BACKGROUND: Results of studies investigating associations between individual endocrine-disrupting chemicals (EDCs) and incidence of uterine leiomyomata (UL), a hormone-dependent gynecological condition, have been inconsistent. However, few studies have evaluated simultaneous exposure to a mixture of EDCs with UL incidence.
METHODS: We conducted a case-cohort analysis (n = 708) of data from the Study of the Environment, Lifestyle and Fibroids (SELF), a prospective cohort study. Participants were aged 23-35 years at enrollment, had an intact uterus, and identified as Black or African American. We measured biomarker concentrations of 21 non-persistent EDCs, including phthalates, phenols, parabens, and triclocarban, in urine collected at baseline, 20-month, and 40-month clinic visits. We ascertained UL incidence and characteristics using ultrasounds at baseline and approximately every 20 months through 60 months. We used probit Bayesian Kernel Machine Regression (BKMR-P) to evaluate joint associations between EDC mixtures with cumulative UL incidence. We estimated the mean difference in the probit of UL incidence over the study period, adjusting for baseline age, education, years since last birth, parity, smoking status and body mass index. We converted probit estimates to odds ratios for ease of interpretation.
RESULTS: We observed that urinary concentrations of the overall EDC mixture were inversely associated with UL incidence in the overall mixtures model, with the strongest inverse associations at the 70th percentile of all biomarkers compared with their 50th percentile (odds ratio = 0.59; 95% confidence interval: 0.36, 0.96). Strongest contributors to the joint association for the mixture were bisphenol S (BPS), ethyl paraben (EPB), bisphenol F (BPF) and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP), which each demonstrated inverse associations except for MECPP. There was suggestive evidence of an interaction between MECPP and EPB.
CONCLUSIONS: In this prospective ultrasound study, we observed evidence of an inverse association between the overall mixture of urinary biomarker concentrations of non-persistent EDCs with UL incidence.

Triclocarban (TCC), a novel antimicrobial agent found in personal care products, has been extensively detected in marine environments. However, research on the toxic effects of TCC on marine organisms remains inadequate. This study delved into the subchronic toxic effects of TCC on the early life stages of marine medaka (Oryzias melastigma, O. melastigma), revealing that TCC could reduce embryo heart rate and hatching rate while diminishing the survival rate of larvae. Biomarker assays indicated that TCC could inflict damage on the embryos\' antioxidant and nervous systems. Transcriptomic analysis suggested that TCC could impact cell growth, reproduction, and various life processes, activating cancer signaling pathways, increasing the likelihood of cancer, and exerting toxic effects on the immune and osmoregulatory systems. To validate and enhance our understanding of TCC\'s unique toxic impact on the osmoregulatory system of O. melastigma, we conducted homology modeling and molecular docking analyses on the protein involved in osmoregulation. The study intuitively revealed the potential binding affinity of TCC to sodium/potassium-transporting ATPase subunit alph (ATP1A1), indicating its ability to disrupt osmotic balance in marine fish by affecting this target protein. In summary, the results of this study will further enhance our comprehension of the potential toxic effects and mechanisms of TCC on the early stages of marine fish, with a specific focus on its unique toxic effects in osmoregulation.

Freshwater organisms are suitable models to study the fate of environmental pollutants. Due to their versatile and everyday use, many environmental pollutants such as triclocarban (TCC) or multi-walled carbon nanotubes (MWCNTs) enter environmental compartments very easily. TCC is known as a disinfectant and is declared as a highly aquatic toxicant. Multi-walled carbon nanotubes are used, e.g., in the automotive industry to improve plastic properties. Both TCCs and MWCNTs can pose major pollution hazards to various organisms. In addition, these substances can bind to each other due to their tendency to interact via strong hydrophobic interactions. Therefore, a short-term test was conducted to investigate the effects of the individual chemicals TCC and weathered MWCNTs (wMWCNTs) on a benthic biofilm and a grazing organism, Lymnaea stagnalis. Furthermore, the two compounds were coupled by an adsorption experiment resulting in a coupled complex formation (TCC + wMWCNTs). L. stagnalis showed no effects in terms of mortality. For benthic biofilm, the coupling test (TCC + wMWCNTs) showed a decrease of 58% in chlorophyll a (Chl-a) concentration. The main effect could be attributed to the wMWCNTs\' exposure alone (decrease of 82%), but not to presence of TCC. The concentration range of Chl-a upon TCC exposure alone was comparable to that in the control group (32 and 37 µg/cm2). With respect to the particulate organic carbon (POC) concentration, very similar results were found for the solvent control, the TCC, and also for the TCC + wMWCNTs group (3, 2.9, and 2.9 mg/cm2). In contrast to the control, a significant increase in POC concentration (100%) was observed for wMWCNTs, but no synergistic effect of TCC + wMWCNTs was detected.

