ABSTRACT
6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) exhibits pronounced estrogenic effects, potentially influencing the etiology of lung cancer. This study assessed the potential associations between serum concentrations of 6:2 Cl-PFESA and lung cancer risk at the population level. Odds ratios (ORs) for lung cancer across serum 6:2 Cl-PFESA quartiles were assessed using conditional logistic regression. Additionally, we investigated potential effect modification by various confounding factors. Elevated serum levels of 6:2 Cl-PFESA were consistently associated with an increased risk of lung cancer in both the crude model (OR = 1.62, 95% CI: 1.08-2.42, p = 0.018) and the adjusted model (OR = 1.59, 95% CI: 1.06-2.39, p = 0.026). Stratified analyses revealed that elevated serum levels of 6:2 Cl-PFESA were associated with increased risk estimates of lung cancer among males (adjusted OR = 2.04, 95% CI: 1.19-3.51, p = 0.006), smokers (adjusted OR = 2.48, 95% CI: 1.25-4.89, p = 0.003), and drinkers (adjusted OR = 2.20, 95% CI: 0.94-5.16, p = 0.049). The results of this study imply that exposure to 6:2 Cl-PFESA at levels considered environmentally relevant may be linked to an elevated risk of developing lung cancer.
ABSTRACT
A variety of per- and polyfluoroalkyl substances (PFASs) have been released into the environment via wastewater treatment plant (WWTP) effluent, with current target and nontarget analytical methods typically focusing on negatively ionized PFASs while largely overlooking positively ionized ones. In this study, five cationic PFASs, perfluoroalkyl sulfonyl quaternary ammonium substances (PFAQASs), were first identified in surface water impacted by the WWTP effluent, applying a metabolomics-based nontarget analysis method. Environmental behaviors of identified novel PFAQASs were further investigated. In surface water, sediment, and fish (Coilia mystus) samples collected from the Yangtze River, 8:3 PFAQA was consistently the predominant PFAQASs, with the mean concentrations of 90 ng/L (< LOD-558 ng/L), 92 ng/g dw (< LOD-421 ng/g dw), and 2.3 ng/g ww (< LOD-4.6 ng/g ww), respectively. This study highlights the necessity to discover other cationic PFASs in the environment. Among PFAQASs, 8:4 PFAQA (4.2, range 3.4 - 4.6) had the highest mean sediment-water partitioning coefficient (log Koc), followed by 8:3 PFAQA (3.9, 2.8 - 4.5) and 6:3 PFAQA (3.7, 3.3 - 4.1). The log Koc of PFAQASs showed a general increase trend with the increasing carbon chain length. Mean bioaccumulation factor (BAF) values of PFAQASs calculated in the collected fish from the Yangtze River ranged from 1.9 ± 0.32 (4:3 PFAQA) to 2.9 ± 0.34 (8:4 PFAQA). The mean BAF values of PFAQASs generally increased with the carbon chain length. Further studies are warranted to elucidate the environmental fate, potential toxicity, and human exposure implications for these identified novel PFASs.
Subject(s)
Environmental Monitoring , Quaternary Ammonium Compounds , Water Pollutants, Chemical , Fluorocarbons/analysis , Animals , Fishes , Rivers/chemistry , Wastewater/chemistryABSTRACT
Bisphenol analogues (BPs) are prevalent in diverse foodstuff samples worldwide. However, the occurrence of conjugated bisphenol A (BPA) and bisphenol S (BPS) metabolites in foodstuff remains poorly understood. This study analyzed eight BPs, and four conjugated BPA and BPS metabolites, in three animal-derived foodstuff and five plant-derived foodstuff samples from China. Results showed that fish foodstuff (9.7 ng/g ww) contained the highest mean concentration of BPA, followed by rice (5.1 ng/g ww) and beans foodstuff (3.6 ng/g ww). BPA-sulfate had higher mean concentrations than BPA-glucuronide in different foodstuff categories, except that in eggs foodstuff (p < 0.05). Compared with other foodstuff items, fish (3.4 ng/g ww) and vegetable (1.6 ng/g ww) foodstuff samples exhibited comparatively higher mean concentrations of BPS. Mean concentrations of BPS-sulfate were consistently higher than BPS-glucuronide in vegetables, meats, and fish foodstuff (p < 0.05). BPA contributed the major total dietary intake (DI) of BPs, with the mean DI of 435 ng/kg bw/day for women and 374 ng/kg bw/day for men, respectively. To our knowledge, this study is the first to investigate the occurrence of conjugated BPA and BPS metabolites in foodstuff, which enhances our comprehension of the origins of these conjugated metabolites in the human body.
