Triclocarban Research Articles

Comparison of triclosan and triclocarban in triggering immunotoxicity in larval zebrafish

As two efficient broad-spectrum sterilizing agents, triclosan (TCS) and triclocarban (TCC) are widely used, especially during the COVID-19 pandemic. The health risks caused by secondary pollution of TCS and TCC have aroused wide concern. Because of the similar mother nucleus structure and high lipophilicity, it remains unknown about the differences in the effect and mechanism of the toxicity (especially immunotoxicity) between TCS and TCC in organisms in the environment. In this study, we used zebrafish as a model to compare the immunotoxicity and mechanisms between the two pollutants at the same exposure concentration (0.6 µmol/L). The results showed that both TCS and TCC led to a hatching rate below 60% at the time point of 72 hours post fertilization (hpf) and the mortality rates of 40% and 50% at 120 hpf in larval zebrafish, respectively. The zebrafish exposed to TCS and TCC displayed malformations, such as shortened body, swimming sac closure, pericardial edema, yolk cyst deposition, and absorption disorder. Moreover, the developmental abnormalities caused by TCC were significantly severer than those caused by TCS. TCS exposure increased the proliferation rate of innate immune cells to 20% and decreased the number of mature T cells by 35%, while TCC exposure inhibited the differentiation of both innate immune cells and T cells, with the inhibition rates of 25% and 60%, respectively. The results of real-time quantitative PCR (RT-qPCR) and ELISA showed that TCS and TCC exposure up-regulated the expression levels of il-1β, il-6, and tnf-α, while il-10 and IgM exhibited opposite expression patterns. Additionally, both compounds slightly decreased C3 expression. The Pearson correlation analysis showed that the developmental toxicity induced by TCS and TCC had positive and negative correlations with the differentiation of immune cells, respectively. However, the toxicity induced by either TCS or TCC was positively correlated with the expression of pro-inflammatory cytokines. GO function and KEGG pathway enrichment analyses demonstrated that the target molecules of TCS and TCC were enriched in different signaling pathways, and the key network hub genes and the enriched regulatory pathways differed between TCS and TCC. The findings provide compelling evidence that TCS and TCC adopt different mechanisms in triggering immunotoxicity and offer a theoretical reference for the recognition, warning, and management of TCS and TCC-induced health risks.

Triclocarban disrupts the activation and differentiation of human CD8+ T cells by suppressing the vitamin D receptor signaling

Triclocarban (TCC) is a widely applied environmental endocrine-disrupting chemical (EDC). Similar to most of EDCs, TCC potentially damages the immunity of various species. However, whether and how TCC impacts the adaptive immunity in mammals has yet to be determined. Herein, we discovered that TCC disrupts the activation and differentiation of CD8+ T cells in primary human peripheral blood samples, purified CD8+ T cells, and in mice in vivo. Mechanistically, TCC might block the activation of the vitamin D receptor (VDR) and reduce the synthesis of cholesterol, a precursor of vitamin D, resulting in inhibition of VDR signaling due to the suppression of both its ligand and the receptor itself by TCC. Our findings elucidate the hazard and potential mechanisms of TCC in mammalian adaptive immunity and highlighted VDR as a potential therapeutic target for the immunodeficiency caused by TCC.

Complexation of Diserinol Isophthalamide with Phosphorylated Biomolecules in Electrospray Ionization Mass Spectrometry