Oxysterols have long been considered as simple by-products of cholesterol metabolism, but they are now fully designed as bioactive lipids that exert their multiple effects through their binding to several receptors, representing endogenous mediators potentially involved in several metabolic diseases. There is also a growing concern that metabolic disorders may be linked with exposure to endocrine-disrupting chemicals (EDCs). To date, there are no studies aimed to link EDCs exposure to oxysterols perturbation-neither in vivo nor in vitro studies. The present research aimed to evaluate the differences in oxysterols levels following exposure to two metabolism disrupting chemicals (propylparaben (PP) and triclocarban (TCC)) in the zebrafish model using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Following exposure to PP and TCC, there were no significant changes in total and individual oxysterols compared with the control group; however, some interesting differences were noticed: 24-OH was detected only in treated zebrafish embryos, as well as the concentrations of 27-OH, which followed a different distribution, with an increase in TCC treated embryos and a reduction in zebrafish embryos exposed to PP at 24 h post-fertilization (hpf). The results of the present study prompt the hypothesis that EDCs can modulate the oxysterol profile in the zebrafish model and that these variations could be potentially involved in the toxicity mechanism of these emerging contaminants.

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 current work aimed to investigate the degradation of the triclocarban (TCC) in aqueous solution using a modified zeolite/TiO2 composite (MZTC) synthesized by applying the electrochemical anodization (ECA). The synthesis process was conducted at different voltages (10, 40, and 60) V in 1 h and using electrophoresis deposition (EPD) in doping zeolite. The MZTC was covered with the array ordered, smooth and optimum elongated nanotubes with 5.1 μm of the length, 120.3 nm of the inner diameter 14.5 nm of the wall thickness with pure titanium and crystalline titania as determined by FESEM/EDS, and XRD. The kinetic study by following Langmuir-Hinshelwood(L-H) model and pseudo first order, the significant constant rate was obtained at pH 11 which was 0.079 ppm/min, 0.75 cm2 of MZTC catalyst loading size achieved 0.076 ppm/min and 5 ppm of TCC initial concentration reached 0.162 ppm/min. The high-performance liquid chromatography (HPLC) analysis for mechanism study of TCC photocatalytic degradation revealed eleven intermediate products after the whole process of photocatalysis. In regard of toxicology assessment by the bacteria which is Photobacterium phosphoreum, the obtained concentration of TCC at minute 60 was less satisfied with remained 0.36 ppm of TCC was detected indicates that the concentration was above allowable level. Where the allowable level of TCC in stream is 0.1 ppm.

Many phenols and parabens are applied in cosmetics, pharmaceuticals and food, to prevent growth of bacteria and fungi. Whether these chemicals affect inflammatory diseases like allergies and overweight is largely unexplored. We aimed to assess the associations of use of personal care products with urine biomarkers levels of phenols and paraben exposure, and whether urine levels (reflecting body burden of this chemical exposures) are associated with eczema, rhinitis, asthma, specific IgE and body mass index.
Demographics, clinical variables, and self-report of personal care products use along with urine samples were collected concurrently from 496 adults (48% females, median age: 28 years) and 90 adolescents (10-17 years of age) from the RHINESSA study in Bergen, Norway. Urine biomarkers of triclosan (TCS), triclocarban (TCC), parabens and benzophenone-3, bisphenols and dichlorophenols (DCP) were quantified by mass spectrometry.
Detection of the urine biomarkers varied according to chemical type and demographics. TCC was detected in 5% of adults and in 45% of adolescents, while propyl (PPB) and methyl (MPB) parabens were detected in 95% of adults and in 94% (PPB) and 99% (MPB) of adolescents. Women had higher median urine concentrations of phenolic chemicals and reported a higher frequency of use of personal care products than men. Urine concentration of MPB increased in a dose-dependent manner with increased frequency of use of several cosmetic products. Overall, urinary biomarker levels of parabens were lower in those with current eczema. The biomarker concentrations of bisphenol S was higher in participants with positive specific IgE and females with current asthma, but did not differ by eczema or rhinitis status. MPB, ethylparaben (EPB), 2,4-DCP and TCS were inversely related to BMI in adults; interaction by gender were not significant.
Reported frequency of use of personal care products correlated very well with urine biomarker levels of paraben and phenols. Several chemicals were inversley related to BMI, and lower levels of parabens was observed for participants with current eczema. There is a need for further studies of health effects of chemicals from personal care products, in particular in longitudinally designed studies.

