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Background: Zearalenone (ZEN), a secondary metabolite of Fusarium fungi, is one of the most common mycotoxins in global food supplies such as cereal grains and processed food. ZEN and its metabolites are commonly referred to as mycoestrogens, due to their ability to directly bind nuclear estrogen receptors α (ER-α) and β (ER-β). Zeranol, a synthetic mycoestrogen, is administered to U.S. cattle as a growth promoter. Despite widespread human exposure and ample evidence of adverse reproductive impacts in vitro and in vivo, there has been little epidemiological research on the health impacts of ZEN exposure during pregnancy. The objective of our study was to examine associations between ZEN and gestational weight gain (GWG)., Methods: Urine samples were collected in each trimester from pregnant participants in the UPSIDE cohort (n = 286, Rochester, NY, USA). High performance liquid chromatography and high-resolution tandem mass spectrometry were used to quantify concentrations of ZEN as well as ∑mycoestrogens (composite sum of ZEN metabolites; ng/ml). Maternal weights at clinical visits were abstracted from medical records. We fitted longitudinal models of specific-gravity adjusted, log-transformed ZEN and ∑mycoestrogens in relation to total GWG (kilograms) and GWG rate (kilograms/week). We additionally examined risk of excessive GWG (in relation to Institute of Medicine guidelines) and considered effect modification by fetal sex., Results: ZEN and ∑mycoestrogens were detected in > 93% and > 95% of samples, respectively. Mycoestrogen concentrations were positively associated with total GWG (ZEN β:0.50 kg; 95%CI: 0.13, 0.87) and GWG rate (ZEN β:0.20 kg/week; 95%CI: 0.01, 0.03). Associations tended to be stronger among participants carrying male (versus female) fetuses and results were robust to adjustment for diet., Conclusions: Mycoestrogen exposure during pregnancy may contribute to greater GWG. Future research is needed to understand potential influences on downstream maternal and offspring health., Competing Interests: Declarations. Ethics approval and consent to participate: This manuscript utilizes data collected from the ongoing prospective Understanding Pregnancy Signals in Development (UPSIDE) birth cohort. Institutional Review Boards (IRB) at the University of Rochester (IRB approval #: 58456, approval date: August 27, 2015) and Rutgers University (IRB approval #: Pro20160001514; January 27, 2017) approved all study activities. Participatns consent was obtained prior to participation in study activities. Consent for publication: Not applicable. Competing interests: OW is currently an employee of Exponent, Inc., which provides scientific consulting to the food and beverage industry and reports no conflict of interest. At the time of the data collection and analyses, OW was a student at University of Rochester. Other authors declare no conflicting interests., (© 2024. The Author(s).)

Although preclinical research has revealed disrupting effects on male reproductive functions of bisphenol A (BPA), as yet clinical studies have led to inconsistent results. The present meta‑analysis aims to establish the existence and the extent of the association between BPA exposure and semen quality. A thorough search of PubMed, Scopus and Web of Science databases was carried out. Only studies reporting data from multivariable linear regression analyses (β-coefficients with 95% CI), assessing the association between urinary levels of BPA and standard semen parameters were included. Nine studies provided information about an overall sample of 2,399 men. Only the negative association between urinary BPA levels and sperm motility reached statistical significance (pooled β-coefficient = -0.82; 95% CI: -1.51 to -0.12, p = 0.02; P for heterogeneity  = 0.1, I 2  = 42.9%). Yet, such a significance was lost after data adjustment for publication bias, as well as at the sensitivity analysis, when each of the two studies that contributed most to the overall estimate was excluded. In conclusion, the overall estimates of data produced by clinical studies point to a clinically negligible, if any, association between urinary BPA concentrations and semen quality. Further studies in workers at high risk of occupational exposure are warranted to corroborate the herein revealed weak correlation with a worse sperm motility., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Research Question: Do bisphenol A (BPA) levels in maternal urine, serum and follicular fluid affect embryo quality and intracytoplasmic sperm hinjection (ICSI) cycle outcomes in women with unexplained infertility?, Design: Prospective study conducted between 1 April 2019 and 30 September 2019. The study cohort consisted of 82 women aged between 23 and 33 years who underwent intracytoplasmic sperm injection owing to unexplained infertility and provided urine, blood and follicular fluid samples on the day of oocyte retrieval. Consumption of drinking water from plastic carboys or bottles at home were considered as chronic BPA exposure. Demographic features and IVF outcomes of the patients were collected., Results: Among the 82 women with unexplained infertility, clinical pregnancy was achieved in 22 (26.8%) patients after the IVF and embryo transfer cycle. The patients who consumed tap water had statistically significantly lower BPA values in three body fluids compared with patients who consumed plastic bottled water (all P < 0.001). Women who had grade 1 embryos transferred had lower serum BPA values than women who had grade 2 embryos transferred (10.8 ± 5.2 versus 26.9 ± 22 ng/ml, P = 0.003). Serum and follicular fluid BPA levels were statistically significantly higher in women who failed to achieve clinical pregnancy (P < 0.001, P = 0.006, respectively) and obtain a live birth (both P = 0.007)., Conclusions: A negative relationship was found between serum and follicular fluid BPA levels and embryo quality, clinical pregnancy and live birth in these women. In addition, the BPA levels of women who consume tap water at home were lower than those who use plastic bottled water., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Bisphenols (BPs) are commonly known plastifiers that are widely used in industry. The knowledge about the impact of BPs on thyroid function is scarce. Proper thyroid functioning is especially important for women of reproductive age, as hypothyroidism affects fertility, pregnancy outcomes and the offspring. There are no studies analyzing the influence of BPs on thyroid function and volume in non-pregnant young women. The aim of this cross-sectional study was to evaluate the relationship between bisphenol A and its 10 analogs (BPS, BPC, BPE, BPF, BPG, BPM, BPP, BPZ, BPFL, and BPBP) on thyroid function and volume in women of reproductive age. Inclusion criteria were: female sex, age 18-40 years. Exclusion criteria were history of any thyroid disease, pharmacotherapy influencing thyroid function, pregnancy or puerperium, and diagnosis of autoimmune thyroid disease during this study. Venous blood was drawn for measurement of thyrotropin (TSH), free thyroxine, thyroid peroxidase antibodies, thyroglobulin antibodies, BPs. Urine samples were analyzed for: ioduria and BPs. Ultrasound examination of thyroid gland was performed. One hundred eighty participants were included into the study. A negative correlation was found between urine BPC and the thyroid volume (R = -0.258; p = 0.0005). Patients with detected urine BPC presented smaller thyroid glands than those with not-detected urine BPC (p = 0.0008). A positive correlation was found between TSH and urine BPC (R = 0.228; p = 0.002). Patients with detected urine BPC presented higher concentrations of TSH versus those with not-detected urine BPC (p = 0.003). There were no relationships between any of serum BPs as well as the other urine BPs and thyroid function and its volume. The only BP that demonstrated the relationship between thyroid function and its volume was BPC, probably because of its chemical structure that most resembles thyroxine. Exposure to this BP may result in the development of hypothyroidism that could have a negative impact on pregnancy and the offspring., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Milczarek-Banach, Rachoń, Bednarczuk, Myśliwiec-Czajka, Wasik and Miśkiewicz.)

Ultra-processed food consumption has been associated with several health outcomes such as obesity, hypertension, cardiovascular disease and cancer. The deleterious nutrient profile of these products, and the presence of food additives, neoformed contaminants and contact materials such as phthalates and bisphenol may be some of the potential pathways through which ultra-processed food influences disease outcomes. The aim of this study was to examine the association between dietary contribution of ultra-processed foods and urinary biomarker concentrations of parent compounds or their metabolites including Di(2-ethylhexyl) phthalate (ΣDEHP), Di-isononyl phthalate (ΣDiNP), Monocarboxynonyl phthalate (mCNP), Mono (3-carboxypropyl) phthalate (mCPP), Monobenzyl phthalate (mBzP), Bisphenol A (BPA), Bisphenol F (BPF) and Bisphenol S (BPS), in the US. Participants from the cross-sectional 2009-2016 National Health and Nutrition Examination Survey, aged 6+ years, with urinary measures and with one 24-hour dietary recall were included in the study. Ultra-processed foods were identified based on the NOVA classification system, a four-group food classification based on the extent and purpose of industrial food processing. Linear regression was used to compare average urinary creatinine-standardized concentrations across quintiles of energy contribution of ultra-processed foods. Models incorporated survey sample weights and were adjusted for different sociodemographic and life-style variables. Adjusted geometric means of ΣDiNP, mCNP, mCPP, mBzP and BPF increased monotonically from the lowest to the highest quintile of ultra-processed food consumption. As both phthalates/bisphenol and ultra-processed foods have been previously associated with insulin resistance, diabetes, general/abdominal obesity and hypertension, our results suggest the possibility of contact materials in ultra-processed foods as one link between ultra-processed food and these health outcomes. Future studies could confirm findings and further explore these mechanisms of action., Competing Interests: The authors have declared that no competing interests exist.