Subject(s)
Benzhydryl Compounds , Food Contamination , Phenols , Sulfones , Phenols/analysis , Benzhydryl Compounds/analysis , China , Food Contamination/analysis , Sulfones/analysis , Environmental Monitoring , Humans , Animals , Environmental Pollutants/analysis , Environmental Pollutants/metabolismABSTRACT
Bisphenol S (BPS), an environmental endocrine disruptor, has been identified in global environmental matrices. Nevertheless, limited studies have investigated the presence of chlorinated analogues of BPS (Clx-BPSs) with potential estrogenic activities in environmental matrices. In this study, the occurrence of BPS and five types of Clx-BPSs was characterized in indoor dust (n = 178) from Hangzhou City. BPS was measurable in 94% of indoor dust samples, with an average level of 0.63 µg/g (
ABSTRACT
Health exposure to benzotriazole ultraviolet stabilizers (BUVSs) may pose diverse toxic impacts on health. Presently, the occurrence of BUVSs in human urine remains inadequately understood. This study analyzed 13 kinds of BUVSs in human urine (n = 182) from the general Chinese adult participants. Totally, nine BUVSs were measurable in these human urine samples. Among the detected BUVSs, 2-(2H-benzotriazol-2-yl)-p-cresol (UV-P) was the most predominant BUVS in the human urine, with the mean concentration of 1.6 µg/g creatinine (
ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC)/pancreatic cancer, is a highly aggressive malignancy with poor prognosis. Gemcitabine-based chemotherapy remains the cornerstone of PDAC treatment. Nonetheless, the development of resistance to gemcitabine among patients is a major factor contributing to unfavorable prognostic outcomes. The resistance exhibited by tumors is modulated by a constellation of factors such as genetic mutations, tumor microenvironment transforms, environmental contaminants exposure. Currently, comprehension of the relationship between environmental pollutants and tumor drug resistance remains inadequate. Our study found that PFOS/6:2 Cl-PFESA exposure increases resistance to gemcitabine in PDAC. Subsequent in vivo trials confirmed that exposure to PFOS/6:2 Cl-PFESA reduces gemcitabine's efficacy in suppressing PDAC, with the inhibition rate decreasing from 79.5 % to 56.7 %/38.7 %, respectively. Integrative multi-omics sequencing and molecular biology analyses have identified the upregulation of ribonucleotide reductase catalytic subunit M1 (RRM1) as a critical factor in gemcitabine resistance. Subsequent research has demonstrated that exposure to PFOS and 6:2 Cl-PFESA results in the upregulation of the RRM1 pathway, consequently enhancing chemotherapy resistance. Remarkably, the influence exerted by 6:2 Cl-PFESA exceeds that of PFOS. Despite 6:2 Cl-PFESA being regarded as a safer substitute for PFOS, its pronounced effect on chemotherapeutic resistance in PDAC necessitates a thorough evaluation of its potential risks related to gastrointestinal toxicity.
