Repeated-dose toxicity and toxicokinetic study of isobutylparaben in rats subcutaneously treated for 13 weeks.

Parabens have historically served as antimicrobial preservatives in a range of consumables such as food, beverages, medications, and personal care products due to their broad-spectrum antibacterial and antifungal properties. Traditionally, these compounds were believed to exhibit low toxicity, causing minimal irritation, and possessing limited sensitization potential. However, recent evidence suggests that parabens might function as endocrine-disrupting chemicals (EDCs). Consequently, extensive research is underway to elucidate potential human health implications arising from exposure to these substances. Among these parabens, particular concerns have been raised regarding the potential adverse effects of iso-butylparaben (IBP). Studies have specifically highlighted its potential for inducing hormonal disruption, significant ocular damage, and allergic skin reactions. This study aimed to evaluate the prolonged systemic toxicity, semen quality, and estrus cycle in relation to endocrine disruption endpoints, alongside assessing the toxicokinetic behavior of IBP in Sprague-Dawley rats following a 13-week repeated subcutaneous administration. The rats were administered either the vehicle (4% Tween 80) or IBP at dosage levels of 2, 10, and 50 mg/kg/day for 13 weeks. Blood collection for toxicokinetic study was conducted on three specified days: day 1 (1st), day 30 (2nd), and day 91 (3rd). Systemic toxicity assessment and potential endocrine effects were based on various parameters including mortality rates, clinical signs, body weights, food and water consumption, ophthalmological findings, urinalysis, hematological and clinical biochemistry tests, organ weights, necropsy and histopathological findings, estrus cycle regularity, semen quality, and toxicokinetic behavior. The findings revealed that IBP induced local irritation at the injection site in males at doses ≥ 10 mg/kg/day and in females at 50 mg/kg/day; however, systemic toxicity was not observed. Consequently, the no-observed-adverse-effect level (NOAEL) for IBP was determined to be 50 mg/kg/day in rats of both sexes, indicating no impact on the endocrine system. The toxicokinetics of IBP exhibited dose-dependent systemic exposure, reaching a maximum dose of 50 mg/kg/day, and repeated administration over 13 weeks showed no signs of accumulation.

A sustainable and innovative method to determine parabens in body creams for exposure and risk assessment.

Methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) are among the most widely used preservatives in cosmetics, drugs, and foods. These compounds have been associated with toxic effects due to the overuse of products with parabens in their formulation. The toxicity of parabens may be correlated to endocrine disruption, owing to their ability to mimic the actions of estradiol. In this paper, a simple, sustainable, robust, and innovative dispersive liquid-liquid microextraction (DLLME) technique was developed and employed to extract these xenobiotics from body cream samples, aiming to calculate the margin of safety (MoS) to assess the risk of exposure. The validated method presented suitable linearity (r > 0.99), lower limits of detection (ranging from 0.01 to 0.04 % w/w), and satisfactory precision and accuracy (ranging from 4.33 to 10.47, and from -14.25 to 13.85, respectively). Seven of the ten analysed samples presented paraben contents within the acceptable concentration according to European legislation. The MoS value obtained for PrP (37.58) suggested its reduced safety, indicating that PrP may significantly contribute to systemic exposure resulting from the use of personal care products.

Long-term impacts of endocrine-disrupting chemicals exposure on kidney function: A community-based cohort study.

This study explores the extended renal effects of endocrine-disrupting chemicals (EDCs) exposure, a linkage already established with adverse health outcomes, notably chronic kidney disease. To delve deeper, the Chang Gung Community Research Center conducted a longitudinal study with 887 participants. Among them, 120 individuals were scrutinized based on EDC scores, analyzing 17 urinary EDCs and renal function. Findings revealed elevated mono-(2-ethylhexyl) phthalate (MEHP) and bisphenol A levels in higher EDC exposure cases. MEHP notably correlated with increased urinary albumin-to-creatinine ratio (UACR), predicting a > 15% decline in estimated glomerular filtration rate. Higher MEHP levels also hinted at declining renal function. UACR escalation linked significantly with specific EDCs: MEHP, methylparaben, nonylphenol, and 4-tert-octylphenol. This research underscores enduring renal hazards tied to environmental EDC exposure, particularly MEHP, emphasizing the urgent call for robust preventive public health strategies.

