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... Several recent studies have found measurable urinary levels of various alternative bisphenols in different study populations (Liao et al., 2012a;Hoffman et al., 2018;Lehmler et al., 2018;Sakhi et al., 2018). However, data on European human exposure levels to these chemicals are limited, particularly in young people, who might be exposed in different ways and to a different extent than adults (Lehmler et al., 2018;Rocha et al., 2018;Frederiksen et al., 2020). It is suspected that endocrine disrupting chemicals could be more harmful during developmental phases such as puberty, so it is necessary to study exposure in such populations (Vandenberg et al., 2009(Vandenberg et al., , 2010Frye et al., 2012). ...
... Although BPA was not the most frequently detected compound in our study population, it was still the predominant bisphenol in terms of measured concentrations. In all studies, BPA was detected with a high frequency, illustrating that it is still used extensively worldwide Lehmler et al., 2018;Rocha et al., 2018;Health Canada, 2019). The detection frequencies and levels of BPF and BPS, however, were more variable and depending on the country, the sampling period and the LOQ of the applied analytical method. ...
... Median levels of both compounds were considerably higher in U.S.A. (Lehmler et al., 2018). On the other hand, BPF and BPS were only detected in respectively 9 and 23% of urine samples from Brazil and median concentrations were below the method LOQ, which could be (partially) explained by the higher LOQ for BPF (Rocha et al., 2018). Lower levels for BPA and BPS were measured in Chinese children, but the median concentration of BPF was higher than the median for our study population . ...
The broadly used industrial chemical bisphenol A (BPA), applied in numerous consumer products, has been under scrutiny in the past 20 years due to its widespread detection in humans and the environment and potential detrimental effects on human health. Following implemented restrictions and phase-out initiatives, BPA is replaced by alternative bisphenols, which have not received the same amount of research attention. As a part of the fourth cycle of the Flemish Environment and Health Study (FLEHS IV, 2016–2020), we monitored the internal exposure to six bisphenols in urine samples of 423 adolescents (14–15 years old) from Flanders, Belgium. All measured bisphenols were detected in the study population, with BPA and its alternatives bisphenol F (BPF) and bisphenol S (BPS) showing detection frequencies > 50%. The reference values show that exposure to these compounds is extensive. However, the urinary BPA level decreased significantly in Flemish adolescents compared to a previous cycle of the FLEHS (2008–2009). This suggests that the replacement of BPA with its analogues is ongoing. Concentrations of bisphenols measured in the Flemish adolescents were generally in the same order of magnitude compared to recent studies worldwide. Multiple regression models were used to identify determinants of exposure based on information on demographic and lifestyle characteristics of participants, acquired through questionnaires. Some significant determinants could be identified: sex, season, smoking behavior, educational level of the parents, recent consumption of certain foods and use of certain products were found to be significantly associated with levels of bisphenols. Preliminary risk assessment showed that none of the estimated daily intakes (EDIs) of BPA exceeded the tolerable daily intake, even in a high exposure scenario. For alternative bisphenols, no health-based guidance values are available, but in line with the measured urinary levels, their EDIs were lower than that of BPA. This study is, to the best of our knowledge, the first to determine internal exposure levels of other bisphenols than BPA in a European adolescent population.
... In vitro and animal studies have suggested that exposure to parabens (Nagar et al., 2020;Okamoto et al., 2008;Pérez Martín et al., 2010) resulted in increased oxidative damage. Moreover, paraben exposure at environmentally relevant levels is associated with elevated concentrations of oxidative damage biomarkers in human beings (Asimakopoulos et al., 2016b;Ferguson et al., 2019;Kang et al., 2013;Rocha et al., 2018;Watkins et al., 2015;Zhao et al., 2021). Children are more vulnerable to the hazards of chemical exposure (compared to adults) owing to their developing organs (WHO, 2011) and higher exposure doses per body weight (WHO, 2011). ...
... Children are more vulnerable to the hazards of chemical exposure (compared to adults) owing to their developing organs (WHO, 2011) and higher exposure doses per body weight (WHO, 2011). However, very few studies have examined the associations of oxidative damage biomarkers with paraben exposure in children from Brazil (Rocha et al., 2018) and South Korea (Kang et al., 2013). Moreover, only single spot urine samples were used in these studies, which could introduce misclassification bias if the exposure levels varied over time. ...
... Urinary concentrations of parabens (medians) were compared with previous reports to further understand paraben exposure in various regions (Table S4). Compared with other studies, the median urinary MeP concentrations in this study were comparable to that in children in Greece (Myridakis et al., 2015), although lower than those in Korea (Lim, 2020), Belgium (Dewalque et al., 2014), Spain (Casas et al., 2011), Brazil (Rocha et al., 2018), and the United States . ...
Previous studies implied that elevated exposure to parabens may result in increased oxidative stress. However, the association between exposure to paraben derivatives and oxidative stress biomarkers in children has been rarely studied. This study examined the associations between exposure to paraben derivatives and oxidative stress biomarkers in Chinese children. Nine parabens and their derivatives including methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP), butyl paraben (BuP), p-hydrox4ybenzoic acid (p-HB), 3,4-dihydroxy benzoic acid (3,4-DHB), benzoic acid, methyl 3,4-dihydroxybenzoate (rOH-MeP), and ethyl 3,4-dihydroxybenzoate (rOH-EtP) were detected in urine collected from 139 children from South and Central China. Additionally, 8-hydroxy-2′-deoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-OHG), and 4-hydroxy-2-nonenal mercapturic acid (HNE-MA) were measured as oxidative markers. All targeted compounds (except for BuP) were frequently detected in urine (detection frequencies ranged 80.8%–100%). The linear mixed model revealed that all target compounds (with detection frequencies >50%), except for EtP, were significantly associated with an increase in 8-OHdG. rOH-EtP was found to be significantly associated with 8-OHG (β = 0.12; 95% confidence interval [95% CI]: 0.08, 0.16) positively. In addition, PrP and benzoic acid were associated with elevated levels of HNE-MA. Weighted quantile sum regression revealed that co-exposure to the target compounds was positively associated with 8-OHdG (β = 0.17; 95% CI: 0.12, 0.22), 8-OHG (β = 0.14; 95% CI: 0.10, 0.18), and HNE-MA (β = 0.43; 95% CI: 0.27, 0.59); rOH-EtP and benzoic acid were the major contributors for the combined effects on oxidative stress of nucleic acids and lipid, respectively. Our findings provide new evidence for the effects of exposure to paraben derivatives on nucleic acid oxidative damage and lipid peroxidation in children.
... The presence of BPA in children's urine samples has already been reported in several countries [7,8], with average concentrations varying between 0.35 and 11 µg/mL. In Brazil, Rocha et al.  reported the first data on the presence of BPA in urine from Brazilian children. ...
... Maximum and minimum concentrations of BPA (creatinine-normalized) were 0.08 and 250.6 ng/mg. The results obtained in this study (for children from Ceilandia, Brazil), were slightly higher than those reported by Rocha et al. , who investigated BPA levels in urine samples from 300 children spread throughout the country. In this case, a nationwide arithmetic mean of 1.74 ng/mL was reported, whereas for creatinine-normalized, a value of 2.09 ng/mL was obtained. ...
... In this case, a nationwide arithmetic mean of 1.74 ng/mL was reported, whereas for creatinine-normalized, a value of 2.09 ng/mL was obtained. It is important to point out that, differently from the data reported by Rocha et al. , our results were all from the same city, being more representative for studies devoted to understand different aspects concerning the presence of BPA in urine, such as contaminant sources, possible adverse effects and behavioral issues. In the study carried out by Rocha et al. , only 31 samples were collected in the Midwest Region of Brazil, where the city of Ceilandia is located. ...
Human exposure to endocrine disrupting chemicals (EDCs) is broadly investigated due to possible adverse effects to human health. Bisphenol A (BPA) is a chemical of great concern due to its wide use in industrial products including canned food. Exposure during childhood is of special concern because the developing endocrine system is particularly sensitive to EDC. Therefore, there is an urgent need to asses degree of exposure and possible adverse effects. In this study, we validated a liquid-liquid microextraction method coupled to liquid chromatography (gradient elution)/tandem high-resolution mass spectrometry (HR-MRM acquisition) to assess BPA (free + deconjugated) in 343 urine samples from children attending public schools in Ceilandia (Federal District, Brazil). For quantification, matrix-matched calibration with internal standardization were used under a linear working range from 1.0 to 2000 ng/mL (R² = 0.998). Limits of quantification and detection of the method were 0.1 and 0.03 ng/mL, respectively. Matrix effect (96 ± 12%) was neglected by the use of deuterated BPA as surrogate, while minimal losses were depicted during the extraction (recovery of 86 ± 14%). Inter- and intra-day precision were below 11 and 12%, respectively. BPA was found in 89.5% of the investigated samples, with concentrations varying from 0.11 to 123 ng/mL. Average BPA (3.88 ng/L) was slightly higher than previous reports investigating Brazilian children, and close to data produced in countries with similar socio-economic indicators, such as India and China.
... Dietary intake is considered to be the major BPA exposure route for humans (Christensen et al., 2012;European Food Safety Authority, 2015;Gonzalez et al., 2020). The presence of BPA in various human matrices such as urine, serum, breast milk and saliva has been reported worldwide (Calafat et al., 2008;Covaci et al., 2015;Deceuninck et al., 2015;Dualde et al., 2019;Geens et al., 2014;Lehmler et al., 2018;Rocha et al., 2018). Multiple studies have found associations between higher BPA exposure and detrimental effects on reproduction, development and metabolic function (Rochester, 2013). ...
... Recently, a number of studies have found measurable levels of various bisphenols in humans, mostly in urine (Hoffman et al., 2018;Lehmler et al., 2018;Liao et al., 2012a;Sakhi et al., 2018). Nevertheless, data on exposure levels to these chemicals are scarce, particularly in children, who might be exposed in different ways and to a different extent than adults (Lehmler et al., 2018;Rocha et al., 2018). ...
... BPA and eight other bisphenols were measured and a higher detection frequency (98%) and higher median urinary concentration (1.66 ng/mL) were reported for BPA, compared to our study population. BPF and BPS showed substantially lower detection frequencies (9 and 23%, respectively) and median concentrations below the LOQ of the method (Rocha et al., 2018). BPF, BPS and other bisphenols were clearly detected more frequently in our Japanese school children, compared to the evaluated Brazilian children. ...
The widely used chemical bisphenol A (BPA), applied in various consumer products, has been under scrutiny in the past 20 years due to its widespread detection in humans and potential detrimental effects on human health. Following the implementation of restrictions and phase-out initiatives, BPA has been replaced by other structurally similar bisphenols, which have not yet received the same level of research attention. In this study, we aimed to 1) investigated the internal exposure to seven bisphenols in morning void urine samples (n = 396) from 7-year-old children from Hokkaido, Japan and 2) assess possible time trends in the concentrations of bisphenols between 2012 and 2017. Information on demographic, indoor environment and dietary characteristics of participants were acquired through a self-administered questionnaire. All bisphenols were detected in the study population, with BPA, BPF and BPS showing detection frequencies > 50%. Concentrations of bisphenols measured in the Japanese children in our study were generally lower compared to studies worldwide. We found that BPA concentrations decreased significantly over the study time period (average 6.5% per year), whereas BPS rose with 2.8% per year. Levels of BPA and BPF were higher in autumn compared to winter. Higher urinary BPF levels were significantly associated with higher concentrations of the oxidative stress biomarker, 8-hydroxy-2'-deoxyguanosine (8-OHdG). BPA and BPF levels were higher in children from families with lower household income. Bisphenol concentrations were significantly influenced by some other personal (e.g. household income), food intake (e.g. vegetables and cow milk) and indoor housing characteristics (e.g. flooring). This is the first study to report longitudinal time trends of bisphenols in Japan. The presented findings imply that further research on bisphenols is warranted in the future to monitor whether these time trends continue.
... The most widely used parabens are methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) (Wei et al., 2021). Adverse effects of parabens such as endocrine disruption (Boberg et al., 2010;Nowak et al., 2018;Parada et al., 2019) and oxidative stress (Asimakopoulos et al., 2016;Kang et al., 2013;Rocha et al., 2018;Wei et al., 2022) in humans have attracted global attention. ...
... Paraben derivatives were identified to be able to increase oxidative stress (Acquaviva et al., 2021;Ajiboye et al., 2017;Lodovici et al., 2001). Paraben derivatives in human urine have been documented by several studies (Rocha et al., 2018;Song et al., 2020;Wei et al., 2022;Yu et al., 2021;Zhang et al., 2020); however, exposure assessment of them among pregnant women (vulnerable) are very limited (Song et al., 2020). ...
... Previous studies have demonstrated the concentration profiles and variations of parabens in three trimesters (Ferguson et al., 2019;Li et al., 2019;Philippat et al., 2013;Shin et al., 2021;Yazdy et al., 2018;Zhao et al., 2017), two selected trimesters (Berger et al., 2018;Rolland et al., 2020;Warembourg et al., 2019), or other selected time windows (Meeker et al., 2013;Watkins et al., 2015) of pregnancy, whereas such data on their derivatives are not available. In addition, paraben derivatives were found to be more associated with oxidative stress biomarkers (OSBs) in human urine, compared with paraben parent compounds (Rocha et al., 2018;Wei et al., 2022). So far, several studies have underscored the correlations between paraben exposure and DNA oxidative stress and/or lipid peroxidation among pregnant women from the United States (Ferguson et al., 2019;Watkins et al., 2015) and Korea (Kang et al., 2013); however, paraben derivatives are not taken into account. ...
