Comprehensive monitoring of a special mixture of prominent endocrine disrupting chemicals in human urine using a carefully adjusted hydrolysis of conjugates.

Many xenobiotics were identified as possible endocrine disruptors during the last decades. Structural analogy of these substances to natural hormones may lead to agonists or antagonists of hormone receptors. For a comprehensive human biomonitoring of such substances, we developed a simple, reliable, and highly sensitive method for the simultaneous monitoring of the parameters bisphenol A, triclosan, methylparaben, ethylparaben, propylparaben, butylparaben, benzophenone-1, benzophenone-3, 3,5,6-trichloropyridin-2-ol, p-nitrophenol, genistein, and daidzein in urine. Thereby, optimization of the enzymatic hydrolysis and the use of ß-glucuronidase from E. coli K12 as well as sulfatase from Aerobacter aerogenes ensures the acquisition of intact analytes without cleavage of ester bonds among parabens. Validation of the method revealed limits of detection between 0.02 and 0.25 µg/L as well as limits of quantification between 0.08 and 0.83 µg/L. Thereby, the use of analyte-free surrogate matrix for calibration and control material influenced the sensitivity of the procedure positively. Furthermore, excellent precision in and between series was observed. Good absolute and relative recoveries additionally proved the robustness of the multimethod. Thus, the procedure can be applied for exploring the exposome to these prominent endocrine disruptors in the general population.

Co-exposure and health risks of several typical endocrine disrupting chemicals in general population in eastern China.

Human exposure to endocrine disrupting chemicals (EDCs) is a health concern due to their wide use and interference with the human endocrine system. Parabens, bisphenols, benzophenones, triclosan (TCC), triclocarban (TCS), and tetrabromobisphenol-A (TBBPA) and its derivatives tetrachlorobisphenol-A (TCBPA) and tetrabromobisphenol-S (TBBPS), are typical EDCs that are frequently detected in environmental and human samples. However, only a few studies have assessed the co-exposure of these chemicals in humans. In this study, urine samples were collected from the general population in the city of Wuxi (n = 121) and a county, Taishun (n = 120), eastern China, and analyzed for these EDCs. Parabens, bisphenols, TCS, and benzophenones were frequently detected in urine, whereas TBBPA and its derivatives were not detected. The geometric mean concentrations of parabens, bisphenols, and benzophenones in urine from the Wuxi population were 25.7, 2.45, and 2.34 ng/mL, respectively, which were substantially higher than those from the Taishun population (17.2, 1.70, and 2.65 ng/mL). These results suggest an urban-rural difference in urinary EDCs. The exposure risks to these EDCs were estimated based on the measured urinary concentrations and acceptable daily intakes (ADIs). Hazard quotient values for EDCs in humans from both locations were generally less than 1, indicating a low exposure risk of EDCs in these regions. Nonetheless, the health risks caused by co-exposure to such EDCs cannot be ignored.

Perinatal urinary benzophenone-3 concentrations and glucose levels among women from a fertility clinic.

BACKGROUND: Subfertile women have higher risk of glucose intolerance during pregnancy. Studies suggest associations between several endocrine disrupting chemicals (EDCs) and pregnancy glucose levels. However, the association between benzophenone-3 (BP-3), an EDC widely found in sunscreen, and pregnancy glucose levels remains unclear. We aimed to assess the association between perinatal exposures to BP-3 and pregnancy glucose levels in subfertile women. METHODS: We evaluated 217 women from a prospective cohort based at a fertility clinic who had urinary BP-3 concentrations measured during 3-month preconception, first and/or second trimesters, and blood glucose measured at glucose load tests (GLTs) during late pregnancy. Multivariable linear and logistic regression models were used to assess associations between time-specific BP-3 in quartiles (Q1 - Q4) and mean glucose levels, as well as odds of abnormal GLT (glucose level ≥ 140 mg/dL), adjusting for potential confounders. Effect modification was assessed by age, season, BMI, infertility diagnosis, sex of fetus (es) and physical activity. RESULTS: Women with higher first trimester BP-3 concentrations had lower mean glucose levels [mean glucose (95% CI) for Q4 vs Q1 = 103.4 (95.0, 112.5) vs. 114.6 (105.8, 124.2) mg/dL]. Women with higher second trimester BP-3 concentrations had lower odds of abnormal GLT [OR (95% CI) for Q3 vs. Q1 = 0.12 (0.01, 0.94)]. The associations between BP-3 and glucose levels were modified by several factors: women with female-factor infertility, urine collected during summer, older age, lower BMI, or carried female fetus (es) had the strongest inverse associations between BP-3 and glucose levels, while no associations were observed in the remaining subgroups. CONCLUSIONS: Time-specific inverse associations between BP-3 and pregnancy glucose levels existed in subfertile women, and especially among certain subgroups of this high-risk-population.