Electrospray ionization (ESI) enables gentle transfer of biomolecules from solution to vacuum, facilitating the study of biomolecular structure under highly controlled conditions. However, biomolecules are desolvated during the ESI process, and the loss of ionic hydrogen bonds to solvent molecules can drive structural rearrangement, most prominently at solvent-exposed charge sites. Microsolvation reagents can bind to these bare charge sites in ESI mass spectrometry (ESI–MS) experiments, providing alternative intermolecular interaction partners. Previously, 18-crown-6 was shown to be an effective reagent for binding to cationic monoalkylammonium residues. More recently, diserinol isophthalamide (DIP) was reported as an analogous anionic microsolvation reagent, primarily for carboxylate residues of small model peptides. Herein, we expand upon this work to examine the complexation of DIP, 1,1’-(1,2-phenylene)bis(3-phenylurea) (PBP), and triclocarban (TCC) with molecules featuring a terminal or linking phosphate moiety. Specifically, using ESI–MS, we assess the binding of these reagents with dimethyl phosphate (DMP), cyclic adenosine monophosphate (cAMP), dibutyryl cAMP, RNA dinucleotides ApU and CpG, and angiotensin II phosphate (DRVpYIHPF). For DMP, the smallest target molecule, reagents TCC, PBP and DIP showed favorable adduction. However, for larger systems, PBP and TCC showed reduced complexation, which was attributed to steric hindrance from the terminal aromatic moieties of PBP and the limited hydrogen bonding network of TCC. Overall, of the three reagents, DIP showed the most consistent performance for anionic microsolvation of phosphate groups, facilitating future studies of gas-phase biomolecular structure and the effects of microsolvation.

How Does Triclocarban Affect Sulfur Transformation in Anaerobic Systems?

Triclocarban (TCC), as a typical antimicrobial agent, accumulates at substantial levels in natural environments and engineered systems. This work investigated the impact of TCC on anaerobic sulfur transformation, especially toxic H2S production. Experimental findings revealed that TCC facilitated sulfur flow from the sludge solid phase to liquid phase, promoted sulfate reduction and sulfur-containing amino acid degradation, and largely improved anaerobic H2S production, i.e., 50-600 mg/kg total suspended solids (TSS) TCC increased the cumulative H2S yields by 24.76-478.12%. Although TCC can be partially biodegraded in anaerobic systems, the increase in H2S production can be mainly attributed to the effect of TCC rather than its degradation products. TCC was spontaneously adsorbed by protein-like substances contained in microbe extracellular polymers (EPSs), and the adsorbed TCC increased the direct electron transfer ability of EPSs, possibly due to the increase in the content of electroactive polymer protein in EPSs, the polarization of the amide group C═O bond, and the increase of the α-helical peptide dipole moment, which might be one important reason for promoting sulfur bioconversion processes. Microbial analysis showed that the presence of TCC enriched the organic substrate-degrading bacteria and sulfate-reducing bacteria and increased the abundances of functional genes encoding sulfate transport and dissimilatory sulfate reduction.

Electro-peroxone process for triclocarban and triclosan removal and reclaimed water disinfection

Water reclamation is a known solution to the water scarcity problem; however, concern over water contamination by emerging contaminants and pathogens is growing. This study investigates the simultaneous removal of emerging contaminants and pathogens by applying the continuous-flow electro-peroxone process. Triclocarban (TCC) and triclosan (TCS) were selected as model contaminants of emerging concern, while Escherichia coli strain DH5α was chosen as a representative pathogen. The effects of the initial concentration, water flow rate, and water matrices (direct reclaimed water (treated wastewater), indirect reclaimed water (groundwater), and natural surface water) on TCC, TCS, and E. coli removal were examined. The removal efficiency of TCC (2 mg/L) was up to 92.54 % in 120 min. TCS (non-ozone-resistant compound) was effectively removed in 15 min, while E. coli was instantly inactivated in 3 min. The increase in flow rate decreased the electrical energy per order (EEO) of TCC removal, with the lowest EEO of 19 kWh/m3 at 45 mL/min. The dissolved organic carbon content in water matrices (consuming O3 and H2O2) markedly inhibited the TCC removal, and the kinetic rate as well as reduced 3,4-dichloroaniline (intermediate product) formation. Overall, these findings show the use of the electro-peroxone process is effective in mitigating ozone- and non-ozone-resistant emerging contaminants (TCC and TCS) and pathogens with consideration of water matrices for reclaimed water application.