Exposure to parabens has been shown to increase oxidative stress, which has a vital impact on the development of numerous diseases. However, few studies reported the effects of the paraben derivatives on oxidative stress, particularly among pregnant women. This study, using repeated measurements, aimed to understand the exposure profiles of urinary paraben derivatives concentrations and their relationships with oxidative stress biomarkers (OSBs). A total of 861 pregnant women, who provided spot urine samples at three trimesters, were included, and 2583 urine samples were used to measure four paraben derivatives [p-hydroxybenzoic acid (p-HB), 3,4-dihydroxybenzoic acid (3,4-DHB), methyl protocatechuate, and ethyl protocatechuate], four parabens (methyl, ethyl, propyl, and butyl), and three OSBs [8-hydroxy-2′-deoxyguanosine (DNA), 8-hydroxyguanosine (RNA), and 4-hydroxy nonenal mercapturic acid (lipid)]. Pregnant women were extensively exposed to parabens and paraben derivatives with detection frequencies (DFs) of 86.1%–100%, except for butylparaben with a DF of 14.9%. p-HB and 3,4-DHB were the two major detected paraben derivatives with the highest concentrations (median: 1394 and 149 ng/mL, respectively). Low reproducibility in paraben derivatives was found across the three trimesters. Sampling season, pre-pregnancy body mass index, and infant sex were predictors of some paraben derivatives/parabens. Linear mixed model analyses showed that all target compounds (DF > 50%) were associated with an increase in all OSBs, where the percent change in OSBs with interquartile range increases in parabens ranged from 9.85% to 24.7%, while those caused by paraben derivatives ranged from 13.8% to 72.1%. Weighted quantile sum model showed that mixture exposure was significantly associated with increased OSBs, and paraben derivatives were stronger contributors to OSBs compared with parabens. Overall, urinary paraben derivatives were associated with increased oxidative stress of nucleic acids and lipid in pregnant women.
... They exhibit endocrine-disrupting properties and are associated to adverse health effects in humans such as obesity, thyroid related diseases, diabetes, and reproductive dysfunction among others (Joensen et al., 2018;Magueresse-Battistoni et al., 2017;Philips et al., 2020). BPs and BzPs have recently attracted increased scientific attention through biomonitoring studies published on humans, aquatic and marine ecosystems (Asimakopoulos et al., 2014(Asimakopoulos et al., , 2016bRocha et al., 2018;Romera-García et al., 2019;Vela-Soria et al., 2014;Yu and Wu, 2014). BPs are a class of chemicals with two phenolic functional groups in their structure, which include several analogues mainly used in the production of polycarbonate plastics and epoxy resins (Asimakopoulos et al., 2016a). ...
... In contrast to the raptor species studied here, the DRs of some BPs and BzPs analogues in human biological media, e.g., adipose tissue and urine, especially for BPA and BP-3, can reach up to 100% (Rocha et al., 2018;Wang et al., 2015). Nonetheless, the concentrations demonstrated similarities between raptors and humans on the order of magnitude. ...
... From the BPs class, BPF was found in an adipose tissue (6.24 ng/g w. w.) and a brain sample (2.48 ng/g w.w.) from the long-eared owls, BPB was found in a brain sample (1.69 ng/g w.w.) from the Eurasian sparrowhawks, while similarly to BPs, BzPs were not found in either adipose tissue or brain matrix. On the contrary, in human adipose tissue, BPA and BP-3 are documented in significant concentrations, similar to those found in human urine (that is established as the main excretory pathway), which could even reach the order of a few tens and thousands of nanograms per gram (ng/g), respectively (Rocha et al., 2018;Wang et al., 2015). This contradiction on the occurrence profile of the target analytes between humans and raptors suggests differences in contaminant metabolism, toxicokinetics and bioaccumulation potential between the species. ...
Environmental exposure to bisphenols and benzophenone UV filters has received considerable attention due to the ubiquitous occurrence of these contaminants in the environment and their potential adverse health effects. The occurrence of bisphenols and benzophenone UV filters is well established in human populations, but data is scarce for wildlife, and especially for raptors (birds of prey, falcons and owls). In this study, concentrations of eight bisphenols and five benzophenone UV filters were determined in six raptor tissues, including muscle, kidney, liver, brain, preen gland (uropygial gland) and adipose. The tissue samples (n = 44) were taken from dead raptor species (1997–2011), including Eurasian sparrowhawks (Accipiter nisus, n = 2) and long-eared owls (Asio otus, n = 2), both from France, and white-tailed eagles (Haliaeetus albicilla, n = 16) from Greenland. Overall, six bisphenols and four benzophenone UV filters were found in the samples. Bisphenol A (BPA), bisphenol F (BPF), benzophenone-8 (BzP-8) and 4-hydroxybenzophenone (4-OH-BzP) were the most abundant contaminants, accounting for median concentrations of 67.5, 3.01, 27.1 and 9.70 ng/g wet weight (w.w.), respectively. The potential role of the preen gland as a major excretory organ for bisphenols and benzophenone UV filters was suggested since the median sum concentration of the two contaminant classes in the white-tailed eagle tissues showed higher bioaccumulation potential in the preen gland (5.86 ng/g w.w.) than the liver (2.92) and kidney (0.71). The concentrations of these contaminants in the tissues of the three raptor species indicated a pattern of increasing detection rates and median concentrations with an increase of the species size and their expected trophic position. To the best of our knowledge, this is the first peer-reviewed study to document multiresidues of both contaminant classes in raptor tissues.
... Available data on exposure to BP analogues, however, are very limited, and only a few studies have focused on the detection of urinary levels of these bisphenols in infants and toddlers [8,28,38]. Indeed, only nine (i.e., BPA, BPAF, BPAP, BPB, BPF, BPM, BPP, BPS, and BPZ) of the most common BPs have previously been analyzed in urine obtained from adults and children [8,28,. The analysis of human urine is a preferred approach in monitoring total BP concentrations, as urinary excretion is the main route of BP elimination, independently of the exposure route [49,51]. ...
... This BP has been rarely analyzed in human biomonitoring studies. Rocha et al. found no detectable concentrations of BPM in 300 urinary samples from Brazilian school children aged 6 to 14 years collected in 2012-2013 . ...
Restrictions on the use of bisphenol A (BPA) in consumer products led to its replacement by various bisphenol (BP) analogues, yet young children's exposure to these analogues has been poorly characterized so far. This study aimed to characterize infants' and toddlers' exposure to BPA and 14 emerging BP analogues (i.e., bisphenol AF, bisphenol AP, bisphenol B, bisphenol BP, bisphenol C (BPC), bisphenol E, bisphenol F (BPF), bisphenol G, bisphenol M (BPM), bisphenol P, bisphenol PH, bisphenol S (BPS), bisphenol TMC, and bisphenol Z). We extracted infants' and toddlers' urine from diapers (n = 109) collected in Swiss daycare centers as a practical and noninvasive alternative approach to urinary biomonitoring. Bisphenols were present in 47% of the samples, with BPC and BPM being the most frequently detected (23% and 25% of all samples, respectively). The mean concentrations of urinary BPS and BPF were greater than that of BPA. This contrasts with data reported previously. Furthermore, statistical analysis revealed a significant and negative correlation between urinary BPM concentration and the population's age. Our results provide a first characterization of infants' and toddlers' exposure to bisphenols in Switzerland. This knowledge can be used to support ongoing biomonitoring studies and to prioritize exposure reduction and prevention strategies.
... In weanling rats, Riad et al. (2018) found that TCS caused testicular DNA damage, increase of malondialdehyde (MDA), and decrease of superoxide dismutase (SOD). In humans, exposure to TCS was associated with high levels of urinary 8-hydroxy-2 -deoxyguanosine (8-OHdG) in children from China (Lv et al., 2016) and from Brazil (Rocha et al., 2018). ...
... As mentioned above, both chemicals are widely used on daily life and there is enough data comprising their hazard to aquatic organisms; however, it still has a lack of information of their behavior in mammalian cells. Both compounds are lipophilic, and it seems to cause damage after phase I drug metabolization system, resulting in compounds with higher toxicity (for a comprehensive review, see Caldwell, 2012;Wu et al., 2019); moreover, previous human biomonitoring studies have detected the coexposure of TCS and DEHP (or their metabolites), in urine samples of children and adults, in several regions worldwide (Casas et al., 2011;Larsson et al., 2014;Braun et al., 2017;Rocha et al., 2017Rocha et al., , 2018Lim, 2020;Li et al., 2021). Therefore, assessing to possible combined effect of TCS and DEHP would provide further information about molecular effects of these toxicants, as well as their interactions, in the environment and/or in organisms (Arambula and Patisaul, 2018). ...
Triclosan (TCS) is an antimicrobial agent widely used in personal care products (PCP) and the di-(2-ethyl hydroxy-phthalate) (DEHP) is a chemical compound derived from phthalic acid, used in medical devices and plastic products with polyvinyl chloride (PVCs). As result of their extensive use, TCS and DEHP have been found in the environment and previous studies demonstrated the association between their exposure and toxic effects, mostly in aquatic organisms, but there is a shortage in the literature concerning the exposure of TCS and DEHP in human cells. The aim of the present study was to assess the impact of exposure to TCS and DEHP, as well as their combinations, on biomarkers related to acute toxicity and DNA instability, in HepG2 cells, by use of cytokinesis-block micronucleus cytome (CBMNCyt) assay. For that, the cultures were exposed to TCS, DEHP and combinations at doses of 0.10, 1.0, and 10 μM for the period of 4 h and the parameters related to DNA damage (i.e., frequencies of micronuclei (MN) and nuclear buds (NBUDs), to cell division (i.e., nuclear division index (NDI) and nuclear division cytotoxic index (NDCI) and to cell death (apoptotic and necrotic cells) were scored. Clear mutagenic effects were seen in cells treated with TCS, DEHP at doses of 1.0 and 10 μM, but no combined effects were observed when the cells were exposed to the combinations of TCS + DEHP. On the other hand, the combination of the toxicants significantly increased the frequencies of apoptotic and necrotic cells, as well as induced alterations of biomarkers related to cell viability (NDI and NDCI), when compared to the groups treated only with TCS or DEHP. Taken together, the results showed that TCS and DEHP are also able to induce acute toxicity and DNA damage in human cells.
... Hydroxyl radical is very active to cause DNA strand damage and DNA base modification by reaction at the C-8 position of guanine via hydroxylation, resulting in DNA Adduct 8-hydroxy-2'deoxyguanosine (8-OHdG) which is then excreted in body fluids (Fig. 1). The presence of 8-OHdG in body fluids such as blood and urine can function as a biomarker of ROS-induced DNA damage . ...
... Previous research has concluded that an exposure to BPA and MeP is strongly associated with oxidative stress which can produce 8-OHdG . According to the results of biomonitoring research, among bisphenol compound, BPA was the main compound that found in the samples, BPA was found in 98 % of the samples analyzed and MeP was detected in all analyzed samples (the sample analyzed was 300 school students in Brazil) . ...
Bisphenol A (BPA) is a chemical that is commonly applied in the manufacture of polycarbonate plastic and epoxy resins which are often used in food and beverage containers. Methylparaben (MeP) is commonly applied as food preservatives, products of personal cares, and medicines. This study was conducted to define the BPA and MeP effects on the formation of DNA-Adduct 8-Hydroxy-2’deoxyguanosine (8-OHdG) compounds. Analysis of 8-OHdG compounds was performed by applying a reverse-phase HPLC with a UV/Vis detector at the wavelength of 254nm. The optimum condition of HPLC was obtained with the mobile phase consisted of phosphate buffer solution and methanol at a ratio of 85:15 (v/v) and a flow rate of 1.2 mL/min. This research was conducted at pH 7.4 and temperature 37 °C with a variation of incubation time of 5 and 7 h. In this study, it was found that the presence of BPA and MeP in the mixtures produced an antagonistic effect to the formation of 8-OHdG compared to BPA and MeP in the separate reaction at the same condition of incubations.
... Even though children are more sensitive to environmental stressors such as EDCs than adults, studies on children's exposure to parabens are limited and have started to emerge only recently. For example, it has been shown that paraben exposure is associated with DNA damage in children (Kang et al., 2013;Rocha et al., 2018) and that paraben exposures may increase the risk of atopic asthma and aeroallergen sensitization (Quiros-Alcala et al., 2019;Spanier et al., 2014). Moreover, EtP might be associated with altered respiratory health (Vernet et al., 2017). ...
... According to a study which compared the urine paraben levels of elementary school students and kindergarten children, the levels of parabens were higher in older children, suggesting that older children are exposed to higher levels of parabens . Meanwhile, a study in Brazil measured urine concentrations of MeP and PrP in children of two age groups (6-10 and 11-14 years old) and two gender groups of female and male children, and found that higher contents of MeP and PrP occurred in older female children (Rocha et al., 2018). This can likely be explained by higher use of cosmetics, PCPs, and processed food containing parabens by older children. ...
Parabens are one of the most widely used preservatives in food, pharmaceuticals and personal care products (PCPs) because of their advantageous properties and low toxicity based on the early assessments. However, recent research indicates that parabens may act as endocrine-disrupting chemicals (EDCs) and thus, are considered as chemicals of emerging concern that have adverse human health effects. To provide the basis for future human health studies, we reviewed relevant literature, published between 2005-2020, regarding the levels of parabens in the consumer products (pharmaceuticals, PCPs and food), environmental matrices and humans, including susceptible populations, such as pregnant women and children. The analysis showed that paraben detection rates in consumer products, environmental compartments and human populations are high, while the levels vary greatly by country and paraben type. The concentrations of parabens reported in pregnant women (~20-120 μg/L) were an order of magnitude higher than in the general population. Paraben concentrations in food and pharmaceuticals were at the ng/g level, while the levels in PCPs reached mg/g levels. Environmental concentrations ranged from ng/L - μg/L in surface waters to tens of μg/g in wastewater and indoor dust. The levels of human exposure to parabens appear to be higher in the U.S. and EU countries than in China and India, which may change with the increasing production of parabens in the latter countries. The review provides context for future studies to connect paraben exposure levels with human health effects.
... Significantly higher IL-6 concentrations were associated with an IQR 8.95% increase in BPA A positive association between BPA (as BPA-G: r = 0.440, p < 0.05; as uBPA: r = 0.398, p = 0.054 (not significant)) and 3-NO2Tyr levels (but not 3-ClTyr and diTyr) was found in plasma from pregnant mothers. In cord blood, 3-NO2Tyr levels were higher (p < 0.10) when mothers belonged to the highest uBPA exposed half Positive associations between maternal BPA and 8-isoprostane levels (β = 4.5, p = 0.05), but no associations between BPA and 8-OHdG, HNE-MA or 8-NO2Gua levels [28,29]. BPA concentrations were inversely associated with maternal (β = −30.98, ...