Associations of urinary levels of phenols and parabens with osteoarthritis among US adults in NHANES 2005-2014.

Phenols and parabens are two major classes of endocrine-disrupting compounds (EDCs) that may be related to multiple human diseases. However, there has been no studies examining the association between phenols as well as parabens and osteoarthritis (OA). We assessed the link between urinary concentrations of triclosan (TCS), benzophenone-3 (BP-3), bisphenol A (BPA), and parabens with OA based on the data collected from National Health and Nutrition Examination Survey in multivariable logistic regression models. Among all the 7114 participants included, the weighted percentage of OA was 12.11% (n = 807). Compared with participants at tertile 1, those at tertile 2 of urinary BP-3, and tertile 3 of urinary BP-3 were more likely to show increased OA prevalence in a fully adjusted model, with odd ratio (OR) as 1.34 [95% confidence interval (CI): 1.01-1.78], 1.55 (95 CI%: 1.17-2.06), and 1.66 (95 CI%: 1.23-2.24), respectively. In subgroup analyses stratified by potential confounders, various subgroups remained to show statistically significant positive association between urinary BP-3 and OA prevalence. Otherwise, we observed no statistically significant associations between urinary TCS, BPA or parabens with OA. In conclusion, this serves as the first study in which we found that the urinary concentration of BP-3 was positively correlated to prevalence of OA among the US population.

A validated UPLC-MS/MS method for the determination of urinary metabolites of Uvinul® A plus.

Uvinul® A plus (DHHB) is a synthetic benzophenone derivative mainly used in sunscreens, and also in other skin care products. The compound is authorized by the EU as UV filter and a maximum concentration of 10% in consumer products is permitted. Despite its high production volume and usage in consumer products,to date, no information about the systemic exposure to Uvinul® A plus in humans is available. Therefore, we developed a human biomonitoring method which allows the simultaneous determination of three major metabolites of Uvinul® A plus in human urine samples. Furthermore, three minor metabolites of Uvinul® A plus were identified by ion trap experiments. Urine samples were enzymatically hydrolyzed, extracted via liquid-liquid extraction with ethyl acetate, and analyzed by means of UPLC-MS/MS. The final method was validated according to FDA guidelines and applied to 58 urine samples retrieved from the general German population. The three major and specific metabolites of Uvinul® A plus were found in about 36% of the samples, proving the suitability of the method for future human biomonitoring studies.

Dermal Uptake of Benzophenone-3 from Clothing.

