Search

Understanding the presence and dynamics of chemical pollutants in individual cells is fundamentally important for their trafficking, fate, and toxicity in humans. The presence of molecular components (i.e., proteins and mRNA) in individual cells of higher organisms is considered a stochastic event. The characteristics of chemical pollutants, as extrinsic compounds, in subpopulation of human cells on single-cell basis have not been explored yet. Here, we demonstrated the lead (Pb) content in individual mature erythrocytes (m-erythrocytes) of Pb-intoxicated patients, and healthy subjects exhibited a unified pattern in probability distribution (gamma distribution) and dynamics, despite being highly heterogeneous. The Pb content in individual m-erythrocytes decreased with the lifetime of m-erythrocytes. Meanwhile, the distribution and dynamics were found to be highly related to the Pb content in m-erythrocytes and was independent of patients and their status. This is the first study to analyze the distribution pattern of chemical pollutants at a single-cell level in higher organisms. This study sheds light on the molecular mechanism of Pb trafficking and fate in humans and the search for an efficient strategy to improve Pb excretion during Pb treatment.

Black phosphorus (BP) has extensive applications in various fields. The release of BP into aquatic ecosystems and the potential toxic effects on aquatic organisms are becoming major concerns. Here, we investigated the developmental toxicity of few-layered BP toward the zebrafish. We found that BP could adsorb on the surface of the chorion and could subsequently penetrate within the embryo. After exposure of embryos to 10 mg/L BP, developmental malformations appeared at 96 hpf, especially heart deformities such as pericardial edema and bradycardia, accompanied by severe circulatory system failure. Using transgenic zebrafish larvae, we further characterized cardiovascular defects with cardiac enlargement and impaired cardiac vessels as indicators of damage to the cardiovascular system upon BP exposure. We performed transcriptomic analysis on zebrafish embryos treated with a lower concentration of 2 mg/L. The results showed disruption in genes associated with muscle development, oxygen involved processes, focal adhesion, and VEGF and MAPK signaling pathways. These alterations also indicated that BP carries a risk of developmental perturbation at lower concentrations. This study provides new insights into the effects of BP on aquatic organisms.

Tetrabromobisphenol A (TBBPA), a ubiquitous environmental pollutant, has been implicated in developmental toxicity of aquatic animals. However, the impact of TBBPA on development and the related mechanism have not been fully elucidated. In this study, using a live imaging technique and transgenic labeling of zebrafish embryos, we described the toxic effects of TBBPA on hematopoietic development in zebrafish. We demonstrated that TBBPA induced erythroid precursor expansion in the intermediate cell mass (ICM), which perturbed the onset of blood circulation at 24-26 hours postfertilization (hpf). Consequently, excessive blood cells accumulated in the posterior blood island (PBI) and vascular cells formed defective caudal veins (CVs), preventing blood cell flow to the heart at 32-34 hpf. We found that the one-cell to 50% epiboly stage was the most sensitive period to TBBPA exposure during hematopoietic development. Furthermore, our results demonstrated that PBI malformation induced by TBBPA resulted from effects on erythroid precursor cells, which might involve THR signaling in complex ways. These findings will improve the understanding of TBBPA-induced developmental toxicity in teleost.

Due to potential applications of black phosphorus nanosheets (BPNSs) in many fields in the near future, the toxicological effects of BPNSs on environmental organisms is becoming a major concern. He...

In this study, we comprehensively explored graphene oxide (GO)-induced systemic immune responses and interference with hematopoiesis in mice upon GO intravenous injection. In the liver and spleen, GO led to alterations in immune components at different time points. GO exposure showed an effect on the populations of different types of hepatic macrophages. In the liver, the populations of macrophages mainly affected by GO including Kupffer cells and monocyte-derived macrophages. Stimulated hepatic inflammation led to the infiltration of platelets from the circulation into the liver and decreased peripheral platelets population at day 1. Interestingly, a decreased platelet population was observed on day 7 in the spleen. GO also led to accelerated hematopoiesis in the spleen. Therefore, the possible forced generation of more platelets and the release of mature platelets from the spleen contributed to the increased circulating platelet count on day 7. Therefore, although GO showed a low potential to induce severe inflammation in the liver and spleen, it disrupted hematopoiesis in the spleen, which contributed to fluctuations in circulating platelet counts. The interaction of GO with the immune system warrants comprehensive study for gaining better understanding.

As typical brominated flame retardants (BFRs), tetrabromobisphenol A (TBBPA) and its derivative TBBPA-bis(2,3-dibromopropyl ether) (TBBPA-BDBPE) are ubiquitous in various environmental compartments. However, the potential health risk posed by these compounds, especially at environmentally relevant levels, remains unclear. In this study, using adult male mice, we investigated the toxicity of orally administered TBBPA and TBBPA-BDBPE at an environmentally relevant dose (57 nmol/kg body weight). After a single exposure and daily exposure, we assessed lipid metabolism homeostasis, the transcriptome, and immune cell components in the liver. We found that the single exposure to TBBPA or TBBPA-BDBPE alone increased the number of hepatic macrophages, induced alterations in the levels of lipids, including triacylglycerol and free fatty acids, and caused transcriptome perturbation. The results from the daily administration groups showed that TBBPA and TBBPA-BDBPE both significantly increased the triacylglycerol content; however, the elevation of hepatic macrophages was observed only in the TBBPA-BDBPE treatment group. This study confirmed that environmentally relevant levels of TBBPA and TBBPA-BDBPE are toxic to the liver. Our findings revealed that dysfunction of the liver is a health concern, following exposure to BFRs, even at very low concentrations. The chronic effects induced by TBBPA and its derivatives should be further investigated.