Subject(s)
Alkanesulfonic Acids , Carcinoma, Pancreatic Ductal , Deoxycytidine , Drug Resistance, Neoplasm , Fluorocarbons , Gemcitabine , Pancreatic Neoplasms , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Pancreatic Neoplasms/drug therapy , Humans , Fluorocarbons/toxicity , Alkanesulfonic Acids/toxicity , Cell Line, Tumor , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/genetics , Drug Resistance, Neoplasm/drug effects , Animals , Ribonucleoside Diphosphate Reductase , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism , Antimetabolites, Antineoplastic/therapeutic use , Female , Mice , Male , Mice, NudeABSTRACT
Bisphenol A (BPA) and bisphenol S (BPS) have been widely spread in the global environment. However, for conjugated BPA and BPS metabolites, limited studies have investigated their occurrence in environmental matrices. We collected paired indoor and outdoor dust (n = 97), as well as human urine (n = 153) samples, from residential houses in Quzhou, China, and measured these samples for 8 conjugated BPA and BPS metabolites. Three BPA metabolites were found in collected indoor and outdoor dust, with BPA sulfate (mean 0.75 and 1.3 ng/g, respectively) and BPA glucuronide (0.13 and 0.26 ng/g) being more abundant. BPA conjugates accounted for a mean of 42 and 56% of total BPA (sum of conjugated BPA and BPA metabolites) in indoor and outdoor dust, respectively. BPS sulfate (mean 0.29 and 0.82 ng/g, respectively) had consistently higher concentrations than BPS glucuronide (0.13 and 0.27 ng/g) in indoor and outdoor samples. BPS conjugates contributed a mean 32% and 45% of total BPS (sum of BPS and BPS metabolites) in indoor and outdoor dust, respectively. Moreover, conjugated BPA and BPS metabolites in indoor or outdoor dust were not significantly correlated with those in urine from residents. Overall, this study first demonstrates the wide presence of conjugated BPA and BPS metabolites, besides BPA and BPS, in indoor and outdoor dust. These data are important for elucidating the sources of conjugated BPA and BPS metabolites in the human body.
Subject(s)
Air Pollution, Indoor , Benzhydryl Compounds , Dust , Environmental Monitoring , Phenols , Sulfones , Phenols/urine , Humans , Benzhydryl Compounds/urine , Dust/analysis , Sulfones/urine , Air Pollution, Indoor/analysis , China , Environmental Pollutants/urine , Environmental Pollutants/metabolism , Environmental Exposure/analysis , Air Pollutants/analysis , Air Pollutants/urineABSTRACT
Anthocyanin is an important pigment responsible for plant coloration and beneficial to human health. Kale (Brassica oleracea var. acephala), a primary cool-season flowers and vegetables, is an ideal material to study anthocyanin biosynthesis and regulation mechanisms due to its anthocyanin-rich leaves. However, the underlying molecular mechanism of anthocyanin accumulation in kale remains poorly understood. Previously, we demonstrated that BoDFR1 is a key gene controlling anthocyanin biosynthesis in kale. Here, we discovered a 369-bp InDel variation in the BoDFR1 promoter between the two kale inbred lines with different pink coloration, which resulted in reduced transcriptional activity of the BoDFR1 gene in the light-pink line. With the 369-bp insertion as a bait, an R2R3-MYB repressor BoMYB4b was identified using the yeast one-hybrid screening. Knockdown of the BoMYB4b gene led to increased BoDFR1 expression and anthocyanin accumulation. An E3 ubiquitin ligase, BoMIEL1, was found to mediate the degradation of BoMYB4b, thereby promoting anthocyanin biosynthesis. Furthermore, the expression level of BoMYB4b was significantly reduced by light signals, which was attributed to the direct repression of the light-signaling factor BoMYB1R1 on the BoMYB4b promoter. Our study revealed that a novel regulatory module comprising BoMYB1R1, BoMIEL1, BoMYB4b, and BoDFR1 finely regulates anthocyanin accumulation in kale. The findings aim to establish a scientific foundation for genetic improvement of leaf color traits in kale, meanwhile, providing a reference for plant coloration studies.