Background: This meta-analytic study explored the relationship between the risk of type 2 diabetes mellitus (T2DM) and bisphenol A concentrations., Methods: The Embase and Medline (PubMed) databases were searched, using relevant keywords, for studies published between 1980 and 2018. A total of 16 studies, twelve cross-sectional, two case-control and one prospective, were included in the meta-analysis. The odds ratio (OR) and its 95% confidence interval (CI) were determined across the sixteen studies. The OR and its 95% CI of diabetes associated with bisphenol A were estimated using both fixed-effects and random-effects models., Results: A total of 41,320 subjects were included. Fourteen of the sixteen studies included in the analysis provided measurements of urine bisphenol A levels and two study provided serum bisphenol A levels. Bisphenol A concentrations in human bio-specimens showed positive associations with T2DM risk (OR 1.28, 95% CI 1.14, 1.44). A sensitivity analysis indicated that urine bisphenol A concentrations were positively associated with T2DM risk (OR 1.20, 95% CI 1.09, 1.31)., Conclusions: This meta-analysis indicated that Bisphenol A exposure is positively associated with T2DM risk in humans.

Biomarker-based strategies to assess human exposure to mycotoxins have gained increased acceptance in recent years. In this study, an improved method based on UPLC-MS/MS following 96-well μElution solid-phase extraction was developed and validated for the sensitive and high-throughput determination of zearalenone (ZEN) and its five metabolites α-zearalenol (α-ZEL), β-zearalenol (β-ZEL), α-zearalanol (α-ZAL), β-zearalanol (β-ZAL), and zearalanone (ZAN) in human urine samples, using 13 C-ZEN as an internal standard for accurate quantification. Two plates of samples (n = 192) could be processed within 2 h, and baseline separation of all the analytes was achieved in a total runtime of 6 min. The proposed method allowed ZEN and its metabolites to be sensitively determined in a high-throughput way for the first time, and with significantly improved efficiency and accuracy with respect to existing methods. The limits of detection (LODs) and limits of quantitation (LOQs) ranged from 0.02 to 0.06 ng mL -1 and from 0.05 to 0.2 ng mL -1 , respectively. The recoveries for the spiked samples were from 87.9 to 100%, with relative standard deviations (RSDs) of less than 7%. 301 urine samples collected from healthy volunteers aged 0-84 years in China were analyzed with and without enzyme hydrolysis to determine total and free ZEN biomarkers, respectively. ZEN, ZAN, α-ZEL, and β-ZEL were detected in 71.4% of the samples at levels of 0.02-3.7 ng mL -1 after enzyme hydrolysis. The estimated mean probable daily intake (PDI) was much lower than the tolerable daily intake (TDI). Adolescents had higher exposure than children, adults, and the elderly. Graphical abstract ᅟ.

In this work, Ru(bpy) 3 2+ encapsulated in metal-organic frameworks (MOFs) UiO-67 (Ru(bpy) 3 2+ /UiO-67) as luminophor was easily prepared and firstly applied in constructing an electrochemiluminescence (ECL) immunosensor to efficiently estimate diethylstilbestrol (DES). The competitive method-based ECL immunosensor platform was fabricated by amino-silicon dioxide which possesses large surface area. The poriness of UiO-67 was splendid so that Ru(bpy) 3 2+ could be easily encapsulated. Ru(bpy) 3 2+ /UiO-67 with excellent ECL luminescence signal existed large specific surface area for easily labeled with antibodies. DES competed with bovine serum albumin-diethylstilbestrol (BSA-DES) for binding to antibody-specific sites in the constructed immunosensor. However DES was micromolecule, which was easier to bond to antibodies than BSA-DES. The ECL signal was gradually decreases with the increase of the concentration of DES. Under optimal conditions, the proposed immunosensor exhibited a wide linear range from 0.01 pg mL -1 to 50 ng mL -1 with a low detetion limit of 3.27 fg mL -1 (S/N = 3). The novel fabricated immunosensor with interference immunity and high stability may cause an attractive approach for the other targets determination., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Mycotoxins may affect animal health, including reproduction. Little is known about the clinical relevance of exposure of horses to contaminated feed. This study aimed at (i) monitoring the levels of the mycotoxins zearalenone (ZEN), with its metabolites α- and β-zearalenol (α- and β-ZOL), and sterigmatocystin (STC) in urine samples from thoroughbred mares in Japan and (ii) relating these findings to the potential effects on reproductive efficacy of breeding mares. Sixty-three urine samples of breeding mares from 59 breeding farms were used. Urine samples and reproductive records were collected from each mare when it was presented to the stallion station. Urinary concentrations of ZEN, α- and β-ZOL, and STC were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). ZEN, α- and β-ZOL were measurable in the urine of all examined mares, indicating the prevalence of ZEN in equine feeds. In seven of the 63 samples, STC was also detected at levels ranging from 1.3 to 18.0 pg/mg creatinine. No significant correlation between the concentrations of mycotoxins and pregnancy status was observed. In conclusion, measurement of mycotoxins in urine samples is a useful non-invasive method for monitoring the systemic exposure of mares to multiple mycotoxins., (© 2017 Blackwell Verlag GmbH.)

Background: Reports on the secular trend of pubertal onset indicate a recent earlier start especially in girls. Bisphenol A (BPA), which posses estrogenic activity, might be a cause of advanced puberty. The objective of the study was to determine the association between BPA and advanced puberty., Methods: A cross-sectional study was conducted in patients with advanced puberty (n=41) compared to age-matched controls (n=47). Anthropometric measurements, estradiol, basal and gonadotropin releasing hormone (GnRH)-stimulated follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels, uterine sizes, ovarian diameters and bone ages were obtained. Urinary BPA concentrations were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MSMS) with the lower limit of quantification (LLOQ) of 0.05 ng/mL., Results: The median adjust-BPA concentration in advanced puberty group was higher than in control groups [1.44 vs. 0.59 μg/g creatinine (Cr): p<0.05]. We also found that the median adjust-BPA concentration in girls with advanced puberty who were overweight/obese, was greater than in the normal pubertal overweight/obese girls (1.74 vs. 0.59 μg/g Cr: p<0.05), and was in the same trend among normal weight girls with advanced and normal puberty (0.83 vs. 0.49 μg/g Cr: p=0.09), but not statistically significant., Conclusions: The present findings suggest that BPA exposure appears to be related to an earlier age at onset of puberty especially in obese girls.

Introduction Estrogen inhibits lactation and bisphenol A (BPA) is a high production environmental estrogen. We hypothesize an inhibitory effect of BPA on lactation and aim to analyze the association between third trimester pregnancy urinary BPA and breastfeeding rates 1 month postpartum. Methods Odds ratios (OR) and 95 % confidence intervals (95 % CI) of breastfeeding and perceived insufficient milk supply (PIM) in relation to maternal peripartum urinary BPA concentrations were calculated in 216 mothers. Results 97.2 % of mothers in the lowest BPA tertile were breastfeeding at 1 month postpartum, compared to 89.9 % in highest (p = 0.01). Adjusted ORs (95 % CI) for not breastfeeding at 1 month were 1.9 (0.3, 10.7) and 4.3 (0.8, 21.6) for second and third BPA tertiles, respectively, compared to the lowest (p = 0.06, trend). 4.2 % reported PIM in the lowest BPA tertile, compared to 8.7 % in the highest (p = 0.03). Adjusted ORs (95 % CI) for PIM were 1.8 (0.4, 7.7) and 2.2 (0.5, 9.5), for the second and third BPA tertiles, respectively, compared to the lowest (p = 0.29, trend). Discussion These results suggest an association between maternal BPA exposure and decreased breastfeeding., Competing Interests: The authors declare that they have no conflict of interest.

