Creatinine-corrected Concentrations Research Articles

Urinary concentrations and elimination half-lives of parabens, benzophenones, bisphenol and triclosan in Japanese young adults.

Environmental phenols are widely distributed in the environment and human samples, suggesting potential exposure to these chemicals. We designed an intervention trial with 30 participants over 6 days to assess the urinary concentrations and half-lives of environmental phenols in Japanese young people. The target environmental phenols include three parabens (methyl paraben, ethyl paraben, and propyl paraben), two benzophenones (benzophenone 1 and 3), two bisphenols (bisphenol F and bisphenol S), and triclosan. Throughout the intervention, the participants consumed the same food and drinks and used personal care products provided by the project. The target phenols were measured in urine from the participants using a liquid chromatography-tandem mass spectrometer. We compared the measured concentrations between the study periods to better understand the exposure tendency. Some statistically significant differences were observed. All target analytes were detected in more than 50% of samples collected on Day 0 (the day before the intervention). Methyl paraben was the dominant phenol detected in urine (1640 μg/g-creatinine), followed by ethyl paraben (119 μg/g-creatinine). Downward trends in creatinine-corrected concentrations were observed for all target analytes in some instances. Non-compartment analysis was performed to estimate urinary excretion parameters. The estimated half-lives ranged from 7.69 to 20.3 h. Use of paraben-free products during the intervention period reduced the body burden.

External Validation of a Urinary Biomarker Risk Score for the Prediction of Steroid Responsiveness in Adults With Nephrotic Syndrome

In idiopathic nephrotic syndrome, response to corticosteroids remains the best indicator of prognosis. Noninvasive markers to predict a patient's response to steroids would allow improved prognostication and a more personalized approach to management. We have previously derived a urinary biomarker risk score which can differentiate steroid sensitive nephrotic syndrome (SSNS) from steroid resistant nephrotic syndrome (SRNS) in children. The goal of this study was to validate this previously derived biomarker risk score in a cohort of steroid-naïve adult patients, to determine whether the panel could be used to predict steroid responsiveness at the time of initial diagnosis. In this external validation study, clinical data, and urinary specimens (obtained before initiation of steroid treatment) from adult patients were used in the Nephrotic Syndrome Study Network (NEPTUNE) cohort. A panel of 5 previously identified and validated urinary biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), vitamin D binding protein (VDBP), Fetuin-A (FetA), Transthyretin (TTR), and alpha-1 acid glycoprotein 2 (AGP2) was measured. A summary risk score for steroid resistance was calculated based on biomarker concentrations. Receiver operating characteristic curves were created for each log-transformed biomarker concentration and for the individual and combined biomarker risk score. The urine biomarker risk score predicted development of steroid resistance, with optimal sensitivity and specificity of 0.74, and area under the receiver operating characteristic curve (AUC) of 0.79 using both absolute and creatinine-corrected concentrations. This study validates the previously derived urinary biomarker risk score to predict steroid resistance in adult patients with nephrotic syndrome at initial diagnosis.

Urinary Concentrations of Endocrine-Disrupting Metals and Prevalent Breast Cancer in US Women.

The toxic metals cadmium, lead, and mercury are endocrine-disrupting agents that could produce estrogenic effects involving breast carcinogenesis. In this study, we further explored the relationship between exposure to these metals and prevalent breast cancer among female participants, aged 20years or older, in the 2007-2016 National Health and Nutrition Examination Survey (NHANES). Exposure was determined by measuring urinary concentrations of metals using inductively coupled plasma mass spectrometry. Urine creatinine-corrected concentrations of metals were calculated for each study participant. Multivariate logistic regression models were constructed to examine the association between urinary metals and prevalent breast cancer, adjusting for potential confounders. Of the 3352 study participants, 106 had been diagnosed with breast cancer (weighted prevalence, 3.13%). The results show that women with breast cancer had significantly higher urinary concentrations of lead and cadmium (both p < 0.0001) than those without breast cancer. After adjusting for all the covariates included in the study, however, only urinary lead was shown to be significantly associated with increased prevalence of breast cancer, with an odds ratio of 2.95 (95% CI: 1.13, 7.70) in the highest quartile of urinary lead concentrations (≥ 0.71µg/g creatinine) as compared with the lowest quartile. No statistically significant associations were observed between urine cadmium or mercury levels and breast cancer. This study demonstrates a potential association between lead exposure and prevalent breast cancer among US women. Prospective and mechanistic studies are warranted to further investigate this interaction and explore the role of lead in breast carcinogenesis.

