood Biochemical Indices in Coke Oven Workers].

Objective: To explore the association of urinary phenol concentration and blood biochemical indices in coke oven workers. Methods: From April to may 2019, we investigated 771 employing coke oven workers from a coke plant in Taiyuan city, and categorized into benzene-exposed group (n=402) and control group (n=369) based on their benzene exposures in workplace and urophenol concentrations. All subjects were interviewed face-to-face using a questionnaire including name, age (year) , gender, smoking and drinking habits, personal vocational history, working length (year) , and occupational protection, etc. Post-shift urine samples detected using a gas chromatography-hydrogen flame ionization detector. Fasting venous blood was drawn in the morning and centrifuged, the separated serum were detected the following items using an automatic blood biochemistry analyzer. Covariance and multiple linear regression were used to test the association of urinary phenol concentration and the levels of all the blood biochemical indices. Results: The subjects were predominantly males (n=719, 93.3%) , with an average age of (42.3±8.2) years and an average working length of (20.6±8.2) years. Compared with the control group, the benzene-exposed group were significantly different in age, working length of years, gender, smoking and drinking habits (P<0.05) . The median (interquartile interval) concentration of urinary phenol was 6.00 (0.00-33.00) µg/ml in the benzene-exposed group, which was significantly higher than that in the control group (P<0.05) . Covariance analysis indicated that the fasting blood glucose, total cholesterol and high density cholesterol in the benzene-exposed group were significantly reduced compared with the control group, yet the serum creatinine, serum uric acid and triglyceride were significantly increased (P<0.05) . Multiple linear regression showed that, an increase of each natural logarithm (Ln) transformed urinary phenol concentration was significantly associated with increases in serum uric acid level [9.82 (95%CI: 2.18-17.47) µmol/L] and cholesterol level[0.10 (95%CI:0.00-0.20) mmol/L]. An increase of each Ln-transformed accumulated benzene exposure levels was significantly associated with an increase in total cholesterol level[0.09 (95%CI: 0.01-0.17) mmol/L]. Conclusion: Occupational benzene exposure is possibly related to the variation of purine and total cholesterol metabolism in coke oven workers.

Identification of the metabolites of erianin in rat and human by liquid chromatography/electrospray ionization tandem mass spectrometry.

RATIONALE: Erianin, a bioactive component isolated from Dctidrobium chrysotoxum Lindl, was demonstrated to have many biological properties relevant to cancer prevention and therapy. However, the metabolic profiles of erianin remain unknown. This study was carried out to investigate the metabolic profiles of erianin in rats and humans. METHODS: Erianin was orally administered to rats at a single dose of 50 mg/kg. Urine and bile samples were collected. For in vitro metabolism, erianin was co-incubated with rat or human hepatocytes at 37°C for 2 h. The samples from incubations and rat were analyzed by liquid chromatography combined with electrospray ionization high-resolution mass spectrometry. The data were processed by MetWorks software. The structures of the metabolites were proposed by comparing the mass spectra with that of the parent compound. RESULTS: A total of twenty-four metabolites were detected in vitro and in vivo, including seven phase I and eighteen phase II metabolites. The phase I metabolic pathways of erianin were hydroxylation, demethylation and dehydrogenation. Erianin undergoes metabolic activation to form reactive metabolites quinoid intermediates, which were further trapped by glutathione (GSH) or N-acetylcysteine. The phase II metabolic pathways were glucuronidation, glutathione and N-acetylcysteine conjugation. CONCLUSIONS: The present study provides an overview pertaining to the in vitro and in vivo metabolic profiles of erianin, which is indispensable for us to understand the efficacy and safety of erianin, as well as the herbal medicine D. chrysotoxum.

Within-Day, Between-Day, and Between-Week Variability of Urinary Concentrations of Phenol Biomarkers in Pregnant Women.