Parabens effects on female reproductive health - Review of evidence from epidemiological and rodent-based studies.

Parabens have been used as antimicrobial preservatives since the 1920s. The prevalent use of parabens increases their detection in the environment and in women's biological samples including reproductive tissues. Recent studies suggest parabens may alter endocrine function and thus female reproductive health may be affected. In this literature review, we summarize findings on parabens and female reproduction while focusing on epidemiological and rodent-based studies. The topics reviewed include paraben effects on cyclicity, pregnancy, newborn and pubertal development, reproductive hormones, and ovarian and uterine specific outcomes. Overall, the scientific literature on paraben effects on female reproduction is limited and with some conflicting results. Yet, some epidemiological and/or rodent-based experimental studies report significant findings in relation to paraben effects on cyclicity, fertility, gestation length, birth weight, postnatal development and pubertal onset, hormone levels, and hormone signaling in reproductive tissues. Future epidemiological and experimental studies are needed to better understand paraben effects on female reproduction while focusing on human related exposures including mixtures, physiologic concentrations of parabens, and multi-generational studies.

The combined effects of preservative chemicals in consumer products: An analysis using embryonic and adult zebrafish.

Benzisothiazolinone (BIT) and propyl paraben (PP) are preservatives in cleaning products; however, their toxicities are not well understood. In this study, zebrafish embryos were exposed to BIT, PP, and mixtures of both for 96 h to investigate the effects on growth hormone (GH), insulin-like growth factor-1 (IGF-1), and the transcription of 19 genes related to the GH/IGFs axis. Concentrations of BIT and PP were measured in the whole body of larvae. Zebrafish pairs were also exposed to BIT, PP, and mixtures for 21 d to evaluate the effects on sex hormones, histology in gonad, and transcription of 22 genes related to the hypothalamus-pituitary-gonad axis and vitellogenin. The mixtures had potentiation effects on development, reproduction, hormones, and gene transcripts than individual exposure. Larvae exposed to 229 µg L-1 BIT, 64.5 µg L-1 PP, and mixtures showed reduced growth. Decreased GH and IGF-1 levels were supported by gene regulation associated with the GH/IGFs axis. In larvae, reactive oxygen species, superoxide dismutase, catalase, and glutathione peroxidase levels were increased under all exposures. The gonadosomatic index in males and number of eggs decreased after mixture exposure. In females exposed to mixtures, the percentage of atretic follicle in ovary was significantly increased. The significant decrease in testosterone in males and significant decrease in 17ß-estradiol in females exposed to mixtures suggest anti-estrogenic and anti-androgenic potential. Thus, preservative mixtures in consumer products may be more toxic than the individual substances, which is important for managing the risks of mixing preservatives.

Association between parabens exposure and neurodevelopment in children.

OBJECTIVE: Parabens are a group of substances commonly employed as antimicrobial preservatives. The effect of parabens on the development of neurotoxicity in children is still controversial. This study aimed to explore the associations between parabens exposure and children's neurodevelopmental performance, emphasizing potential sex differences and the combined effects of parabens. METHODS: We used the long-term follow-up study of Taiwanese generation, Taiwan Birth Panel Study II (TBPS II). We recruited the group of children at 6-8 years old. And, we measured parabens in children urine, including methylparaben (MP), ethylparaben (EP), propylparaben (PP) and butylparaben (BP). Children's attention-related performance was evaluated using the Conners Kiddie Continuous Performance Test 2nd Edition (K-CPT 2). The study employed both linear regression and mixture analysis quantile g-computation (QGC) methods to discern associations. A stratified analysis by sex and QGC was implemented to delve deeper into the cumulative effects of parabens. RESULTS: A total of 446 subjects completed both the parabens analysis and the K-CPT 2 survey. The overall association between parabens and neurodevelopmental performance was not pronounced, but discernible sex differences emerged. In the single pollutant analysis, elevated PP concentrations were associated with higher K-CPT 2 scores particularly in detectability (d') (ß = 0.92 [95 % CI = 0.15 to 1.69]) and commissions (ß = 0.95 [95 % CI = 0.12 to 1.78]), among girls. Further, in the mixture analysis, a significant association between PP and detectability (d') was observed in girls (ß = 1.68 [95 % CI = 0.11 to 3.26]). CONCLUSIONS: This study identified sex-specific associations between parabens and attention performance. Consistent outcomes across single and mixture analysis methods. Further research is crucial to clarify these causal associations.