Subject(s)
Anthocyanins , Brassica , Gene Expression Regulation, Plant , Plant Proteins , Anthocyanins/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Brassica/genetics , Brassica/metabolism , Promoter Regions, Genetic/genetics , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Plant Leaves/metabolism , Plant Leaves/genetics , Plants, Genetically Modified , Transcription Factors/metabolism , Transcription Factors/geneticsABSTRACT
The comprehensive understanding of the occurrence of benzotriazole UV stabilizers (BZT-UVs) in environmental surface water is imperative due to their widespread application and potential aquatic toxicity. We conducted an analysis of 13 traditional BZT-UVs in surface water samples collected from Taihu Lake (TL, n = 23) and Qiantang River (QR, n = 22) in China. The results revealed that 5chloro-2-(3,5-di-tertbutyl-2-hydroxyphenyl)-benzotriazole (UV-327) was consistently the predominant BZT-UV in water samples from TL (mean 16 ng/L; detection frequency 96 %) and QR (14 ng/L; 91 %). Furthermore, we developed a characteristic fragment ion-based strategy to screen and identify unknown BZT-UVs in collected surface water, utilizing a high-resolution mass spectrometer. A total of seven novel BZT-UVs were discovered in water samples, and their chemical structures were proposed. Four of these novel BZT-UVs were further confirmed with standards provided by industrial manufacturers. Semi-quantitative analysis revealed that among discovered novel BZT-UVs, 2-(2hydroxy-3tertbutyl5-methylphenyl)-benzotriazole was consistently the predominant novel BZT-UV in TL (mean 4.1 ng/L, detection frequency 70 %) and QR (2.8 ng/L, 77 %) water. In TL water, the second predominant novel BZT-UV was 2-(3-allyl-2hydroxy-5-methylphenyl)-2H-benzotriazole (mean 3.9 ng/L, Subject(s)
Triazoles
, Water Pollutants, Chemical
, Triazoles/chemistry
, Water Pollutants, Chemical/chemistry
, China
, Lakes/chemistry
, Ultraviolet Rays
, Rivers/chemistry
, Environmental Monitoring
ABSTRACT
Studies have shown that bisphenol S (BPS) is mainly present as its conjugated metabolites in human blood. However, the distribution of conjugated BPS metabolites in different human blood matrices has not been characterized. In this study, paired human serum and whole blood samples (n = 79) were collected from Chinese participants, and were measured for the occurrence of BPS and 4 BPS metabolites. BPS was detectable in 49% of human serum (Subject(s)
Phenols
, Sulfones
, Humans
, Phenols/blood
, Phenols/metabolism
, Sulfones/blood
, Sulfones/metabolism
, Male
, Female
, Environmental Pollutants/blood
, Environmental Pollutants/metabolism
, Adult
, Glucuronides/blood
, Glucuronides/metabolism
, Sulfuric Acid Esters/blood
, Middle Aged
ABSTRACT
Exposure to carbazole (CZ) and polyhalogenated carbazoles (PHCZs) may pose a threat to human health, owing to their potential dioxin-like toxicity. Until now, the presence of these chemicals in the human urine from the general population is still unclear. Human urine samples (n = 210) were taken from the general population in Quzhou, China in this study, and were analyzed for CZ and 14 PHCZs. CZ and nine PHCZs were detected in collected human urine. CZ (detection frequency 100 %), 3-chlorocarbazole (3-CCZ; 88 %), 3,6-dichlorocarbzole (36-CCZ; 84 %), and 3-bromocarbazole (3-BCZ; 80 %) were more frequently detected. Among detected PHCZs, 3-CCZ (mean 0.49 ng/mL, < LOD-4.3 ng/mL) had comparatively higher urinary levels, followed by 3-BCZ (0.30 ng/L, < LOD-1.9 ng/mL) and 36-CCZ (0.20 ng/L, < LOD-1.4 ng/mL). Urinary concentrations of CZ in male participants (1.3 ± 0.26 ng/mL) were significantly (p < 0.05) higher than that in female participants (0.92 ± 0.24 ng/mL). No obvious trend in urinary concentrations with the age of participants was found for CZ and detected PHCZs. The mean daily excretion was found highest for CZ (31 ng/kg bw/day), followed by 3-CCZ (19 ng/kg bw/day) and 3-BCZ (8.5 ng/kg bw/day). This study provides the first data, to our knowledge, on the presence and levels of CZ and PHCZs in human urine, which is necessary for conducting the human exposure risk assessment.