Despite its very low oral bioavailability and rapid elimination, multiple reports of unexpectedly high bisphenol A (BPA) concentrations in the serum of pregnant mothers or cord blood have raised questions about BPA exposures during pregnancy. Thirty healthy pregnant women recruited to the study were evaluated for total BPA exposure over a 30-h period comprising one-half day in the field and one day in a clinical setting. BPA and its metabolites were measured in serum and total BPA was measured in matching urine samples. The mean total exposure was similar to the 50(th) percentile of exposure for U.S. women and pregnant women in a large North American cohort. Twenty volunteers had total daily exposures equal to or exceeding the U.S. mean, and six volunteers had exposures exceeding the 75th percentile. Women working as cashiers did not have higher total BPA exposure. BPA was detected in some serum samples (0.25-0.51 ng/ml), but showed no relationship to total BPA in corresponding urine samples, no relationship to total BPA exposure, and had unconjugated BPA fractions of 60-80%, consistent with established criteria for sample contamination. We conclude that typical exposures of North American pregnant women produce internal exposures to BPA in the picomolar range., (Copyright © 2016. Published by Elsevier Ltd.)

Aim: To explore the effect of phenolic environmental estrogens (EE) on women with uterine leiomyoma (UL)., Methods: Urine and blood plasma samples were collected from 300 patients diagnosed with UL at the Affiliated Zhongda Hospital of Southeast University between December 2013 and December 2014. Control urine and blood plasma samples were collected from 300 women who are either patients without UL or healthy volunteers presenting to the same hospital for physical examination during the same period. Bisphenol A (BPA), nonylphenol (NP) and octylphenol (OP) concentration in these samples was measured using solid phase extraction (SPE) coupled with liquid chromatography-tandem mass spectrometry., Results: The OP concentration in urine and blood plasma was significantly higher in the UL group compared with the control group (r = 0.224, P = 0.001). Urine BPA concentration was not significantly different between the UL group and the control group (r = 0.009, P = 0.896). There was also no statistically significant difference in urine NP concentration between the two groups (r = 0.057, P = 0.419). On logistic regression, exposure concentration of urine BPA (OR, 1.129; 95%CI: 1.081-1.179) and NP (OR, 1.165; 95%CI: 1.025-1.324) was associated with UL genesis (P < 0.05). Nevertheless, there was no significant difference in blood plasma concentration of BPA, OP and NP between the two groups (P > 0.05)., Conclusion: Urine and blood plasma EE exposure levels in women, especially the urine level, was related to the incidence of UL., (© 2016 Japan Society of Obstetrics and Gynecology.)

Study Question: Are urinary BPA concentrations associated with in vitro fertilization (IVF) outcomes among women attending an academic fertility center?, Summary Answer: Urinary BPA concentrations were not associated with adverse reproductive and pregnancy outcomes among women from a fertility clinic., What Is Known Already: Bisphenol A (BPA), an endocrine disruptor, is detected in the urine of most Americans. Although animal studies have demonstrated that BPA reduces female fertility through effects on the ovarian follicle and uterus, data from human populations are scarce and equivocal., Study Design, Size and Duration: This prospective cohort study between 2004 and 2012 at the Massachusetts General Hospital Fertility Center included 256 women (n = 375 IVF cycles) who provided up to two urine samples prior to oocyte retrieval (total N = 673)., Participants/materials, Settings, Methods: Study participants were women enrolled in the Environment and Reproductive Health (EARTH) Study. Intermediate and clinical end-points of IVF treatments were abstracted from electronic medical records. We used generalized linear mixed models with random intercepts to evaluate the association between urinary BPA concentrations and IVF outcomes adjusted by age, race, body mass index, smoking status and infertility diagnosis., Main Results and the Role of Chance: The specific gravity-adjusted geometric mean of BPA was 1.87 µg/l, which is comparable to that for female participants in the National Health and Nutrition Examination Survey, 2011-2012. Urinary BPA concentrations were not associated with endometrial wall thickness, peak estradiol levels, proportion of high quality embryos or fertilization rates. Furthermore, there were no associations between urinary BPA concentrations and implantation, clinical pregnancy or live birth rates per initiated cycle or per embryo transfer. Although we did not find any associations between urinary BPA concentrations and IVF outcomes, the relation between BPA and endometrial wall thickness was modified by age. Younger women (<37 years old) had thicker endometrial thickness across increasing quartiles of urinary BPA concentrations, while older women (≥37 years old) had thinner endometrial thickness across increasing quartiles of urinary BPA concentrations., Limitations, Reasons for Caution: Limitations to this study include a possible misclassification of BPA exposure and difficulties in extrapolating the findings to the general population., Wider Implications of the Findings: Data on the relation between urinary BPA concentrations and reproductive outcomes remain scarce and additional research is needed to clarify its role in human reproduction., Study Funding/competing Interests: This work was supported by NIH grants R01ES022955, R01ES009718 and R01ES000002 from the National Institute of Environmental Health Sciences (NIEHS) and grant T32DK00770316 from the National Institute of Child Health and Human Development (NICHD). None of the authors has any conflicts of interest to declare. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Zearalenone (ZON) is a non-steroidal estrogenic mycotoxin produced by Fusarium species. The exposure risk to humans and animals is the consumption of contaminated food and animal feeds. It has been reported that ZON and some of its metabolites promote the development of hormone-dependent tumors. The aim of this case-control study was to estimate exposure to ZON and its five metabolites (α-zearalenol [α-ZOL], β-zearalenol [β-ZOL], α-zearalanol [zeranol, α-ZAL], β-zearalanol [teranol, β-ZAL] and zearalanone [ZAN]) by measuring urinary concentrations of these compounds, and to evaluate the risk of breast cancer related to this exposure. Chemical analyses were carried out by liquid-liquid extraction (LLE) and ultra-high performance liquid chromatography with tandem mass spectrometry detection (UHPLC-MS/MS). Statistical analyses were performed in order to determine the association between exposure to these compounds and the development of breast cancer. Crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by unconditional logistic regression to estimate the magnitude of the associations. The obtained results (adjusted OR=1.54, 95% CI=1.10-2.77) suggest a potential role of α-ZAL in the risk of developing breast cancer., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Identification of maternal environmental factors influencing preterm birth risks is important to understand the reasons for the increase in prematurity since 1990. Here, we utilized a health survey, the US National Health and Nutrition Examination Survey (NHANES) to search for personal environmental factors associated with preterm birth. 201 urine and blood markers of environmental factors, such as allergens, pollutants, and nutrients were assayed in mothers (range of N: 49-724) who answered questions about any children born preterm (delivery <37 weeks). We screened each of the 201 factors for association with any child born preterm adjusting by age, race/ethnicity, education, and household income. We attempted to verify the top finding, urinary bisphenol A, in an independent study of pregnant women attending Lucile Packard Children's Hospital. We conclude that the association between maternal urinary levels of bisphenol A and preterm birth should be evaluated in a larger epidemiological investigation., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Precocious puberty (PP) refers to the appearance of physical and hormonal signs of pubertal development at an abnormally early age. Urinary steroid signatures obtained from 42 patients with central PP and 40 patients with peripheral PP were assessed to compare metabolic changes. Levels of androgens such as testosterone, androstenedione, androstenediol, 16α-hydroxy-dehydroepiandrosterone, and 5α-androstenedione tended to be high in both PP groups, and the level of 17β-estradiol was higher in the central-PP group (P<0.01) than in the peripheral-PP and 32 age-matched healthy girls. Altered steroid metabolism was also associated with urinary BPA levels, and levels of testosterone, 17β-estradiol, and pregnenolone were significantly increased among individuals with high BPA levels. In particular, a correlation was observed between estrogen metabolism and BPA levels irrespective of the type of PP. These findings suggest that in girls, BPA exposure causes metabolic changes in steroidogenesis, but not the early onset of PP., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Bisphenol A (BPA) is used primarily in the production of polycarbonate plastics and epoxy resins. Widespread exposure to BPA has created a great deal of concern regarding its potential adverse effects on human health. This study examined the relationship between prenatal BPA exposure and birth outcomes, including birth weight, birth length, and ponderal index considering gender difference. A multi-center birth cohort study, Mothers and Children's Environmental Health (MOCEH) has been established in Korea since 2006. Study subjects are 757 pregnant women from the original cohort, who had their urinary BPA level measured during the third trimester, as well as information on birth outcome, prior medical history, psychosocial status, health behavior, environmental exposure as well as socio-demographic characteristics. Regression analysis was performed to assess the effect of BPA on birth outcome. The geometric mean concentration of BPA in pregnant women was 1.29 μg/L (1.87 μg/g creatinine) during late pregnancy. Urinary BPA concentrations were shown to be higher in women with a higher income level. Univariate regression analysis revealed a significant association between BPA levels and birth weight. In adjusted analysis, the second tertile of maternal BPA exposure exhibited an increase in birth weight, relative to the first tertile (p=0.04). These relationships were more pronounced in male neonates. Also, prenatal exposure to BPA was associated with an increase of ponderal index in total, and especially female neonates. This study shows that the association of prenatal exposure to BPA with anthropometric measures, such as birth weight and birth length, differed by gender. Further study is required to more fully elaborate this relationship between prenatal BPA exposure and birth outcome., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