... BPA was inversely associated with penis length (β = −4.43 mm, p = 0.005) among boys who were born to mothers high in 8-isoprostane  Huang 2017  and 2018  Cross-sectional within a pregnancy cohort (Taiwan) An inverse association between urinary BPA and serum bilirubin levels (β = −0.071, p < 0.0001) was found, whereas no association was found between serum BPA and serum bilirubin ...
Bisphenols, particularly bisphenol A (4,4′-(hexafluoroisopropylidene)-diphenol) (BPA), are suspected of inducing oxidative stress in humans, which may be associated with adverse health outcomes. We investigated the associations between exposure to bisphenols and biomarkers of oxidative stress in human studies over the last 12 years (2008‒2019) related to six health endpoints and evaluated their suitability as effect biomarkers. PubMed database searches identified 27 relevant articles that were used for data extraction. In all studies, BPA exposure was reported, whereas some studies also reported other bisphenols. More than a dozen different biomarkers were measured. The most frequently measured biomarkers were 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoprostane) and malondialdehyde (MDA), which almost always were positively associated with BPA. Methodological issues were reported for MDA, mainly the need to handle samples with caution to avoid artefact formation and its measurements using a chromatographic step to distinguish it from similar aldehydes, making some of the MDA results less reliable. Urinary 8-OHdG and 8-isoprostane can be considered the most reliable biomarkers of oxidative stress associated with BPA exposure. Although none of the biomarkers are considered BPA- or organ-specific, the biomarkers can be assessed repeatedly and non-invasively in urine and could help to understand causal relationships.
... Recent studies have shown an association 52 between female infertility and exposure to endocrine-disrupting chemicals (EDCs) 53 (Messerlian et al. 2016;Bloom et al. 2017;Wang et al. 2017a). Bisphenol A (BPA) is a 54 widespread EDC employed in the manufacture of plastics and epoxy resins used in 55 several consumer goods, such as polycarbonate water bottles, the inside lining of cans, 56 food packaging, toys and cash register receipts (Rocha et al. 2018). Studies in mice and 57 chimps have shown that BPA exposure adversely affects reproduction resulting in 58 aneuploidy and infertility (Hunt et al. 2003;Susiarjo et al. 2007), whereas in humans it is 59 associated with an increased risk of miscarriages, delayed menarche in girls and late 60 pubertal progression in boys ( Lawson et al. 2011;Hunt et al. 2012;Lathi et al. 2014;61 Shen et al. 2015;Wang et al. 2017b;Watkins et al. 2017). ...
... Rocha et al. 2018) and we observe that the antioxidant CoQ10 rescues many of467 the germline defects caused by BPA. Three genes were significantly upregulated 468 specifically in the germline of BPA-treated worms: hus-1, which encodes for a 469 checkpoint protein required for DNA damage-induced CEP-1/p53-dependent apoptosis 470 ...
Studies have shown an association between female infertility and exposure to endocrine-disrupting chemicals (EDCs), yet strategies for neutralizing such effects are lacking. Bisphenol A (BPA) is a prevalent EDC that affects...
Endocrine-disrupting chemicals are ubiquitously present in our environment, but the mechanisms by which they adversely affect human reproductive health and strategies to circumvent their effects remain largely unknown. Here, we show in Caenorhabditis elegans that supplementation with the antioxidant Coenzyme Q10 (CoQ10) rescues the reprotoxicity induced by the widely used plasticizer and endocrine disruptor bisphenol A (BPA), in part by neutralizing DNA damage resulting from oxidative stress. CoQ10 significantly reduces BPA-induced elevated levels of germ cell apoptosis, phosphorylated checkpoint kinase 1 (CHK-1), double-strand breaks (DSBs), and chromosome defects in diakinesis oocytes. BPA-induced oxidative stress, mitochondrial dysfunction, and increased gene expression of antioxidant enzymes in the germline are counteracted by CoQ10. Finally, CoQ10 treatment also reduced the levels of aneuploid embryos and BPA-induced defects observed in early embryonic divisions. We propose that CoQ10 may counteract BPA-induced reprotoxicity through the scavenging of reactive oxygen species and free radicals, and that this natural antioxidant could constitute a low-risk and low-cost strategy to attenuate the impact on fertility by BPA.
... The conversion of TCS to dichlorophenols is the cause of this contaminant in the urine of children and adolescents, and as a result, there is a significant relationship between the concentration levels of triclosan and dichlorophenols, indicating that triclosan is the main source of dichlorophenols. TCS and 2,4-DCP concentrations were 8.26 and 2.60 (µg/L), respectively, in research on Brazilian children done by Rocha et al., which is higher than the concentration reported in this study and might suggest reduced exposure of children and adolescents in Kerman, Iran, with products such as toothpaste, detergents, soaps, and personal care products are the primary sources of these pollutants (Rocha et al. 2018;Iyer et al. 2018). 2,4-DCP is less harmful than TCS in terms of toxicity (Surampalli et al. n.d.). ...
... In terms of gender, the concentration of pollutants was greater in the sexual group of girls than in the sexual group of boys, suggesting that girls and children aged 6 to 11 are more exposed to products containing these pollutants. Similar results were found in Iyer et al. and Rocha et al. investigations, as well as the current study's findings (Iyer et al. 2018;Rocha et al. 2018). ...
Endocrine-disrupting chemicals (EDCs) can be a major risk factor for noncommunicable illnesses, especially when children are exposed to them. The purpose of this study was to assess the urine concentrations of triclosan (TCS), methyl triclosan (MTCS), triclocarban (TCC), and 2,4-dichlorophenol (2,4-DCP) and its association with anthropometric and demographic parameters in children and adolescents aged 6–18 living in Kerman, Iran, in 2020. A GC/MS instrument was used to measure the concentrations of the analytes. TCS, MTCS, TCC, and 2,4-DCP geometric mean concentrations (µg/L) were 4.32 ± 2.08, 1.73 ± 0.88, 4.66 ± 10.25, and 0.19 ± 0.14, respectively. TCS, MTCS, TCC, and 2,4-DCP were shown to have a positive and significant association with BMI z-score and BMI (p-value < 0.01). TCS and MTCS have a positive, strong, and substantial association (p-value < 0.01, r = 0.74). There was no significant association between the waist circumference (WC) and the analytes studied. In addition, there was a close association between analyte concentration and demographic parameters (smoking, education, income, etc.) overall. In Kerman, Iran, the current study was the first to look into the association between TCS, MTCS, TCC, and 2,4-DCP analytes and anthropometric and demographic data. The levels of urinary TCS, MTCS, TCC, 2,4-DCP, and anthropometric parameters in children and adolescents are shown to have a significant association in this study. However, because the current study is cross-sectional and it is uncertain if a single experiment accurately reflects long-term exposure to these analytes, more research is needed to determine the impact of these analyses on the health of children and adolescents.
... The majority of the nonspecific metabolites, p-hydroxybenzoic and p-hydroxyhippuric acids, are excreted conjugated to glucuronides and sulphates in the urine (Soni et al. 2005;Mathews et al. 2013). The unchanged form can be found in biological matrices such as urine (Jardim et al. 2015;Kang et al. 2016;Rocha et al. 2018), serum (Tahan et al. 2016), plasma (Roldão et al. 2017), hair (Martín et al. 2016), breast milk (Ye et al. 2008;Souza et al. 2016), saliva (Zotou et al. 2010), and even menstrual blood (Jiménez-Díaz et al. 2016). ...
... Studies have been conducted demonstrating the dermal and oral exposure of the population to parabens. A recent study reported the presence of MP in 100% and PP in 97% of urine samples in children aged 6 to 14 years old (Rocha et al. 2018). Another study conducted to determine parabens levels in adult women demonstrated a strong association between serum parabens concentrations and lipstick use (Tahan et al. 2016). ...
The present study assessed the exposure to methylparaben (MP) and propylparaben (PP) from antiperspirants in serum of 24 women aged 20–30 years old and an in vitro skin assay. An effective liquid chromatography–tandem mass spectrometry method for the determination of MP and PP levels in serum was developed and validated in the range of 10–100 μg/L; the method was fast, simple, sensitive, linear, precise, and accurate. In addition, a simple and rapid liquid chromatography–ultraviolet detection method for the determination of MP and PP levels in antiperspirants was developed and validated in the range of 2–26 mg/L, which presented satisfactory linearity, precision, and accuracy. Using these two methods, 20 commercial antiperspirants were evaluated, and only three showed MP and PP in the formulation. The antiperspirant containing 0.2% and 0.1% w/w MP and PP, respectively, was given to the volunteers, to estimate the internal dose, and submitted to a pig ear skin permeation assay in Franz diffusion cells, presenting a permeation flux of 32% for MP and 71% for PP. In this assay, both MP and PP permeated the skin; however, there was no correlation between antiperspirant use and paraben serum concentration in the volunteers.
... However, the differences regarding BPA concentrations found between those studies cannot be attributed to different population-exposure levels but to the variability in sample size, children's age, analytical procedure and sampling period. The concentrations in Poland are also in the same range than those found in US studies, including the 2013-14 NHANES report and the Ohio cohort (US), as well as in Hong Kong and Brazil, with GM concentrations ranging from 1.4 μg/l to 1.7 μg/l [49,52,54,57], but twice higher than those found in Canada, Turkey or South Korea (0.6-1.0 μg/l) [48,51,55]. The concentrations were, however, much higher in studies performed in Asian populations, such as one conducted in China (2.7 μg/l) and another in India (5.1 μg/l) [53,56]. ...
Bisphenol A (BPA) is an industrial chemical mostly used in the manufacture of plastics, resins and thermal paper. Several studies have reported adverse health effects with BPA exposures, namely metabolic disorders and altered neurodevelopment in children, among others. The aim of this study was to explore BPA exposure, its socio-demographic and life-style related determinants, and its association with neurodevelopmental outcomes in early school age children from Poland.
A total of 250 urine samples of 7 year-old children from the Polish Mother and Child Cohort Study (REPRO_PL) were analyzed for BPA concentrations using high performance liquid chromatography with online sample clean-up coupled to tandem mass spectrometry (online-SPE-LC-MS/MS). Socio-demographic and lifestyle-related data was collected by questionnaires or additional biomarker measurements. Emotional and behavioral symptoms in children were assessed using mother-reported Strengths and Difficulties Questionnaire (SDQ). Cognitive and psychomotor development was evaluated by Polish adaptation of the Intelligence and Development Scales (IDS) performed by trained psychologists.
Urinary BPA concentrations and back-calculated daily intakes (medians of 1.8 μg/l and 46.3 ng/kg bw/day, respectively) were similar to other European studies. Urinary cotinine levels and body mass index, together with maternal educational level and socio-economic status, were the main determinants of BPA levels in Polish children. After adjusting for confounding factors, BPA has been found to be positively associated with emotional symptoms (β: 0.14, 95% CI: 0.022; 0.27). Cognitive and psychomotor development were not found to be related to BPA levels.
This study represents the first report of BPA levels and their determinants in school age children in Poland. The exposure level was found to be related to child emotional condition, which can have long-term consequences including social functioning and scholastic achievements. Further monitoring of this population in terms of overall chemical exposure is required.
... Segundo o respondente 273 "Preocupação com o meu bem-estar e o bem-estar das pessoas à minha volta". A saúde é um dos principais fatores de preocupação dos respondentes, e há respostas com informações de pesquisas(Rocha et al., 2018). Dados atuais de uso de cosméticos, além de possíveis encargos à saúde, demonstram que há conhecimento ou ao menos curiosidade dos consumidores sobre esse tipo de produto.De acordo com o arcabouço teórico e com as perguntas do questionário, os fatores internos e externos possivelmente são os mais influenciadores na intenção de compra de cosméticos sustentáveis. ...
Esse artigo tem como objetivo identificar os principais aspectos que os brasileiros consideram ao comprar cosméticos sustentáveis. Os cosméticos sustentáveis englobam produtos de beleza, perfumaria e higiene com preocupação sobre a formulação, saúde, descarte, o meio ambiente e a vertente social. Esse setor é um dos mais rentáveis do Brasil, destacando-se como o quarto maior do mundo. Os cosméticos sustentáveis têm diretrizes que devem estar em conformidade com o Instituto Biodinâmico de Certificações; apresentam-se dentre as especificações componentes naturais, orgânicos e livre de matérias-primas não renováveis. Considerando-se a revisão da literatura, gerou-se um modelo explicativo de quais aspectos são influenciadores nos consumidores que baseou o questionário aplicado. Foram coletadas 529 respostas com questões abertas no Brasil. Após a análise da frequência, foi verificado que certos aspectos respondem ao modelo proposto que contém as dimensões “Atitude de consumo ambiental”, “Bem-estar”, “Saúde”, “Grupos de Referência” e “Atributos percebidos” como preponderantes. Dentre os resultados obtidos, os aspectos qualidade, saúde, meio ambiente, preço, embalagem e teste em animais preponderaram como principais intenções de compra. Tais aspectos correspondem aos fatores internos e externos que guiam ao comportamento de compra. Esses achados podem auxiliar a despertar mais estudos sobre o setor cosmético na área de sustentabilidade na academia, podendo as organizações desenvolverem novos produtos e estratégias de marketing para esse segmento.
... As a consequence, BPS is the second leading bisphenol found in humans following BPA (Liao et al., 2012a;Philips et al., 2018;Ye et al., 2015). Bisphenols can be detected in urine, blood, breast milk, amniotic fluid and cord blood, highlighting the ubiquitous exposure humans have to these chemicals (Asimakopoulos et al., 2016;Lehmler et al., 2018;Liao et al., 2012b;Philips et al., 2018;Rocha et al., 2018;Xue et al., 2015;Ye et al., 2015). Several studies have shown that even at low concentrations, exposure to BPA during gestation can result in negative effects on the development of the fetus (Gingrich et al., 2020;Veiga-Lopez et al., 2018). ...