BACKGROUND: Toxicology studies have shown adverse effects of developmental exposure to industrial phenols. Evaluation in humans is challenged by potentially marked within-subject variability of phenol biomarkers in pregnant women, which is poorly characterized. OBJECTIVES: We aimed to characterize within-day, between-day, and between-week variability of phenol urinary biomarker concentrations during pregnancy. METHODS: In eight French pregnant women, we collected all urine voids over a 1-wk period (average, 60 samples per week per woman) at three occasions (15±2, 24±2, and 32±1 gestational weeks) in 2012-2013. Aliquots of each day and of the whole week were pooled within-subject. We assayed concentrations of 10 phenols in these pools, and, for two women, in all spot (unpooled) samples collected during a 1-wk period. We characterized variability using intraclass correlation coefficients (ICCs) with spot samples (within-day variability), daily pools (between-day variability), and weekly pools (between-week variability). RESULTS: For most biomarkers, the within-day variability was high (ICCs between 0.03 and 0.50). The between-day variability, based on samples pooled within each day, was much lower, with ICCs >0.60 except for bisphenol S (0.14, 95% confidence interval [CI]: 0.00, 0.39). The between-week variability differed between compounds, with triclosan and bisphenol S having the lowest ICCs (<0.3) and 2,5-dichlorophenol the highest (ICC >0.9). CONCLUSION: During pregnancy, phenol biomarkers showed a strong within-day variability, while the variability between days of a given week was more limited. One biospecimen is not enough to efficiently characterize exposure; collecting biospecimens during a single week may be enough to represent well the whole pregnancy exposure for some but not all phenols. https://doi.org/10.1289/EHP1994.

Environmental phenol associations with ultrasound and delivery measures of fetal growth.

Environmental phenols are used commonly in personal care products and exposure is widespread in pregnant women. In this study, we sought to assess the association between maternal urinary phenol concentrations in pregnancy and fetal growth. The study population included 476 mothers who participated in the prospective LIFECODES birth cohort between 2006 and 2008 at Brigham and Women's Hospital in Boston, Massachusetts, USA. Dichlorophenols (DCPs), benzophenone-3, parabens, triclosan, triclocarban, and bisphenol-S were measured in urine from three time points during pregnancy and averaged. Outcome measures were all standardized to create gestational-age specific z-scores and included: 1) birth weight; 2) ultrasound parameters measured at up to two time points in pregnancy (head and abdominal circumference and femur length); and 3) ultrasound estimates of fetal weight from two time points in combination with birth weight. Models were stratified to investigate sex differences. Inverse associations were observed between average 2,4- and 2,5-DCP concentrations and birth weight z-scores in males. For example, an interquartile range difference in 2,4-DCP was associated with a 0.18 standard deviation decrease in birth weight z-score (95% confidence interval [CI]=-0.33, -0.02). These associations were observed in models that included repeated ultrasound estimates of fetal weight during gestation as well. Also in males, we noted inverse associations between average triclosan exposure over pregnancy and estimated fetal weight combined with birth weight in repeated measures models. For females, associations were generally null. However, mothers with a detectable concentration of bisphenol-S at any of the study visits had lower weight females. In conclusion, we observed inverse associations between indicators of maternal phenol exposure during pregnancy and fetal growth, with several differences observed by sex.

Non-parametric estimation of low-concentration benzene metabolism.

Two apparently contradictory findings in the literature on low-dose human metabolism of benzene are as follows. First, metabolism is approximately linear at low concentrations, e.g., below 10 ppm. This is consistent with decades of quantitative modeling of benzene pharmacokinetics and dose-dependent metabolism. Second, measured benzene exposure and metabolite concentrations for occupationally exposed benzene workers in Tianjin, China show that dose-specific metabolism (DSM) ratios of metabolite concentrations per ppm of benzene in air decrease steadily with benzene concentration, with the steepest decreases below 3 ppm. This has been interpreted as indicating that metabolism at low concentrations of benzene is highly nonlinear. We reexamine the data using non-parametric methods. Our main conclusion is that both findings are correct; they are not contradictory. Low-concentration metabolism can be linear, with metabolite concentrations proportional to benzene concentrations in air, and yet DSM ratios can still decrease with benzene concentrations. This is because a ratio of random variables can be negatively correlated with its own denominator even if the mean of the numerator is proportional to the denominator. Interpreting DSM ratios that decrease with air benzene concentrations as evidence of nonlinear metabolism is therefore unwarranted when plots of metabolite concentrations against benzene ppm in air show approximately straight-line relationships between them, as in the Tianjin data. Thus, an apparent contradiction that has fueled heated discussions in the recent literature can be resolved by recognizing that highly nonlinear, decreasing DSM ratios are consistent with linear metabolism.

Evidence for non-linear metabolism at low benzene exposures? A reanalysis of data.