Benzophenone-3 (also known as BP-3 or oxybenzone) is added to sunscreens, plastics, and some coatings to filter UV radiation. The suspected endocrine disruptor BP-3 has been detected in the air and settled dust of homes and is expected to redistribute from its original sources to other indoor compartments, including clothing. Given its physical and chemical properties, we hypothesized that dermal uptake from clothing could contribute to the body burden of this compound. First, cotton shirts were exposed to air at an elevated concentration of BP-3 for 32 days; the final air concentration was 4.4 µg/m3. Next, three participants wore the exposed shirts for 3 h. After 3 h of exposure, participants wore their usual clothing during the collection of urine samples for the next 48 h. Urine was analyzed for BP-3, a metabolite (BP-1), and six other UV filters. The rate of urinary excretion of the sum of BP-1 and BP-3 increased for all participants during and following the 3 h of exposure. The summed mass of BP-1 and BP-3 excreted during the first 24 h attributable to wearing exposed t-shirts were 12, 9.9, and 82 µg for participants 1, 2, and 3, respectively. Analysis of these results, coupled with predictions of steady-state models, suggest that dermal uptake of BP-3 from clothing could meaningfully contribute to overall body burden.

Urinary benzophenone concentrations and their association with demographic factors in a South Korean population.

Benzophenone (BP) and its derivatives are widely used in various cosmetics, personal care products, and food packaging ink. The use of BP has raised concerns about the potential health risks associated with its endocrine-disrupting effects. This study evaluated urinary concentrations of BP derivatives in a national sample of the South Koreans population aged 6-89 years. From July to September in each 2010 and 2011, 1576 urine samples were collected. Urinary concentrations of benzophenone-1 (BP-1), benzophenone-2 (BP-2), benzophenone-3 (BP-3), benzophenone-4 (BP-4), benzophenone-8 (BP-8), and 4-hydroxybenzophenone (4-OH-BP) were analyzed using liquid chromatography-mass spectrometry. The detection rate for BP-1 and 4-OH-BP were 56% [limit of detection (LOD) 0.59ng/mL] and 88% (LOD 0.04ng/mL), respectively, whereas those for BP-2, BP-3, BP-4, and BP-8 were all below 25%. The geometric means of urinary BP-1 and 4-OH-BP concentrations were 1.24ng/mL and 0.45ng/mL, respectively. Multiple linear regression analysis indicated that concentrations of BP-1 in and of 4-OH-BP in adults were associated with sex and age. The BP-1 and 4-OH-BP concentration of children and adolescents was associated with sex, age, income, and current area of residence. The correlation was observed between urinary concentrations of BP derivatives, which is an important indication of exposure biomarkers and the metabolic pathways from BP-3. This is the first national study to evaluate the presence of BP derivatives in urine samples from the South Korean population, stratified by demographic factors.

Urinary biomarkers of exposure to 57 xenobiotics and its association with oxidative stress in a population in Jeddah, Saudi Arabia.

Oxidative stress arises from excessive free radicals in the body and is a trigger for numerous diseases, such as cancer and atherosclerosis. Elevated exposure to environmental chemicals can contribute to oxidative stress. The association between exposure to xenobiotics and oxidative stress, however, has rarely been studied. In this study, urinary concentrations of 57 xenobiotics (antimicrobials, parabens, bisphenols, benzophenones, and phthalates metabolites) were determined in a population from Jeddah, Saudi Arabia, to delineate association with the oxidative stress biomarker, 8-hydroxy-2'-deoxyguanosine (8OHDG). We collected 130 urine samples and analyzed for 57 xenobiotics using liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods. The association between unadjusted and creatinine- or specific gravity-adjusted concentrations of xenobiotics and 8OHDG was examined by Pearson correlations and multiple regression analysis. High concentrations of mCPP (a metabolite of di-n-octyl phthalate; DnOP) and mCMHP (a metabolite of diethylhexyl phthalate; DEHP) were found in urine. In addition, the concentrations of bisphenol S (BPS) were higher than those of bisphenol A (BPA). The concentrations of metabolites of DEHP, phthalic acid, BPA, BPS, and methyl-protocatechuic acid were significantly associated with 8OHDG. This is the first biomonitoring study to report exposure of the Saudi population to a wide range of environmental chemicals and provides evidence that environmental chemical exposures contribute to oxidative stress.

The Association Between Urinary Benzophenone Concentrations and Personal Care Product Use in Korean Adults.