Distribution of parabens and 4-HB in human blood.

Human blood has been commonly and routinely analyzed to determine internal human exposure to parabens. However, data on the occurrence of parabens and their common metabolite, p-hydroxybenzoic acid (4-HB), in different human blood matrixes is still limited. In this study, 139 pairs of serum and whole blood samples were collected from Chinese adults, and then analyzed them for 5 parabens and 4-HB. Methylparaben (MeP) and propylparaben (PrP) were consistently the predominant parabens in human serum (mean 2.3 and 2.1 ng/mL, respectively) and whole blood (1.9 and 1.3 ng/mL, respectively). Mean concentrations of 4-HB in human serum and whole blood were 7.7 and 12 ng/mL, respectively. Concentrations of parabens, except benzylparaben (BzP), and 4-HB in human serum were significantly (p < 0.01) correlated with that in whole blood. Distribution pattern of parabens and 4-HB in human blood was evaluated, for the first time, based on their partitioning between human serum and whole blood (Kp). Mean Kp values of parabens, except BzP, increased with the alkyl chain length from 0.83 to 1.6. BzP (mean 1.4) had a comparable mean Kp value to PrP (mean 1.4). Among target analytes, 4-HB had the lowest mean Kp value (0.75). These data are important to select appropriate blood matrixes for conducting human exposure assessment and epidemiological studies on parabens.

Substrate specificity modification of paraben hydrolase and tannase from Aspergillus oryzae.

Paraben hydrolase and tannase catalyze the hydrolysis of parabens (4-hydroxybenzoic acid esters) and gallic acid (3,4,5-trihydroxybenzoic acid) esters, respectively. Paraben hydrolase (AoPrbA) and tannase (AoTanB) from Aspergillus oryzae belong to the tannase family in the ESTHER database. However, the substrate specificities of AoPrbA and AoTanB are narrow. Based on structural information of Aspergillus niger tannase (PDB code 7k4o), we constructed five single variants of AoPrbA (Thr200Glu, Phe231Gln, Leu232Gln, Ile361Tyr, and Leu428Ser) and four of AoTanB (Glu203Asp, Glu203Thr, His237Ala, and Ser440Leu) to investigate substrate discrimination between AoPrbA and AoTanB. Each variant was expressed in Pichia pastoris and were purified from the culture supernatant. Five purified variants of AoPrbA and four variants of AoTanB showed reduced paraben hydrolase and tannase activities compared with AoPrbA and AoTanB wild types, respectively. Interestingly, the AoPrbA wild type did not hydrolyze gallic acid methyl ester, whereas the Thr200Glu, Leu232Gln, and Leu428Ser variants did, indicating that these three variants acquired tannase activity. In particular, the Leu428Ser variant exhibited considerably greater hydrolysis of gallic acid and protocatechuic acid methyl esters. Meanwhile, the AoTanB wild type, and Glu203Asp, His237Ala and Ser440Leu variants hydrolyzed the protocatechuate methyl and 4-hydroxybenzoate ethyl esters; however, the Glu203Thr variant did not hydrolyze above-mentioned substrates. Additionally, the ratio of paraben hydrolase activity to tannase activity in Ser440Leu was markedly elevated.