Association between urinary bisphenol analogue concentrations and lung cancer in adults: A case-control study

Elevated urinary bisphenol A (BPA) concentrations have been associated with lung cancer in humans. However, toxicological studies demonstrated that the proliferation of lung cancer cells was inhibited by BPA exposure. Therefore, it is still necessary to determine whether exposure to BPA and other bisphenol analogues (BPs) is associated with lung cancer in humans. In this study, 226 lung cancer patients and 243 controls were randomly recruited. Concentrations of three BPs in human urine were quantified and their relationships with the risk of human lung cancer were evaluated. BPA (mean 1.03 ng/mL, 0.87 μg/g Cre) was the predominant BP in human urine, followed by bisphenol S (BPS) (0.72 ng/mL, 0.53 μg/g Cre) and bisphenol F (0.32 ng/mL, 0.37 μg/g Cre). Significant correlations between creatinine-corrected urinary BPA concentrations and the lung cancer risk (odds ratio (OR) adjusted = 1.28, 95% confidence interval (CI): 1.17, 1.40; Ptrend = 0.04) were found using logistical regression analysis. Creatinine-corrected urinary concentrations of BPS in participants showed significant correlations with lung cancer (ORadjusted = 1.23, 95% CI: 1.04, 1.59; Ptrend = 0.01) in the adjusted model. In the stratification analysis, the significant correlation between urinary creatinine-corrected concentrations of BPA and the risk of lung cancer still observed in male participants (OR = 1.36, 95% CI: 1.09, 1.62, p = 0.040). This study demonstrates that elevated human exposure to BPA and BPS may be associated with the increased lung cancer risk.

Antibiotic exposure and potential risk of depression in the Chinese elderly: a biomonitoring-based population study.

To examine the associations between urinary antibiotics from various sources and depression in the elderly using the biomonitoring method. In the current study, we investigated 990 elderly individuals (≥ 60 years old) from a community-based elderly cohort in West Anhui, China. The participants were interviewed by the Geriatric Depression Scale and self-developed questionnaires. A total of 45 antibiotics belonging to nine categories were screened in urine samples by the developed liquid chromatography electrospray tandem mass spectrometry method. Creatinine-corrected concentrations of antibiotics in urines were used to assess their exposure. Logistic regression analysis was employed to test the relationships between exposure to antibiotics and depression. Compared to the control group, the multinomial logistic regression analyses showed the elderly exposed to higher concentrations of azithromycin (OR = 1.81, 95% CI: 1.09-3.00) and sulfaclozine (OR = 1.54, 95% CI: 1.05-2.28) had increased risks of depression, respectively. After categorizing the detected antibiotics, tetracyclines (OR = 1.48, 95% CI: 1.02-2.16) and veterinary antibiotics (VAs) (OR = 1.53, 95% CI: 1.06-2.20) were positively correlated with increased risks of depression. After stratified by sex, the VAs (OR = 2.04, 95% CI: 1.13-3.71) at higher concentrations were associated with elevated risks of depression in males, while the associations between depression and antibiotic exposures were observed in tetracyclines (OR = 1.74, 95% CI: 1.04-2.85) and all antibiotics (OR = 2.24, 95% CI: 1.01-2.94) at higher levels in females, respectively. Notably, after the stratification by age, the significant associations were mainly present in the subjects under the age of 70. Our findings reveal that azithromycin, sulfaclozine, tetracyclines, and the VAs were significantly associated with elevated risks of depression in the elderly. Importantly, sex- and age-specific differences were observed in the associations between antibiotic exposures and depression.

Maternal antibiotic concentrations in pregnant women in Shanghai and their determinants: A biomonitoring-based prospective study

Consumption of antibiotics is continuing to increase, with China accounting for approximately one quarter of the global intake. As a class of emerging environmental contaminants, antibiotics may pose a potential threat to human health, especially in children. However, the internal antibiotic exposure levels in pregnant women and their determinants remain unclear. Here we investigated the urinary creatinine-corrected concentration of 15 antibiotics in 762 pregnant women from the Shanghai Prenatal Cohort, by liquid chromatography-tandem mass spectrometry. Logistic regression analysis identified associations between high-antibiotic-level and maternal dietary factors. Results show that cumulatively antibiotics were detected at a frequency of 0.13 – 82.7%, with veterinary antibiotics (VAs) and preferred veterinary antibiotics (PVAs) detected in 76.9% and 98.2% of samples, respectively; PVAs were the most significant contributors to hazard index values > 1. Further, ciprofloxacin was the predominant antibiotic (median: 73.5 μg/mg creatinine), followed by norfloxacin (54.2 μg/mg creatinine); while sulfamethoxazole, enrofloxacin, and ciprofloxacin levels, used as a PVA or VA, were significantly higher in normal-weight and underweight women compared to overweight and obese women. Also, sulfamethoxazole, sulfadiazine, and ciprofloxacin were more frequently detected in mothers with a relatively low education degree. Interestingly, pregnant women with higher milk intake had a 1.96-times (95% CI: 1.10–3.49) greater risk of high-VA-exposure-level than the lower-intake group. The odds of exposure to high PVA, VA, PVA + VA, and all antibiotics levels for mothers with high egg consumption frequency were more than twice that of low-consumption individuals. Collectively, pregnant women in Shanghai are exposed to multiple environmental antibiotics, primarily as PVAs and VAs. Herein, we provide evidence for the association between dietary factors and maternal environmental antibiotic exposure in China. Special attention to antibiotic exposure and confirmation of potential determinants should be taken in the future.