The presence of a high-affinity metabolic pathway for low level benzene exposures of less than one part per million (ppm) has been proposed although a pathway has not been identified. The variation of metabolite molar fractions with increasing air benzene concentrations was suggested as evidence of significantly more efficient benzene metabolism at concentrations <0.1 ppm The evidence for this pathway is predicated on a rich data set from a study of Chinese shoe workers exposed to a wide range of benzene concentrations (not just "low level"). In this work we undertake a further independent re-analysis of this data with a focus on the evidence for an increase in the rate of metabolism of benzene exposures of less than 1 ppm. The analysis dataset consisted of measurements of benzene and toluene from personal air samplers, and measurements of unmetabolised benzene and toluene and five metabolites (phenol hydroquinone, catechol, trans, trans-muconic acid and s-phenylmercapturic acid) from post-shift urine samples for 213 workers with an occupational exposure to benzene (and toluene) and 139 controls. Measurements from control subjects were used to estimate metabolite concentrations resulting from non-occupational sources, including environmental sources of benzene. Data from occupationally exposed subjects were used to estimate metabolite concentrations as a function of benzene exposure. Correction for background (environmental exposure) sources of metabolites was achieved through a comparison of geometric means in occupationally exposed and control populations. The molar fractions of the five metabolites as a function of benzene exposure were computed. A supra-linear relationship between metabolite concentrations and benzene exposure was observed over the range 0.1-10 ppm benzene, however over the range benzene exposures of between 0.1 and 1 ppm only a modest departure from linearity was observed. The molar fractions estimated in this work were near constant over the range 0.1-10 ppm. No evidence of high affinity metabolism at these low level exposures was observed. Our reanalysis brings in to question the appropriateness of the dataset for commenting on low dose exposures and the use of a purely statistical approach to the analysis.

The duration of pregnancy in ecologically-challenged area. The effects of environmental pollution with aromatic hydrocarbons on the angiogenesis and elements of the mesenchymal tissue of the human placenta.

INTRODUCTION: The literature presents only few reports regarding the effects of elevated levels of aromatic hydrocarbons (AH) on the functions of the human placenta. The effects of environmental contamination with AH (including phenol and 1-hydroxypyrene) have certain negative effects on parenchymal organs such as human placenta. OBJECTIVE: The paper aimed to assess the effects of elevated levels of AH on the placental angiogenesis and elements of the mesenchymal tissue of the placenta. MATERIAL AND METHODS: Tissue material from 50 afterbirths from Plock constituted a study group, whereas 50 afterbirths from Kutno constituted a control group. Immunohistochemical reactions with the peroxidase method using LSAB kits (DAKO) were performed. The extent and intensity of reactions were analysed. The levels of phenols and 1-hydroxypyrene in the excreted urine of pregnant women (undergoing delivery) were detected using gas chromatography and colorimetry. RESULTS: The levels of phenol and 1-hydroxypyrene in the excreted urine were demonstrated to be statistically significantly higher in patients living in the area of Plock. Statistically significantly higher expression of antibodies indicating placental angiogenesis was observed in the placentas in the Plock group (p < 0.01). Moreover, lower expression of vimentin indicating reactions with proteins in mesenchymal cells was observed in the Kutno group (p < 0.01). CONCLUSIONS: Pregnancy in the environment with elevated levels of aromatic hydrocarbons has detrimental effects on the human placenta. The foetus is protected by activation of adaptation and compensation mechanisms that are manifested as significant angiogenesis and greater development and differentiation of mesenchymal cells compared to the control group.

Proliferation and apoptosis of human placental cells exposed to aromatic hydrocarbons.

OBJECTIVES: The objective of this study is to assess the effect of elevated urinary levels of aromatic hydrocarbons (AH) on the proliferation and apoptosis of human placental trophoblast cells obtained in the course of normal pregnancy in an AH-polluted region. MATERIAL AND METHODS: Tissue material was obtained for study purposes from 50 afterbirths from Plock as the study group and 50 afterbirths from Kutno as the control group. The extent and intensity of reactions were analyzed. The levels of phenol and 1-hydroxypyrene in the excreted urine of pregnant (in labor) patients were determined by gas chromatography and colorimetry. The proliferative activity of trophoblast cells was assessed using MPM-2 antibodies against phosphoprotein synthesized upon mitotic induction and Ki-67 antigen while the intensity of apoptosis in trophoblast cells was assessed using p53 and bcl-2 oncoproteins involved in apoptosis-regulating mechanisms. The immunohistochemical reactions were assessed for their extent and intensity. RESULTS: The levels of phenol and 1-hydroxypyrene excreted in the urine were statistically significantly higher in patients from Plock region. The proliferative activity of trophoblast cells was statistically significantly higher in the study group (p < 0.05). The activity of oncoprotein bcl-2 was significantly higher in the study group while the activity of p53 was sig¬nificantly higher in the control group. Pregnancy in an aromatic hydrocarbon-polluted environment has a significantly negative impact on placental tissue. Ad¬aptation mechanisms are induced as manifested by increased proliferative activity within the trophoblast and extensive inhibition of apoptosis in the study group.