Objective: To evaluate whether urinary bisphenol A (BPA) levels in men adversely influence semen quality and embryo development after medically assisted reproduction., Design: Prospective, cohort study., Setting: University-based tertiary care center., Patient(s): A total of 149 couples undergoing their first or second IVF or intracytoplasmic sperm injection (ICSI) procedure., Intervention(s): None., Main Outcome Measure(s): Semen quality and embryo development parameters until the blastocyst stage after the IVF or ICSI procedure., Result(s): Bisphenol A was detected in 98% (n = 146) of the samples with 0.1 ng/mL limit of detection. The geometric mean BPA concentration was 1.55 ng/mL. After the adjustment for potential confounders using linear regression models, an increase of natural logarithm transformed urinary BPA concentration was associated with lower natural logarithm transformed sperm count (β = -0.241, 95% confidence interval [CI] -0.470 to -0.012), natural logarithm transformed sperm concentration (β = -0.219, 95% CI -0.436 to -0.003), and sperm vitality (β = -2.660, 95% CI -4.991 to -0.329). The embryo development parameters from oocyte fertilization to the blastocyst formation stage were not affected by BPA exposure., Conclusion(s): Urinary BPA concentrations in male partners of subfertile couples may influence semen quality parameters, but do not affect embryo development up to the blastocyst stage after medically assisted reproduction., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the effect of phenolic environmental estrogens on uterine leiomyoma from the perspective of clinical epidemiology., Methods: Urine and blood samples were collected from Han women with uterine leiomyoma and women without uterine leiomyoma, living in Nanjing, China, between September 2011 and February 2013. A total of 156 urine samples and 214 blood samples were collected from the uterine leiomyoma group and 106 urine samples and 126 blood plasma samples from the control group. Bisphenol A (BPA), nonylphenol (NP) and octylphenol (OP) concentrations were determined by solid-phase extraction (SPE) coupled with liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)., Results: Phenolic environmental estrogens in the uterine leiomyoma and control groups were compared based on: gravida>3 and gravida ≤ 3. In participants with gravida>3, urine OP concentration was significantly (P<0.05) higher in the uterine leiomyoma group than in the control group. In participants with gravida ≤ 3, urine NP concentration was significantly (P<0.05) higher in the uterine leiomyoma group compared to controls. Despite obstetric history, urine BPA mean exposure concentration was significantly (P<0.05) different between uterine leiomyoma group and control group. The urine BPA concentration was not significantly (P>0.05) different between gravida>3 and gravida ≤ 3 patients. There was no significant (P>0.05) difference in plasma concentrations of BPA, OP and NP between the leiomyoma group and control group. Mean exposure concentration and range of distribution of BPA, OP and NP plasma concentration differed between the uterine leiomyoma and control group., Conclusion: Exposure level of phenolic environmental estrogens in human was related with leiomyoma tumorigenesis.

A method was established for the determination of three phenolic environmental estrogens, namely bisphenol A (BPA), nonylphenol (NP) and octylphenol (OP), in urine from women of uterine leiomyoma group (n=49) and control group (n=29), by using solid-phase extraction (SPE) coupled with liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Urine samples were spiked with 2,4,6-tribromophenyl-terminated tetrabromobisphenol-A carbonate oligomer (TBBPA) and nonylphenol D8 (NP-D8) as internal standard (I.S.) and de-conjugated by adding β-glucuronidase and sulfatase before the SPE. The extraction recoveries of BPA, NP and OP were more than 73.3%; the standard curve was linear over the validated concentrations in the range of 1.0-100.0ng/mL and the limits of detection (LOD) of BPA, NP and OP were 0.32ng/mL, 0.18ng/mL and 0.15ng/mL, respectively. Moreover, by analysing quality control urine samples in 5 days, the results showed that the method was precise and accurate, for the intra- and inter-day CV% within 15.2%. Except that OP was not found (3). NP levels were significantly higher in uterine leiomyoma patients than control group in low gravidity subgroup. Though BPA levels in experimental and control groups were not significantly different, the mean levels and concentration distribution were different. The study suggested that there is certain relationship between exposure concentrations of phenolic environmental estrogens and uterine leiomyoma disease., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Bisphenol A (BPA), a chemical widely used in the manufacture of polycarbonate plastics, has raised considerable concern in recent decades because of its hormone-like properties. Whether BPA exposure is a health risk remains controversial in many countries. A metabolomics study based on capillary electrophoresis time-of-flight mass spectrometry (CE-TOF/MS) was performed to study the urine metabolic profiles of Sprague-Dawley rats fed with four dose levels of BPA (0, 1, 10, and 100 μg/kg body weight) for 45 days. Multivariate pattern recognition directly reflected the metabolic perturbations caused by BPA. On the basis of univariate analysis, 42 metabolites including amino acids, polyamines, nucleosides, organic acids, carbohydrates, pterins, polyphenols, and sugar phosphates were found as the most significantly differential metabolites. The marked perturbations were related with valine, leucine and isoleucine biosynthesis, D-glutamine and D-glutamate metabolism, etc. Significant alterations of neurotransmitters (glutamate, gamma-aminobutyric acid, and noradrenaline) and neurotransmitter-related metabolites (tyrosine, histamine, valine, and taurine) suggested that the toxic effects of small-dose BPA (below 50 mg/kg/day) may contribute to its interactions with the neuromediating system. Our study demonstrated that metabolomics may offer more specific insights into the molecular changes underlying the physiological effects of BPA.

Background: Bisphenol A (BPA) is used widely to manufacture food container linings. Mouse models suggest exposure to BPA might increase allergic inflammation., Objectives: We hypothesized that BPA exposure, as assessed based on urinary BPA concentrations, would be associated with increased odds of wheeze and asthma and increased fraction of exhaled nitric oxide (Feno) values in children., Methods: The Columbia Center for Children's Environmental Health recruited pregnant women for a prospective birth cohort study (n = 568). Mothers during the third trimester and children at ages 3, 5, and 7 years provided spot urine samples. Total urinary BPA concentrations were measured by using online solid-phase extraction, high-performance liquid chromatography, isotope-dilution tandem mass spectrometry. Wheeze in the last 12 months was measured by using questionnaires at ages 5, 6, and 7 years. Asthma was determined by a physician once between ages 5 and 12 years. Feno values were measured at ages 7 to 11 years., Results: Prenatal urinary BPA concentrations were associated inversely with wheeze at age 5 years (odds ratio [OR], 0.7; 95% CI, 0.5-0.9; P = .02). Urinary BPA concentrations at age 3 years were associated positively with wheeze at ages 5 years (OR, 1.4; 95% CI, 1.1-1.8; P = .02) and 6 years (OR, 1.4; 95% CI, 1.0-1.9; P = .03). BPA concentrations at age 7 years were associated with wheeze at age 7 years (OR, 1.4; 95% CI, 1.0-1.9; P = .04) and Feno values (β = 0.1; 95% CI, 0.02-0.2; P = .02). BPA concentrations at ages 3, 5, and 7 years were associated with asthma (OR, 1.5 [95% CI, 1.1-2.0], P = .005; OR, 1.4 [95% CI, 1.0-1.9], P = .03; and OR, 1.5 [95% CI, 1.0-2.1], P = .04, respectively)., Conclusions: This is the first report of an association between postnatal urinary BPA concentrations and asthma in children., (Published by Mosby, Inc.)