A biomonitoring assessment of secondhand exposures to electronic cigarette emissions.

Electronic cigarette (e-cigarette) conventions regularly bring together thousands of users around the world. In these environments, secondhand exposures to high concentrations of e-cigarette emissions are prevalent. Some biomarkers for tobacco smoke exposure may be used to characterize secondhand e-cigarette exposures in such an environment. Participants who did not use any tobacco product attended four separate e-cigarette events for approximately six hours. Urine and saliva samples were collected from participants prior to the event, immediately after the event, 4-h after the event, and the next morning (first void). Urine samples from 34 participants were analyzed for cotinine, trans-3'-hydroxycotinine, S-(3-hydroxypropyl)-N-acetylcysteine (3-HPMA), S-carboxyethyl-N-acetylcysteine (CEMA), select tobacco-specific nitrosamines (TSNAs), and 8-isoprostane. Saliva samples were analyzed for cotinine and trans-3'-hydroxycotinine. Data from 28 of 34 participants were used in the data analysis. Creatinine-adjusted urinary cotinine concentrations increased up to 13-fold and peaked 4-h after completed exposure (range of adjusted geometric means [AGMs] = 0.352-2.31 μg/g creatinine). Salivary cotinine concentrations were also the highest 4-h after completed exposure (range of AGMs = 0.0373-0.167 ng/mL). Salivary cotinine and creatinine-corrected concentrations of urinary cotinine, trans-3'-hydroxycotinine, CEMA, and 3-HPMA varied significantly across sampling times. Urinary and salivary cotinine, urinary trans-3'-hydroxycotinine, and urinary 3-HPMA concentrations also varied significantly across events. Secondhand e-cigarette exposures lasting six hours resulted in significant changes in exposure biomarker concentrations of both nicotine and acrolein but did not change exposure to tobacco-specific nitrosamines. Additional research is needed to understand the relationship between biomarker concentrations and environmental concentrations of toxicants in e-cigarette emissions.

Correlates of exposure to phenols, parabens, and triclocarban in the Study of Environment, Lifestyle and Fibroids.

We performed a cross-sectional analysis to identify correlates of urinary concentrations of seven phenols (bisphenols A, F, and S, 2,4-dichlorophenol, 2,5-dichlorophenol, benzophenone-3, triclosan), triclocarban, and four parabens (butyl, ethyl, methyl, and propyl). We analyzed baseline data from 766 participants in the Study of Environment, Lifestyle, and Fibroids, a prospective cohort study of 1 693 Black women aged 23–34 years residing in Detroit, Michigan (2010–2012). We collected data on demographic, behavioral, and anthropometric factors via telephone interviews, clinic visits, and self-administered questionnaires. For each biomarker, we used linear regression models to estimate mean differences in log-transformed, creatinine-corrected concentrations across factors of interest. Each biomarker was detected in >50% of participants. Median creatinine-corrected concentrations were highest for methyl paraben (116.8 μg/g creatinine), propyl paraben (16.8 μg/g creatinine), and benzophenone-3 (13.4 μg/g creatinine). Variables most strongly associated with biomarker concentrations included season of urine collection, education, and body mass index (BMI). BMI was positively associated with bisphenol A and S and triclocarban concentrations and inversely associated with butyl and methyl paraben concentrations. In this cohort of Black women, exposure to phenols, parabens, and triclocarban was prevalent and several factors were associated with biomarker concentrations.