DnsID in MyCompoundID for rapid identification of dansylated amine- and phenol-containing metabolites in LC-MS-based metabolomics.

High-performance chemical isotope labeling (CIL) liquid chromatography-mass spectrometry (LC-MS) is an enabling technology based on rational design of labeling reagents to target a class of metabolites sharing the same functional group (e.g., all the amine-containing metabolites or the amine submetabolome) to provide concomitant improvements in metabolite separation, detection, and quantification. However, identification of labeled metabolites remains to be an analytical challenge. In this work, we describe a library of labeled standards and a search method for metabolite identification in CIL LC-MS. The current library consists of 273 unique metabolites, mainly amines and phenols that are individually labeled by dansylation (Dns). Some of them produced more than one Dns-derivative (isomers or multiple labeled products), resulting in a total of 315 dansyl compounds in the library. These metabolites cover 42 metabolic pathways, allowing the possibility of probing their changes in metabolomics studies. Each labeled metabolite contains three searchable parameters: molecular ion mass, MS/MS spectrum, and retention time (RT). To overcome RT variations caused by experimental conditions used, we have developed a calibration method to normalize RTs of labeled metabolites using a mixture of RT calibrants. A search program, DnsID, has been developed in www.MyCompoundID.org for automated identification of dansyl labeled metabolites in a sample based on matching one or more of the three parameters with those of the library standards. Using human urine as an example, we illustrate the workflow and analytical performance of this method for metabolite identification. This freely accessible resource is expandable by adding more amine and phenol standards in the future. In addition, the same strategy should be applicable for developing other labeled standards libraries to cover different classes of metabolites for comprehensive metabolomics using CIL LC-MS.

Associations between urinary phenol and paraben concentrations and markers of oxidative stress and inflammation among pregnant women in Puerto Rico.

Phenols and parabens are used in a multitude of consumer products resulting in ubiquitous human exposure. Animal and in vitro studies suggest that exposure to these compounds may be related to a number of adverse health outcomes, as well as potential mediators such as oxidative stress and inflammation. We examined urinary phenol (bisphenol A (BPA), triclosan (TCS), benzophenone-3 (BP-3), 2,4-dichlorophenol (24-DCP), 2,5-dichlorophenol (25-DCP)) and paraben (butyl paraben (B-PB), methyl paraben (M-PB), propyl paraben (P-PB)) concentrations measured three times during pregnancy in relation to markers of oxidative stress and inflammation among participants in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) project. Serum markers of inflammation (c-reactive protein (CRP), IL-1ß, IL-6, IL-10, and tumor necrosis factor-α (TNF-α)) were measured twice during pregnancy (n=105 subjects, 187 measurements) and urinary markers of oxidative stress (8-hydroxydeoxyguanosine (OHdG) and isoprostane) were measured three times during pregnancy (n=54 subjects, 146 measurements). We used linear mixed models to assess relationships between natural log-transformed exposure and outcome biomarkers while accounting for within individual correlation across study visits. After adjustment for urinary specific gravity, study visit, maternal pre-pregnancy BMI, and maternal education, an interquartile range (IQR) increase in urinary BPA was associated with 21% higher OHdG (p=0.001) and 29% higher isoprostane (p=0.0002), indicating increased oxidative stress. The adjusted increase in isoprostane per IQR increase in marker of exposure was 17% for BP-3, 27% for B-PB, and 20% for P-PB (all p<0.05). An IQR increase in triclosan (TCS) was associated with 31% higher serum concentrations of IL-6 (p=0.007), a pro-inflammatory cytokine. In contrast, IQR increases in BP-3 and B-PB were significantly associated with 16% and 18% lower CRP, a measure of systemic inflammation. Our findings suggest that exposure to BPA, select parabens, and TCS during pregnancy may be related to oxidative stress and inflammation, potential mechanisms by which exposure to these compounds may influence birth outcomes and other adverse health effects, but additional research is needed.