Endocrine-Disrupting Chemicals Exposure and Neurocognitive Function in the General Population: A Community-Based Study.

BACKGROUND: Endocrine-disrupting chemicals (EDCs) are pervasive in everyday environments. The impacts of these chemicals, along with EDC-related lifestyle and dietary habits on neurocognitive function, are not well understood. METHODS: The Chang Gung Community Medicine Research Center conducted a cross-sectional study involving 887 participants. From this initial cohort, 120 individuals were selected based on their EDC exposure scores for detailed analysis. Among these, 67 participants aged 55 years or older were further chosen to undergo cognitive impairment assessments using the Ascertain Dementia-8 (AD-8) questionnaire. RESULTS: These 67 older participants did not significantly differ in age, albuminuria, or estimated glomerular filtration rate compared to those with lower impairment scores. This study revealed that mono-(2-ethylhexyl) phthalate (MEHP) levels (8.511 vs. 6.432 µg/g creatinine, p = 0.038) were associated with greater risk of cognitive impairment (AD-8 ≥ 2). Statistical models adjusting for age, gender, and diabetes indicated that MEHP levels positively correlated with AD-8 scores, achieving statistical significance in more comprehensive models (ß ± SE: 0.160 ± 0.076, p = 0.042). Logistic regression analysis underscored a significant positive association between high MEHP levels and higher AD-8 scores (odds ratio: 1.217, p = 0.006). Receiver operating characteristic curves highlighted the association of high MEHP levels and EDC exposure scores for significant cognitive impairment, with areas under the curve of 66.3% and 66.6%, respectively. CONCLUSION: Exposure to EDCs, specifically di-(2-ethylhexyl) phthalate, the precursor to MEHP, may be associated with neurocognitive impairment in middle-aged and older adults.

Dose-dependent effects of different parabens on food waste biorefinery for volatile fatty acids production: Insight into specific fermentation processes, substrates transformation and microbial metabolic traits.

Parabens are largely concentrated in food waste (FW) due to their large consumption as the widely used preservative. To date, whether and how they affect FW resource recovery via anaerobic fermentation is still largely unknown. This work unveiled the hormesis-like effects of two typical parabens (i.e., methylparaben and n-butylparaben) on VFAs production during FW anaerobic fermentation (i.e., parabens increased VFAs by 6.73-14.49 % at low dose but caused 82.51-87.74 % reduction at high dose). Mechanistic exploration revealed that the parabens facilitated the FW solubilization and enhanced the associated substrates' biodegradability. The low parabens enriched the functional microorganisms (e.g., Firmicutes and Actinobacteria) and upregulated those critical genes involved in VFAs biosynthesis (e.g., GCK and PK) by activating the microbial adaptive capacity (i.e., quorum sensing and two-component system). Consequently, the metabolism rates of fermentation substrates and subsequent VFAs production were accelerated. However, due to increased biotoxicity of high parabens, the functional microorganisms and relevant metabolic activities were depressed, resulting in the significant reduction of VFAs biosynthesis. Structural equation modeling clarified that microbial community was the predominant factor affecting VFAs generation, followed by metabolic pathways. This work elucidated the dose-dependent effects and underlying mechanisms of parabens on FW anaerobic fermentation, providing insights for the effective management of FW resource recovery.

Associations of urinary non-persistent endocrine disrupting chemical biomarkers with early-to-mid pregnancy plasma sex-steroid and thyroid hormones.