As a kind of unicellular eukaryotic protozoa, Tetrahymena is located at the bottom of the aquatic food webs and plays an essential role in the bioaccumulation of mercury (Hg). To track Hg in individual Tetrahymena, a capillary single-cell inductively coupled plasma mass spectrometry (ICPMS) online system was developed. The experimental and instrumental conditions were optimized to ensure the signal detected was the Hg uptake in individual Tetrahymena. Moreover, a quantitative method was established and validated by detecting Hg2+ standard solutions. The limit of quantity was calculated to be approximately 3.8 × 10-15 g Hg/cell, and the detection limit for Hg2+ exposure of Tetrahymena was 0.05 μg/L. By using the proposed method, we found the peak became wider with increasing of exposure concentrations, indicating the accumulated Hg by different Tetrahymena varied greatly, and the difference was more significant at higher exposure concentration. This novel method has the advantages of high sensitivity and real-time detection in individual Tetrahymena, and it could be widely used for further tracking the accumulation of mercury and other metals at the single cell level.

Use of legacy brominated flame retardants (BFRs), including polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD), has been reduced due to adverse effects of these chemicals. Several novel brominated flame retardants (NBFRs), such decabromodiphenyl ethane (DBDPE) and bis(2,4,6-tribromophenoxy) ethane (BTBPE), have been developed as replacements for PBDEs. NBFRs are used in various industrial and consumer products, which leads to their ubiquitous occurrence in the environment. This article reviews occurrence and fate of a select group of NBFRs in the environment, as well as their human exposure and toxicity. Occurrence of NBFRs in both abiotic, including air, water, dust, soil, sediment and sludge, and biotic matrices, including bird, fish, and human serum, have been documented. Evidence regarding the degradation, including photodegradation, thermal degradation and biodegradation, and bioaccumulation and biomagnification of NBFRs is summarized. The toxicity data of NBFRs show that several NBFRs can cause adverse effects through different modes of action, such as hormone disruption, endocrine disruption, genotoxicity, and behavioral modification. The primary ecological risk assessment shows that most NBFRs exert no significant environmental risk, but it is worth noting that the result should be carefully used owing to the limited toxicity data.

Background Very few studies have focused on the relationship between ambient apparent temperature (AT) and admission of mental and behaviour disorders (MDs). Therefore, a time-series study was conducted in Yancheng, China, to explore the effects of AT on the daily emergency admissions of patients with MDs over the period of 2014–17. Methods A quasi-Poisson generalized linear model (GLM) combined with a distributed lag non-linear model (DLNM) was adopted to explore the associations after adjusting for time trend, day of the week, humidity, sunshine duration, rainfall, holidays and air pollutants. In the subgroup analysis, the modification effects of age and sex were also examined. Results Overall, 8438 cases of MDs emergency admissions were identified. With the apparent temperature with the minimum number of admissions (− 3.4 °C) serving as a reference, a positive correlation emerged between high AT and daily emergency admissions of patients with MDs in Yancheng, China, with the lagged effect of 1 to 5 days. The subgroup analysis demonstrated a positive relationship between AT and MDs emergency admissions among males and individuals younger than 45 years old, with no lagged effect. Conclusions The results will provide important scientific evidence for mental health policy-makers and practitioners for possible intervention, especially among the vulnerable populations.

Growing developments in engineered nanomaterials (NMs) and their wide applications inevitably raise environmental and human health concerns. Upon contact with biological fluids, NMs can attract proteins onto their surfaces to form dynamic layers called protein corona. Such new biological identities are what the bio-systems “see” and react with. Formation of protein corona around NMs determines the biological behavior of NMs and the transformation patterns of proteins. Therefore, characterization of the protein corona on NMs' surface is the first step towards understanding the nature of NMs-mediated biological effects. In this review, the roles of protein corona in NMs' bio-application and biosafety were summarized, with an emphasis on methods for characterizing NMs-protein interactions and the dynamic biological identities. Moreover, we extrapolated the discussion to environmentally relevant nanoparticles (e.g. PM 2.5) and macromolecules, and discussed the possible methods and challenges for studying their interactions with proteins.