Exposure to phytoestrogens in utero and age at menarche in a contemporary British cohort

Phytoestrogens are estrogenic compounds that occur naturally in plants. Phytoestrogens can cross the placenta, and animal studies have found associations between in utero exposure to phytoestrogens and markers of early puberty. We investigated the association between in utero exposure to phytoestrogens and early menarche (defined as <11.5 years of age at onset) using data from a nested case-control study within the Avon Longitudinal Study of Parents and Children, a longitudinal study involving families living in the South West of England. Concentrations of six phytoestrogens were measured in maternal urine samples collected during pregnancy. Logistic regression was used to explore associations between tertiles of phytoestrogen concentrations and menarche status, with adjustment for maternal age at menarche, maternal education, pre-pregnancy body mass index (BMI), child birth order, duration of breastfeeding, and gestational age at sample collection. Among 367 mother-daughter dyads, maternal median (interquartile range) creatinine-corrected concentrations (in µg/g creatinine) were: genistein 62.1 (27.1–160.9), daidzein 184.8 (88.8–383.7), equol 4.3 (2.8–9.0), O-desmethylangolensin (O-DMA) 13.0 (4.4–34.5), enterodiol 76.1 (39.1–135.8), and enterolactone 911.7 (448.1–1558.0). In analyses comparing those in the highest tertile relative to those in the lowest tertile of in utero phytoestrogen exposure, higher enterodiol levels were inversely associated with early menarche (odds ratio (OR)=0.47; 95% confidence interval (CI): 0.26–0.83), while higher O-DMA levels were associated with early menarche (OR=1.89; 95% CI: 1.04–3.42). These findings suggest that in utero exposure to phytoestrogens may be associated with earlier age at menarche, though the direction of association differs across phytoestrogens.

Exposure to phytoestrogens in utero and age at menarche in a contemporary British cohort

Background Phytoestrogens are estrogenic compounds that occur naturally in plants. Phytoestrogens can cross the placenta, and animal studies have found associations between in utero exposure to phytoestrogens and markers of early puberty. Methods We investigated the association between in utero exposure to phytoestrogens and early menarche (&lt;11.5 years at onset) using data from a nested case-control study within the Avon Longitudinal Study of Parents and Children. Concentrations of six phytoestrogens were measured in maternal urine samples collected during pregnancy. Logistic regression was used to explore associations between quartiles of phytoestrogen concentrations with menarcheal status, with adjustment for maternal age at menarche, maternal education, pre-pregnancy BMI, maternal age at delivery, child birth order, duration of breastfeeding, childhood BMI Z-score, and child ethnicity. Results Among 370 mother-daughter dyads, maternal geometric mean (95% confidence interval (CI)) creatinine-corrected concentrations (in µg/g creatinine) were as follows: daidzein 184 (162-208), enterodiol 71.5 (64.6-79.1), enterolactone 755 (674-846), equol 5.65 (4.91-6.49), genistein 63.5 (54.9-73.4), and O-desmethylangolensin (O-DMA) 11.2 (9.34-13.5). In preliminary analyses comparing in utero phytoestrogen exposure in the highest quartile (Q4) to the lowest quartile (Q1), no significant associations with onset of menarche were found. Higher O-DMA levels were nonsignificantly associated with early menarche (odds ratio (OR) = 1.51; CI: 0.65-3.29). O-DMA is an intestinal bacterial metabolite of daidzein; not all individuals harbor bacteria capable of metabolizing daidzein to O-DMA. Conclusions These findings suggest that in utero exposure to phytoestrogens may not be associated with earlier age at menarche. Future analyses will examine the associations between phytoestrogens and age at menarche through survival analysis techniques.

Second-hand smoke measured with urinary cotinine during pregnancy and offspring’s neurodevelopment at age of 24 months

Introduction The research on association between the exposure to second hand smoke (SHS) during pregnancy and the children’s neurodevelopment is limited, but the results still remain unclear. Thus, we explored the association between prenatal exposure to SHS on neurodevelopment of offspring’s upto 24 months of age considering exposure of polycyclic aromatic hydrocarbons (PAHs). Methods We analyzed 1207 mothers and their offsprings from Korean multicentric birth cohort study: Mothers and Children Environmental Health (MOCEH). We measured urinary cotinine to represent SHS repeatedly both at early pregnancy and at delivery from mothers. Children’s mental developmental index (MDI) and psychomotor developmental index (PDI) were measured using the Bayley Scales of Infant Development at 6, 12 and 24 months of age. To assess the relationship between urinary cotinine level and neurodevelopment, we used generalized linear model, piecewise linear regression model and further implemented generalized linear mixed model to consider repeated data. Creatinine-corrected concentrations of urinary cotinine were used. Results The MDI score of 24months aged infants was inversely associated with cotinine [β= -2.25; confidence interval (CI), -4.44 to -0.05] in mothers with early pregnancy urinary cotinine levels ≥1.95 micrograms per gram creatinine (μg/g cr), whereas there were no such associations in mothers with cotinine levels &lt;1.95μg/g cr. Further, this negative association was more pronounced in boys [β= -3.37; CI, -6.35 to -0.38] but no association was detected in girls. Conclusions These findings suggest that maternal exposure to SHS along with co-exposure to PAHs during pregnancy may result in delayed MDI in early childhood, especially in boys.