Benzophenone (BP) derivatives are widely used in personal care products (PCPs) for protection from ultraviolet radiation. Because of their broad applications, BP derivatives have been found in various human bodily fluids. In the present study, we investigated the relationship between urinary concentrations of BP derivatives and PCP use in Korean adults. A urinary BP biomonitoring survey was conducted in Korea by the Ministry of Food and Drug Safety in 2014. BP derivatives (BP-1, BP-3, and 4-OH-BP) were measured in urine samples from 168 Korean adults (mean age, 43.2 ± 15.4 years) by high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry. Information about the use of PCPs in the past 7 days was obtained by direct interviews. The mean levels of BP-1, BP-3, and 4-OH-BP were 0.87, 5.87, and 0.13 ng/g creatinine, respectively. The geometric mean levels of BP-1, BP-3, and 4-OH-BP were significantly higher in female than those in male. The medians of the urinary concentration of BP derivatives were significantly higher among users of the following PCPs than those in non-users; the PCPs included sunscreen, skin care products, functional cosmetics, makeup base, makeup, lip cosmetics, eye cosmetics, color cosmetics, perfume products, and nail products. A regression analysis revealed a significant linear association between urinary BP-3 concentrations and the number of additional cosmetic products used. These findings provide evidence of a positive association between exposure to PCPs and urinary BP derivative concentrations in Korean adults.

Self-reported sunscreen use and urinary benzophenone-3 concentrations in the United States: NHANES 2003-2006 and 2009-2012.

BACKGROUND: Sunscreens protect against skin cancer and other harmful effects of solar ultraviolet radiation (UVR). Epidemiologic and public health surveys often rely on self-reported sunscreen use to estimate sun exposure and avoidance, but questions remain about the validity of self-reports. Benzophenone-3 (BP-3), a common sunscreen ingredient, can be detected in the urine. Prior studies suggest that BP-3 concentrations increase after application of sunscreen. OBJECTIVES: The goal of this study was to assess the validity of self-reported frequency of sunscreen use in relation to urinary BP-3 concentrations in a representative sample of the general US population, including in sub-groups defined by age, sex and race/ethnicity. METHODS: To assess the relationship between categorical self-reported sunscreen use and creatinine-corrected urinary BP-3 concentrations, we conducted a linear regression adjusted for age, sex, race/ethnicity, six-month time period, body mass index, education, and sun avoidance behaviors. We tested for effect modification by age, sex, ethnicity and time period of measurement using multiplicative interaction terms and a F test. RESULTS: BP-3 was positively associated with self-reported frequency of sunscreen use across all ages, sexes, race/ethnicities, and time periods. Crude and multivariate adjusted models were all statistically significant. R-square was relatively low for all models, ranging from 0.15 to 0.43. CONCLUSIONS: Urinary BP-3 is positively associated with self-reported frequency of sunscreen use in the general US population, even in groups with overall low sunscreen use. These results suggest that self-report is a valid, although weak, way of assessing relative frequencies of sunscreen usage in a population-based study.

Temporal variability of urinary concentrations of phthalate metabolites, parabens and benzophenone-3 in a Belgian adult population.

In the present study, we investigated the temporal within-person variability of the exposure biomarker for phthalates, parabens and benzophenone-3 (BP3) in 32 Belgian adults, each providing 11 urine spots during 4 months. We calculated the intraclass coefficient correlation (ICC), the sensitivity and the specificity to assess the temporal reproducibility and to investigate the predictive ability of the spot measurements for these classes of chemicals. Additionally, we explored the temporal variability of the estimation of the cumulative risk of exposure to phthalates (hazard index; HI). We observed fair ICC ranging from 0.55 to 0.68 for parabens, monoethyl phthalate (MEP), mono-iso-butyl phthalate (MiBP) and BP3, but lower ICC, from 0.20 to 0.49, for monobenzyl phthalate (MBzP), mono-n-butyl phthalate (MnBP), mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxo-hexyl phthalate (5-oxo-MEHP) and mono-2-ethyl-5-hydroxy-hexyl phthalate (5-OH-MEHP). The ICC estimated for HI (0.49) reflected a moderate reproducibility. The measurements in spot samples were moderate to good predictor of the 4-month level of exposure for parabens, MEP, MnBP, MiBP, BP3 and HI (sensitivity ranging from 0.67 to 0.77), but lower predictor for MEHP, 5-oxo-MEHP, 5-OH-MEHP and MBzP (sensitivity ranging from 0.58 to 0.63). The sensitivity could be increased when several spot urinary levels were averaged to predict the long-term level of exposure. Globally, our results indicate that a single spot measurement seems to correctly represent the long-term exposure for parabens, BP3, MEP, MiBP and HI. Additional spot samples seemed to be needed for the proper exposure assessment of the other target compounds.