Subject(s)
Dioxins , Polychlorinated Dibenzodioxins , Humans , Female , Male , Carbazoles/toxicity , ChinaABSTRACT
Environmental occurrence of perfluorobutane sulfonamide (PFBSA) has only been recently discovered. The current knowledge regarding the occurrence and environmental behaviors of PFBSA in the marine environment is still relatively limited. In this study, PFBSA and other 37 poly- and perfluoroalkyl substances were analyzed in seawater (n = 43), sediment (n = 43), and marine fish (n = 176) samples collected from East China Sea and Antarctic Ocean. PFBSA was detected in > 90% of seawater from East China Sea and Antarctic Ocean, with the concentrations of 1.0 - 19 ng/L and < LOD-228 pg/L, respectively. The field-based mean log-transformed sediment-seawater partitioning coefficients of PFBSA were 1.6 ± 0.19 L/kg dw and 1.1 ± 0.19 L/kg dw in East China Sea and Antarctic Ocean, respectively, which are lower than that of perfluorooctanoate and perfluorooctane sulfonate. This indicates its long-range transport potential in global oceans with ocean currents. The mean log-transformed bioaccumulation factor values of PFBSA determined in the multiple species of whole-body marine fishes from East China Sea and Antarctic Ocean were 2.3 L/kg ww and 2.4 L/kg ww, respectively, which are comparable to that of perfluoroheptanoate (2.3 L/kg ww) in marine fishes from East China Sea. We did not observe an obvious biomagnification or biodilution of PFBSA along the marine food chain in East China Sea or Antarctic Ocean. This study provides the first data on the environmental behaviors of PFBSA in the marine environment.
ABSTRACT
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are synthetic chemicals, encompassing compounds like perfluorooctane sulfonate (PFOS), which have widespread applications across various industries, including food packaging and firefighting. In recent years, China has increasingly employed 6:2 Cl-PFESA as an alternative to PFOS. Although the association between PFAS exposure and hepatocellular carcinoma (HCC) has been demonstrated, the underlying mechanisms that promote HCC proliferation are uncleared. Therefore, we aimed to investigate the effects and differences of PFOS and 6:2 Cl-PFESA on HCC proliferation through in vivo and in vitro tumor models. Our results reveal that both PFOS and 6:2 Cl-PFESA significantly contribute to HCC proliferation in vitro and in vivo. Exposure led to reduced population doubling times, enlarged cell colony sizes, enhanced DNA synthesis efficiency, and a higher proportion of cells undergoing mitosis. Furthermore, both PFOS and 6:2 Cl-PFES) have been shown to activate the PI3K/AKT/mTOR signaling pathway and inhibit necroptosis. This action consequently enhances the proliferation of HCC cells. Our phenotypic assay findings suggest that the tumorigenic potential of 6:2 Cl-PFESA surpasses that of PFOS; in a subcutaneous tumor model using nude mice, the mean tumor weight for the 6:2 Cl-PFESA-treated cohort was 2.33 times that observed in the PFOS cohort (p < 0.01). Despite 6:2 Cl-PFESA being considered a safer substitute for PFOS, the pronounced effects of this chemical on HCC cell growth warrant a thorough assessment of hepatotoxicity risks linked to its usage.