Background: Bisphenol A (BPA) is an endocrine disruptor that in animal studies can bind to the thyroid hormone receptor and affect thyroid function. Relevant epidemiologic studies are limited and results are inconsistent. We explored the relationship between urinary BPA and thyroid function in a Chinese population., Methods: The study population included 3394 subjects age 40 years or older who were enrolled in a population-based study from Songnan Community, Baoshan District, Shanghai, China, from June through August 2009. We analyzed the association between urinary BPA and thyroid function using multivariate linear regression. Participants were further divided according to thyroid function status, and logistic regression was applied to determine the relationship between urinary BPA and thyroid function., Results: Each one-quartile increase in BPA was related to an increase of 0.068 pmol/l (95% confidence interval = 0.065- 0.071) in free triiodothyronine and a 0.084 μIU/ml decline (-0.099 to -0.069) in thyroid-stimulating hormone (TSH) in men. For women, there was a 0.10 pmol/l (0.09 to 0.11) increase in free triiodothyronine and a 0.13 μIU/ml decline (-0.14 to -0.11) in TSH. High urinary BPA level was associated with increased thyroid function (adjusted odds ratio= 1.71 [1.26 to 2.32])., Conclusions: Our results support previous reports of associations between BPA exposure and altered thyroid hormones in animal models and epidemiologic studies. Because our study is cross-sectional, no causal relationships can be established.

Objective: Bisphenol A (BPA) is being increasingly associated with adverse health effects. Our objective was to determine whether urinary BPA concentration is associated with allergic asthma in a representative US population., Methods: Data for this analysis were obtained from the National Health and Nutrition Examination Survey 2005-2006 survey and included asthma-related questions, total immunoglobulin E (IgE), 19 allergen-specific IgE levels, and urinary environmental phenol measurements. Allergic asthma was defined as a history of asthma ever, high eosinophil count, and high total IgE or atopy. Association analyses included dichotomous and polychotomous logistic regression, receiver operating characteristic curves, Akaike information criterion, and likelihood ratio χ(2)., Results: We found that 10-fold increase in BPA was independently associated with a higher likelihood of allergic asthma in females [odds ratio (OR) = 2.21, p = .032] but not in males (OR = 0.83, p = .474). These findings were reaffirmed when allergic asthma was defined based on atopy rather than total IgE (OR = 2.45, p = .001 in females and OR = 0.83, p = .605 in males). Urinary BPA was significantly associated with sensitization to various specific allergens in a dose-response manner. Lastly, urinary BPA independently predicted an asthma episode in the past 12 months in females but not in males., Conclusions: Urinary BPA is significantly associated with allergic asthma in females.

Benzophenone (BP)-type UV filters are widely used in a variety of personal care products for the protection of skin and hair from UV irradiation. Despite the estrogenic potencies of BP derivatives, few studies have examined the occurrence of these compounds in human matrices. Furthermore, associations among exposure to these compounds and estrogen-dependent diseases (such as endometriosis) have not been examined previously. In this study, we determined the concentrations of five BP derivatives, 2-hydroxy-4-methoxybenzophenone (2OH-4MeO-BP), 2,4-dihydroxybenzophenone (2,4OH-BP), 2,2'-dihydroxy-4-methoxybenzophenone (2,2'OH-4MeO-BP), 2,2',4,4'-tetrahydroxybenzophenone (2,2',4,4'OH-BP), and 4-hydroxybenzophenone (4OH-BP), in urine collected from 625 women in Utah and California, using liquid chromatography (LC)-tandem mass spectrometry (MS/MS). The association of urinary concentrations of BP derivatives with an increase in the odds of a diagnosis of endometriosis was examined in 600 women who underwent laparoscopy/laparotomy (n = 473: operative cohort) or pelvic magnetic resonance imaging (n = 127: population cohort), during 2007-2009. 2OH-4MeO-BP, 2,4OH-BP, and 4OH-BP respectively were detected in 99.0%, 93.3%, and 83.8% of the urine samples analyzed, whereas the detection rates for 2,2',4,4'OH-BP and 2,2'OH-4MeO-BP were below 6.0%. Significant regional differences (higher concentrations in California) and monthly variations (higher concentrations in July and August) were found for urinary concentrations of 2OH-4MeO-BP and 2,4OH-BP. In addition, urinary concentrations of 2OH-4MeO-BP and 2,4OH-BP tended to be higher in more affluent, older, and leaner women. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for the urinary concentrations of BP derivatives and the odds of an endometriosis diagnosis; ORs increased across quartiles of 2OH-4MeO-BP and 2,4OH-BP concentrations, but a significant trend was observed only between 2,4OH-BP and the odds of an endometriosis diagnosis in the operative cohort (OR = 1.19; 95% CI = 1.01, 1.41). When women in the highest quartile of 2,4OH-BP concentrations were compared with women in the first three quartiles, the OR increased considerably (OR = 1.65; 95% CI = 1.07, 2.53). Given that 2,4OH-BP possesses an estrogenic activity higher than that of 2OH-4MeO-BP, our results invite the speculation that exposure to elevated 2,4OH-BP levels may be associated with endometriosis.

Background: Exposure to endocrine active compounds, including bisphenol A (BPA), remains poorly characterized in developing countries despite the fact that behavioral practices related to westernization have the potential to influence exposure. BPA is a high production volume chemical that has been associated with metabolic dysfunction as well as behavioral and developmental effects in people, including children. In this pilot study, we evaluate BPA exposure and assess likely pathways of exposure among girls from urban and rural Egypt., Methods: We measured urinary concentrations of total (free plus conjugated) species of BPA in spot samples in urban (N = 30) and rural (N = 30) Egyptian girls, and compared these concentrations to preexisting data from age-matched American girls (N = 47) from the U.S. National Health and Nutrition Examination Survey (NHANES). We also collected anthropometric and questionnaire data regarding food storage behaviors to assess potential routes of exposure., Results: Urban and rural Egyptian girls exhibited similar concentrations of urinary total BPA, with median unadjusted values of 1.00 and 0.60 ng/mL, respectively. Concentrations of urinary BPA in this group of Egyptian girls (median unadjusted: 0.70 ng/mL) were significantly lower compared to age-matched American girls (median unadjusted: 2.60 ng/mL) according to NHANES 2009-2010 data. Reported storage of food in plastic containers was a significant predictor of increasing concentrations of urinary BPA., Conclusions: Despite the relatively low urinary BPA concentrations within this Egyptian cohort, the significant association between food storage behaviors and increasing urinary BPA concentration highlights the need to understand food and consumer product patterns that may be closing the gap between urban and rural lifestyles.

Aims: Bisphenol A (BPA)-based dental composites have commonly been used to fill dental cavities or seal pits and fissures on teeth. However, epidemiological evidence with regard to the BPA exposure from dental composites among children has rarely been reported. This study investigated whether there is a relationship between the BPA concentration in urine and the presence of composite restorations and sealants among South Korean children., Methods: Oral examinations and urine sample analyses were conducted on a total of 495 children aged 8-9 years. We classified the participants into four groups by the number of resin composites and sealant surfaces (0, 1-5, 6-10 and 11+)., Results: BPA concentrations in urine were higher in children with 11 or more surfaces restored with sealants and resin composites than in those with zero restored surfaces, although no difference was seen in the group with 1-10 surfaces. After adjusting for gender and age, the urinary BPA concentration in children with 11 or more resin composite surfaces was 2.67 μg/g creatinine, which was higher than the concentration found in those with no filling surfaces (P < 0.01)., Conclusions: Having many dental composite filling surfaces on teeth may increase the urinary BPA concentration in children., (© 2012 FDI World Dental Federation.)