Bisphenol A, benzophenone-type ultraviolet filters, and phthalates in relation to uterine leiomyoma

Bisphenol A, benzophenone-type UV filters, and phthalates are chemicals in high production and use including in a range of personal care products. Exposure of humans to these chemicals has been shown to affect endocrine function. Although short-lived, widespread exposure may lead to continual opportunity for these chemicals to elicit health effects in humans. The association of these chemicals with incident uterine leiomyoma, an estrogen sensitive disease, is not known. Urinary concentrations of bisphenol A (BPA), five benzophenone-type UV filters (2-hydroxy-4-methoxybenzophenone (2OH-4MeO-BP), 2,4-dihydroxybenzophenone (2,4OH-BP), 2,2׳-dihydroxybenzophenone (2,2׳OH-4MeO-BP), 2,2׳4,4׳-tetrahydroxybenzophenone (2,2׳4,4׳OH-BP), and 4-hydroxybenzophenone (4OH-BP), and 14 phthalate monoesters were quantified in 495 women who later underwent laparoscopy/laparotomy at 14 clinical sites for the diagnosis of fibroids. Significantly higher geometric mean creatinine-corrected concentrations of BPA, 2,4OH-BP, and 2OH-4MeO-BP were observed in women with than without fibroids [BPA: 2.09µg/g vs. 1.46µg/g p=0.004; 2,4OH-BP:11.10µg/g vs. 6.71µg/g p=0.01; 2OH-4MeO-BP: 11.31µg/g vs. 6.10µg/g p=0.01]. Mono-methyl phthalate levels were significantly lower in women with than without fibroids (1.78µg/g vs. 2.40µg/g). However, none of the exposures were associated with a significant odds ratio even when adjusting for relevant covariates. There was a lack of an association between select nonpersistent chemicals and the odds of a fibroid diagnosis.

Prenatal exposure to phthalate esters and behavioral syndromes in children at 8 years of age: Taiwan Maternal and Infant Cohort Study.

Background: Few studies have shown an association between prenatal phthalate exposure and adverse effects on neurodevelopment and behavior in young children.Objectives: We aimed to assess the relationship between prenatal exposure to phthalate esters and behavior syndromes in children at 8 years of age.Methods: A total of 122 mother–child pairs from the general population in central Taiwan were studied from 2000 to 2009. Mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), and three di-(2-ethylhexyl) phthalate (DEHP) metabolites—mono-2-ethylhexyl, mono-2-ethyl-5-hydroxyhexyl, and mono-2-ethyl-5-oxohexyl phthalates (MEHP, MEHHP, and MEOHP)—were measured in maternal urine collected during the third trimester of pregnancy using liquid chromatography–electrospray ionization–tandem mass spectrometry. Behavioral syndromes of children at 8 years of age were evaluated using the Child Behavior Checklist (CBCL). Associations between log10-transformed creatinine-corrected phthalate concentrations and standardized scores of the CBCL were estimated using linear regression models or multinomial logistic regressions with adjustments for potential confounders.Results: Externalizing problem scores were significantly higher in association with a 1-unit increase in log10-transformed creatinine-corrected concentrations of maternal MBP (β = 4.29; 95% CI: 0.59, 7.99), MEOHP (β = 3.74; 95% CI: 1.33, 6.15), and MEHP (β = 4.28 ; 95% CI: 0.03, 8.26) after adjusting for the child’s sex, intelligence, and family income. Meanwhile, MBP and MEOHP were significantly associated with Delinquent Behavior and Aggressive Behavior scores. The same pattern was found for borderline and/or clinical ranges.Conclusions: Our findings suggest positive associations between maternal DEHP and dibutyl phthalate (DBP) exposure and externalizing domain behavior problems in 8-year-old children.Citation: Lien YJ, Ku HY, Su PH, Chen SJ, Chen HY, Liao PC, Chen WJ, Wang SL. 2015. Prenatal exposure to phthalate esters and behavioral syndromes in children at 8 years of age: Taiwan Maternal and Infant Cohort Study. Environ Health Perspect 123:95–100; http://dx.doi.org/10.1289/ehp.1307154

Comparison of 24-h Urinary Aldosterone Level and Random Urinary Aldosterone-to-Creatinine Ratio in the Diagnosis of Primary Aldosteronism