Endocrine-disrupting chemicals can interfere with hormonal homeostasis and have adverse effects for both humans and the environment. Their identification is increasingly difficult due to lack of adequate toxicological tests. This difficulty is particularly problematic for cosmetic ingredients, because in vivo testing is now banned completely in the European Union.
The aim was to identify candidate preservatives as endocrine disruptors by in silico methods and to confirm endocrine receptors\' activities through nuclear receptors in vitro.
We screened preservatives listed in Annex V in the European Union Regulation on cosmetic products to predict their binding to nuclear receptors using the Endocrine Disruptome and VirtualToxLab™ version 5.8 in silico tools. Five candidate preservatives were further evaluated for androgen receptor (AR), estrogen receptor (ERα), glucocorticoid receptor (GR), and thyroid receptor (TR) agonist and antagonist activities in cell-based luciferase reporter assays in vitro in AR-EcoScreen, hERα-HeLa-9903, MDA-kb2, and GH3.TRE-Luc cell lines. Additionally, assays to test for false positives were used (nonspecific luciferase gene induction and luciferase inhibition).
Triclocarban had agonist activity on AR and ERα at 1μM and antagonist activity on GR at 5μM and TR at 1μM. Triclosan showed antagonist effects on AR, ERα, GR at 10μM and TR at 5μM, and bromochlorophene at 1μM (AR and TR) and at 10μM (ERα and GR). AR antagonist activity of chlorophene was observed [inhibitory concentration at 50% (IC50) IC50=2.4μM], as for its substantial ERα agonist at >5μM and TR antagonist activity at 10μM. Climbazole showed AR antagonist (IC50=13.6μM), ERα agonist at >10μM, and TR antagonist activity at 10μM.
These data support the concerns of regulatory authorities about the endocrine-disrupting potential of preservatives. These data also define the need to further determine their effects on the endocrine system and the need to reassess the risks they pose to human health and the environment. https://doi.org/10.1289/EHP6596.

Triclocarban (TCC) is used as a broad-spectrum antimicrobial agent, the intensive detection of TCC in aquatic environments and its potential risks to aquatic organisms are concerned worldwide. In this study, 8 Chinese resident aquatic organisms from 3 phyla and 8 families were used for the toxicity tests, and four methods were employed to derive the aquatic life criteria (ALC). A criterion maximum concentration (CMC) of 1.46 μg/L and a criterion continuous concentration (CCC) of 0.21 μg/L were derived according to the USEPA guidelines. The acute predicted no effect concentrations (PNECs) derived by species sensitivity distribution (SSD) methods based on log-normal, log-logistic and Burr Type Ⅲ models were 2.64, 1.88 and 3.09 μg/L, respectively. The comparisons of ALCs derived with resident and non-resident species showed that the CMC and CCC of TCC derived with Chinese resident species could provide a sufficient protection for non-resident species. The higher toxicity of TCC on aquatic organisms was found compared with other antimicrobial agents (except for Clotrimazole) in aquatic environment. The strong positive linear correlation was observed between the TCC and TCS concentrations in aquatic environment with a correlation coefficient (R2) of 0.8104, it is of great significance in environmental monitoring and risk assessment for TCC and TCS. Finally, the ecological risk assessment showed that the TCC in Yellow River basin and Pearl River basin had higher risk with the mean potential affected fractions (PAFs) of 9.27% and 7.09%, and 22.10% and 15.00% waters may pose potential risk for 5% aquatic organisms, respectively. In general, the risk of TCC in Asian waters was higher than that in Europe and North America.

Prenatal exposure to some phenols and parabens has been associated with adverse birth outcomes. Hormones may play an intermediate role between phenols and adverse outcomes. We examined the associations of phenol and paraben exposures with maternal reproductive and thyroid hormones in 602 pregnant women in Puerto Rico. Urinary triclocarban, phenol and paraben biomarkers, and serum hormones (estriol, progesterone, testosterone, sex-hormone-binding globulin (SHBG), corticotropin-releasing hormone (CRH), total triiodothyronine (T3), total thyroxine (T4), free thyroxine (FT4) and thyroid-stimulating hormone (TSH)) were measured at two visits during pregnancy.
Linear mixed models with a random intercept were constructed to examine the associations between hormones and urinary biomarkers. Results were additionally stratified by study visit. Results were transformed to hormone percent changes for an inter-quartile-range difference in exposure biomarker concentrations (%Δ).
Bisphenol-S was associated with a decrease in CRH [(%Δ -11.35; 95% CI: -18.71, - 3.33), and bisphenol-F was associated with an increase in FT4 (%Δ: 2.76; 95% CI: 0.29, 5.22). Butyl-, methyl- and propylparaben were associated with decreases in SHBG [(%Δ: -5.27; 95% CI: -9.4, - 1.14); (%Δ: -3.53; 95% CI: -7.37, 0.31); (%Δ: -3.74; 95% CI: -7.76, 0.27)]. Triclocarban was positively associated with T3 (%Δ: 4.08; 95% CI: 1.18, 6.98) and T3/T4 ratio (%Δ: 4.67; 95% CI: -1.37, 6.65), and suggestively negatively associated with TSH (%Δ: -10.12; 95% CI: -19.47, 0.32). There was evidence of susceptible windows of vulnerability for some associations. At 24-28 weeks gestation, there was a positive association between 2,4-dichlorophenol and CRH (%Δ: 9.66; 95% CI: 0.67, 19.45) and between triclosan and estriol (%Δ: 13.17; 95% CI: 2.34, 25.2); and a negative association between triclocarban and SHBG (%Δ: -9.71; 95% CI:-19.1, - 0.27) and between bisphenol A and testosterone (%Δ: -17.37; 95% CI: -26.7, - 6.87).
Phenols and parabens are associated with hormone levels during pregnancy. Further studies are required to substantiate these findings.