BACKGROUND/OBJECTIVES: Pregnant women are exposed to numerous endocrine disrupting chemicals (EDCs) that can affect hormonal pathways regulating pregnancy outcomes and fetal development. Thus, we evaluated overall and fetal sex-specific associations of phthalate/replacement, paraben, and phenol biomarkers with sex-steroid and thyroid hormones. METHODS: Illinois women (n = 302) provided plasma for progesterone, estradiol, testosterone, free T4 (FT4), total T4 (TT4), and thyroid stimulating hormone (TSH) at median 17 weeks gestation. Women also provided up-to-five first-morning urine samples monthly across pregnancy (8-40 weeks), which we pooled to measure 19 phthalate/replacement metabolites (reflecting ten parent compounds), three parabens, and six phenols. We used linear regression to evaluate overall and fetal sex-specific associations of biomarkers with hormones, as well as weighted quantile sum and Bayesian kernel machine regression (BKMR) to assess cumulative associations, non-linearities, and chemical interactions. RESULTS: In women of relatively high socioeconomic status, several EDC biomarkers were associated with select hormones, without cumulative or non-linear associations with progesterone, FT4, or TT4. The biomarker mixture was negatively associated with estradiol (only at higher biomarker concentrations using BKMR), testosterone, and TSH, where each 10% mixture increase was associated with -5.65% (95% CI: -9.79, -1.28) lower testosterone and -0.09 µIU/mL (95% CI: -0.20, 0.00) lower TSH. Associations with progesterone, testosterone, and FT4 did not differ by fetal sex. However, in women carrying females, we identified an inverted u-shaped relationship of the mixture with estradiol. Additionally, in women carrying females, each 10% increase in the mixture was associated with 1.50% (95% CI: -0.15, 3.18) higher TT4, whereas in women carrying males, the mixture was associated with -1.77% (95% CI: -4.08, 0.58) lower TT4 and -0.18 µIU/mL (95% CI: -0.33, -0.03) lower TSH. We also identified select chemical interactions. CONCLUSION: Some biomarkers were associated with early-to-mid pregnancy hormones. There were some sex-specific and non-linear associations. Future studies could consider how these findings relate to pregnancy/birth outcomes.

The mixed effect of Endocrine-Disrupting chemicals on biological age Acceleration: Unveiling the mechanism and potential intervention target.

INTRODUCTION: Although previous studies investigated the potential adverse effects of endocrine-disrupting chemicals (EDCs) on biological age acceleration and aging-related diseases, the mixed effect of multiple types of EDCs on biological age acceleration, including its potential underlying mechanism, remains unclear. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) were used to analyze biological age measures, including Klemera-Doubal method biological age (KDM-BA), phenotypic age, and homeostatic dysregulation (HD). Weight quantile sum (WQS) regression was performed to screen biological age-related EDCs (BA-EDCs) and assess the mixed effect of BA-EDCs on biological age acceleration and aging-related disease. Targets of BA-EDCs were obtained from three databases, while heart aging-related genes were obtained from the Aging Anno database. Protein-protein interaction (PPI) network and MCODE algorithm were applied to identify potential interactions between BA-EDC targets and heart aging-related genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to identify related pathways. RESULTS: This cross-sectional study included 1,439 participants. A decile increase in BA-EDCs co-exposure was associated with 0.31 years and 0.17 years of KDM-BA and phenotypic age acceleration, respectively. The mixed effect of BA-EDCs was associated with an increased prevalence of atherosclerotic cardiovascular disease (ASCVD). Vitamins C and E demonstrated a significant interaction effect on the association between BA-EDCs and KDM-BA acceleration. PPI network and functional enrichment analysis indicated that the AGE-RAGE signaling pathway in diabetic complications was significantly enriched. CONCLUSION: Our results showed that the co-exposure effect of BA-EDCs was associated with biological age acceleration and ASCVD, with the AGE-RAGE signaling pathway being the underlying mechanism. Vitamins C and E may also be an actionable target for preventing EDC-induced biological aging.

Exposure assessment of dairy cows to parabens using hair samples analysis.