BackgroundHistorically, urinary aldosterone level measurement was a commonly employed confirmatory test to detect primary aldosteronism (PA). However, 24-h urine collection is inconvenient and cumbersome. We hypothesized that random urinary aldosterone measurements with correction for creatinine concentration might be comparable to 24-h urinary aldosterone levels (Uald-24 h) in the diagnosis of PA.MethodsThe non-concurrent prospective study was conducted between June 2006 and March 2008 in patients admitted for confirmation of aldosteronism by salt loading test. A 24-h urine sample, which was collected during hospitalization on the day before saline infusion testing after restoration of serum hypokalemia, was collected from all subjects. Moreover, participants were asked to collect a first bladder voiding random urine sample during clinic visits. Uald-24 h and the random urinary aldosterone-to-creatinine ratio (UACR) were calculated accordingly.ResultsA total of 102 PA patients (71 patients diagnosed of aldosterone-producing adenoma, 31 with idiopathic hyperaldosteronism) and 65 patients with EH were enrolled. The receiver operating characteristic curve showed comparable areas under the curves of UACR and Uald-24 h. The Bland-Altman plot showed mean bias but no obvious heteroscedasticity between the two tests. When using random UACR >3.0 ng/mg creatinine as the cutoff value, we obtained a specificity of 90.6% to confirm PA from essential hypertension.ConclusionsOur study reinforce that the diagnostic accuracy of random UACR was comparable to that of Uald-24 h in PA patients. With the quickness and simplicity of the UACR method and its equivalence to Uald-24 h, this assay could be a good alternative diagnostic tool for PA confirmation.

Personal Exposure to PM2.5 and Urinary Hydroxy-PAH Levels in Bus Drivers Exposed to Traffic Exhaust, in Trujillo, Peru

Public transport vehicle drivers, especially in highly polluted or trafficked areas, are exposed to high levels of air pollutants. In this study, we assessed the influence of traffic on levels of hydroxy polycyclic aromatic hydrocarbons (OH-PAHs) in commercial bus drivers in Trujillo, Peru, by measuring the within-shift changes in the urinary whole weight and creatinine-corrected concentrations of the PAH metabolites. We measured personal PM2.5 as a proxy of exposure to traffic emission. Urine samples were collected daily from two bus drivers and three minivan drivers in Trujillo, pre-, mid-, post-work shift and on days when the drivers were off work (total n = 144). Ten OH-PAH metabolites were measured in the urine samples. Drivers were also monitored for exposure to PM2.5 (n = 41). Daily work shift (mean = 13.1 ± 1.3 hr) integrated PM2.5 was measured in the breathing zones of the drivers for an average of 10.5 days per driver. The differences across shift in OH-PAH concentrations were not statistically significant except for urinary 2-hydroxyfluorene (2-FLU) (p = 0.04) and 4-hydroxyphenanthrene (4-PHE) (p = 0.01) and creatinine-corrected 4-hydroxyphenanthrene (p = 0.01). Correlation between pairs of hydroxy-PAHs (ρ = 0.50 to 0.93) were highest for mid-shift samples. Concentrations of PM2.5 (geometric mean = 64 μg/m3; 95% confidence limits = 52 μg/m3, 78 μg/m3) is similar to those measured in many other studies of traffic exposure. There was significant change across work shift for concentrations of only two of the OH-PAHs (2-FLU and 4-PHE). Results indicate that the drivers may have had limited time for clearance of PAH exposure from the body between work shifts. Comparisons of the concentrations of creatinine-corrected hydroxy-PAH to those reported in other studies indicate that exposure of public transport drivers to PAH could be similar. By following the subjects over multiple days, this study gives an indication of appropriate exposure situations for the use of hydroxy-PAHs and will be beneficial in designing future occupational studies of PAH exposure.

Exposure to polycyclic aromatic hydrocarbons, arsenic and environmental tobacco smoke, nutrient intake, and oxidative stress in Japanese preschool children

The association between oxidative stress and exposure to environmental chemicals was assessed in a group of Japanese preschool children. The concentrations of 8-hydroxy-2′-deoxyguanosine (8-OHdG), 1-hydroxypyrene (1-OHP), inorganic arsenic (iAs) and monomethylarsonic acid (MMA), and cotinine in spot urine samples, collected from 134 children (3–6 yrs) from a kindergarten in Kanagawa, Japan, were measured as biomarkers of oxidative stress or exposure to environmental chemicals. For 76 subjects of the 134, intakes of anti-oxidant nutrients (vitamins A, C, and E, manganese, copper, zinc and selenium (Se)) were estimated from a food consumption survey carried out 2–4 weeks after urine sampling and by urine analysis (Se). The median (min–max) creatinine-corrected concentrations of urinary biomarkers were 4.45 (1.98–12.3), 0.127 (0.04–2.41), 4.78 (1.18–12.7), and 0.62 (< 0.6–19.0) μg/g cre for 8-OHdG, 1-OHP, iAs + MMA, and cotinine, respectively. Multiple regression analysis was carried out using 8-OHdG concentration as a dependent variable and urinary biomarkers of exposure and Se intake, intakes of vitamins and biological attributes of the subjects as independent variables. To explain 8-OHdG concentrations, intake of vitamin A and age were significant variables with negative coefficients, while 1-OHP concentration had a positive coefficient. These results indicated that oxidative stress of children is affected by chemical exposure at environmental levels, by nutrient intake and by physiological factors in a complex manner. On the other hand, unstable statistical results due to sub-grouping of subject, based on the availability of food consumption data, were found: the present results should further be validated by future studies with suitable research design.