TiO2 nanotubes zeolite nanophotocatalyst performance efficacy toward the photocatalytic degradation of triclocarban in bathroom greywater

Triclocarban (TCC) is persistent in aquatic environments, where it can remain stable for extended periods. It can cause long-term exposure, potentially affecting ecosystems and human health through contaminated fish or water. Therefore, this study aims to investigate the degradation of TCC in bathroom greywater by the application of TiO2 nanotubes coated with zeolite (TNZPC) in photocatalytic degradation. Electrochemical anodization (ECA) and electrophoretic deposition (EPD) were applied to form TNZPC. Field Emission-Scanning Electron Microscopy (FESEM), Energy Dispersive Spectroscopy (EDS), X-ray Diffraction (XRD), and X-ray Fluorescence (XRF) verified the characterization of TNZPC accordingly and the degradation kinetics of TCC followed the pseudo-first-order model of Hinshelwood. The highest degradation rate, reaching 95.2%, was observed at pH 11, while the lowest rate was at pH 3, with a degradation efficiency of only 72.6% after 60 minutes of irradiation with utilization of 0.75 cm2 of TNZPC. The mechanism study has verified eleven intermediate products were produced during TCC degradation by the process of oxidation, ozonation, hydroxyl radical (*OH), and dichlorination. The study suggests that finding the optimum conditions such as photocatalyst modification, cationic material, light sources, TCC initial concentration, pH, and TNZPC size play crucial roles in significant TCC photocatalytic degradation.

Association of same-day urinary phenol levels and cardiac electrical alterations: analysis of the Fernald Community Cohort

BackgroundExposure to phenols has been linked in animal models and human populations to cardiac function alterations and cardiovascular diseases, although their effects on cardiac electrical properties in humans remains to be established. This study aimed to identify changes in electrocardiographic (ECG) parameters associated with environmental phenol exposure in adults of a midwestern large cohort known as the Fernald Community Cohort (FCC).MethodsDuring the day of the first comprehensive medical examination, urine samples were obtained, and electrocardiograms were recorded. Cross-sectional linear regression analyses were performed.ResultsBisphenol A (BPA) and bisphenol F (BPF) were both associated with a longer PR interval, an indication of delayed atrial-to-ventricle conduction, in females (p < 0.05) but not males. BPA combined with BPF was associated with an increase QRS duration, an indication of delayed ventricular activation, in females (P < 0.05) but not males. Higher triclocarban (TCC) level was associated with longer QTc interval, an indication of delayed ventricular repolarization, in males (P < 0.01) but not females. Body mass index (BMI) was associated with a significant increase in PR and QTc intervals and ventricular rate in females and in ventricular rate in males. In females, the combined effect of being in the top tertile for both BPA urinary concentration and BMI was an estimate of a 10% increase in PR interval. No associations were found with the other phenols.ConclusionHigher exposure to some phenols was associated with alterations of cardiac electrical properties in a sex specific manner in the Fernald cohort. Our population-based findings correlate directly with clinically relevant parameters that are associated with known pathophysiologic cardiac conditions in humans.

Characterizing the effects of triclosan and triclocarban on the intestinal epithelial homeostasis using small intestinal organoids

Intestinal epithelium has the largest surface of human body, contributes dramatically to defense of toxicant-associated intestinal injury. Triclosan (TCS) and triclocarban (TCC), extensively employed as antibacterial agents in personal care products (PCPs) and healthcare facilities, caused serious damage to human intestine. However, the role of the intestinal epithelium in TCS/TCC-induced intestinal toxicity and its underlying toxic mechanisms remain incompletely understood. In this study, a novel 3D intestinal organoid model was utilized to investigate that exposure to TCS/TCC led to a compromised self-renewal and differentiation of intestinal stem cells (ISCs). Consequently, this disrupted intestinal epithelial homeostasis ultimately caused a reduction in nutrient absorption and deficient of epithelial defense to exogenous and endogenous pathogens stimulation. The inhibition of the Wnt signaling pathway in intestinal stem cell was contributed to the intestinal toxicity of TCS/TCC. These results were further confirmed in vivo with mice exposed to TCS/TCC. The findings of this study provide evidence that TCS/TCC possess the capacity to disturb the homeostasis of the intestinal epithelium, and emphasize the credibility of organoids as a valuable model for toxicological studies, as they could faithfully recapitulate in vivo phenomena.