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

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

Urinary concentrations of benzophenone-type ultraviolet radiation filters and couples' fecundity.

Concern has arisen about benzophenone (BP) ultraviolet (UV) radiation filters, given their use in sunscreen and personal-care products and their reported estrogenic and antiandrogenic activity. We recruited 501 couples who were discontinuing use of contraceptives in order to become pregnant for the Longitudinal Investigation of Fertility and the Environment (LIFE) Study (Michigan and Texas, 2005-2009). Couples provided urine specimens and completed daily journals until they either achieved pregnancy or had tried for 12 months. Women used fertility monitors to time sexual intercourse and digital pregnancy tests. Urinary concentrations of 5 UV filters (ng/mL) were determined using triple-quadrupole mass spectrometry: 2,4-dihydroxybenzophenone (also called BP-1); 2,2',4,4'-tetrahydroxybenzophenone (BP-2); 2-hydroxy-4-methoxybenzophenone (BP-3); 2,2'-dihydroxy-4-methoxybenzophenone (BP-8); and 4-hydroxybenzophenone. Fecundability odds ratios were estimated for each UV filter (dichotomized at the 75th percentile) and adjusted for age, creatinine concentration, body mass index (weight (kg)/height (m)(2)), cotinine concentration, season, and site, while accounting for time off contraception. Separate models were fitted for each UV filter and partner; final models included partners' concentrations. Male partners' concentrations of BP-2 and 4-hydroxybenzophenone were associated with reduced fecundity in adjusted models (fecundability odds ratio (FOR) = 0.69 (95% confidence interval (CI): 0.50, 0.95) and FOR = 0.74 (95% CI: 0.54, 1.00), respectively). In models adjusting for both partners' concentrations, male BP-2 concentration remained associated with reduced fecundity (FOR = 0.69, 95% CI: 0.49, 0.97). These data suggest that male exposure to select UV filters may diminish couples' fecundity, resulting in a longer time to pregnancy.

Association between percutaneous absorption of benzophenone-3 and N, N-diethyl-m-toluamide among the general adult population.

BACKGROUND: Multiple studies have confirmed the mutual enhancement of percutaneous permeation of benzophenone-3 (BP-3) and N,N-diethyl-m-toluamide (DEET), which are effective ingredients in sunscreen products and insect repellents, respectively. However, the association between percutaneous absorption of BP-3 and DEET in a large general adult population remains to be elucidated. METHODS: This cross-sectional study included US adults who had available data on urinary BP-3 and two DEET metabolites, 3-(diethylcarbamoyl) benzoic acid (DCBA) and 3-(ethylcarbamoyl) benzoic acid (ECBA), from the National Health and Nutrition Examination Survey (NHANES) conducted in 2015-2016. We conducted three weighted multivariable linear regression models to investigate the potential correlation between percutaneous absorption of BP-3 and DEET, along with trend tests, smooth curve fitting, and subgroup analysis to assess the robustness of the findings. RESULTS: Weighted multivariable linear logistic regression revealed a positive correlation between log10 BP-3 and log10 DCBA (ß = 0.1678, 95 % CI: 0.0970 to 0.2386) as well as log10 ECBA (ß = 0.1416, 95 % CI: 0.0707 to 0.2125), after adjusting for all covariates. After converting log10 BP-3 from a continuous variable to a categorical variable (quartiles), the trend tests showed that the results were stable (all P for trend < 0.05). Smoothed curve fitting demonstrated a linear positive correlation between log10 BP-3 and both log10 DCBA and log10 ECBA. In subgroup analyses, the positive correlation between BP-3 and DEET metabolites was more pronounced in participants who were male, middle-aged, non-Hispanic white, had a moderate PIR level and reported always or most of the time using sunscreen. CONCLUSIONS: Our findings revealed a statistically significant linear and positive correlation between the percutaneous absorption of BP-3 and DEET in the general adult population.