T13.5 Placental growth factor as a diagnostic for early onset pre-eclampsia and normotensive intrauterine growth restriction of placental origin

T13.6 – Table 2. Comparison table Normal Chronic hypertension Superimposed hypertension Pre-eclampsia Gestational hypertension Normal – P = 0.377 P = 0.031 P< 0.0001 P = 0.002 Chronic hypertension P = 0.377 – P = 0.107 P = 0.003 P = 0.021 Superimposed hypertension P = 0.031 P = 0.107 – P = 0.218 P = 0.673 Pre-eclampsia P< 0.0001 P = 0.003 P = 0.218 – P = 0.201 Gestational hypertension P = 0.002 P = 0.021 P = 0.673 P = 0.201 – sensitivity and specificity increased to 100% and 92%, respectively. Combined, a positive PlGF test was able to diagnosis early onset pre-eclampsia or nIUGR with 94% sensitivity and 93% specificity. Conclusion: This evidence suggests that PlGF can be used to confirm diagnosis of early onset pre-eclampsia and identify nIUGR of placental origin from mimics. Funding: Biosite, CIHR, MSFHR, CFRI T13.6 Urinary placental growth factor differentiates the hypertensive disorders of pregnancy Neil Campbell1, Robert Ogle1, Annemarie Hennessy2, Charlene Thornton1. 1Royal Prince Alfred Hospital, Sydney, Australia; 2University of Western Sydney and Heart Research Institute, Australia Objective: The objective of this study is to establish whether urinary placental growth factor (uPlGF) is capable of discriminating between the different types of hypertensive disease in pregnancy in the third trimester. Design: This is a prospective descriptive case control study. Setting: Royal Prince Alfred Hospital, Urban tertiary referral hospital in Sydney, Australia. The Canterbury Hospital, district general hospital, Sydney, Australia Patients: Women in the third trimester of pregnancy who were currently inpatients on the antenatal ward or patients attending the antenatal outpatients department. Interventions: Patients in the third trimester of pregnancy were selected from the above settings, reviewed for eligibility and demographic data extracted. Patients were then asked to provide a urine specimen some of which was analysed for protein and creatinine and the rest stored and then later analysed for urine PlGF level. These levels after correction for creatinine concentration were then used in the final analysis. Measurements & main results: We have identified 36 women in the hypertensive group (preeclampsia (n=15), Gestational hypertension (n=13), Chronic hypertension (n=8), Preeclampsia superimposed on chronic hypertension (n=5)) and 47 women in the normal control group. There is a statistically significant difference in PlGF levels between the preeclamptic group and the normotensive controls (P<0.0001) and also between the gestational hypertensive group and the normotensive group (P=0.002) Distributions of the preeclamptic group and gestational hypertensive group taken as a whole when compared to the chronic hypertensive group and preeclampsia superimposed on chronic hypertension group also taken as a whole showed a significant difference as well (P=0.007). Table 1. Group characteristics

Prenatal exposure to phthalate esters and PAHs and birth outcomes

The purpose of this study was to investigate the relationship between the levels of prenatal exposure to phthalate ester and PAHs and birth outcomes among 149 Japanese pregnant women. Urinary concentrations of 9 phthalate ester metabolites, mono methyl phthalate (MMP), mono ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), mono-iso-nonyl phthalate (MINP) and mono-n-octyl phthalate (MnOP) and PAHs metabolite (1-hydroxypyrene, 1-OHP) were analyzed in spot urine samples collected from pregnant women. Correlation analysis and multiple regression analysis were conducted between the concentrations of maternal urinary metabolites and birth outcomes such as birth weight, birth length, head circumference and gestational age. Creatinine-corrected concentration (geometric mean; µg/g cre) was 9.14 (MMP), 9.76 (MEP), 51.6 (MnBP), 5.62 (MBzP), 5.45 (MEHP), 10.6 (MEHHP), 11.3 (MEOHP), 0.031 (MINP), 0.025 (MnOP) and 0.121 (1-OHP). These concentrations are comparable with literature value. The relationships between prenatal exposure to phthalate esters and birth outcomes were not significant. Statistically significant negative correlation was observed between 1-OHP and birth weight, birth length and head circumstances although the correlation was insignificant when only non-smokers were included in multiple regression analysis. In conclusion, we found that prenatal exposure to phthalate esters or PAHs did not affect birth outcomes at the exposure level of the present subjects.