Background: Bisphenol A (BPA) is a common chemical used in the manufacture of polycarbonate plastics and epoxy resins, with >93% of US adults having detectable BPA levels in urine. Recent animal studies have suggested that BPA exposure may have a role in several mechanisms involved in the development of hypertension, including weight gain, insulin resistance, thyroid dysfunction, endothelial dysfunction, and oxidative stress. However, no previous human study has examined the association between markers of BPA exposure and hypertension., Methods: We examined urinary BPA levels in 1380 subjects from the National Health and Nutritional Examination Survey 2003-2004. Main outcome-of-interest was hypertension, defined as blood pressure-reducing medication use and/or blood pressures >140/90 mm of Hg (n = 580)., Results: We observed a positive association between increasing levels of urinary BPA and hypertension independent of confounding factors such as age, gender, race/ethnicity, smoking, body mass index (BMI), diabetes mellitus and total serum cholesterol levels. Compared to tertile 1 (referent), the multivariate-adjusted odds ratio (95% confidence interval) of hypertension associated with tertile 3 was 1.50 (1.12-2.00); P-trend = 0.007. The association was consistently present in subgroup analyses by race/ethnicity, smoking status, BMI, and diabetes mellitus., Conclusions: Urinary BPA levels are associated with hypertension, independent of traditional risk factors.

Background: Despite extensive research and interest in endocrine disruptors, there are essentially no epidemiologic studies of estrogenic mycotoxins, such as zeranol and zearalenone (ZEA). ZEA mycoestrogens are present in grains and other plant foods through fungal contamination, and in animal products (e.g., meat, eggs, dairy products) through deliberate introduction of zeranol into livestock to enhance meat production, or by indirect contamination of animals through consumption of contaminated feedstuff. Zeranol is banned for use in animal husbandry in the European Union and other countries, but is still widely used in the US. Surprisingly, little is known about the health effects of these mycoestrogens, including their impact on puberty in girls, a period highly sensitive to estrogenic stimulation., Objectives and Methods: We conducted a cross-sectional analysis among 163 girls, aged 9 and 10 years, participating in the Jersey Girl Study to measure urinary mycoestrogens and their possible relationship to body size and development., Results: We found that mycoestrogens were detectable in urine in 78.5% of the girls, and that urinary levels were predominantly associated with beef and popcorn intake. Furthermore, girls with detectable urinary ZEA mycoestrogen levels tended to be shorter and less likely to have reached the onset of breast development., Conclusions: Our findings suggest that ZEA mycoestrogens may exert anti-estrogenic effects similar to those reported for isoflavones. To our knowledge, this was the first evaluation of urinary mycoestrogens and their potential health effects in healthy girls. However, our findings need replication in larger studies with more heterogeneous populations, using a longitudinal approach., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Zeranol ((7R,11S)-7,15,17-trihydroxy-11-methyl-12-oxabicyclo[12.4.0]octadeca-1(14),15,17-trien-13-one, also referred to as 7α-zearalanol, Ralone®, Frideron®, Ralgro®, etc.) is a semi-synthetic estrogenic veterinary drug with growth-promoting properties. Its use regarding animal husbandry has been prohibited in the European Union since 1981 and, due to its anabolic effects, it is further recognized as a banned substance in sport. Numerous studies were conducted concerning the identification of the illicit application of zeranol to domestic livestock. These studies also considered the natural occurrence of zeranol as a metabolite of the mycotoxin zearalenone and the issue of differentiating both scenarios, i.e. illegal use or unintended contamination. Human sports drug testing authorities are facing comparable challenges since the deliberate misuse of the (for human application non-approved) drug should be discriminated from adverse analytical findings resulting from the biotransformation of the mycotoxin zearalenone possibly ingested with contaminated food. The active drug (zeranol), its major human metabolites (zearalanone, 7β-zearalanol) and the mycotoxin (zearalenone) plus its major and unique metabolic products (α-zearalenol, β-zearalenol) have been monitored in routine doping controls by means of validated gas chromatography-(tandem) mass spectrometry (GC-(MS/)MS) methods since 1996, and between 2005 and 2010 four samples providing suspicious signals were detected. In agreement with literature data, in vitro metabolism studies demonstrated the metabolic pathway from zearalenone towards zeranol (and common metabolites). In contrast, an administration study urine sample (collected after oral application of 20 mg of zeranol) yielded only ultra-trace amounts of zearalenone and its characteristic metabolites, which supported the assumption that a mycotoxin contamination caused the finding of zeranol in the doping control specimens rather than a misuse of the anabolic agent., (Copyright © 2011 John Wiley & Sons, Ltd.)

By virtue of its binding to steroid hormone receptors, bisphenol A (BPA, the unconjugated bioactive monomer) is hypothesized to be estrogenic when present in sufficient quantities in the body, raising concerns that widespread exposure to BPA may impact human health. To better understand the internal exposure of adult humans to BPA and the relationship between the serum and urinary pharmacokinetics of BPA, a clinical exposure study was conducted. Blood and urine samples were collected approximately hourly over a 24-h period from 20 adult volunteers who ingested 100% of one of three specified meals comprising standard grocery store food items for breakfast, lunch, and dinner. The volunteers' average consumption of BPA, estimated from the urinary excretion of total BPA ((TOT)BPA = conjugated BPA + BPA), was 0.27 μg/kg body weight (range, 0.03-0.86), 21% greater than the 95th percentile of aggregate exposure in the adult U.S. population. A serum time course of (TOT)BPA was observable only in individuals with exposures 1.3-3.9 times higher than the 95th percentile of aggregate U.S. exposure. The (TOT)BPA urine concentration T(max) was 2.75 h (range, 0.75-5.75 h) post-meal, lagging the serum concentration T(max) by ∼1 h. Serum (TOT)BPA area under the curve per unit BPA exposure was between 21.5 and 79.0 nM•h•kg/μg BPA. Serum (TOT)BPA concentrations ranged from less than or equal to limit of detection (LOD, 1.3 nM) to 5.7 nM and were, on average, 42 times lower than urine concentrations. During these high dietary exposures, (TOT)BPA concentrations in serum were undetectable in 83% of the 320 samples collected and BPA concentrations were determined to be less than or equal to LOD in all samples.

Infants may be particularly sensitive regarding hormonally active compounds such as Bisphenol A (BPA), which is widely distributed and exhibits weak oestrogenic activity. Since only free (unconjugated) BPA exhibits endocrine activity, both free and total (after hydrolysis of conjugates) BPA were determined in urine samples of infants to support valid risk assessments. Free BPA was observed above the LOQ in only 3 of 91 (3%) samples from 47 infants. As total BPA was observed in only 38 (42%) urine samples, with concentrations between

The aims of the present study were to investigate the efficacy of measuring bovine urinary zearalenone (ZEN) concentrations by using a commercially available ELISA method in cattle kept under different feeding conditions to monitor the natural contamination of feeds at the farm level, and to investigate the effects of supplementation of a mycotoxin adsorbent (MA) product in the feed based on urinary ZEN concentration. First, Japanese Black cattle herds kept for breeding (4 herds) and fattening (4 herds) purposes were provided with similar feeding conditions. Then, urinary samples from 5 cows in each herd were collected and analyzed. Second, dairy cows from 1 herd fed with total mixed rations (TMR) were selected. After thorough mixing of the MA (40 g/d) with TMR, the supplemented TMR was fed according to the following schedule: with MA for 2 wk, without MA for 3 wk; then with MA for 2 wk and without MA for 6 wk. Urine samples were collected from cows (n = 6 to 7) and examined before and after each interval. Zearalenone concentrations were measured by the ELISA and liquid chromatography-tandem mass spectrometry methods. The concentration of ZEN and its metabolites was expressed after creatinine (Crea) correction [ZEN or metabolites (pg/mL)/Crea (mg/dL); pg/mg of Crea]. In the first experiment, the urinary concentrations of ZEN and its metabolites were variable in all herds, and significant differences were observed between herds. In 1 fattening herd, in particular, urinary ZEN concentrations were greater (P < 0.001) than in the other 3 herds. This might reflect significant natural ZEN contamination of the feed at the farm level. In Exp. 2, urinary ZEN concentrations displayed peculiar trends after supplementation with MA. After 2 wk of supplementation, a significant decrease of ZEN (P < 0.05) was observed. Zearalenone concentrations remained at a reduced amount during 3 wk without MA supplementation and 2 wk with MA supplementation. When MA was not added to the feed for the next 6 wk, the concentrations increased to the original quantity. These findings indicate the usefulness of measuring concentrations of urinary ZEN and its metabolites not only for monitoring the natural ZEN contamination of cattle feed at the farm level but also for in vivo evaluation of MA function after supplementing feeds with MA.