Predictions from physiologically based toxicokinetic (PBTK) models can help inform human health risk assessment for potentially toxic chemicals in the environment. Bisphenol S (BPS) is the second most abundant bisphenol detected in humans in the United States, after bisphenol A (BPA). We have recently demonstrated that BPS, much like BPA, can cross the placental barrier and disrupt placental function. Differences in physicochemical properties, toxicokinetics, and exposure outcomes between BPA and other bisphenols prevent direct extrapolation of existing BPA PBTK models to BPS. The current study aimed to develop pregnancy-specific PBTK (p-PBTK) models for BPA and BPS, using a common p-PBTK model structure. Novel paired maternal and fetal pregnancy data sets for total, unconjugated, and conjugated BPA and BPS plasma concentrations from three independent studies in pregnant sheep were used for model calibration. The nine-compartment (maternal blood, liver, kidney, fat, placenta and rest of body, and fetal liver, blood and rest of body) models simulated maternal and fetal experimental data for both BPA and BPS within one standard deviation for the majority of the experimental data points, highlighting the robustness of both models. Simulations were run to examine fetal exposure following daily maternal exposure to BPA or BPS at their tolerable daily intake dose over a two-week period. These predictive simulations show fetal accumulation of both bisphenols over time. Interestingly, the steady-state approximation following this dosing strategy achieved a fetal concentration of unconjugated BPA to levels observed in cord blood from human biomonitoring studies. These models advance our understanding of bisphenolic compound toxicokinetics during pregnancy and may be used as a quantitative comparison tool in future p-PBTK models for related chemicals.
... Within the scope of human biomonitoring (HBM) actions, which have been implemented in various countries, several studies investigated exposure of different vulnerable populations, such as children and adolescents to EDCs. (Casas et al., 2011;Frederiksen et al., 2013;Larsson et al., 2017;Liu et al., 2019;Myridakis et al., 2015;Rocha et al., 2018) Furthermore, many studies indicated potential determinants and sources of exposure to EDCs, such as, among others, consumption of canned food and social class for BPA (Covaci et al., 2015) and use of personal care products, such as makeup and skincare products for parabens. (Sanchis et al., 2019) Even though certain determinants have been previously described, further research is needed to provide more comprehensive data on specific exposure sources, especially for vulnerable populations. ...
Chemicals such as bisphenols, parabens and triclosan are endocrine disrupting chemicals. They are used in a wide variety of consumer products, making human exposure to those chemicals widespread.In the present study, levels of three bisphenols (bisphenol A, F and S), 7 parabens (methyl-, ethyl-, isopropyl-, propyl-, isobutyl-, butyl-, benzyl paraben) and triclosan were measured in first morning void from 246 Slovenian children and adolescents, aged 6–9 and 11–15 years and living in a rural region of Slovenia. Median levels of specific-gravity corrected levels for bisphenol A, bisphenol F, methyl paraben and ethyl paraben were 1.9, 0.085, 5.4 and 2.5 µg/L for children and 1.6, 0.11, 7.2 and 6.0 µg/L for adolescents, respectively. Median levels for all other endocrine disrupting chemicals were
... Moreover, for each one-fold increase in 8-OHdG level, the risk of asthma in children increased approximately nine-fold. Furthermore, level of 8-OHdG in asthmatic children (4.23 μg/g Crt.) from this study was far higher than those general children from Ghana and Thailand (ranged from 0.407 to 1.91 ng/mL or μg/g Crt.) and approached to those children from Brazil (4.40 ng/mL) (Bortey-Sam et al., 2017;Hinhumpatch et al., 2013;Rocha et al., 2018). Thus, oxidative DNA damage may play a crucial role in the development of childhood asthma. ...
Volatile organic compounds (VOCs) are important and ubiquitous air pollutants, which may lead to a significant increase in the prevalence of respiratory diseases. To investigate the relationships between VOCs exposure and childhood asthma, 252 asthmatic children and 69 healthy children were recruited. Urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG, a biomarker of oxidative DNA damage), trans-3′-hydroxycotinine (OH-Cot, a biomarker of passive smoking) and 27 VOC metabolites were simultaneously determined by an ultra-high-performance liquid chromatography-tandem mass spectrometer. Results showed that levels of 8-OHdG and most VOC metabolites in asthmatic children were significantly higher than those in healthy children. More than half of the VOC metabolites were significantly and positively associated with OH-Cot with maximal β coefficient of 0.169, suggesting that second-hand smoking is one important source of VOCs exposure for children in Guangzhou. Significant dose-response relationships between most VOC metabolites and 8-OHdG were observed. Each unit increase in ln-transformed VOC metabolite levels was significantly associated with 5.5–32% increase in ln-transformed 8-OHdG level. Moreover, each unit increase in ln-transformed 8-OHdG level was associated with an 896% increased odd ratios (OR) of asthma in children (OR = 9.96, 95% confidence intervals (CI): 4.75, 20.9), indicating that oxidative stress induced by VOCs exposure may have a significant impact on childhood asthma. Urinary 3-&4-Methylhippuric acid (3-&4-MHA, OR: 5.78, 95% CI: 3.50, 9.54), rac 2-Aminothiazoline-4-carboxylic acid (ATCA, OR: 2.90, 95% CI: 1.69, 4.99) and N-Acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBMA, OR: 2.76, 95% CI: 1.73, 4.43) which may derive from m/p-xylene, cyanide and 1,3-butadiene exposure, respectively, could significantly and maximally increase the odds of asthma. Interestingly, they also had the strongest associations with 8-OHdG among all investigated VOC metabolites. Moreover, DHBMA strongly correlated with most VOC metabolites. Hence, DHBMA is a suitable biomarker to indicate not only VOCs exposure profile, but also the DNA damage-mediated asthma induced by VOCs.
... Urinary BPA was positively associated with 8-hydroxy-2 -deoxyguanosine (8-OHdG), 8-isoprostane, and 4-hydroxy-2-nonenalmercapturic acid (HNE-MA), while BPF was associated with HNE-MA and 8-isoprostane in a Chinese cross-sectional study [62,63]. Similar associations between bisphenols and oxidative damage have been found in pregnant women and fetuses/newborns [64,65], or children and adolescents [66,67]. DEHP exposure in adolescents affected lipid metabolism by regulating the expression of lipid metabolism-related genes . ...
Much evidence on the adverse health effects of endocrine-disrupting chemicals (EDCs) has accumulated during recent decades. EDCs are commonly found in various foods and personal care products (PCP). Data documenting a diurnally varying EDC metabolism in humans is scarce. This study examined (i) the time-of-day effect on the diurnal magnitude and variance of urinary biomarkers of exposure to EDCs, and (ii) the association between EDC exposures and oxidative damage in a Norwegian adult subpopulation. This was a cross-sectional panel study using biobanked samples from the EuroMix project. During a typical weekday, participants were asked to collect all day’s urine voids and record dietary and PCP habitual uses in a diary. Collected time stamps of urine voids were classified into three distinct periods in the day (morning 6 a.m.–12 p.m., mid-day 12 p.m.–6 p.m., evening 6 p.m.–6 a.m.). Questionnaires regarding demographic characteristics, personal care product usage, and dietary habits were completed. Urinary levels of EDCs (phthalates, parabens, and bisphenols) were measured using mass spectrometry and adjusted for urinary volume using specific gravity. Urinary 4-hydroxynonenal (4HNE), a lipid peroxidation marker, was measured using an immunoassay kit. Linear mixed-effect models identified EDCs under the influence of a diurnal variation effect that was adjusted for dietary habits and PCP use and examined associations between EDC and 4HNE. p-values were FDR-adjusted. Most phthalates appeared to be diurnally varying with higher urinary levels towards the evening (q < 0.001) than those measured during mid-day; this strong diurnal variation effect was not present for parabens and bisphenols. Significant (q < 0.001) positive associations were observed between all phthalates, parabens, and bisphenols (except bisphenol S) and 4HNE. This study’s findings highlighted the diurnal variation of excretion for certain EDC, but not for others, in real-life conditions. The degree of EDC chronotoxicity in distinct diurnal windows of the day warrants further investigation with longitudinal human studies.
... Human biomonitoring (HB) programs have been implemented in various countries by public health agencies to assess human exposure to environmental pollutants. On the other hand, in Brazil, few HB studies are describing the prevalence of emerging pollutants in children (Rocha et al. 2017(Rocha et al. , 2018. The evaluation of the prevalence of PAHs and the assessment of the levels in Brazilians may provide support in a subsequent determination of reference values and the association with adverse health effects in exposed groups (Oliveira et al. 2017;Sinha and Banda 2018). ...
Monitoring human exposure to polycyclic aromatic hydrocarbons (PAHs) is a public health concern. Children are a vulnerable subgroup of the population with limited human biomonitoring data worldwide. Thus, this study aimed to measure the levels of seven PAH metabolites in urine from Brazilian children and provide risk assessment values for this exposure. Our data show naphthalene was the major contributor to children’s exposure to PAHs, with a 100% detection rate. Children in urban regions presented higher exposure to PAHs, with higher concentrations of 2-naphthol in the southeast (1.09 ng/mL, p < 0.05). Furthermore, the highest concentration of 2-naphthol was found in older children (p = 0.02), suggesting a possible difference in dietary habits. Exposure to the carbaryl insecticide is suggested based on the high concentrations of 1-naphthol (1.29 ng/mL) and considering the ratio 1-naphthol/2-naphthol (1.78). Moreover, the positive correlation between the metabolites of fluorine and pyrene also suggests exposure to PAHs by petrol combustion. The risk assessment of the PAH exposure was evaluated using the estimated daily intake (EDI) for two naphthalene metabolites in the study with a 100% detection rate. The EDI was 14.47 ng/kg BW/day. The risk assessment to the PAH exposure revealed a non-carcinogenic risk profile, with a hazard quotient of 0.71. To the best of our knowledge, this study is the first to provide levels of PAHs in Brazilian children.
... A study using the Flemish Environment and Health studies (FLEHS) 2007-2012 data showed that GM of urinary 2,5-DCP in 14-15-year-old Belgian adolescents was 1.54 ng/mL Abbreviations: LOQ, limit of quantification; LOD, limit of detection; GM, geometric mean; CIs, confidence intervals (Croes et al. 2015). Meanwhile, in another study conducted in 2012-2013, GMs of urinary 2,4-DCP and 2,5-DCP of 6-14year-old Brazilian children were 2.60 and 4.59 ng/mL, respectively (Rocha et al. 2018). In a more recent study conducted in 2016, the means of urinary 2,4-DCP, 2,5-DCP, 2,4,5-TCP, and 2,4,6-TCP in 5-18-year-old Iranian children were 3.1, 8.6, 1.6, 1.3 ng/mL, respectively (Parastar et al. 2018). ...
This study aimed to assess the association between urinary concentrations of chlorophenols and childhood central obesity. The study subjects were 165 girls (91 with central obesity and 74 with non-central obesity) aged 7-8 years who visited a hospital for regular health check-ups. The urinary concentrations of chlorophenols including 2,4-dichlorophenol (2,4-DCP), 2,5-dichlorophenol (2,5-DCP), 2,4,5-trichlorophenol (2,4,5-TCP), and 2,4,6-trichlorophenol (2,4,6-TCP) were analyzed using liquid chromatography-tandem mass spectrometry. The central obesity group showed significantly higher urinary concentrations of 2,5-DCP (0.56 vs. 0.28 ng/mL) and 2,4,5-TCP (0.06 vs. 0.03 ng/mL) than the non-central obesity group. The sum of molar concentrations of urinary chlorophenols was also significantly higher in the central obesity group than in the non-central obesity group (9.83 vs. 5.26 nmol/L). Girls in the highest quartile of the molar sum of chlorophenols showed significantly higher body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) compared with the lowest quartile after adjusting for covariates. WC and WHtR, but not BMI, were significantly associated with higher quartiles of the molar sum of chlorophenols (P-for-trend = 0.025 and 0.028, respectively). We found a positive association between chlorophenol exposure and central obesity in Korean girls. Large-scale prospective studies are needed to confirm our findings.
... In general, it seems like populations in several Asian countries, Brazilian and US are more exposed to 2,4dichlorophenol and 2,5-dichlorophenol or their precursors than Europeans. However, only few studies have been conducted in Europe Rocha et al., 2018;Vernet et al., 2018). ...
During the past two decades human exposure to bisphenol A (BPA) and phthalates such as di-iso-butyl phthalate (DiBP), di-n-butyl phthalate (DnBP), butylbenzyl phthalate (BBzP) and di-(2-ethyl-hexyl) phthalate (DEHP) has received substantial interest due to widespread population exposures and potential endocrine disrupting effects. Therefore, these chemicals have gradually been restricted and phased out through legislation. However, humans are still exposed to a wide range of other less studied phthalates, phthalate substitutes and BPA analogues as well as other polychlorinated and phenolic substances. In this study, we investigated human exposure to these chemicals over the past decade. Three hundred urine samples collected in 2009, 2013 and 2017 (100 samples each year) from young Danish men of the general population, participating in a large on-going cross-sectional study, were selected for the present time trend study. The urinary concentration of metabolites of 15 phthalates, di-2-ethylhexyl terephthalate (DEHTP) and di-iso-nonyl-cyclohexane-1,2-dicarboxylate (DINCH), seven bisphenols including BPA, bisphenol S (BPS) and bisphenol F (BPF), as well as triclosan, triclocarban, benzophenone-3, three chlorophenols and two phenylphenols were analyzed by two new sensitive LC-MS/MS methods developed and validated for the present study. A significant decrease in urinary concentrations over time was observed for the majority of the chemicals. Median concentrations of BPA and the metabolites of DiBP, DnBP, BBzP and DEHP were more than halved from 2009 to 2017. Similar decreases were observed for triclosan and the chloro- and phenylphenols. In contrast, metabolites of the two phthalate substitutes DEHTP and DINCH increased more than 20 and 2 times, respectively. The potential BPA substitutes; BPS and BPF also increased, but only slightly. Despite these new exposure patterns, the exposure to the old well-known chemicals, such as DiBP, DnBP, BBzP, DEHP and BPA was still higher in 2017 compared to the exposure level of the new substitutes such as DEHTP, DINCH, BPS and BPF. A significant decrease in internal exposure to most of the common phthalates and BPA over the past decade was observed, reflecting market changes and regulatory measures implemented in EU. Despite increasing exposures to some of the known phthalate substitutes and BPA analogues, the total amount of each measured chemical group (original and substitute analytes combined) was lower in the more recently collected samples. This indicates only partial direct substitution or substitution by chemicals not covered in this approach, or a general decline in the exposure to these chemical/product groups over the last decade.