Integrated multi-omics approaches reveal the neurotoxicity of triclocarban in mouse brain

Triclocarban (TCC) is an antimicrobial ingredient that commonly incorporated in many household and personal care products, raising public concerns about its potential health risks. Previous research has showed that TCC could cross the blood–brain barrier, but to date our understanding of its potential neurotoxicity at human-relevant concentrations remains lacking. In this study, we observed anxiety-like behaviors in mice with continuous percutaneous exposure to TCC. Subsequently, we combined lipidomic, proteomic, and metabolic landscapes to investigate the underlying mechanisms of TCC-related neurotoxicity. The results showed that TCC exposure dysregulated the proteins involved in endocytosis and neurodegenerative disorders in mouse cerebrum. Brain energy homeostasis was also altered, as evidenced by the perturbation of pyruvate metabolism, TCA cycle, and oxidative phosphorylation, which in turn caused mitochondrial dysfunction. Meanwhile, the changing trends of sphingolipid signaling pathway and overproduction of mitochondrial reactive oxygen species (mROS) could enhance the neural apoptosis. The in vitro approach further demonstrated that TCC exposure promoted apoptosis, accompanied by the overproduction of mROS and alteration in the mitochondrial membrane potential in N2A cells. Together, dysregulated endocytosis, mROS-related mitochondrial dysfunction and neural cell apoptosis are considered to be crucial factors for TCC-induced neurotoxicity, which may contribute to the occurrence and development of neurodegenerative disorders. Our findings provide novel perspectives for the mechanisms of TCC-triggered neurotoxicity.

Influence of Organic Carbon from Weathered Sediments on Triclocarban Distribution in Environmental Aqueous Systems

In this study, the chemical distribution of triclocarban (TCC), in natural aqueous systems, between water and sediment, with different chemical compositions of the aqueous phase and different percentages of organic carbon (OC%) in the sediments is presented. The influences of the temperature, of the composition of the aqueous matrices of natural waters and (OC%) in the sediment over the solubility of triclocarban, and its distribution coefficient Kd values were studied. log KD at 25 °C varied between 1.94 and 3.27 for a sediment with 5.50% OC and between 3.95 and 5.93% for a sediment with 6.75% OC, in the studied aqueous systems, with different concentrations of OC in the sediment.

Association of Phenols, Parabens, and Their Mixture with Maternal Blood Pressure Measurements in the PROTECT Cohort.

Phenols and parabens are two classes of high production volume chemicals that are used widely in consumer and personal care products and have been associated with reproductive harm and pregnancy complications, such as preeclampsia and gestational diabetes. However, studies examining their influence on maternal blood pressure and gestational hypertension are limited. We investigated associations between individual phenols, parabens, and their mixture on maternal blood pressure measurements, including systolic and diastolic blood pressure (SBP and DBP) and hypertension during pregnancy (defined as stage 1 or 2 hypertension), among Puerto Rico PROTECT study participants. We examined these relationships cross-sectionally at two time points during pregnancy (16-20 and 24-28 wks gestation) and longitudinally using linear mixed models (LMMs). Finally, we used quantile g-computation to examine the mixture effect on continuous (SBP, DBP) and binary (hypertension during pregnancy) blood pressure outcomes. We observed a trend of higher odds of hypertension during pregnancy with exposure to multiple analytes and the overall mixture [including bisphenol A (BPA), bisphenol S (BPS), triclocarbon (TCC), triclosan (TCS), benzophenone-3 (BP-3), 2,4-dichlorophenol (2,4-DCP), 2,5-dichlorophenol (2,5-DCP), methyl paraben (M-PB), propyl paraben (P-PB), butyl paraben (B-PB), and ethyl paraben (E-PB)], especially at 24-28 wk gestation, with an adjusted mixture (95% CI: 1.03, 2.38). Lower SBP and higher DBP were also associated with individual analytes, with results from LMMs most consistent for methyl paraben (M-PB) or propyl paraben (P-PB) and increased DBP across pregnancy [adjusted M-PB (95% CI: 0.17, 1.38) and adjusted P-PB (95% CI: 0.19, 1.51)] and for BPA, which was associated with decreased SBP (adjusted ; 95% CI: , ). Consistent with other literature, we also found evidence of effect modification by fetal sex, with a strong inverse association observed between the overall exposure mixture and SBP at visit 1 among participants carrying female fetuses only. Our findings indicate that phenol and paraben exposure may collectively increase the risk of stage 1 or 2 hypertension during pregnancy, which has important implications for fetal and maternal health. https://doi.org/10.1289/EHP14008.