Subject(s)
Alkanesulfonic Acids , Carcinoma, Hepatocellular , Cell Proliferation , Fluorocarbons , Liver Neoplasms , Carcinoma, Hepatocellular/chemically induced , Carcinoma, Hepatocellular/pathology , Humans , Liver Neoplasms/pathology , Liver Neoplasms/chemically induced , Cell Proliferation/drug effects , Animals , Mice , Cell Line, Tumor , Signal Transduction/drug effects , ChinaABSTRACT
Neonicotinoids, widely used on farmland, are ubiquitous in food; however, their distribution among various crops and associated exposure risks at the provincial level in China remain unclear. We collected 19 types of crop samples (fruits, vegetables, and tea) from farmland in nine prefectural cities in Zhejiang Province, China. We analyzed nine commonly used neonicotinoids in the edible portions of these crops. A notable detection rate (42.1 %-82.9 %) and high residual neonicotinoid concentrations (278 ± 357 ng/g) were observed. Tea exhibited the highest residue, followed by fruits, and vegetables showed the lowest (P < 0.05). Neonicotinoid ratios in crops to soil (R_C/S) and soil to water (R_S/W) were defined to discern insecticide distribution across different environments. Increased water solubility leads to increased migration of neonicotinoids (R_S/W) from agricultural soils to water through runoff, thereby increasing the relative contribution of nitenpyram and dinotefuran in water. In comparison with other studied compounds, all crops demonstrated the strongest soil uptake of thiamethoxam, denoted by the highest R_C/S value. Elevated R_C/S values in tea, pickled cabbage, and celery suggest increased susceptibility of these crops to neonicotinoid absorption from the soil (P < 0.05). Estimated dietary intake for teenagers, adults and elders was 8.9 ± 0.5, 8.9 ± 0.6, and 8.8 ± 0.3 µg/kg/d, respectively, below the reference dose (57 µg/kg/d). Teenagers, compared to adults and elders, exhibited significantly higher neonicotinoid exposure through fruit consumption, emphasizing the need for increased attention to neonicotinoid exposure among vulnerable populations.
Subject(s)
Dietary Exposure , Insecticides , Neonicotinoids/analysis , Insecticides/analysis , Nitro Compounds , Vegetables/chemistry , Water , Soil/chemistry , TeaABSTRACT
Exposure to endocrine-disrupting chemicals (EDCs) has been linked to various immune deficiency disorders, including autoimmune diseases like Sjögren Syndrome (SjS). However, the detrimental effects of exposure to EDCs, including bisphenols, parabens, and triclosan (TCS), on SjS have been inadequately documented. Thus, we conducted a cross-sectional study that included both healthy individuals (controls) and patients with SjS (cases). We assessed serum concentrations of bisphenol A (BPA), bisphenol S (BPS), methyl parabens (MeP), ethyl parabens (EtP), and TCS. The relationship between the five EDCs levels and the risk of SjS was also explored. Additionally, we conducted an in-depth analysis of the collective influence of these EDCs mixtures on SjS, employing a weighted quantile sum regression model. Out of the five EDCs analyzed, EtP displayed the highest mean concentration (2.80 ng/mL), followed by BPA (2.66 ng/mL) and MeP (1.99 ng/mL), with TCS registering the lowest level (0.36 ng/mL). Notably, BPS exposure was significantly positively associated with the risk of being diagnosed with SjS (with an odds ratio [OR] of 1.17, p = 0.042). No statistically significant associations with SjS were observed for BPA, MeP, EtP, and TCS (p > 0.05). And we did not observe any significant effects of the EDCs mixture on SjS. To the best of our knowledge, this study is the first to suggest that BPS may potentially increase the risk of SjS. Although no significant effects were observed between other EDCs and SjS risk, we cannot disregard the potential harm of EDCs due to their non-monotonic dose response.
Subject(s)
Endocrine Disruptors , Phenols , Sjogren's Syndrome , Sulfones , Triclosan , Humans , Triclosan/analysis , Parabens/analysis , Cross-Sectional Studies , Benzhydryl Compounds/analysis , China , Endocrine Disruptors/analysisABSTRACT
p-Phenylenediamine antioxidants (PPDs) and PPDs-derived quinones (PPDQs) may pose a threat to the river ecosystem. However, the knowledge on the occurrence and environmental behaviors of PPDs and PPDQs in the natural river environment remains unknown. In this study, we collected paired water (n = 30) and sediment samples (n = 30) from Jiaojiang River, China and analyzed them for nine PPDs and seven PPDQs. Our results showed that target PPDs and PPDQs are frequently detected in water samples, with the dominance of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD; mean 12 ng/L, range 4.0-72 ng/L) and 6PPD-derived quinone (6PPDQ; 7.0 ng/L,
ABSTRACT
General populations are widely exposed to various p-phenylenediamine antioxidants (PPDs). N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), a typical p-phenylenediamine antioxidant, has been detected in human urine samples. However, the occurrence of other widely used PPDs in human urine is still unclear. This study comprehensively characterized the occurrence of 9 PPDs in human urine from 151 Chinese adults. Our results showed that all target PPDs were detected in human urine samples, with the total concentrations of PPDs ranging from 0.41 to 38 ng/mL. PPDs in human urine was dominated by 6PPD (mean 1.2 ng/mL, range < LOD - 3.8 ng/mL), followed by N-phenyl-N'-cyclohexyl-p-phenylenediamine (CPPD; 0.85 ng/mL, Subject(s)
Antioxidants
, Nitro Compounds
, Phenylenediamines
, Adult
, Humans
, Male
, Female
ABSTRACT
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.