Parabens (PBs) are used as preservatives in various products. They pollute the environment and penetrate living organisms, showing endocrine disrupting activity. Till now studies on long-term exposure of farm animals to PBs have not been performed. Among matrices using in PBs biomonitoring hair samples are becoming more and more important. During this study concentration levels of methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP) butyl paraben (BuP) and benzyl paraben (BeP) were evaluated using liquid chromatography-mass spectrometry (LC-MS) in hair samples collected from dairy cows bred in the Kyrgyz Republic. MeP was noted in 93.8% of samples (with mean concentration levels 62.2 ± 61.8 pg/mg), PrP in 16.7% of samples (12.4 ± 6.5 pg/mg) and EtP in 8.3% of samples (21.4 ± 11.9 pg/mg). BuP was found only in one sample (2.1%) and BeP was not detected in any sample included in the study. Some differences in MeP concentration levels in the hair samples depending on district, where cows were bred were noted. This study has shown that among PBs, dairy cows are exposed mainly to MeP, and hair samples may be a suitable matrix for research on PBs levels in farm animals.

Comparative study on estrogen receptor alpha dimerization and transcriptional activity of parabens.

Parabens are used as preservatives in various household products, including oral products, cosmetics, and hair/body washes. In recent years, the widespread use of parabens has raised concerns due to the potential health risks associated with their estrogenic effects. In the present study, we evaluated and compared the estrogenic activity of parabens using two cell-based in vitro tests: (1) bioluminescence resonance energy transfer (BRET)-based estrogen receptor alpha (ERα) dimerization using HEK293 cells that were stably transfected with ERα-fused NanoLuc luciferase (Nluc) and HaloTag (HT) expression vector, and (2) stably transfected transcriptional activation (STTA) assays using ERα-HeLa9903 cells. The following parabens were tested using the BRET-based ERα dimerization assay and showed estrogenic activity (PC20 values): methyl paraben (MP, 5.98 × 10-5 M), ethyl paraben (EP, 3.29 × 10-5 M), propylparaben (PP, 3.09 × 10-5 M), butyl paraben (BP, 2.58 × 10-5 M), isopropyl paraben (IsoPP, 1.37 × 10-5 M), and isobutyl paraben (IsoBP, 1.43 × 10-5 M). Except MP, all other parabens tested using the STTA assay also showed estrogenic activity: EP, 7.57 × 10-6 M; PP, 1.18 × 10-6 M; BP, 3.02 × 10-7 M; IsoPP, 3.58 × 10-7 M; and IsoBP, 1.80 × 10-7 M. Overall, EP, PP, BP, IsoPP, and IsoBP tested positive for estrogenic activity using both assays. These findings demonstrate that most parabens, albeit not all, induce ERα dimerization and possess estrogenic activity.

Associations between urinary paraben levels and obesity of 10-year-old children / 环境与职业医学

Background Parabens, a widely used class of preservatives, are suspected to be potential obesogens as emerging endocrine disrupting chemicals with reproductive and developmental toxicity. Objective To analyze five urinary parabens (PBs) and estimate the associations of exposure to PBs with adiposity measures in 10-year-old school-age children. Methods A total of 471 school-age children aged 10 years from the Sheyang Mini Birth Cohort were enrolled in this study. A questionnaire survey was conducted to collect socio-demographic information, physical activity, and dietary intake. Weight, height, and waist circumference of children were measured, and age- and sex-adjusted body mass index (BMI-Z score) was calculated. Spot urine samples were collected during the follow-up visits. Urinary concentrations of five PBs including methyl-paraben (MeP), ethyl-paraben (EtP), propyl-paraben (PrP), butyl-paraben (BuP), and benzyl-paraben (BzP) were detected by gas chromatography-tandem mass spectrometry (GC-MS/MS). Generalized linear models (GLMs) and Bayesian kernel machine regression (BKMR) models were applied to estimate associations of individual/overall urinary PBs concentrations with BMI Z-score and waist circumference. Results The positive rates of selected five urinary PBs were in the range from 78.98% to 98.94%. The urinary PBs concentrations (geometric mean) were in the range of 0.31-5.43 μg·L−1. The children's BMI Z-score and waist circumference (mean ± standard deviation) were (0.56±1.40) and (67.62±10.07) cm respectively. The GLMs results showed that the urinary BzP concentration was negatively associated with waist circumference (b=−0.08, 95%CI: −0.14, −0.02; P=0.01). In sex-stratified analysis, the urinary concentration of BzP was negatively associated with BMI-Z score (b=−0.59, 95%CI: −0.88, −0.30; P<0.001) and waist circumference (b=−0.80, 95%CI: −1.23, −0.37; P<0.001) in boys, but not in girls. The BKMR results also found significant negative correlations of urinary BzP concentrations with BMI-Z score and waist circumference, which were consistent with the GLM results. Conclusion The selected 10-year-old children are extensively exposed to PBs in the study area. Furthermore, childhood PBs exposure may have potential impacts on childhood adiposity measures with sex-specific effects.