... Ada kekhawatiran yang tinggi mengenai efek kesehatan yang merugikan dari BPA pada anak-anak(J. M. Lee, Gebremariam, Meeker, Peterson, & Padmanabhan, 2013;Rocha, Asimakopoulos, Honda, & Nattane, 2018).Bayi juga lebih rentan terhadap paparan bahan kimia daripadaorang dewasa karena sistem organ mereka tidak seperti orang dewasa (termasuk saraf,kekebalan tubuh, dan sistem pernapasan), perkembangan fisik yang cepat,dan tingkat respirasi serta metabolisme yang lebih tinggi (J. Lee et al., 2019).Paparan BPA telah terdeteksi pada konsentrasi yang lebih tinggi pada anak-anak daripada orang dewasa (Donohue et al., n.d.;Frederiksen et al., 2013). The Children's Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants (CTEPP) menyelidikipaparan potensial dari 257 anak prasekolah, usia 1,5 -5 tahun, dan pengasuh mereka lebih dari 50 antropogenikbahan kimia (Wilson, Chuang, Morgan, Lordo, & Sheldon, 2007). ...
... BADGE.2H 2 O and BFDGE.2H 2 O have been detected in human urine, blood plasma and adipose tissue samples. (Wang et al., 2015;Liu et al., 2019;Rocha et al., 2018) However, as these compounds can be easily formed through non-specific hydrolysis reactions, one can never be sure that the detected amounts of these compounds solely derive from (human) metabolism (Lane et al., 2015;Poustková et al., 2004;Losada et al., 1993). For example, Losada et al. have identified the formation of the hydrolysis products of BADGE, BADGE.H2O and BADGE.2H2O, in different food simulants (Losada et al., 1993). ...
Root canal sealers are commonly used to endodontically treat teeth with periapical infections. Some root canal sealers based on epoxy resin contain bisphenol A diglycidyl ether (BADGE) and bisphenol F diglycidyl ether (BFDGE). The presence of these chemicals is of concern due to the close contact to the blood stream at the apex and the long setting times of up to 24 hours. These chemicals, or any of their degradation products or metabolites, can then exert their toxic effects before being excreted. This study aimed to identify the phase I in vitro biotransformation products of BADGE and BFDGE using human liver microsomes. During incubation with microsomal fractions, the epoxides were rapidly hydrolysed in a NADPH independent manner resulting in the formation of BADGE.2H2O and BFDGE.2H2O. Further, oxidative reactions, such as hydroxylation and carboxylation, generated other BADGE metabolites, such as BADGE.2H2O-OH and BADGE.H2O.COOH, respectively. For BFDGE, further oxidation of BFDGE.2H2O led to the newly reported carboxylic acid, BFDGE.H2O.COOH. In total, three specific metabolites have been identified which can serve in future human biomonitoring studies of BADGE and BFDGE.
... As a result, its detection is frequent in human tissue, such as fingernails and body fluids, including blood, urine and seminal plasma , thus causing a potential hazard to human health. It is noteworthy that TCC may represent a risk for children, as it has been recently found in urine of Brazilian children and its use also seems to be associated to DNA damage . Human exposure to triclocarban is widely studied in several Asian countries, especially in Vietnam, Kuwait, and Japan . ...
In the late 1930s and early 1940s, it was discovered that the substitution on aromatic rings of hydrogen atoms with chlorine yielded a novel chemistry of antimicrobials. However, within a few years, many of these compounds and formulations showed adverse effects, including human toxicity, ecotoxicity, and unwanted environmental persistence and bioaccumulation, quickly leading to regulatory bans and phase-outs. Among these, the triclocarban, a polychlorinated aromatic antimicrobial agent, was employed as a major ingredient of toys, clothing, food packaging materials, food industry floors, medical supplies, and especially of personal care products, such as soaps,
toothpaste, and shampoo. Triclocarban has been widely used for over 50 years, but only recently some concerns were raised about its endocrine disruptive properties. In September 2016, the U.S. Food and
Drug Administration banned its use in over-the-counter hand and body washes because of its toxicity. The withdrawal of triclocarban has prompted the efforts to search for new antimicrobial compounds
and several analogues of triclocarban have also been studied. In this review, an examination of different facets of triclocarban and its analogues will be analyzed.
... During pregnancy, parabens are associated with dysfunction in reproductive and thyroid hormone levels. They increase oxidative stress and inflammation biomarker levels [16,17] . This increase can disrupt normal cellular signaling and trigger different diseases, such as cancer, cardiovascular disease, and infertility  . ...
Accumulation of estrogenic compounds and other carcinogens in normal breast tissues contributes to unpredictable breast cancer incidence during adolescence and throughout life. To assess the role of parabens in this phenomenon, the paraben content of adjacent normal-malignant breast tissues is measured in women with breast cancer living in Isfahan Province, Iran.
Adjacent normal-malignant breast tissue samples were obtained from 53 subjects. The parabens including methyl-paraben (MePB), ethyl-paraben (EtPB), propyl-paraben (PrPB), and butylparaben (BuPB) were extracted from the sample supernatant and then subjected to gas chromatography analysis.
Some risk factors for breast cancer were stimulated by parabens in adjacent malignant-normal breast tissues among young and middle-aged women with breast cancer. We observed a significant association for dose-response pattern of MePB [OR = 98.34 (11.43-185.2), P = 0.027] for both ER+ and PR+ women and MePB [OR = 164.3 (CI: 112.3-216.3), P < 0.001] for HER2+ women than women with negative receptors. The risk of 95-fold increase in MePB dose and 164-fold increase in ΣPBs dose were significant for women with hereditary breast cancer in first-degree relatives.
These results may promote future epidemiology studies and strategies to improve women's lifestyle and consume paraben-free products.
... Nevertheless, young children, especially infants, may have an imbalance between oxidation and anti-oxidation (Table S6) (Gan et al., 2018). Additionally, among multiple environmental factors (Asimakopoulos et al., 2016;Rocha et al., 2018;Kuang et al., 2019;Yu et al., 2020), 2,4-D might not be a major contributor to DNA damage. This is the first study to explore the relationship between urinary concentrations of 2,4-D and 8-OHdG in young Chinese children. ...
Herbicide 2,4-Dichlorophenoxyacetic acid (2,4-D) and its analogues are widely used in agriculture. Although the occurrence of 2,4-D in urine has been widely reported in North America, it has scarcely been investigated in China, especially in young children. In addition, both in vivo and in vitro studies have shown that high-level 2,4-D exposure is associated with oxidative stress, but their association in a general sensitive population has rarely been studied. In this study, 2,4-D and its analogues were measured in 417 urine samples collected from 139 children aged 0–7 during the non-peak season of pesticide application in Wuhan, central China, and Shenzhen, south China. Each of them provided three samples in three consecutive days. An oxidative stress biomarker, 8-hydroxy-2-deoxyguanosine (8-OHdG), was also measured. The geometric mean (GM) of unconjugated urinary 2,4-D concentration was 0.10 μg/L (corrected by urinary specific gravity, SG-corrected). After β-glucuronidase hydrolysis, the GM of SG-corrected urinary 2,4-D was 0.15 μg/L, and the detection frequency was 100%. Moderate inter-day reproducibility was found within individuals, with an intraclass correlation coefficient of 0.68 for SG-corrected urinary deconjugated 2,4-D. The GM of estimated daily intake of 2,4-D was 6.05 ng/kg-bw/day. A significant positive correlation was found between urinary 2,4-D and 8-OHdG, whereas no association was found after SG-correction. This is the first study to characterize the occurrence of urinary 2,4-D, its inter-day reliability, and its association with urinary 8-OHdG in young children from China.
Bisphenol A diglycidyl ether (BADGE) is an epoxy resin used for the inner coating of canned food and beverages. BADGE can easily migrate from the containers and become a contaminant. In this study, we examined the effects of BADGE exposure to the dams on the behavioral, structural, and developmental abnormalities in the offspring. Female pregnant mice were fed with a diet containing BADGE (0.15 or 1.5 mg/kg/day) during gestation and lactation periods. In an open field test, the time spent in the corner area significantly increases in male mice of high-dose BADGE group at 5 weeks old. The histological analysis using offspring brain at postnatal day 1 delivered from BADGE (1.5 mg/kg/day)-treated dams demonstrates that positive signals of Forkhead box P2- and COUP-TF interacting protein 2 are restricted in each cortical layer, but not in the control brain. In addition, the maternal BADGE exposure reduces nestin-positive fibers of the radial glia and T-box transcription factor 2-positive intermediate progenitors in the inner subventricular zone. Furthermore, a direct BADGE exposure promotes neurite outgrowth and neuronal connection in the primary cultured cortical neurons. These data suggest that maternal BADGE exposure can accelerate neuronal differentiation in fetuses and induce anxiety-like behavior in juvenile mice.
Polycyclic aromatic hydrocarbons (PAHs) and certain ingredients in personal care products, such as parabens, bisphenols, triclosan and phthalate metabolites, have become ubiquitous in the world. Concerns of human exposure to these pollutants have increased during recent years because of various adverse health effects of these chemicals. Multiple compounds including parabens, bisphenols, triclosan, phthalate metabolites (mPAEs) and hydroxyl PAHs (OH-PAHs) in urine samples from Guangzhou were determined simultaneously to identify the human exposure pathways without external exposure data combined with data analysis, and the toxicants posed the highest risk to human health were screened in the present study. The detection frequencies for the chemicals exceeded 90%. Among the contaminants, mPAEs showed the highest concentrations, followed by OH-PAHs, with triclosan present at the lowest concentrations. Mono-n-butyl phthalate, methylparaben, bisphenol A, and hydroxynaphthalene represented the most abundant mPAE, parabens, bisphenol, and OH-PAH compounds, respectively. The present PAHs are mainly exposed to human through inhalation, while the chemicals added to personal care products are mainly exposed to human through oral intake and dermal contact. The urine samples from suburban subjects showed significantly higher OH-PAH levels than the urine samples from urban subjects, and females had lower OH-PAH levels than males. Urinary concentrations of the analyzed contaminants were significantly correlated with age, body mass index, residence time, as well as the frequencies of alcohol consumption and swimming. Risk assessments based on Monte Carlo simulation indicated that approximately 30% of the subjects suffered non-carcinogenic risks from mPAEs and OH-PAHs, with mPAEs accounting for 89% of the total risk.
Osteoporosis and its consequence of fragility fracture represent a major public health problem. Human exposure to heavy metals has received considerable attention over the last decades. However, little is known about the influence of co-exposure to multiple heavy metals on bone density. The present study aimed to examine the association between exposure to metals and bone mineral density (BMD) loss. Blood and urine concentrations of 20 chemical elements were selected from 3 cycles (2005–2010) NHANES (National Health and Nutrition Examination Survey), in which we included white women over 50 years of age and previously selected for BMD testing (N = 1892). The bone loss group was defined as participants having T-score < − 1.0, and the normal group was defined as participants having T-score ≥ − 1.0. We developed classification models based on support vector machines capable of determining which factors could best predict BMD loss. The model which included the five-best features-selected from the random forest were age, body mass index, urinary concentration of arsenic (As), cadmium (Cd), and tungsten (W), which have achieved high scores for accuracy (92.18%), sensitivity (90.50%), and specificity (93.35%). These data demonstrate the importance of these factors and metals to the classification since they alone were capable of generating a classification model with a high prediction of accuracy without requiring the other variables. In summary, our findings provide insight into the important, yet overlooked impact that arsenic, cadmium, and tungsten have on overall bone health.
Parabens, a group of p-hydroxybenzoic acid esters, are extensively used in cosmetics, personal care products, pharmaceuticals, and foodstuff. In the present study, the total forms (free plus conjugated) of four parent parabens, such as methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP), and four metabolites, namely methyl protocatechuate (OH–MeP), ethyl protocatechuate (OH–EtP), p-hydroxy benzoic acid (4-HB), and 3,4-dihydroxy benzoic acid (3,4-DHB), were detected in paired urine and blood samples collected from 196 Chinese university students. The median urinary and blood parabens and their metabolites concentrations ranged from 0.24 to 167 ng/mL and from <0.02 to 2.88 ng/mL, respectively. MeP was the predominant parent parabens, accounting for 68% and 52% of urine and blood samples, respectively. Furthermore, 4-HB predominantly contributed to the parabens and their metabolites in urine (54%) and blood (41%). Significant positive correlations were observed between the urinary levels and blood levels. Moreover, relatively high levels of parabens and their metabolites were detected in urine samples. Our results imply that urinary concentrations are good predictors of human exposure to parabens and metabolites. Gender-related difference in urinary concentrations of parabens and their metabolites were found. The median urinary levels of the tested compounds in females were significantly higher than those in males (Mann Whitney U test, p < 0.05 or 0.01). The estimated daily intakes (EDIs) of MeP, EtP, and PrP were also evaluated. The median values of EDIMeP, EDIEtP, and EDIPrP for all of the university students were estimated to be 25.9, 1.61, and 3.82 μg/kg bw/day, respectively. The median values (μg/kg bw/day) of EDIMeP, EDIEtP, and EDIPrP were higher in females (53.7, 8.65, and 5.22) than in males (8.41, 0.85, and 2.57). This study is the first study to report the occurrence of parabens and their metabolites in paired urine and blood samples in China.
Triclosan (TCS) is a fat-soluble antimicrobial that is mainly used in personal care products such as shampoos, toothpastes, and cosmetics. Methyl triclosan (MTCS) is the main metabolite of TCS. Exposure to TCS can exacerbate or cause non-communicable diseases such as cardiovascular disease, diabetes, asthma and allergies, as well as endocrine disorders. These analytes are mostly excreted in the urine and are also the best and most accessible matrix for biological monitoring in the human body. The aim of this study was to investigate a new method extraction using Dispersive Liquid-Liquid Micro-Extraction (DLLME) method to identify and measure TCS and MTCS in urine samples of children and adolescents in Kerman. The results showed that the RSD method used for TCS and MTCS was 4.6 and 3.9 percent, respectively. The LOD and LOQ methods used for TCS and MTCS were 1.9-1.8 and 6.3-6.0, respectively. Mean urinary TCS and MTCS (μg/L) were observed at 4.62 ± 2.08 and 1.91 ± 0.88, respectively. In the urine samples of all subjects (79 patients), TCS and MTCS were identified, which indicates that all subjects are exposed to TCS, as a result, it is necessary to limit the Ways of exposure by increasing the awareness of the public and the relevant authorities and the legislature.