Urinary concentrations of bisphenol A, parabens and benzophenone-type ultra violet light filters in relation to sperm DNA fragmentation in young men: A chemical mixtures approach.

People are daily exposed to multiple endocrine disruptor compounds (EDCs) that may interfere with different molecular and cellular processes, promoting a potential estrogenic, androgenic, or anti-androgenic state. However, most epidemiological studies attempting to establish relationships between EDCs exposure and health effects are still considering individual compounds. A few studies have shown associations between exposure to individual non-persistent EDCs and sperm DNA fragmentation (SDF) in different male populations. Thus, the aim of this study was to investigate associations between combined exposure to non-persistent EDCs and SDF index in young men. A cross-sectional study was conducted with 158 healthy university students from Southeaster Spain. The participants provided spot urine and semen samples on the same day. The concentrations of urinary bisphenol A (BPA), benzophenones [2,4-dihydroxybenzophenone (BP-1); 2,2',4,4'-tetrahydroxybenzophenone (BP-2), 2-hydroxy-4-methoxybenzophenone (BP-3), 2,2'-dihydroxy-4-methoxybenzophenone (BP-8), 4-hydroxybenzophenone (4OHBP)], and parabens (methylparaben, ethylparaben, propylparaben, butylparaben) were measured by dispersive liquid-liquid microextraction and ultrahigh-performance liquid chromatography with tandem mass spectrometry detection. SDF was analysed using a Sperm Chromatin Dispersion test. Statistical analyses were carried out using Bayesian Kernel Machine Regression models to evaluate associations between combined exposure to these compounds and SDF index while adjusting by relevant covariates. The increase in urinary concentration of 4OHBP was found to be the most important contributor to the negative association between urinary EDCs concentrations and SDF index, being of -5.5 % [95 % CI: -10.7, -0.3] for those in percentile 50, and - 5.4 % [95 % CI: -10.8, -0.1] for those in percentile 75. No significant associations were observed between other EDCs and SDF index. Our findings show that urinary 4OHBP levels may be associated with a decrease in the SDF index. Nonetheless, the effects we observed were likely to be small and of uncertain clinical significance. Further research is needed to replicate our findings in other male populations.

The associations between high-levels of urine benzophenone-type UV filters (BPs) and changes in serum lipid concentrations.

Little is known about the potential health impacts of benzophenone-type UV filters (BPs) exposure among the general population. In our study conducted in Wuxi, China, we investigated the associations between the concentrations of eight BP-derivatives and five target lipid molecules. We collected basic information, serum, and urine samples from 120 residents aged 9 to 80 in Wuxi. We determined BPs in urine samples and lipid levels in serum samples. Generalized linear models were used to evaluate the differences in ln-transformed serum target lipids levels (µg/L) with different urine BPs quartiles compared to the lowest quartile. Benzophenone-4 (BP-4) had the highest detection rate (95.0%) and geometric mean concentration (1.96 µg/L) among all the BP-derivatives in our study population. The exposure levels of BPs were generally higher in females than in males. Participants in the 9-17 and 18-50 age groups exhibited greater levels of exposure to BPs than those in the 51-80 age group. We observed statistically significant changes in LysoPC (18:0), LysoPE (18:0), ΣLPL, and ΣTL concentrations between the highest and lowest quartiles of BP-4. Similar changes were found in LysoPE (18:0) concentration between the highest and lowest quartiles of ΣBP-3 and ΣBPs. High urine BP concentrations were associated with variations in our target serum lipids involved in neurological and metabolic disorders, and posed a potential health risk. Future studies are warranted to further validate and elucidate our findings.