Exposure to paraben and triclosan and allergic diseases in Tokyo: A pilot cross-sectional study

BACKGROUND: Previous studies have reported that exposure to paraben (Pb) and triclosan (TCS) is associated with allergies. However, Pb and TCS exposure in the Japanese population is not fully understood. OBJECTIVES: The present study was aimed to examine such exposure among Japanese individuals with allergic diseases. METHODS: This cross-sectional study included the International Study of Asthma and Allergies in Childhood questionnaire survey to evaluate allergic outcomes and the collection of urine samples to examine Pb and TCS exposure. RESULTS: Pb containing daily commodities was used in 84.8% children. Pb use was positively associated with current atopic dermatitis (adjusted odds ratio, 4.61; 95% confidence interval, 1.23–17.3). Urinary Pb concentrations were increased significantly in those with current atopic dermatitis (AD) (median, 4.58 vs. 0; p < 0.0001), and showed an increased tendency in those with current wheeze (median, 3.45 vs. 1.81; p = 0.0535) in participants ≤15 years old. Urinary TCS concentration was under the limit of detection in all children. CONCLUSION: Urinary levels of Pb were associated with current AD in children. We should pay more attention about Pb and TCS.

Validity and Reliability of the Wristband Activity Monitor in Free-living Children Aged 10-17 Years / 生物医学与环境科学（英文）

OBJECTIVE@#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.@*METHODS@#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.@*RESULTS@#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.@*CONCLUSION@#These results may promote future epidemiology studies and strategies to improve women's lifestyle and consume paraben-free products.

UPLC-QTOF mass spectrometry detection of four endocrine disrupting chemicals (Methyl Paraben, 2,4-Dichlorophenoxyacetic acid, Monobutyl Phthalate, and Bisphenol A) in urine of Filipino women

Background and Objective@#Endocrine Disrupting Chemicals (EDCs) are ubiquitously found as low-level contaminants and pose serious threat to women’s health. EDCs may result in various reproductive disorders, fetal birth and developmental abnormalities, and endocrine and metabolic disorders. EDCs can be detected in body fluids of exposed individuals including blood and urine. This study aimed to detect four EDCs — Methyl Paraben (MP), 2,4-Dichlorophenoxyacetic acid (2,4-D), Monobutyl Phthalate (MBP), and Bisphenol A (BPA) in urine samples of women using Ultra-Performance Liquid Chromatography – Quadrupole Time-of-Flight (UPLC-QTOF) mass spectrometry.@*Methods@#Sequential steps of enzymatic deconjugation, liquid-liquid extraction, solid phase extraction, and liquid chromatography separation and mass spectrometry detection were optimized in urine samples. The method was used to analyze 70 urine samples from women of reproductive age.@*Results@#The sample preparation method showed a recovery ranging from 86.6% (MBP) to 100 % (2,4-D). The method demonstrated limits of quantitation ranging from 1.52 ng/m(MP) to 6.46 ng/mL(2,4D). Intra-day precisions expressed as relative standard deviation were all below 15% while accuracy was shown to range from 67.10% (2,4-D) to 102.39% (MBP). MP was detected in nine samples (12.86%) with a geometric mean value of 10.15 ng/ml (range: 3.62-52.39 ng/ml). MBP was detected in 68 samples (97.14%) with a geometric mean value of 97.62 ng/ml (range: 15.32-698.18 ng/ml). BPA was detected only once (9.58 ng/ml) while 2, 4-D was not detected in all samples.@*Conclusion@#A UPLC-QTOF mass spectrometry method to detect four EDCs at parts per billion level (ng/ml) was adapted and applied for analysis of urine samples. This method can find applicability in routine testing of clinical specimens as well as surveillance and other epidemiological studies.