The usage of parabens, bisphenol A and triclosan in diverse consumer products is in widespread. Nevertheless, there are limited data concerning exposure to these chemicals in human being, especially in primiparas. Biomonitoring of chemicals in primiparas is useful for the estimation of chemical exposure risks for both primiparas and their offspring. This study aims to investigate urinary levels of parabens, bisphenol A and triclosan of 84 primiparas from Shenzhen, China and to evaluate their potential health risks. Methyl, ethyl, and n-propyl parabens bisphenol A and triclosan exhibited high detection rates (DRs) (> 97%) in urine samples, suggesting that primiparas are exposed to them widely. The median concentrations of methyl, ethyl, and n-propyl parabens, bispenol A and triclosan in urine were 2.14, 4.10, 0.46, 1.30 and 3.00 µg/L, respectively. Ethyl paraben was the predominant paraben accounting for nearly half of Σ3parabens (The sum concentrations of methyl, ethyl, n-propyl parabens). Positive associations with significance (p < 0.05) were found between the usage of plastic containers and urinary concentrations of ethyl paraben or BPA, indicating plastic containers might be an important factor influencing primipara exposure to these two chemicals. Urinary concentrations of methyl paraben were positively associated (p < 0.05) with the time of computer use by participant, suggesting that indoor dust might constitute an important source of parabens. The estimated daily intakes of parabens, bisphenol A and triclosan contrasted with the acceptable daily intakes in a comparatively low level. The hazard quotients (HQs) of these chemicals were all less than 1, suggesting no health risks for primiparas from South China.
The online version contains supplementary material available at 10.1007/s40201-020-00599-1.
Neste capítulo, abordamos (1) a diversidade de habitats de substrato consolidado da Baía de Guanabara, (2) os costões da baía, (3) os substratos duros naturais, (4) os substratos duros artificiais, (5) os substratos duros artificiais móveis, tais como cascos de navios e plataformas de petróleo, (6) os organismos típicos de substratos duros da baía, (7) as comunidades bentônicas como modelo ecológico e (8) os substratos não consolidados. É apresentada também uma tabela não exaustiva das espécies exóticas de substrato duro encontradas na Baía de Guanabara.
Parabens are widely used preservatives, mainly in personal care products, cosmetics, medicines, and foods. These compounds have been detected in various environmental matrices at low (in the order of µg L⁻¹ or ng L⁻¹) and high concentrations (mg L⁻¹), being recognized as emerging contaminants. In this work, the efficiency of vortex-assisted liquid-liquid microextraction using hydrophobic deep eutectic solvents (HDES) was evaluated in the separation and concentration of parabens (methyl, ethyl, propyl, and butylparaben) in an aqueous solution. The results indicated that the solvents DL-menthol + Caprylic Acid (2:1), DL-menthol + Lactic Acid (1:2), and DL-menthol + Lauric Acid (2:1) are efficient to extract hydrophobic compounds, such as the parabens. The experimental results were supported by the COSMO-SAC predictive thermodynamic model concerning the evaluation of the sigma profile of the molecules. In addition, this model predicts the excess properties of the binaries and explains the behavior of the systems. The potential of liquid-liquid microextraction was demonstrated, given the results presented, and the applicability of the method as an alternative in the removal of micropollutants in aqueous media can be considered.
To determine if higher exposures measured in early childhood to environmental phenols, phthalates, pesticides, and/or trace elements, are associated with increased odds of having a diagnosis of Autism Spectrum Disorder (ASD), Developmental Delay (DD), or Other Early Concerns (OEC) compared to typically developing children (TD).
This study included 627 children between the ages of 2–5 who participated in the Childhood Autism Risks from Genetics and Environment (CHARGE) study. Urine samples were collected at the same study visit where diagnostic assessments to confirm diagnosis indicated during the recruitment process were performed. Adjusted multinomial regression models of each chemical with diagnosis as the outcome were conducted. Additionally, two methods were used to analyze mixtures: repeated holdout multinomial weighted quantile sum (WQS) regression for each chemical class; and a total urinary mixture effect was assessed with repeated holdout random subset WQS.
Many urinary chemicals were associated with increased odds of ASD, DD or OEC compared to TD; however, most did not remain significant after false discovery rate adjustment. Repeated holdout WQS indices provided evidence for associations of both a phenol/paraben mixture effect and a trace element mixture effect on DD independently. In analyses adjusted for confounders and other exposures, results suggested an association of a pesticide mixture effect with increased risk for ASD. Results also suggested associations of a total urinary mixture with greater odds of both ASD and DD separately.
Higher concentrations of urinary biomarkers were associated with ASD, DD, and OEC compared to TD, with consistency of the results comparing single chemical analyses and mixture analyses. Given that the biospecimens used for chemical analysis were generally collected many months after diagnoses were made, the direction of any causal association is unknown. Hence findings may reflect higher exposures among children with non-typical development than TD children due to differences in behaviors, metabolism, or toxicokinetics.
Following the restriction of bisphenol A (BPA) in certain products, a number of bisphenol analogues (BPs) have been used as BPA replacements in different applications, raising environmental and health concerns. The present study determined a total of 13 bisphenol analogues in house dust and children urine from South China families (n = 46). Among all BPs, BPA, bisphenol S (BPS) and bisphenol F (BPF) were frequently detected in house dust, with concentrations ranging from 0.54 to 26.2 μg/g (median: 2.60 μg/g), 0.07–11.5 μg/g (median: 0.32 μg/g) and 0.02–2.4 μg/g (median: 0.29 μg/g), respectively. BPA (median: 2.43 ng/mL) was also the dominant BP in children urine samples, accounting for 75.2 ± 27.4% of the total concentrations of urinary BPs, followed by BPS (0.23 ng/mL), whereas BPF was only detected in less than 30% of urine samples. Children's daily intake of bisphenols through dust ingestion and total daily intakes were estimated based on the dust and urine concentrations, respectively. The estimated intake of BPA, BPS and BPF via house dust ingestion accounted for 9%, 12% and 38% of the total intakes predicted based on urinary concentrations, respectively, and exhibited very low exposure risks.
The development of a rapid analytical approach for determining levels of antibacterial agents, plasticizers, and ultraviolet filters in biosamples is crucial for individual exposure assessment. We developed an analytical method to determine the levels of four parabens—bisphenols A (BPA) and its analogs, triclosan (TCS), triclocarban, and benzophenone-3 (BP-3)—in human urine. We further measured the levels of these chemicals in children and adolescents. We used a supported liquid extraction (SLE) technique coupled with an isotope-dilution ultraperformance liquid chromatography-tandem mass spectrometry (ID-UPLC-MS/MS) method to assess the detection performance for these chemicals. Forty-one urine samples from 13 children and 28 adolescents were assessed to demonstrate the capability and feasibility of our method. An acceptable recovery (75.6–102.4%) and matrix effect (precision < 14.2%) in the three-level spiked artificial urine samples were achieved, and good performance of the validated ID-UPLC-MS/MS method regarding linearity, limits of detection, and quantitation was achieved. The within-run and between-run accuracy and precision also demonstrated the sensitivity and stability of this analytical method, applied after SLE. We concluded that the ID-UPLC-MS/MS method with SLE pretreatment is a valuable analytical method for the investigation of urinary antibacterial agents, plasticizers, and ultraviolet filters in humans, useful for human biomonitoring.
Triclosan (TCS) is a fat-soluble antimicrobial that is mainly used in personal care products such as shampoos, toothpastes, and cosmetics. Methyl triclosan (MTCS) is the main metabolite of TCS. Exposure to TCS can exacerbate or cause non-communicable diseases such as cardiovascular disease, diabetes, asthma and allergies, as well as endocrine disorders. These analytes are mostly excreted in the urine and are also the best and most accessible matrix for biological monitoring in the human body. The aim of this study was to investigate a new method extraction using Dispersive Liquid-Liquid Micro-Extraction (DLLME) method to identify and measure TCS and MTCS in urine samples of children and adolescents in Kerman. The results showed that the RSD method used for TCS and MTCS was 4.6 and 3.9 percent, respectively. The LOD and LOQ methods used for TCS and MTCS were 1.9-1.8 and 6.3-6.0, respectively. Mean urinary TCS and MTCS (μg/L) were observed at 4.62 ± 2.08 and 1.91 ± 0.88, respectively. In the urine samples of all subjects (79 patients), TCS and MTCS were identified, which indicates that all subjects are exposed to TCS, as a result, it is necessary to limit the Ways of exposure by increasing the awareness of the public and the relevant authorities and the legislature.
Benzophenone-1 (BP-1) belongs to personal care product-related contaminants of emerging concern and has been recently reported to induce xenoestrogenic effects. However, the underlying mechanisms leading to the activation of target receptors and subsequent various adverse outcomes remain unclear, which is beneficial to safety and health risk assessment of benzophenone-type ultraviolet filters with their widespread occurrence. Herein, we investigated disrupting effects of BP-1 at environmentally relevant concentrations (10⁻⁹–10⁻⁶ M) on estrogen receptor (ER) α-associated signaling pathways. Molecular dynamics simulations together with yeast-based assays revealed the steady binding of BP-1 to ERα ligand binding domain (LBD) and hence the observed agonistic activity. BP-1 triggered interaction between ERα and β-catenin in human SKOV3 ovarian cancer cells and caused translocation of β-catenin from the cytoplasm to the nucleus, leading to aberrant activation of Wnt/β-catenin. BP-1 consequently induced dissemination of SKOV3 via regulating epithelial-mesenchymal transitions (EMT) biomarkers including minimally downregulating ZO-1 gene to 78.0 ± 10.1% and maximally upregulating MMP9 gene to 144.1 ± 29.7% and promoted 1.03–1.83 fold proliferation, migration and invasion of SKOV3. We provide the first evidence that the BP-1 activated ERα triggers crosstalk between ERα and Wnt/β-catenin pathway, leading to the abnormal stimulation and progression of SKOV3 cancer cells.
Bisphenol A (BPA) analogues, used in a range of products due to health concerns regarding BPA, have emerged as ubiquitous environmental contaminants worldwide. This study aims to evaluate the levels of nine bisphenols (BPs) and eight biomarkers (malondialdehyde, MDA; 8-hydroxy-2′-deoxyguanosine, 8-OHdG; estradiol, E2; follicle-stimulating hormone, FSH; luteinizing hormone, LH; complement compound 3, C3; immunoglobulin M, IgM and c-reaction protein, CRP) in human serum (n = 353) to explore their potential relationships. The detection rates (DRs) of eight BPs in serum samples taken from people working in a dense industrial area of Shenzhen (Guangdong Province, China) were over 72% except for bisphenol B (BPB) (DR = 27.5%). The mean concentrations of BPA, bisphenol P (BPP), BPB, bisphenol F (BPF), bisphenol FL (BPFL), 4,4′-dihydroxy-benzophenone (DHBP), bisphenol AF (BPAF), 4,4′-thiodiphenol (TDP) and bisphenol S (BPS) were 42.062, 2.083, 0.765, 0.578, 0.423, 0.402, 0.191, 0.120, and 0.071 ng/mL, respectively. BPA and BPFL were significantly correlated with the level of oxidative stress indices MDA and 8-OHdG; BPAF, BPB, and DHBP were strongly correlated with the level of endocrine disturbance indices E2, FSH, and LH; and BPF, DHBP, and BPAF were apparently related to the level of immune interference indices C3 and IgM. This study also suggests multiple impacts (oxidative stress, endocrine disturbance, and immune interference) mediated by BPs contaminants in vivo. To our knowledge, this is the first study to report the correlations among these nine serum BPs and oxidative stress and endocrine and immune system indices in human serum samples collected from dense industrial areas.
This study aimed to evaluate the degradation of methylparaben (MeP) and propylparaben (PrP) in synthetic wastewater in a membrane bioreactor (MBR) whose operation involved three stages: stage 1 (stabilization period), with no addition of parabens; stage 2, in which the MBR was fed with 0.5 mg L⁻¹ of each paraben; and stage 3, in which both MeP and PrP were added, at 10 mg L⁻¹each. The system performance was assessed by monitoring pH, temperature, effluent flow rate, transmembrane pressure, BOD, COD, suspended solids, and paraben concentration. The results confirmed that the MBR showed a good organic matter removal efficiency (> 92.2% for BOD; >91.6% for COD) and was not significantly affected by the addition of parabens at either low or high dosages. The volatile to total suspended solids ratio remained nearly constant, suggesting that the addition of parabens at a high concentration did not negatively impact the control of suspended solids. It was possible to achieve 96.0% of MeP and PrP removal in stage 2 ([parabens]0 = 0.5 mg L⁻¹), and 86.0% of PrP removal in stage 3 ([PrP]0 = 10 mg L⁻¹). Finally, biodegradation was found to be the main removal mechanism of parabens in the investigated MBR.
Parabens are a group of chemical additive extensively utilized in various health care products and ubiquitously observed in the different environmental matrixes. Nevertheless, the exposure of women working in beauty salons to these pollutants is not well-documented. For this purpose, 50.00 women working in beauty salons were chosen as the exposed group (EG) and 35.00 housewives were chosen as the control group (GC). The concentration of methyl paraben (MeP), ethyl paraben (EtP), butyl paraben (BuP), propyl paraben (PrP), benzyl paraben (BzP), heptyl paraben (HepP), and para-hydroxybenzoic acid (4-HB) metabolite were quantified in the collected urine samples. It was seen that paraben sexist with a high detection frequency (DF) in the urine of women working in beauty salons. The results also revealed that the significant difference between the urinary parabens level in the EG and CG (P value < 0.05). The median concentration of Σparaben and HB-4 metabolite in the before exposure (BE) samples was 124.00 and 219.00 μg/L, while in the after exposure (AE) samples, it was 156.00 and 249.00 μg/L, respectively. Moreover, the parabens levels in the AE samples were considerably higher than in BE samples in women working in beauty salons (P value < 0.05). This research also documented that “personal care products (PCPs) usage” can be known as a leading factor for the urinary paraben level in the studied individuals. The median total estimated daily intakes (TEsDI) for MeP, EtP, and PrP for the studied women were obtained as 8.02, 4.57, and 7.88 μg/L respectively. Also, a significant and positive association was observed between EtP, PrP as well as BuP and 8-OhdG (as a DNA oxidative stress biomarker) (P value < 0.01). Further, a significant and positive association was found between EtP as well as BuP and some biomarkers of kidney damage (like uTIMP-1 and uKim-1). Accordingly, it can be stated that women working in beauty salons are at a high risk in terms of DNA oxidative stress and kidney damage.