Long-term impacts of triclocarban on nitrogen removal via the anammox process: Focusing on triclocarban fate and microbial community shift

The presence of triclocarban (TCC) in municipal wastewater has potentially inhibitive effect on anammox process. In the present study, the long-term impact of TCC on the anammox process was investigated via determining nitrogen removal efficiency, TCC fate and microbial community. Results showed that TCC exerted an inhibitory effect on nitrogen removal performance with a 22.9 % decrease in ammonium removal efficiency (ARE) at the first 15 day, but it gradually recovered after 45 days TCC exposure. The secretion of extracellular polymeric substances (EPS) was increased to resist the TCC, and the long-term operation enhanced the activity of enzymes associated with anammox process due to the Hormesis effect exerted by microorganisms, indicating the adaption of anammox bacteria. The TCC degradation could reach 73.4 % and reduce the stress to anammox bacteria, leading to the recovery of nitrogen removal. The microbiological analysis revealed that after 45 days of exposure to TCC, there was a gradual shift in the dominant bacterial group from Candidatus_Jettenia to Candidatus_Brocadia due to its higher semi-saturation constant (Ks) to NH4+-N. Moreover, the denitrifying bacteria (i.e., Thauera) was detected and the TCC degraded product (e.g., β-ketoadipic acid) could be as its carbon source. The Pseudomonas capable of degrading TCC was accumulated, consistent with TCC degradation. Overall, the findings in present study provided the insight mechanism of TCC on annamox process.

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.

Integrated remediation and detoxification of triclocarban-contaminated water using waste-derived biochar-immobilized cells by long-term column experiments

Triclocarban (TCC), an antibacterial agent commonly used in personal care products, is one of the top ten contaminants of emerging concern in various environmental media, including soil and contaminated water in vadose zone. This study aimed to investigate TCC-contaminated water remediation using biochar-immobilized bacterial cells. Pseudomonas fluorescens strain MC46 (MC46), an efficient TCC-degrading isolate, was chosen, whereas agro-industrial carbonized waste as biochar was directly used as a sustainable cell immobilization carrier. According to the long-term TCC removal performance results (160 d), the biochar-immobilized cells consistently exhibited high TCC removal efficiencies (84–97%), whereas the free MC46 removed TCC for 76–94%. At 100 days, the detachment of the MC46 cells from the immobilized cell column was observed. The micro-Fourier-transform infrared spectroscopy results indicated that extracellular polymeric substance (EPS) was produced, but polysaccharide and protein fractions were washed out of the column. The lipid fraction of EPS adhered to the biochar, promoting TCC sorption for long-term treatment. The shortening of MC46 cells improved the tolerance of TCC toxicity. The TCC-contaminated water was successfully detoxified by the biochar-immobilized MC46 cells. Overall, the waste-derived biochar-immobilized cell system proposed in this study for the removal of emerging contaminants, including TCC, is efficient, economical, and aligned with the sustainable development concept of value-added utilization of waste.

Critical roles of soil composition and pollutant properties on the degradation of PPCPs during ferrous/persulfate processes

Pharmaceuticals and personal care products (PPCPs) are widely used worldwide and cause potential soil pollution. Fe2+-activated persulfate (PS) processes (Fe-PAPs) are promising techniques for soil remediation. However, a knowledge gap exists in the mechanistic insights into the dominant factors affecting the degradation of different PPCPs in varied soil types. This study systematically investigated the roles of soil components and pollutant properties in the degradation of three PPCPs (triclosan (TCS), triclocarban (TCC), and naproxen (NPS)) in the nine soils in the Fe2+/PS system. The degradation efficiencies of TCS and NPS ranged from 10.92 % to 91.62 % and 46.59 % to 99.81 %, respectively, whereas nearly no degradation was observed for TCC. PPCPs with high water solubility, high energies of the highest occupied molecular orbital (EHOMO), low pKa values, low energy gap (ΔE), or low vertical ionization potential (VIP) were more favorable for degradation. XPS analysis suggested that aliphatic carbon (Ali–C–C(H)), ether or alcohol carbon (C–O), and aldehyde or ketonic carbon (CO) on SOM significantly inhibited TCS degradation. The results of ROS quenching experiments showed that SO4•− and 1O2 played major roles in TCS and NPS degradation in the six soils, with the relative contributions ranged from 24.82 % to 99.14 % and 0.15 % to 73.40 %, respectively. The interaction between soil components, active species, and pollutants resulted in the distinct intermediates of TCS and NPS in different soils. Our findings provide in-depth insights into the role of soil composition and pollutant properties on the remediation of PPCP-contaminated soils in Fe-PAPs.