Association of urinary phenols with increased body weight measures and obesity in children and adolescents.

OBJECTIVE: To examine the association of urinary levels of the environmental phenol pesticides 2,5-dichlorophenol, 2,4-dichlorophenol, and triclosan with body weight outcomes in children and adolescent participants in the National Health and Nutrition Examination Survey 2007-2010. STUDY DESIGN: We performed multivariate linear and multinomial logistic regressions to analyze the association of body mass index (BMI) z-score, waist circumference (WC), and obesity with urinary pesticide concentration in children and adolescents. RESULTS: After adjustment for covariates, we found a statistically significant positive association (P < .05) between both 2,5-dichlorophenol and 2,4-dichlorophenol with BMI z-score, WC, and obesity in children and adolescents. After stratification by age, the significant associations remained only in adolescents (ages 12-19). No associations were found between triclosan and any of the body weight outcomes. CONCLUSIONS: We found an association between dichlorophenols and increased body weight measures (BMI z-score, WC, and obesity) in adolescents. However, further studies, such as a longitudinal study, are needed to confirm and elucidate on our findings.

Health effects of benzene exposure among children following a flaring incident at the British Petroleum Refinery in Texas City.

Human exposure to benzene is associated with multiple adverse health effects leading to hematological malignancies. The objective of this retrospective study was to evaluate the health consequences of benzene exposure in children following a flaring incident at the British petroleum (BP) refinery in Texas City, Texas. The study included children aged <17 years who had been exposed and unexposed to benzene. Using medical charts, clinical data including white blood cell (WBC) counts, platelets counts, hemoglobin, hematocrit, blood urea nitrogen (BUN), creatinine, alkaline phosphatase (ALP), aspartate amino transferase (AST), alanine amino transferase (ALT), and somatic symptom complaints by the children exposed to benzene were reviewed and analyzed. A total of 312 subjects (benzene exposed, n = 157 and unexposed, n = 155) were included. Hematologic analysis showed that WBC counts were significantly decreased in benzene-exposed children compared with the unexposed children (6.8 ± 2.1 versus 7.3 ± 1.7, P = .022). Conversely, platelet (X 10(3) per µL) counts were increased significantly in the benzene-exposed group compared with the unexposed group (278.4 ± 59.9 versus 261.6 ± 51.7, P = .005). Similarly, benzene-exposed children had significantly higher levels of ALP (183.7± 95.6 versus 165 ± 70.3 IU/L, P = .04), AST (23.6 ± 15.3 versus 20.5 ± 5.5 IU/L, P = .015), and ALT (19.2 ± 7.8 versus 16.9 ± 6.9 IU/L, P = .005) compared with the unexposed children. Together, the results of the study reveal that children exposed to benzene experienced significantly altered blood profiles, liver enzymes, and somatic symptoms indicating that children exposed to benzene are at a higher risk of developing hepatic or blood related disorders.

Death following injection sclerotherapy due to phenol toxicity.

Prolapse rectum (PR) or protrusion of the rectum beyond the anus occurs frequently in populations at both extremes of age. In the pediatric population, in developed countries, the commonest cause for PR is thought to be cystic fibrosis (CF). Treatment options for CF include conservative management, surgical resection and fixation, suturing, and injection sclerotherapy (IS). The last is considered an attractive treatment option because it is minimally invasive. In this case report, the authors present the details about a 2-year-old female child, with PR and CF, who died after IS, using phenol as the sclerotherapeutic agent. Autopsy findings and toxicology tests performed to establish phenol toxicity are documented. The available literature is reviewed. This case report underscores the risks of using phenol for IS and emphasizes the point that the procedure is not innocuous and an adverse outcome including fatality is a possibility.

Structural elucidation and quantification of phenolic conjugates present in human urine after tea intake.