The presence of zeranol (alpha-zearalanol) in urine samples due to natural contamination or illegal treatment is under debate within the European Union. The simultaneous determination of zeranol, its epimer taleranol (beta-zearalanol), zearalanone and the structurally related mycotoxin zearalenone with the corresponding alpha- and beta-zearalenol metabolites appears to be critical in deciding whether an illegal use has occurred. The aim of this study is to develop and validate a simple analytical procedure applicable to bovine and swine urine samples for the determination of all six resorcylic acid lactones. After an enzymatic deconjugation, the urine was subjected to a one-step cleanup on a commercially available immunoaffinity chromatography cartridge. The analytes were detected by liquid chromatography-negative-ion electrospray tandem mass spectrometry using deuterium-labelled internal standards. The method was validated as a quantitative confirmatory method according to European Commission Decision 2002/657/EC. The evaluated parameters were: linearity, specificity, precision (repeatability and intra-laboratory reproducibility), recovery, decision limit, detection capability and ruggedness. The decision limits (CCalpha) obtained, were between 0.56 and 0.68 microgL(-1); recovery above 66% for all the analytes. Repeatability was between 1.4 and 5.3% and within-laboratory reproducibility between 1.9 and 16.1% for the six resorcylic acid lactones.

Objective: We previously demonstrated that exposure to polyvinyl chloride plastic medical devices containing di(2-ethylhexyl) phthalate (DEHP) was associated with higher urinary concentrations of several DEHP metabolites in 54 premature infants in two neonatal intensive care units than in the general population. For 42 of these infants, we evaluated urinary concentrations of several phenols, including bisphenol A (BPA), in association with the use of the same medical devices., Measurements: We measured the urinary concentrations of free and total (free plus conjugated) species of BPA, triclosan, benzophenone-3, methyl paraben, and propyl paraben., Results: The percentage of BPA present as its conjugated species was > 90% in more than three-quarters of the premature infants. Intensity of use of products containing DEHP was strongly associated with BPA total concentrations but not with any other phenol. Adjusting for institution and sex, BPA total concentrations among infants in the group of high use of DEHP-containing products were 8.75 times as high as among infants in the low use group (p < 0.0001). Similarly, after adjusting for sex and DEHP-containing product use category, BPA total concentrations among infants in Institution A were 16.6 times as high as those among infants in Institution B (p < 0.0001)., Conclusion: BPA geometric mean urinary concentration (30.3 microg/L) among premature infants undergoing intensive therapeutic medical interventions was one order of magnitude higher than that among the general population. Conjugated species were the primary urinary metabolites of BPA, suggesting that premature infants have some capacity to metabolize BPA. The differences in exposure to BPA by intensity of use of DEHP-containing medical products highlight the need for further studies to determine the specific source(s) of exposure to BPA.

Investigations into human exposure to bisphenol A (BPA) have, for the most part, assessed intake based on food consumption estimates combined with measurements or estimates of BPA in foods. In this study, nationally representative data on urinary levels of BPA in the United States (US) from the 2003-2004 National Health and Nutrition Examination Survey (NHANES) were used to estimate daily intake of BPA, assuming steady-state excretion. Distributions of intakes for the US population were determined for (i) all NHANES participants with urinary BPA data; (ii) participants by the following age groups: 6-11 years, 12-19 years, 20-39 years, 40-59 years, and 60+ years; and (iii) participants by gender. On the basis of the NHANES urinary BPA data and the assumptions described in this paper, daily BPA intakes for male participants are statistically significantly higher than for female participants, and there are statistically significant differences in daily BPA intakes according to age groups, with the oldest group having the lowest estimated intakes. Median intake was approximately three orders of magnitude below health-based guidance values of 50 microg/kg-day.

Bisphenol A (BPA) is widely distributed and exhibits weak estrogenic activity. In contrast to BPA, the corresponding glucuronide metabolite is not estrogenic. Therefore, free and total BPA were determined in human urine samples to assess the significance of free BPA for risk assessment. In only 10% of 474 samples from 287 subjects was free BPA detected in a range from

Twelve derivatives of benzophenone (BP1-BP12) are widely used as UV-screens to protect industrial products from light induced damage. There is growing public concern about industrially produced chemicals that might interfere with hormonal signalling pathways, thus having potential adverse effects on human health. The derivative 2,2',4,4'-tetrahydroxybenzophenone (BP2) which is used in cosmetic products and in packaging materials, was previously shown to be an estrogenic endocrine active chemical (EAC). While the metabolisation of BP3 has been analyzed in vivo, according to our knowledge little is known about the pharmacokinetics of BP2. Therefore we performed a dose-response experiment with 5 dosages of BP2 which was applied per gavage to adult ovariectomised (ovx) rats for 5 days. Serum samples were analyzed via HPLC. Metabolites were further identified by Helix pomatia glucuronidase treatment and subsequent ion-trap-mass spectrometry. Additionally we analyzed the time dependent metabolisation and excretion of BP2 in a kinetic study. The parent compound BP2 is metabolised to glucuronide - and sulfate-conjugates. In the serum maximum levels of BP2, BP2-glucuronide and BP2-sulfate were observed already 30 min after BP2 application while highest concentrations of BP2 and its metabolites in urine were measured 120 min after treatment. It is suggested that this biotransformation occurs via a first-pass effect in the gut wall or the liver. Despite this rapid metabolisation and excretion, the amount of unconjugated BP2 was sufficient to induce a dose dependent estrogenic effect in the uterotrophic assay.

Background: Bisphenol A (BPA) and 4-tertiary-octylphenol (tOP) are industrial chemicals used in the manufacture of polycarbonate plastics and epoxy resins (BPA) and nonionic surfactants (tOP). These products are in widespread use in the United States., Objectives: We aimed to assess exposure to BPA and tOP in the U.S. general population., Methods: We measured the total (free plus conjugated) urinary concentrations of BPA and tOP in 2,517 participants > or = 6 years of age in the 2003-2004 National Health and Nutrition Examination Survey using automated solid-phase extraction coupled to isotope dilution-high-performance liquid chromatography-tandem mass spectrometry., Results: BPA and tOP were detected in 92.6% and 57.4% of the persons, respectively. Least square geometric mean (LSGM) concentrations of BPA were significantly lower in Mexican Americans than in non-Hispanic blacks (p = 0.006) and non-Hispanic whites (p = 0.007); LSGM concentrations for non-Hispanic blacks and non-Hispanic whites were not statistically different (p = 0.21). Females had statistically higher BPA LSGM concentrations than males (p = 0.043). Children had higher concentrations than adolescents (p < 0.001), who in turn had higher concentrations than adults (p = 0.003). LSGM concentrations were lowest for participants in the high household income category (> $45,000/year)., Conclusions: Urine concentrations of total BPA differed by race/ethnicity, age, sex, and household income. These first U.S. population representative concentration data for urinary BPA and tOP should help guide public health research priorities, including studies of exposure pathways, potential health effects, and risk assessment.