Toxicities of Four Parabens and Their Mixtures to Daphnia magna and Aliivibrio fischeri

The objective of this study was to determine toxicities of four parabens (methyl paraben, MP; ethyl paraben, EP; n-propyl paraben, PP; and n-butyl paraben; BP) and their mixtures to two aquatic microorganisms, Daphnia magna and Aliivibrio fischeri. Parabens are one of the widely used preservatives for personal care products, such as cosmetics, pharmaceuticals and food also. First, each paraben was treated to D. magna to measure the toxicity levels as LC₂₀ and LC₅₀. The results showed their value of MP (25.2 mg/L, 73.4 mg/L), EP (18.4 mg/L, 43.7 mg/L), PP (10.4 mg/L, 21.1 mg/L) and BP (3.3 mg/L, 11.2 mg/L). Then, each of the parabens was treated to A. fischeri and calculated their EC₂₀ and EC₅₀ by bioluminescence inhibition test. The results showed the values of MP (2.93 mg/L, 16.8 mg/L), EP (1.18 mg/L, 6.74 mg/L), PP (0.51 mg/L, 5.85 mg/L) and BP (0.21 mg/L, 2.34 mg/L). These four parabens belong to the group classified as being ‘harmful to aquatic organisms’ (above 10 mg/L, below 100 mg/L). After measuring the toxicity, EC₂₀ values of two or more parabens were tested in order to investigate their toxicity. A total of ten combinations of four parabens were tested. As a result, the bioluminescence inhibition test of A. fischeri showed that the toxicity of mixture parabens was stronger than that of a single compound and combinations of three parabens showed the highest bioluminescence inhibition. These results showed that independent toxicity of paraben was maintained. Therefore, it can be predictable that the toxicity of paraben is getting stronger by the addition of other parabens.

Toxicities of Four Parabens and Their Mixtures to Daphnia magna and Aliivibrio fischeri

The objective of this study was to determine toxicities of four parabens (methyl paraben, MP; ethyl paraben, EP; n-propyl paraben, PP; and n-butyl paraben; BP) and their mixtures to two aquatic microorganisms, Daphnia magna and Aliivibrio fischeri. Parabens are one of the widely used preservatives for personal care products, such as cosmetics, pharmaceuticals and food also. First, each paraben was treated to D. magna to measure the toxicity levels as LC₂₀ and LC₅₀. The results showed their value of MP (25.2 mg/L, 73.4 mg/L), EP (18.4 mg/L, 43.7 mg/L), PP (10.4 mg/L, 21.1 mg/L) and BP (3.3 mg/L, 11.2 mg/L). Then, each of the parabens was treated to A. fischeri and calculated their EC₂₀ and EC₅₀ by bioluminescence inhibition test. The results showed the values of MP (2.93 mg/L, 16.8 mg/L), EP (1.18 mg/L, 6.74 mg/L), PP (0.51 mg/L, 5.85 mg/L) and BP (0.21 mg/L, 2.34 mg/L). These four parabens belong to the group classified as being ‘harmful to aquatic organisms’ (above 10 mg/L, below 100 mg/L). After measuring the toxicity, EC₂₀ values of two or more parabens were tested in order to investigate their toxicity. A total of ten combinations of four parabens were tested. As a result, the bioluminescence inhibition test of A. fischeri showed that the toxicity of mixture parabens was stronger than that of a single compound and combinations of three parabens showed the highest bioluminescence inhibition. These results showed that independent toxicity of paraben was maintained. Therefore, it can be predictable that the toxicity of paraben is getting stronger by the addition of other parabens.