In dietary polyphenol exposure studies, annotation and identification of urinary metabolites present at low (micromolar) concentrations are major obstacles. To determine the biological activity of specific components, it is necessary to have the correct structures and the quantification of the polyphenol-derived conjugates present in the human body. We present a procedure for identification and quantification of metabolites and conjugates excreted in human urine after single bolus intake of black or green tea. A combination of a solid-phase extraction (SPE) preparation step and two high pressure liquid chromatography (HPLC)-based analytical platforms was used, namely, accurate mass fragmentation (HPLC-FTMS(n)) and mass-guided SPE-trapping of selected compounds for nuclear magnetic resonance spectroscopy (NMR) measurements (HPLC-TOFMS-SPE-NMR). HPLC-FTMS(n) analysis led to the annotation of 138 urinary metabolites, including 48 valerolactone and valeric acid conjugates. By combining the results from MS(n) fragmentation with the one-dimensional (1D)-(1)H NMR spectra of HPLC-TOFMS-SPE-trapped compounds, we elucidated the structures of 36 phenolic conjugates, including the glucuronides of 3',4'-di- and 3',4',5'-trihydroxyphenyl-γ-valerolactone, three urolithin glucuronides, and indole-3-acetic acid glucuronide. We also obtained 26 h-quantitative excretion profiles for specific valerolactone conjugates. The combination of the HPLC-FTMS(n) and HPLC-TOFMS-SPE-NMR platforms results in the efficient identification and quantification of less abundant phenolic conjugates down to nanomoles of trapped amounts of metabolite corresponding to micromolar metabolite concentrations in urine.

Consumption of breads containing in situ-produced arabinoxylan oligosaccharides alters gastrointestinal effects in healthy volunteers.

Arabinoxylan oligosaccharides (AXOS) are studied as food compounds with prebiotic potential. Here, the impact of consumption of breads with in situ-produced AXOS on intestinal fermentation and overall gastrointestinal characteristics was evaluated in a completely randomized, double-blind, controlled, cross-over study. Twenty-seven healthy volunteers consumed 180 g of wheat/rye bread with or without in situ-produced AXOS (WR(+) and WR(-), respectively) daily for 3 wk. Consumption of WR(+) corresponded to an AXOS intake of ~2.14 g/d. Refined wheat flour bread without AXOS (W(-)) (180 g/d) was provided during the 3-wk run-in and wash-out periods. At the end of each treatment period, participants collected urine for 48 h as well as a feces sample. Additionally, all participants completed a questionnaire about stool characteristics and gastrointestinal symptoms during the last week of each period. Urinary phenol and p-cresol excretions were significantly lower after WR(+) intake compared to WR(-). Consumption of WR(+) significantly increased fecal total SCFA concentrations compared to intake of W(-). The effect of WR(+) intake was most pronounced on butyrate, with levels 70% higher than after consumption of W(-) in the run-in or wash-out period. Consumption of WR(+) tended to selectively increase the fecal levels of bifidobacteria (P = 0.06) relative to consumption of W(-). Stool frequency increased significantly after intake of WR(+) compared to WR(-). In conclusion, consumption of breads with in situ-produced AXOS may favorably modulate intestinal fermentation and overall gastrointestinal properties in healthy humans.

Renal excretion of phenol from physicians after nail matrix phenolization: an observational prospective study.

BACKGROUND: Animal studies have shown that many signs of acute poisoning result from phenol entry into the systemic circulation by absorption or ingestion. While no evidence of systemic complications in patients who have undergone phenol nail matrixectomies have been reported, the safety of phenol vapour inhalation by physicians performing this treatment has yet to be investigated. OBJECTIVE: The goal of this study was to determine whether the levels of phenol to which physicians are exposed to during a phenol-based matrixectomy procedure are within the limits of safe exposure. METHODS: A continuous prospective study was carried out to measure the urinary phenol concentrations from physicians after performing chemical matrixectomy for ingrown toenails. RESULTS: The highest concentration of urinary phenol was measured at almost 10 mg/L within the first 2 h after exposure, and subsequently decreased approximately 1 mg/L every 2 h for the first 10 h post exposure. The levels dropped to 3 mg/L at 72 h post exposure. CONCLUSIONS: The risk associated with phenol exposure while performing chemical phenol matrixectomy was well below the current safety limits when the physician is exposed to 90% phenol vapour for approximately 20 min. Thus, no further specific safety recommendations are required for physicians performing this procedure.

[Substantiating the blood concentrations of phenol and alkylphenols (o-, m-, and p-cresols) providing the acceptable risk to human health].

The paper considers the current nontraditional approaches to revealing the causal effects and criteria for significance of an exposure-response relationship. The study has used the elements of methodology for assessing the risk and the techniques of environmental epidemiology to examine causal effects. A blood toxicant-response marker relationship was assessed and the quantitative characteristics of the association between the concentrations of the test compounds and the risk of noxious effects were ascertained. On the basis of exposure marker-response marker models, the authors revealed the priority types of functional changes and established the blood concentrations of phenol and m- and n-cresols at an acceptable risk level.