Eleven pregnant sows with a body weight between 153 and 197 kg were fed a control diet (CON, 0.15 mg DON and 0.0035 mg ZON/kg diet) or a diet containing 15% of Fusarium toxin contaminated triticale (MYCO, 4.42 mg DON and 0.048 mg ZON/kg diet) in the period of day 35 and 70 of gestation. The indirect effect of feed intake was separated from the direct effects of the Fusarium toxins by the restricted feeding regimen where all sows were fed the same amount of feed (2000 g/d) over the whole study. At the end of experiment, fetuses were delivered by Caesarian section and samples of serum, bile, urine, liver, kidney and spleen of euthanatized sows and fetuses were taken to analyze the concentrations of DON, ZON and their metabolites. Feeding the Fusarium toxin contaminated diet to pregnant sows caused neither adverse effects on performance, organ weights and maintenance of pregnancy of sows nor on fetus weight and length. Furthermore, no teratogenic or embryolethal effects could be observed in the MYCO group. Hematological and clinical-chemical parameters of sows and fetuses were not affected by feeding, with the exception of significantly lower GLDH (glutamate dehydrogenase) serum activities in MYCO sows. The carry over of DON and ZON from the diet to the sow or fetus tissues was calculated by the diet ratio (sum of concentrations of all metabolites in the physiological specimen divided by the dietary toxin concentration), while the fetus ratio was evaluated by the sum of concentrations of all metabolites in the physiological specimen of the fetus divided by that of the sows. DON and deepoxy-DON were found in urine, bile, serum, liver, kidney and spleen of sows of the MYCO group, but not in the bile of fetuses (spleen not analyzed). ZON and its metabolite alpha-zearalenol (alpha-ZOL) were detected in urine and bile of sows, while all specimens of fetuses as well as serum and liver of sows were negative for ZON metabolites. The maximum diet ratios for urine and bile in sows of the MYCO group were 0.84 and 0.05 for DON metabolites and 1.2 and 3.8 for ZON metabolites, underscoring the differences in metabolism and excretion of both toxins. The maximum diet ratio of DON and deepoxy-DON into liver, kidney and spleen of MYCO sows were 0.003, 0.007 and 0.003, respectively. The maximum fetus ratio of DON and deepoxy-DON into urine, bile, serum, liver and kidney of fetuses were 0.006, 0, 0.5, 0.88, and 0.33, while the maximum placental ratio (sum of toxin concentrations in the physiological specimen of the fetus divided by the toxin serum concentration of the sow) were 0.64, 0, 0.50, 0.70 and 0.52, respectively. Therefore, it can be concluded that the developing fetus is exposed to DON between the gestation days 35 and 70 when the sows are fed a Fusarium toxin contaminated diet. ZON concentration in the MYCO diet was too low to get reliable results for fetus or placental ratios.

In veal calf production plant-based proteins are frequently included in milk replacer fed to the animals. Since soy products, which are mostly used, are known for their high levels of phyto-oestrogens, the effects of these feeds on the veal calf prostate were examined. Goal was to determine whether these compounds could interfere with histological screening for oestrogenic growth promoters. In a feeding experiment, four groups of veal calves fed plant-based protein-supplemented milk replacer (PBM), containing 5% soy concentrate, 5% soy isolate, 5% wheat gluten and 2% potato protein, for 4 weeks were compared to animals fed dairy-based control feed (DBM); animals treated with estradiol benzoate, diethylstilbestrol and ethinylestradiol served as positive controls. Daidzein and genistein levels measured in feed and urine showed high levels of genistein and daidzein in the soy isolate and soy concentrate supplemented feeds. Genistein and daidzein were also found in the urine of the animals that were fed these feeds. Haematoxylin-eosin-stained prostate sections of PBM-fed animals showed slight hyperplasia and some dilated tubules as compared to the DBM-fed group, but no metaplasia, which is used for screening for oestrogenic hormones. The positive controls showed extensive squamous metaplasia. Immunohistochemical staining for cytokeratin 5 (using RCK 103 monoclonal antibody) in basal cells showed a normal staining pattern of basal cells in the DBM-fed calves and extensive basal cell proliferation and squamous metaplasia in the oestrogen-treated positive control animals. PBM-fed calves showed no increase of basal cell staining but showed elongations of the basal cells in most animals, sometimes resulting in circular figures. It is concluded that the feeds examined in this study did not interfere with histological screening for oestrogens in male veal calves.

Bisphenol A (BPA) is a weak estrogen. Pharmacokinetic studies of BPA have demonstrated a rapid and extensive metabolism of BPA to the nonestrogenic BPA-monoglucuronide (BPA-gluc). Some investigators have reported that BPA was found at parts per billion concentrations in the tissues or urine of humans without known exposure to BPA. This work developed a rapid and sensitive method for the determination of BPA and BPA-gluc in plasma and urine based on liquid chromatography-tandem mass spectrometry. The liquid chromatography-electrospray ionization-tandem mass spectrometry method for quantitation of BPA and BPA-gluc uses stable isotope-labeled internal standards. A linear ion trap mass spectrometer permits identification and quantitation of BPA-gluc and BPA without sample workup. Development of separation conditions reduced the BPA-background in solvent samples to below 2.5 pmol/ml for BPA. Limit of quantitation (LOQ) for BPA in control urine was 15 pmol/ml; LOQ for BPA-gluc was 65 pmol/ml. Application of the method to urine samples from human subjects (n = 6) after administration of 25 microg of BPA/person (estimated maximum human daily intake) permitted the determination of excretion kinetics for BPA-gluc; BPA was below the LOD in all except two of the samples. In urine or blood samples of human subjects (n = 19) without intentional exposure to BPA, BPA concentrations were always below the limit of detection ( approximately 2.5 pmol/ml) with or without prior glucuronidase treatment. The results show that care is required for analysis of BPA and its major metabolite BPA-gluc. The LOD obtained and the absence of detectable levels of BPA in samples from individuals suggests that general exposure of humans to BPA is much lower than the worst-case exposure scenario developed.

The fate of a single bolus of the Fusarium mycotoxin zearalenone (ZON) given intravenously to pigs was followed up. Pigs were equipped with duodenal re-entrant cannulas, post-valvular T-shape cannulas and with a urinary bladder balloon catheter. The animals were divided into three groups. Pigs of the control group were injected with ZON (Co), and pigs of the second group were also injected with ZON but their duodenal digesta was quantitatively exchanged for 12 h with corresponding pigs of the third group, not injected with ZON. Therefore, the second group had a disrupted entero-hepatic cycling of ZON (DEHC) and the third one had an induced entero-hepatic cycling of ZON (IEHC). The kinetic profile of ZON and its metabolites in plasma and their flow with urine, duodenal and ileal digesta and with faeces was examined over the next 72 h after the bolus was given. Eleven days later, pigs were slaughtered for collection of bile, urine and liver to analyse ZON residues. In all specimens examined, alpha-zearalenol (ZOL) was detected as the only metabolite of ZON. Kinetic evaluation of the plasma data revealed that the terminal elimination half-life of ZON was reduced from 2.63 h in pigs of Co-group to 1.1 h when EHC of ZON was disrupted for 12 h (DEHC-group). The maximum ZON concentration in plasma of pigs with the IEHC was found at 2.73 h after the bolus was given to their counterparts. The percentage of the alpha-ZOL- and ZON-area under the curves (AUC) estimated for the IEHC-group amounted to approximately 18% of the corresponding AUC of the Co-group which would suggest that a substantial proportion of both substances are re-cycled via entero-hepatic re-circulation. Cumulative recovery of ZON and alpha-ZOL, expressed as percentage of the ZON-bolus was characterized by a saturation kinetics in urine and duodenal digesta, and after 72 h, the respective values for Co-, DEH-, and IEHC-groups were 70%, 55% and 12%; and 35%, 22% and 11%. Faecal excretion started to increase steeply after 48 h and still continued to increase after 72 h when the cumulative excretion was 6%, 3% and 2% for Co-, DEHC- and IEHC-groups respectively. Fourteen days after the bolus injection, ZON and alpha-ZOL concentrations in bile, liver and urine were lower than the detection limits of the applied method. The results would suggest that within this period of time a massive single bolus of ZON is nearly completely eliminated from the body.

There is currently little information concerning the prevalence of zeranol and taleranol in animal urine following metabolism of the naturally occurring Fusarium spp. toxins. An epidemiological study is described which involves four European Union control laboratories in which 8008 urine samples were screened for the presence of zeranol using a time-resolved fluoroimmunoassay (TR-FIA). Of these samples, 93.6% screened negative for zeranol. All samples testing positive for zeranol were then analysed with a confirmatory method. Based on the confirmatory results, the TR-FIA-positive samples were then categorized as false-positive, true-positive or 'equivocal' (zeranol/taleranol and the Fusarium spp. toxins detected). The true-positive samples represented only 0.05% of the total number of samples (n = 4). After statistical analysis, 170 of 174 equivocal samples proved to belong to a 'normal' population in which the amount of zeranol/taleranol could be related to the total amount of Fusarium spp. toxins through a linear regression with a 99% prediction interval. This suggested that the presence of zeranol in these samples might be due to in vivo metabolism of the Fusarium spp. toxins. The presence of zeranol in the four remaining 'outliers' might be attributable to zeranol abuse rather than to natural contamination. The results are of interest for control laboratories as they might provide an analytical tool to help distinguish between abuse and natural contamination in zeranol testing.