Subject(s)
Blood , Parabens , Adult , Humans , Parabens/pharmacokineticsABSTRACT
Perfluorooctanoic acid (PFOA), a synthetic alkyl chain fluorinated compound, has emerged as a persistent organic pollutant of grave concern, casting a shadow over both ecological integrity and humans. Its insidious presence raises alarms due to its capacity to bioaccumulate within the human liver, potentially paving the treacherous path toward liver cancer. Yet, the intricate mechanisms underpinning PFOA's role in promoting the growth of hepatocellular carcinoma (HCC) remain shrouded in ambiguity. Here, we determined the proliferation and transcription changes of HCC after PFOA exposure through integrated experiments including cell culture, nude mice tests, and colony-forming assays. Based on our findings, PFOA effectively promotes the proliferation of HCC cells within the experimental range of concentrations, both in vivo and in vitro. The proliferation efficiency of HCC cells was observed to increase by approximately 10% due to overexposure to PFOA. Additionally, the cancer weight of tumor-bearing nude mice increased by 87.0% (p < 0.05). We systematically evaluated the effects of PFOA on HCC cells and found that PFOA's exposure can selectively activate the PI3K/AKT/mTOR/4E-BP1 signaling pathway, thereby playing a pro-cancer effect on HCC cells Confirmation echoed through western blot assays and inhibitor combination analyses. These insights summon a response to PFOA's dual nature as both an environmental threat and a promoter of liver cancer. Our work illuminates the obscured domain of PFOA-induced hepatoxicity, shedding light on its ties to hepatocellular carcinoma progression.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Animals , Mice , Humans , Carcinoma, Hepatocellular/chemically induced , Liver Neoplasms/chemically induced , Mice, Nude , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Cell Line, Tumor , Cell Proliferation , Mammals/metabolismABSTRACT
The p-phenylenediamine antioxidants (PPDs) have been widely detected in various dust samples. Nevertheless, the knowledge on occurrence of their environmental transformation products, PPD-derived quinones (PPDQs), in indoor dust remains limited. In this study, indoor dust samples (n = 97) were collected from Hangzhou, China, and analyzed for PPDs and PPDQs. Results showed that nine PPDs were detected in indoor dust samples, with the total concentrations of 1.7-223 ng/g. N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD, mean 17 ng/g) was the predominant PPDs in indoor dust, followed by N, N'-di(o-tolyl)-p-phenylenediamine (DTPD, 8.6 ng/g) and N-(1,3-dimethylbutyl)-N'-(p-tolyl)-p-phenylenediamine (DMTPD, 4.7 ng/g). Five PPDQs were detected in indoor dust samples. Among detected PPDQs, 6PPDQ (14 ng/g, 0.33-82 ng/g) had the highest mean concentration, followed by DTPDQ (5.9 ng/g, < LOD-31 ng/g) and DPPDQ (2.2 ng/g, < LOD-11 ng/g). We also estimated the daily intake (DI) of PPDs and PPDQs through indoor dust ingestion. Infants had higher mean DIs of PPDs and PPDQs than children and adults. Notably, to our knowledge, this study first reports the occurrence of three novel PPDs and four novel PPDQs in indoor dust samples. More studies are needed to reveal the potential human health risks of exposure to these newly identified chemicals.