Enhancement of triclocarban biodegradation: Metabolic division of labor in co-culture of Rhodococcus sp. BX2 and Pseudomonas sp. LY-1

Triclocarban (TCC) and its metabolite, 3,4-dichloroaniline (DCA), are classified as emerging organic contaminants (EOCs). Significant concerns arise from water and soil contamination with TCC and its metabolites. These concerns are especially pronounced at high concentrations of up to approximately 20 mg/kg dry weight, as observed in wastewater treatment plants (WWTPs). Here, a TCC-degrading co-culture system comprising Rhodococcus rhodochrous BX2 and Pseudomonas sp. LY-1 was utilized to degrade TCC (14.5 mg/L) by 85.9% in 7 days, showing improved degradation efficiency compared with monocultures. A combination of high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), genome sequencing, transcriptomic analysis, and quantitative reverse transcription-PCR (qRT-PCR) was performed. Meanwhile, through the combination of further experiments involving heterologous expression and gene knockout, we proposed three TCC metabolic pathways and identified four key genes (tccG, tccS, phB, phL) involved in the TCC degradation process. Moreover, we revealed the internal labor division patterns and connections in the co-culture system, indicating that TCC hydrolysis products were exchanged between co-cultured strains. Additionally, mutualistic cooperation between BX2 and LY-1 enhances TCC degradation efficiency. Finally, phytotoxicity assays confirmed a significant reduction in the plant toxicity of TCC following synergistic degradation by two strains. The in-depth understanding of the TCC biotransformation mechanisms and microbial interactions provides useful information for elucidating the mechanism of the collaborative biodegradation of various contaminants.

Spatial metabolomics reveal metabolic alternations in the injured mice kidneys induced by triclocarban treatment

Triclocarban (TCC) is a common antimicrobial agent that has been widely used in medical care. Given the close association between TCC treatment and metabolic disorders, we assessed whether long-term treatment to TCC at a human-relevant concentration could induce nephrotoxicity by disrupting the metabolic levels in a mouse model. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was applied to investigate the alterations in the spatial distributions and abundances of TCC, endogenous and exogenous metabolites in the kidney after TCC treatment. The results showed that TCC treatment induced the changes in the organ weight, organ coefficient and histopathology of the mouse kidney. MSI data reveled that TCC accumulated in the all regions of the kidney, while its five metabolites mainly distributed in the cortex regions. The abundances of 79 biomolecules associated with pathways of leukotriene E4 metabolism, biosythesis and degradation of glycerophospholipids and glycerolipids, ceramide-to-sphingomyelin signaling were significantly altered in the kidney after TCC treatment. These biomolecules showed distinctive distributions in the kidney and displayed a favorable spatial correlation with the pathological damage. This work offers new insights into the related mechanisms of TCC-induced nephrotocicity and exhibits the potential of MALDI-MSI-based spatial metabolomics as a promising approach for the risk assessment of agents in medical care.

Mitigation of Triclocarban Inhibition in Microbial Electrolysis Cell-Assisted Anaerobic Digestion.