Temporal trends in exposure to parabens, benzophenones, triclosan, and triclocarban in adult females in Kyoto, Japan, from 1993 to 2016.

Products used in daily life can contain chemicals such as parabens, benzophenones, triclosan, and triclocarban that have potential endocrine-disrupting effects. Little is known about the temporal trends of exposure levels to some of these chemicals in Japan. Our study assessed the intake and risk associated with exposure to commonly used chemicals. We measured the concentrations of five parabens, four benzophenones, and triclosan and triclocarban in 133 single spot urine samples. The urine samples were collected in 1993, 2000, 2003, 2009, 2011, and 2016 from healthy female residents in Kyoto, Japan. With the exception of methylparaben, ethylparaben, and butylparaben, there were no significant fluctuations in the concentrations of target chemicals over the study period; however, methylparaben, ethylparaben, and butylparaben showed temporal changes in concentrations. Methylparaben concentrations peaked in 2003 with a median value of 309 µg/g creatinine, ethylparaben concentrations peaked in 1993 with a median value of 17.3 µg/g creatinine, and butylparaben showed a decline, with the median values becoming non-detectable in 2009 and 2016. We calculated estimated daily intakes and hazard quotients for each chemical. In the analysis of total samples, 2.3% (3 samples) for butylparaben and 0.8% (1 sample) for propylparaben were found to surpass a hazard quotient of 1. Overall, 3% (n = 4) of the study participants exceeded a hazard index of 1. The potential health risks associated with exposure to butylparaben and propylparaben emphasize the need for further monitoring and research.

Co-exposure of parabens, benzophenones, triclosan, and triclocarban in human urine from children and adults in South China.

Endocrine-disrupting chemicals (EDCs) are pervasive in the environment, prompting significant public concern regarding human exposure to these pollutants. In this study, we analyzed the levels of various endocrine-disrupting compounds, including parabens (PBs), benzophenones (BzPs), triclocarban (TCC) and triclosan (TCS), across 565 urine samples collected from residents of South China. All 11 target chemicals were detected at relatively high frequencies (41-100%), with the most prevalent ones being 3,4-dihydroxybenzoic acid (5.39 ng/mL), methyl-paraben (5.12 ng/mL), ethyl-paraben (3.11 ng/mL) and triclosan (0.978 ng/mL). PBs emerged as the most predominant group with a median concentration of 32.2 ng/mL, followed by TCs (sum of TCC and TCS, 0.998 ng/mL) and BzPs (0.211 ng/mL). Notably, urinary concentrations of PBs in adults were significantly higher (p < 0.01) compared to children, while BzPs and TCs were elevated in children (p < 0.001). The increased presence of BzPs and TCs in children is a cause for concern, given their heightened sensitivity and vulnerability to chemicals. Significant correlations were found between urinary target compounds and demographic factors, including gender, age and body mass index. Specifically, females, younger adults (18 ≤ age ≤ 35) and individuals with under/normal weight (16 ≤ BMI ≤ 23.9) were found to have higher exposure levels to EDCs, as indicated by the median values of their estimated daily intakes. Despite these higher levels still being lower than the acceptable daily intake thresholds, the health risks stemming from simultaneous exposure to these EDCs must not be overlooked.

Development of a robust non-targeted analysis approach for fast identification of endocrine disruptors and their metabolites in human urine for exposure assessment.