In recent years, the occurrence of organic UV-filters (UVFs) and bisphenol derivatives (BPs) in the marine environment has raised high concerns all over the world, due to the potentially adverse impacts on marine organism and, indirectly on human health. This paper reports, for the first time in Romania, the occurrence, distribution pattern and environmental risk assessment of UVFs, BPs and their metabolites in seawater, sediment and algae collected from the Romania Black Sea coastal region. BP-3 (2-hydroxy-4-methoxy-benzophenone) was the most abundant contaminant in seawater samples, with detection frequency of 100%. Sediment samples were dominated by ES (Ethylhexyl salicylate), with concentration values up to 5823 ng/g d.w., while for algae, concentrations of several hundreds of ng/g d.w. were determined for BP-3, BS (Benzyl salicylate) and BPE (Bisphenol E). Environmental risk assessment revealed that some UVFs and BPs detected in seawater samples were hazardous to the marine organism of the Black Sea.
p-Dichlorobenzene (DCB) and naphthalene (NP) used as moth repellents in indoor environments are suspected to be carcinogenic. To evaluate their adverse effects on health with chronic exposure in the general population, especially children, we need to know their amounts absorbed by the body and the relationships between their amounts and air quality in residences. At present, little is known worldwide about them.
This study examined the daily intakes of DCB and NP by Japanese children via all exposure pathways and the contribution of indoor air quality to the intakes. First-morning void urine samples from the subjects aged 6 to 15 years and air samples in their bedrooms were collected. Airborne NP and DCB and their urinary metabolites were measured.
Significant correlations were detected between their airborne concentrations and the urinary excretion amounts of their corresponding metabolites. The absorption amounts of DCB and NP by inhalation of the children while at home were calculated to be 26 and 2.0 ng/kg b.w./h, respectively, as median values. The daily intake was estimated to be 2.4 and 0.90 μg/kg b.w./d (median), respectively. The fractions (median) of inhalation absorption amounts to overall absorption amounts for DCB and NP were 30% and 5%, respectively. In children living in residences where the indoor air concentrations of these compounds were more than half the level of each guideline value for indoor air quality, the main exposure route for their absorption was considered to be inhalation while at home. The indoor concentrations of DCB exceeded the lifetime excess cancer risk level of 10⁻⁴ in 22% of the residences and 10⁻³ in 9% of them. Our findings indicate the need to further reduce airborne concentrations of DCB in Japanese residences to prevent its adverse effects on the health of Japanese children.
Benzophenone-1 (BP-1), one of the commonly used ultraviolet filters, has caused increasing public concern due to frequently detected residues in environmental and recreational waters. Its susceptibility to residual chlorine and the potential to subsequently trigger endocrine disruption remain unknown. We herein investigated the chlorination of BP-1 in swimming pool water and evaluated the endocrine disruption toward the human androgen receptor (AR). The structures of monochlorinated (P1) and dichlorinated (P2) products were separated and characterized by mass spectrometry and 1H-1H NMR correlation spectroscopy. P1 and P2 exhibited significantly higher antiandrogenic activity in yeast two-hybrid assays (EC50, 6.13 μM and 9.30 μM) than did BP-1 (12.89 μM). Our 350 ns Gaussian accelerated molecular dynamics simulations showed the protein dynamics in a long-time scale equilibrium, and further energy calculations revealed that although increased hydrophobic interactions are primarily responsible for enhanced binding affinities between chlorinated products and the AR ligand binding domain, the second chloride in P2 still hinders the complex motion because of the solvation penalty. The mixture of BP-1-P1-P2 elicited additive antiandrogenic activity, well fitted by the concentration addition model. P1 and P2 at 1 μM consequently downregulated the mRNA expression of AR-regulated genes, NKX3.1 and KLK3, by 1.7-9.1-fold in androgen-activated LNCaP cells. Because chlorination of BP-1 occurs naturally by residual chlorine in aquatic environments, our results regarding enhanced antiandrogenic activity and disturbed AR signaling provided evidence linking the use of personal care products with potential health risks.
A high demand exists in human biomonitoring studies for reliable and straightforward methods that generate data faster and simultaneously. Thus, the present study combines microextraction by packed sorbent (MEPS) and liquid chromatography coupled to mass spectrometry (LC-MS/MS) for simultaneous extraction and determination of various classes of endocrine-disrupting chemicals (EDCs), including parabens, benzophenones, bisphenols, and the antimicrobial, triclocarban in human urine samples. Optimized MEPS conditions were: i) MEPS sorbent (C18), ii) pH of sample (3), iii) volume of sample (250 μL), iv) number of draws-eject cycles (5) and (vi) desorption solvent conditions (100 μL of CH3OH:H2O 80:20 v/v). The calibration curves were linear over the selected ranges for all studied compound, with correlation coefficients higher than 0.99. The variation coefficient for precision was lower than 20% at lower concentrations and lower than 15% at the higher concentrations studied. The accuracy ranged from 90% to 118%. The proposed strategy affords several advantages over currently published approaches, including simplicity of operation and reduction of sample and solvent volumes and time for matrix clean-up. Moreover, the analytical performance of each MEPS cartridge remained stable over the analysis of at least 70 samples (RSD < 10%). Thus, the current procedure may be an interesting high-throughput alternative for large routine human biomonitoring studies. Urinary geometric mean concentrations of EDCs obtained in this study were close than those previously reported for Brazilian children.
Exposure to ambient air pollution is associated with adverse cardiovascular outcomes. These are manifested through several, likely overlapping, pathways including at the functional level, endothelial dysfunction, atherosclerosis, pro-coagulation and alterations in autonomic nervous system balance and blood pressure. At numerous points within each of these pathways, there is potential for cellular oxidative imbalances to occur. The current review examines epidemiological, occupational and controlled exposure studies and research employing healthy and diseased animal models, isolated organs and cell cultures in assessing the importance of the pro-oxidant potential of air pollution in the development of cardiovascular disease outcomes. The collective body of data provides evidence that oxidative stress (OS) is not only central to eliciting specific cardiac endpoints, but is also implicated in modulating the risk of succumbing to cardiovascular disease, sensitivity to ischemia/reperfusion injury and the onset and progression of metabolic disease following ambient pollution exposure. To add to this large research effort conducted to date, further work is required to provide greater insight into areas such as (a) whether an oxidative imbalance triggers and/or or worsens the effect and/or is representative of the consequence of disease progression, (b) OS pathways and cardiac outcomes caused by individual pollutants within air pollution mixtures, or as a consequence of inter-pollutant interactions and (c) potential protection provided by nutritional supplements and/or pharmacological agents with antioxidant properties, in susceptible populations residing in polluted urban cities.
The generation of reactive oxygen species (ROS) plays a relevant role in the pathogenesis of atherosclerosis and of cardiovascular disease (CVD). High levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), a biomarker of oxidative damage of DNA have been found in patients with cardiovascular risk factors. We performed a meta-analysis of literature to investigate the association among 8-OHdG levels and CVD. Methods A systematic search was performed in the PubMed, Web of Science, Scopus, EMBASE databases without any language or publication year restriction. The reference lists of all retrieved articles were manually reviewed. All studies evaluating 8-OHdG levels in CVD patients and controls were included. Differences among cases and controls were expressed as mean difference (MD) or standard men difference (SMD) with pertinent 95% confidence intervals (95%CI). Impact of clinical and demographic features on effect size was assessed by meta-regression.
Fourteen studies (810 CVD patients and 1106 controls) were included in the analysis. We found that CVD patients showed higher 8-OHdG levels than controls (SMD: 1.04, 95%CI: 0.61, 1.47, p <0.001, I2=94%, P<0.001). The difference was confirmed both in studies in which 8-OHdG levels were assessed in urine (MD: 4.43, 95%CI: 1.71, 7.15, p=0.001) and in blood samples (MD: 1.42, 95%CI: 0.64, 2.21, p=0.0004). Meta-regression models showed that age, hypertension and male gender significantly impacted on the difference in 8-OHdG levels among CVD patients and controls.
8-OHdG levels are higher in patients with CVD than in controls. However, larger prospective studies are needed to test 8-OHdG as a predictor of CVD.
Exposure to toxicants present in the environment, especially the so-called endocrine-disrupting chemicals (EDCs), has been associated with decreased sperm quality and increased anomalies in male reproductive organs over the past decades. Both human and animal populations are continuously exposed to ubiquitous synthetic and natural-occurring EDCs through diet, dermal contact and/or inhalation, therefore potentially compromising male reproductive health. Although the effects of EDC are likely induced via multiple genomic-based pathways, their non-genomic effects may also be relevant. Furthermore, spermatozoa are transcriptionally inactive cells that can come in direct contact with EDCs in reproductive fluids and secretions and are therefore a good model to address non-genomic effects. This review thus focuses on the non-genomic effects of several important EDCs relevant to mammalian exposure. Notably, EDCs were found to interfere with pre-existing pathways inducing a panoply of deleterious effects to sperm function that included altered intracellular Ca2+ oscillations, induction of oxidative stress, mitochondrial dysfunction, increased DNA damage and decreased sperm motility and viability, among others, potentially jeopardizing male fertility. Although many studies have used non-environmentally relevant concentrations of only one compound for mechanistic studies, it is important to remember that mammals are not exposed to one, but rather to a multitude of environmental EDCs, and synergistic effects may occur. Furthermore, some effects have been detected with single compounds at environmentally relevant concentrations.
Download at : http://www.jstatsoft.org/v61/i06/paper
Clustering is the partitioning of a set of objects into groups (clusters) so that objects within a group are more similar to each others than objects in different groups. Most of the clustering algorithms depend on some assumptions in order to define the subgroups present in a data set. As a consequence, the resulting clustering scheme requires some sort of evaluation as regards its validity.
The evaluation procedure has to tackle difficult problems such as the quality of clusters, the degree with which a clustering scheme fits a specific data set and the optimal number of clusters in a partitioning. In the literature, a wide variety of indices have been proposed to find the optimal number of clusters in a partitioning of a data set during the clustering process. However, for most of indices proposed in the literature, programs are unavailable to test these indices and compare them.
The R package NbClust has been developed for that purpose. It provides 30 indices which determine the number of clusters in a data set and it offers also the best clustering scheme from different results to the user. In addition, it provides a function to perform kmeans and hierarchical clustering with different distance measures and aggregation methods. Any combination of validation indices and clustering methods can be requested in a single function call. This enables the user to simultaneously evaluate several clustering schemes while varying the number of clusters, to help determining the most appropriate number of clusters for the dataset of interest.
Chemicals such as phthalates, parabens, bisphenol A (BPA) and triclosan (TCS), used in a wide variety of consumer products, are suspected endocrine disrupters although their level of toxicity is thought to be low. Combined exposure may occur through ingestion, inhalation and dermal exposure, and their toxic as well as combined effects are poorly understood.The objective of the study was to estimate the exposure to these chemicals in Swedish mothers and their children (6–11 years old) and investigate potential predictors of the exposure. Urine samples from 98 mother–child couples living in either a rural or an urban area were analyzed for the concentrations of four metabolites of di-(2-ethylhexyl) phthalate (DEHP), three metabolites of di-iso-nonyl phthalate (DiNP), mono-ethyl phthalate (MEP), mono-benzyl phthalate (MBzP) and mono-n-butyl phthalate (MnBP), methylparaben (MetP), ethylparaben (EthP), propylparaben (ProP), butylparaben, benzylparaben, BPA, and TCS. Information on sociodemographics, food consumption habits and use of personal care products, obtained via a questionnaire, was used to investigate the associations between the urinary levels of chemicals and potential exposure factors.There were fairly good correlations of biomarker levels between the mothers and their children. The children had generally higher levels of phthalates (geometric mean ΣDEHP 65.5 μg/L; ΣDiNP 37.8 μg/L; MBzP 19.9 μg/L; MnBP 76.9 μg/L) than the mothers (ΣDEHP 38.4 μg/L; ΣDiNP 33.8 μg/L; MBzP 12.8 μg/L; MnBP 63.0 μg/L). Conversely, the mother's levels of parabens (MetP 37.8 μg/L; ProP 13.9 μg/L) and MEP (43.4 μg/L) were higher than the children's levels of parabens (MetP 6.8 μg/L; ProP 2.1 μg/L) and MEP (28.8 μg/L). The urinary levels of low molecular weight phthalates were higher among mothers and children in the rural area (MBzP p
2,4-Dichlorophenol (2,4-DCP), 2,5-dichlorophenol (2,5-DCP) and their precursors are widely used in industry and in consumer products. Urinary concentrations of these dichlorophenols (DCPs) have been measured as part of four National Health and Nutrition Examination Survey (NHANES) cycles to assess the exposure to these compounds or their precursors among the U.S. general population.
To identify predictors and evaluate trends in concentrations of DCPs according to race/ethnicity, age, sex, family income, and housing type.
We used analysis of covariance to examine associations of various demographic parameters and survey cycle with urinary concentrations of DCPs during 2003-2010. We also conducted weighted logistic regressions to estimate associations of DCP concentrations above the 95th percentile with housing type, race/ethnicity, and income.
We detected DCPs in at least 81% of participants. Geometric mean (GM) urinary concentrations were higher for 2,5-DCP (6.1-12.9 µg/L) than 2,4-DCP (0.8-1.0 µg/L) throughout 2003-2010. Adjusted GM concentrations of the DCPs among children (age 6-11 years) and adults older than 60 years were higher than among adolescents and other adults. Adjusted GM concentrations among non-Hispanic whites were lower than among non-Hispanic blacks and Mexican Americans, though differences according to race/ethnicity were less pronounced among participants in high-income households. Among non-Hispanic blacks and Mexican Americans adjusted GM concentrations were lowest among high-income participants relative to other income groups, with a monotonic decrease with income among Mexican Americans. Type of housing and race/ethnicity were significant predictors of DCPs urinary concentrations above the 95th percentile. Furthermore, urinary DCP concentrations showed a downward trend since 2003.