Triclocarban (TCC), as a widely used antimicrobial agent, is accumulated in waste activated sludge at a high level and inhibits the subsequent anaerobic digestion of sludge. This study, for the first time, investigated the effectiveness of microbial electrolysis cell-assisted anaerobic digestion (MEC-AD) in mitigating the inhibition of TCC to methane production. Experimental results showed that 20 mg/L TCC inhibited sludge disintegration, hydrolysis, acidogenesis, and methanogenesis processes and finally reduced methane production from traditional sludge anaerobic digestion by 19.1%. Molecular docking revealed the potential inactivation of binding of TCC to key enzymes in these processes. However, MEC-AD with 0.6 and 0.8 V external voltages achieved much higher methane production and controlled the TCC inhibition to less than 5.8%. TCC in the MEC-AD systems was adsorbed by humic substances and degraded to dichlorocarbanilide, leading to a certain detoxification effect. Methanogenic activities were increased in MEC-AD systems, accompanied by complete VFA consumption. Moreover, the applied voltage promoted cell apoptosis and sludge disintegration to release biodegradable organics. Metagenomic analysis revealed that the applied voltage increased the resistance of electrode biofilms to TCC by enriching functional microorganisms (syntrophic VFA-oxidizing and electroactive bacteria and hydrogenotrophic methanogens), acidification and methanogenesis pathways, multidrug efflux pumps, and SOS response.

Triclocarban and triclosan promote breast cancer progression in vitro and in vivo via activating G protein-coupled estrogen receptor signaling pathways

Triclocarban (TCC) and triclosan (TCS) have been detected ubiquitously in human body and evoked increasing concerns. This study aimed to reveal the induction risks of TCC and TCS on triple negative breast cancer through non-genomic GPER-mediated signaling pathways. Molecular simulation indicated that TCC exhibited higher GPER binding affinity than TCS theoretically. Calcium mobilization assay displayed that TCC/TCS activated GPER signaling pathway with the lowest observed effective concentrations (LOEC) of 10 nM/100 nM. TCC and TCS also upregulated MMP-2/9, EGFR, MAPK3 but downregulated MAPK8 via GPER-mediated signaling pathway. Proliferation assay showed that TCC/TCS induced 4 T1 breast cancer cells proliferation with the LOEC of 100 nM/1000 nM. Wound-healing and transwell assays showed that TCC/TCS promoted 4 T1 cells migration in a concentration-dependent manner with the LOEC of 10 nM. The effects of TCC on breast cancer cells proliferation and migration were stronger than TCS and both were regulated by GPER. TCC/TCS induced migratory effects were more significantly than proliferative effect. Mechanism study showed that TCC/TCS downregulated the expression of epithelial marker (E-cadherin) but upregulated mesenchymal markers (snail and N-cadherin), which was reversed by GPER inhibitor G15. These biomarkers results indicated that TCC/TCS-induced 4 T1 cells migration was a classic epithelial to mesenchymal transition mechanism regulated by GPER signaling pathway. Orthotopic tumor model verified that TCC promoted breast cancer in-situ tumor growth and distal tissue metastasis via GPER-mediated signaling pathway at human-exposure level of 10 mg/kg/d. TCC-induced tissue metastasis of breast cancer was more significantly than in-situ tumor growth. Overall, we demonstrated for the first time that TCC/TCS could activate the GPER signaling pathways to induce breast cancer progression.

Triclocarban induces lipid droplet accumulation and oxidative stress responses by inhibiting mitochondrial fatty acid oxidation in HepaRG cells

Mitochondrial fatty acid oxidation (mtFAO) plays an important role in hepatic energy metabolism. Severe mtFAO injury leads to nonalcoholic fatty liver disease (NAFLD) and liver failure. Several drugs have been withdrawn owing to safety issues, such as induction of fatty liver disease through mtFAO disruption. For instance, the antimicrobial triclocarban (TCC), an environmental contaminant that was removed from the market due to its unknown safety in humans, induces NAFLD in rats and promotes hepatic FAO in mice. Therefore, there are no consistent conclusions regarding the effects of TCC on FAO and lipid droplet accumulation. We hypothesized that TCC induces lipid droplet accumulation by inhibiting mtFAO in human hepatocytes. Here, we evaluated mitochondrial respiration in HepaRG cells to investigate the effects of TCC on fatty acid-driven oxidation in cells, electron transport chain parameters, lipid droplet accumulation, and antioxidant genes. The results suggest that TCC increases oxidative stress gene expression (GCLM, p62, HO-1, and NRF2) through lipid droplet accumulation via mtFAO inhibition in HepaRG cells. The results of the present study provide further insights into the effect of TCC on human NAFLD through mtFAO inhibition, and further in vivo studies could be used to validate the mechanisms.