Endocrine disrupting chemicals are of concern because of possible human health effects, thus they are frequently included in biomonitoring studies. Current analytical methods are focused on known chemicals and are incapable of identifying or quantifying other unknown chemicals and their metabolites. Non-targeted analysis (NTA) methods are advantageous since they allow for broad chemical screening, which provides a more comprehensive characterization of human chemical exposure, and can allow elucidation of metabolic pathways for unknown chemicals. There are still many challenges associated with NTA, which can impact the results obtained. The chemical space, i.e., the group of known and possible compounds within the scope of the method, must clearly be defined based on the sample preparation, as this is critical in identifying chemicals with confidence. Data acquisition modes and mobile phase additives used with liquid chromatography coupled to high-resolution mass-spectrometry can affect the chemicals ionized and structural identification based on the spectral quality. In this study, a sample preparation method was developed using a novel clean-up approach with CarbonS cartridges, for endocrine-disrupting chemicals in urine, including new bisphenol A analogues and benzophenone-based UV filters, like methyl bis (4-hydroxyphenyl acetate). The study showed that data dependent acquisition (DDA) had a lower identification rate (40%) at low spiking levels, i.e., 1 ng/mL, compared to data independent acquisition (DIA) (57%), when Compound Discoverer was used. In DDA, more compounds were identified using Compound Discoverer, with an identification rate of 95% when ammonium acetate was compared to acetic acid (82%) as a mobile phase additive. TraceFinder software had an identification rate of 53% at 1 ng/mL spiking level using the DDA data, compared to 40% using the DIA data. Using the developed method, 2,4 bisphenol F was identified for the first time in urine samples. The results show how NTA can provide human exposure information for risk assessment and regulatory action but standardized reporting of procedures is needed to ensure study results are reproducible and accurate. His Majesty the King in Right of Canada, as represented by the Minister of Health, 2024.

Urinary benzophenone-3 concentrations and ovarian reserve in a cohort of subfertile women.

OBJECTIVE: To evaluate the association between the urinary benzophenone-3 concentrations and measures of ovarian reserve (OR) among women in the Environment and Reproductive Health study seeking fertility treatment at Massachusetts General Hospital (MGH) in Boston, Massachusetts. DESIGN: Prospective cohort study. SETTING: MGH infertility clinic in Boston, Massachusetts. PATIENT(S): Women in the Environment and Reproductive Health cohort seeking fertility treatment. INTERVENTION(S): Women contributed spot urine samples prior to assessment of OR outcomes that were analyzed for benzophenone-3 concentrations. MAIN OUTCOME MEASURE(S): Antral follicle count (AFC) and day 3 follicle-stimulating hormone (FSH) levels were evaluated as part of standard infertility workups during unstimulated menstrual cycles. Quasi-Poisson and linear regression models were used to evaluate the association of the specific gravity-adjusted urinary benzophenone-3 concentrations with AFC and FSH, with adjustment for age and physical activity. In the secondary analyses, models were stratified by age. RESULT(S): This study included 142 women (mean age ± standard deviation, 36.1 ± 4.6 years; range, 22-45 years) enrolled between 2009 and 2017 with both urinary benzophenone-3 and AFC measurements and 57 women with benzophenone-3 and FSH measurements. Most women were White (78%) and highly educated (49% with a graduate degree). Women contributed a mean of 2.7 urine samples (range, 1-10), with 37% contributing ≥2 samples. Benzophenone-3 was detected in 98% of samples. The geometric mean specific gravity-corrected urinary benzophenone-3 concentration was 85.9 µg/L (geometric standard deviation, 6.2). There were no associations of benzophenone-3 with AFC and day 3 FSH in the full cohort. In stratified models, a 1-unit increase in the log geometric mean benzophenone-3 concentration was associated with a 0.91 (95% confidence interval, 0.86-0.97) times lower AFC among women aged ≤35 years and an increase in the FSH concentration of 0.73 (95% confidence interval, 0.12-1.34) IU/L among women aged >35 years. CONCLUSION(S): In the main models, urinary benzophenone-3 was not associated with OR. However, younger patients may be vulnerable to the potential effects of benzophenone-3 on AFC. Further research is warranted.