Exposure to DCPs and their precursors was prevalent in the general U.S. population in 2003-2010. We identified age and race/ethnicity, family income, and housing type as predictors of exposure to these compounds.
DNA damage, largely owing to oxidative stress, is a leading cause of defective sperm
function. High levels of oxidative stress result in damage to sperm DNA, RNA transcripts, and
telomeres and, therefore might provide a common underlying aetiology of male infertility and
recurrent pregnancy loss, in addition to congenital malformations, complex neuropsychiatric
disorders, and childhood cancers in children fathered by men with defective sperm cells.
Spermatozoa are highly vulnerable to oxidative stress owing to limited levels of antioxidant
defence and a single, limited DNA-damage detection and repair mechanism. Oxidative stress is
predominantly caused by a host of lifestyle-related factors, the majority of which are modifiable.
Antioxidant regimens and lifestyle modifications could both be plausible therapeutic approaches
that enable the burden of oxidative-stress-induced male factor infertility to be overcome.
Lifestyle interventions including yoga and meditation can substantially improve the integrity of
sperm DNA by reducing levels of oxidative DNA damage, regulating oxidative stress and by
increasing the expression of genes responsible for DNA repair, cell-cycle control and
anti-inflammatory effects. Oxidative stress is caused by various modifiable factors, and the use of
simple interventions can decrease levels of oxidative stress, and therefore reduce the incidence
of both infertility and complex diseases in the resultant offspring.
The variations found in the elemental composition in ecstasy samples result in spectral profiles with useful information for data analysis, and cluster analysis of these profiles can help uncover different categories of the drug. We provide a cluster analysis of ecstasy tablets based on their elemental composition. Twenty-five elements were determined by ICP-MS in tablets apprehended by Sao Paulo's State Police, Brazil. We employ the K-means clustering algorithm along with C4.5 decision tree to help us interpret the clustering results. We found a better number of two clusters within the data, which can refer to the approximated number of sources of the drug which supply the cities of seizures. The C4.5 model was capable of differentiating the ecstasy samples from the two clusters with high prediction accuracy using the leave-one-out cross-validation. The model used only Nd, Ni, and Pb concentration values in the classification of the samples.
Triclocarban is widely used as an antibacterial agent in personal care products, and the potential for human exposure exists. We present here the first nationally representative assessment of exposure to triclocarban among Americans ≥ 6 years of age who participated in the 2013–2014 National Health and Nutrition Examination Survey. We detected triclocarban at concentrations above 0.1 µg/L in 36.9% of 2,686 urine samples examined. Triclocarban was detected more frequently in adolescents and adults than in children, and in non-Hispanic black compared to other ethnic groups. In univariate analysis, log-creatinine, sex, age, race, and body surface area (BSA) were significantly associated with the likelihood of having triclocarban concentrations above the 95th percentile. In multiple regression models, persons with BSA at or above the median (≥1.86 m2) were 2.43 times more likely than others, and non-Hispanic black and non-Hispanic white were 3.71 times and 2.23 times more likely than “all Hispanic,” respectively, to have urinary concentrations above the 95th percentile. We found no correlations between urinary concentrations of triclocarban and triclosan, another commonly used antibacterial agent. Observed differences among demographic groups examined may reflect differences in physiological factors (i.e., BSA) as well as use of personal care products containing triclocarban.
The steep slopes of rivers can easily lead to large variations in river water quality during typhoon seasons in Taiwan, which may poses significant impacts on riverine eco-hydrological environments. This study aims to investigate the relationship between fish communities and water quality by using artificial neural networks (ANNs) for comprehending the upstream eco-hydrological system in northern Taiwan. We collected a total of 276 heterogeneous datasets with 8 water quality parameters and 25 fish species from 10 sampling sites. The self-organizing feature map (SOM) was used to cluster, analyze and visualize the heterogeneous datasets. Furthermore, the structuring index (SI) was adopted to determine the relative importance of each input variable of the SOM and identify the indicator factors. The clustering results showed that the SOM could suitably reflect the spatial characteristics of fishery sampling sites. Besides, the patterns of water quality parameters and fish species could be distinguishably (visually) classified into three eco-water quality groups: 1) typical upstream freshwater fishes that depended the most on dissolved oxygen (DO); 2) typical middle-lower reach riverine freshwater fishes that depended the most on total phosphorus (TP) and ammonia nitrogen; and 3) low lands or pond (reservoirs) freshwater fishes that depended the most on water temperature, suspended solids and chemical oxygen demand. According to the results of the SI, the representative indicators of water quality parameters and fish species consisted of DO, TP and Onychostoma barbatulum. This grouping result suggested that the methodology can be used as a guiding reference to comprehensively relate ecology to water quality. Our methods offer a cost-effective alternative to more traditional methods for identifying key water quality factors relating to fish species. In addition, visualizing the constructed topological maps of the SOM could produce detailed inter-relation between water quality and the fish species of stream habitat units.
General population human biomonitoring programs such as the National Health and Nutrition Examination Survey (NHANES) in the United States suggest that chemical exposures are common. Exposures during childhood may affect health later in life, but biomonitoring data in NHANES among pre-school aged children are limited.
A convenience group of 122 3-5year old American boys and girls were recruited in 2013 for a pilot study to assess the feasibility of collecting urine from young children and analyzing it for select chemical exposure biomarkers for future NHANES. Children were primarily Hispanic (64.8%); the remainder was divided between non-Hispanic black, and non-Hispanic white and "other." We measured 52 urinary biomarkers: 13 phthalates and one non-phthalate plasticizer, five phenols and four parabens, 10 polycyclic aromatic hydrocarbons (PAHs), and 19 pesticides. For each biomarker, we calculated descriptive statistics. We also calculated the number of biomarkers detected within each child, and performed principal components analysis (PCA).
NHANES staff obtained permission to attempt collection of 60mL urine from 3 to 5year olds who participated in the 2013 NHANES health examination; 83% of children successfully provided the target volume. We detected 24 individual biomarkers of pesticides, phenols and parabens, phthalates/non-phthalate plasticizers, and PAHs in 95-100% of children. The median number of biomarkers detected was 37: nine pesticides, five phenols and parabens, 13 phthalates and non-phthalate plasticizers, and 10 PAHs. Biomarkers concentrations appear to be similar to national estimates among 6-11year old children from previous NHANES. PCA suggested high within-class correlations among biomarkers.
These young children successfully adhered to the collection protocol and produced enough urine for the quantification of environmental biomarkers currently being measured in NHANES participants 6 years of age and older. Using the same analytical methods employed for the analysis of samples collected from older NHANES participants, in this sample of pre-school aged children we detected multiple chemicals including plasticizers, combustion products, personal-care product chemicals, and pesticides. Starting with NHANES 2015-2016, the NHANES biomonitoring program will include urinary biomarkers for 3-5year old children to provide exposure data to select chemicals at the national level among this age group.
As a part of the Chemicals Management Plan launched in 2006, the Government of Canada is assessing and managing, where appropriate, the potential health and ecological risks associated with approximately 4300 substances under the Canadian Environmental Protection Act (1999). Since that time, nearly 3,000 substances have been assessed, with human biomonitoring (HBM) data playing an increasingly important role for some substances. Case studies are presented, including both inorganic and organic substances (i.e., selenium, triclosan, phthalates), which highlight the impact and overall role HBM has had in regulatory decision making in Canada for these three substances as well as criteria used in the application of HBM data in human health risk assessment. An overview of its limitations in terms of how and when HBM data can be applied, when assessing human health in a regulatory setting, is discussed as well as the role HBM data can play in priority setting.
The Everglades ecosystem in Florida, USA, is naturally phosphorus (P) limited, and faces threats of ecosystem change and associated losses to habitat, biodiversity, and ecosystem function if subjected to high inflows of P and other nutrients. In addition to changes in historic hydropattern, upstream agriculture (sugar cane, vegetable, citrus) and urbanization has placed the Everglades at risk due to nutrient-rich runoff. In response to this threat, the Stormwater Treatment Areas (STAs) were constructed along the northern boundary of the Everglades as engineered ecological systems designed to retain P from water flowing into the Everglades. This research investigated data collected over a period from 2002 to 2014 from the interior of the STAs using data mining and analysis techniques including (a) exploratory methods such as Principal Component Analysis to test for patterns and groupings in the data, and (b) modelling approaches to test for predictive relationships between environmental variables. The purpose of this research was to reveal and compare spatial trends and relationships between environmental variables across the various treatment cells, flow-ways, and STAs. Common spatial patterns and their drivers indicated that the flow-ways do not function along simple linear gradients; instead forming zonal patterns of P distribution that may increasingly align with the predominant flow path over time. Findings also indicate that the primary drivers of the spatial distribution of P in many of these systems relate to soil characteristics. The results suggest that coupled cycles may be a key component of these systems; i.e. the movement and transformation of P is coupled to that of nitrogen (N).
Bisphenol-A (BPA) exposure occurs commonly and may adversely impact pregnancy. Endocrine disruption is posited as the primary mechanism of action, but oxidative stress and inflammation pathways may also be important. We investigated associations between BPA exposure and oxidative stress and inflammation in 482 pregnant women. Participants were recruited early in pregnancy and provided urine and plasma at up to four visits. We measured total BPA and two biomarkers of oxidative stress (8-hydroxydeoxyguanosine and 8-isoprostane) in urine from each visit. Inflammation markers, including C-reactive protein and four cytokines were measured in plasma from the same time points. In adjusted models, an interquartile range increase in BPA was associated with significant increases in both oxidative stress biomarkers (5–9% increase). Additionally, we observed significantly higher IL-6 concentrations in association with an interquartile range increase in BPA (8.95% increase). These systemic changes consequent to BPA exposure may mediate adverse birth outcomes and/or fetal development.
Endocrine disrupting chemicals (EDCs) are released into the environment from different sources. They are mainly used in packaging industries, pesticides and food constituents. Clinical evidence, experimental models, and epidemiological studies suggest that EDCs have major risks for humans by targeting different organs and systems in the body (e.g. reproductive system, breast tissue, adipose tissue, pancreas, etc.). Due to the ubiquity of human exposure to these compounds the aim of this review is to describe the most recent data on the effects induced by phthalates, bisphenol A and parabens in a critical window of exposure: in utero, during pregnancy, infants, and children. The interactions and mechanisms of toxicity of EDCs in relation to human general health problems, especially those broadening the term of endocrine disruption to 'metabolic disruption', should be deeply investigated. These include endocrine disturbances, with particular reference to reproductive problems and breast, testicular and ovarian cancers, and metabolic diseases such as obesity or diabetes.
Endometriosis is an estrogen dependent gynecologic disease with lasting implications for many women's fertility, somatic health, and overall quality of life. Growing evidence suggests that endocrine disrupting chemicals (EDCs) may be etiologically involved in the development and severity of disease. We weigh the available human evidence focusing on EDCs and endometriosis, restricting to research that has individually quantified chemical concentrations for women, included a comparison group of unaffected women, and used multivariable analytic techniques. Evidence supporting an environmental etiology for endometriosis includes metals/trace elements, dioxins, and other persistent organic pollutants, as well as nonpersistent chemicals, such as benzophenones and phthalates. To address the equivocal findings for various EDCs, future research directions for filling data gaps include  use of integrated clinical and population sampling frameworks allowing for incorporation of new diagnostic modalities;  the collection of various biologic media, including target tissues for quantifying exposures;  study designs that offer various comparison groups to assess potentially shared etiologies with other gynecologic disorders; and  novel laboratory and statistical approaches that fully explore all measured EDCs for the assessment of mixtures and low dose effects and the use of directed acyclic graphs and supporting causal analysis for empirically delineating relationships between EDCs and endometriosis.
Emission of polycyclic aromatic hydrocarbons (PAHs) from e-waste recycling activities in China is known. However, little is known on the association between PAH exposure and oxidative damage to DNA and lipid content in people living near e-waste dismantling sites. In this study, ten hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and two biomarkers [8-hydroxy-2′-deoxyguanosine (8-OHdG) and malondialdehyde (MDA)] of oxidative stress were investigated in urine samples collected from people living in and around e-waste dismantling facilities, and in reference population from rural and urban areas in China. The urinary levels of ∑10OH-PAHs determined in e-waste recycling area (GM: 25.4 μg/g Cre) were significantly higher (p < 0.05) than those found in both rural (11.7 μg/g Cre) and urban (10.9 μg/g Cre) reference areas. The occupationally exposed e-waste workers (36.6 μg/g Cre) showed significantly higher (p < 0.01) urinary Σ10OH-PAHs concentrations than non-occupationally exposed people (23.2 μg/g Cre) living in the e-waste recycling site. The differences in urinary Σ10OH-PAHs levels between smokers (23.4 μg/g Cre) and non-smokers (24.7 μg/g Cre) were not significant (p > 0.05) in e-waste dismantling sites, while these differences were significant (p < 0.05) in rural and urban reference areas; this indicated that smoking is not associated with elevated levels of PAH exposure in e-waste dismantling site. Furthermore, we found that urinary concentrations of Σ10OH-PAHs and individual OH-PAHs were significantly associated with elevated 8-OHdG, in samples collected from e-waste dismantling site; the levels of urinary 1-hydroxypyrene (1-PYR) (r = 0.284, p < 0.01) was significantly positively associated with MDA. Our results indicate that the exposure to PAHs at the e-waste dismantling site may have an effect on oxidative damage to DNA among selected participants, but this needs to be validated in large studies.
Endocrine disrupting chemicals (EDCs) are harmful, xenobiotic compounds requiring a multi-tiered analytical approach for a reliable management. Although worth efforts worldwide, comprehensive EDCs monitoring and risk-assessment still require improvements. This article covers possible risks for public health due to EDCs exposure, and revises the maturity reached in different analytical detection fields, with a special focus on biosensor technology. Among validated laboratory-techniques, hyphenated mass-spectrometry-based chromatography provides high selectivity and multi-analyte detection, while in vitro bioassays enable reliable toxicological testing. However, none of these methods is suitable for fast in field, continuous or semi-continuous operations. Due to advances in material science and synthetic biology, now biosensor technology holds the promise to close this gap and, although not included yet in routinely screening programs, fulfill the necessary requirements to sustain a coherent and global strategy to assess the state of environmental pollution.