Stability and Reproducibility of a Single-Sample Urinary C-Peptide/Creatinine Ratio and Its Correlation with 24-h Urinary C-Peptide

C-peptide measurement in blood or 24-h urine samples provides useful information regarding endogenous insulin secretion, but problems related to the rapid degradation of C-peptide in blood and difficulty of 24-h urine collection have limited widespread routine clinical use of this test. We assessed the feasibility of measuring urinary C-peptide (UCP) with correction for creatinine concentration in single urine samples. We analyzed UCP using a routine electrochemiluminescence immunoassay in samples from 21 healthy volunteers. We investigated the stability of UCP with different preservatives and storage conditions and compared the reproducibility of urinary C-peptide/creatinine ratio (UCPCR) in first- and second-void fasting urines, then assessed correlations with 24-h collections. UCPCR was unchanged at room temperature for 24 h and at 4 degrees C for 72 h even in the absence of preservative. UCPCR collected in boric acid was stable at room temperature for 72 h. UCPCR remained stable after 7 freeze-thaw cycles but decreased with freezer storage time and dropped to 82%-84% of baseline by 90 days at -20 degrees C. Second-void fasting UCPCRs were lower than first-void (median 0.78 vs 1.31, P = 0.0003) and showed less variation (CV 33% vs 52%), as second-void UCPCRs were not influenced by evening food-related insulin secretion. Second-void fasting UCPCR was highly correlated with 24-h UCP (r = 0.8, P = 0.00006). Second-void fasting UCPCR is a reproducible measure that correlates well with 24-h UCP in normal samples. The 3-day stability of UCPCR at room temperature greatly increases its potential clinical utility.

Comparative evaluation of biomarkers of occupational exposure to toluene

This study was initiated to make comparative evaluation of five proposed urinary markers of occupational exposure to toluene, i.e., benzyl alcohol, benzylmercapturic acid, omicron-cresol, hippuric acid and un-metabolized toluene. In practice, six plants in Japan were surveyed, and 122 Japanese workers (mostly printers; all men) together with 12 occupationally nonexposed control subjects (to be called controls; all men) agreed to participate in the study. Surveys were conducted in the second half of working weeks. Time-weighted average exposure (about 8 h) to toluene and other solvents were monitored by diffusive sampling. End-of-shift urine samples were collected and analyzed for the five markers by the methods previously described; simultaneous determination of omicron-cresol was possible by the method originally developed for benzyl alcohol analysis. The toluene concentration in the six plants was such that the grand geometric mean (GM) for the 122 cases was 10.4 ppm with the maximum of 121 ppm. Other solvents coexposed included ethyl acetate (26 ppm as GM), methyl ethyl ketone (26 ppm), butyl acetate (1 ppm) and xylenes (1 ppm). By simple regression analysis, hippuric acid correlated most closely with toluene in air (r = 0.85 for non-corrected observed values) followed by un-metabolized toluene (r = 0.83) and o-cresol (r = 0.81). In a plant where toluene in air was low (i.e., 2 ppm as GM), however, un-metabolized toluene and benzylmercapturic acid in urine showed better correlation with air-borne toluene (r = 0.79 and 0.61, respectively) than hippuric acid (r = 0.12) or o-cresol (r = 0.17). Benzyl alcohol tended to increase only when toluene exposure was intense. Correction for creatinine concentration or specific gravity of urine did not improve the correlation in any case. Multiple regression analysis showed that solvents other than toluene did not affect the levels of omicron-cresol, hippuric acid or un-metabolized toluene. Levels of benzylmercapturic acid and un-metabolized toluene were below the limits of detection [limit of detections (LODs); 0.2 and 2 microg/l, respectively] in the urine from the control subjects. In over-all evaluation, hippuric acid, followed by un-metabolized toluene and omicron-cresol, is the marker of choice for occupational toluene exposure. When toluene exposure level is low (e.g., 2 ppm), un-metabolized toluene and benzylmercapturic acid in urine may be better indicators. Detection of un-metabolized toluene or benzylmercapturic acid in urine at the levels in excess of the LODs may be taken as a positive evidence of toluene exposure, because their levels in urine from the controls are below the LODs. The value of benzyl alcohol as an exposure marker should be limited.