Particulate air pollution caused by human activities has drawn global attention due to its potential health risks. Considering the inevitable contact of inhaled airborne fine particulate matter (PM) with plasma, the hematological effects of PM are worthy of study. In this study, the potential effect of PM on hematological homeostasis through triggering the crosstalk of the kallikrein-kinin system (KKS), complement, and coagulation systems in plasma was investigated. The ex vivo, in vitro, and in vivo KKS activation assays confirmed that PM samples could efficiently cause the cascade activation of key zymogens in the KKS, wherein the particles coupled with lipopolysaccharide attachment provided substantial contribution. The binding of Hageman factor XII (FXII) with PM samples and its subsequent autoactivation initiated this process. The crucial elements in the complement cascade, including complement 3 (C3) and complement 5 (C5), and coagulation system (prothrombin) were also found to be actively induced by PM exposure, which was regulated by the interplay of KKS activation. The data provided solid evidence on hematological effects of airborne PM through inducing the activation of the KKS, complement, and coagulation systems, which would be valuable in the risk assessment on air-pollution-related cardiovascular diseases.

The structural identification as well as quantitative analysis of transformation and degradation (T/D) products of tetrabromobisphenol A (TBBPA) and its derivatives can provide useful information on the corresponding T/D mechanism as well as environmental impact. However, it is still a great challenge to analyze trace levels of T/D products, both unknown and known products, as a result of the complexity of environmental matrices and the lack of commercial/artificial standard chemicals. This critical review summarized the T/D model experiments, sample preparation and the associated analytical methods, including extraction, purification, concentration, derivatization, quantitation analysis and 14C-labeling technologies. Furthermore, the mass spectral analysis of TBBPA related compounds using different analytical instruments and T/D products predicted by computer programs are also described.

Although the abiotic and biotic transformation/degradation (T/D) processes of tetrabromobisphenol A (TBBPA) have been widely investigated in model experiments, few reviews have focused on these processes along with their metabolites or degradation products. In this paper, we summarize the current knowledge on the T/D of TBBPA and its derivatives, including abiotic and biotic T/D strategies/conditions, mechanisms, metabolites and environmental occurrences. Various treatments, such as pyrolysis, photolysis, chemical reactions and biotransformation, have been employed to study the metabolic mechanism of TBBPA and its derivatives and to remediate associated contaminated environments. To date, more than 100 degradation products and metabolites have been identified, dominated by less brominated compounds such as bisphenol A, 2,6-dibromo-4-isopropylphenol, 2,6-dibromo-4-hydroxyl-phenol, 2,6-dibromophenol, isopropylene-2,6-dibromophenol, 4-(2-hydroxyisopropyl)-2,6-dibromophenol, etc. It can be concluded that the T/D of TBBPA mainly takes place through debromination and β-scission. In some environmental media and human and animal tissues, brominated metabolites, glucoside and sulfate derivatives are also important T/D products. Here, the T/D products of TBBPA and its derivatives have been most comprehensively presented from the literature in recent 20 years. This review will enhance the understanding of the environmental behaviors of TBBPA-associated brominated flame retardants along with their ecological and health risks.

Coronavirus is named for its crown shape. Encoded by the genetic material inherited from the coronavirus itself, this intrinsic well-known “viral corona” can be considered the “inherited corona”. After contact with mucosa or the entrance into the host, bare coronaviruses could become covered by a group of dissolved biomolecules to form one or multiple layers of biomolecules. Different from this inherited corona, the layers acquired from the surrounding environment could be named as “acquired corona”. We highlight here the possible role of the acquired corona absorbing onto the surface of coronaviruses, which will generate fresh insight into the nature of various coronavirus-host interactions., Graphical abstract

Organophosphate esters (OPEs) can exhibit various toxicities including endocrine disruption activity. Unfortunately, the low-dose endocrine-disrupting effects mediated by estrogen receptors (ERs) are commonly underestimated for OPEs and their metabolites. Here, structure-oriented research was performed to investigate the estrogenic/antiestrogenic effect of 13 OPEs (including three metabolites) and the potential mechanism. All of the OPEs exerted antiestrogenic activities in both E-screen and MVLN assays. OPEs with bulky substituents, such as phenyl rings (triphenyl phosphate (TPP), tricresyl phosphate (TCP), diphenylphosphoryl chloride, and diphenylphosphite) or relatively long alkyl chains (dibutylbutylphosphonate (DBBP)), exerted relatively strong ER antagonism potency at micromolar concentrations. The established quantitative structure-activity relationship indicated that the antiestrogenic activities of the OPEs mainly depended on the volume, leading eigenvalue, and hydrophobicity of the molecule. Molecular docking revealed that the three OPEs with the bulkiest substituents on the phosphate ester group (TPP, TCP, and DBBP) have a similar interaction mode to the classical ER antagonist 4-hydroxytamoxifen. The correlation between the antiestrogenic activity and the corresponding ER binding affinity was statistically significant, strongly suggesting that the OPEs possess the classical antagonism mechanism of interfering with the positioning of helix 12 in the ER.

Background: Tetrabromobisphenol A (TBBPA) mono-ether structural analogs, identified as the by-products or transformation products of commercial TBBPA bis-ether derivatives, have been identified as emerging widespread pollutants. However, there is very little information regarding their toxicological effects. Objective: We aimed to explore the potential thyroid hormone (TH) system–disrupting effect of TBBPA mono-ether structural analogs. Methods: The binding potencies of chemicals toward human TH transport proteins [transthyretin (TTR) and thyroxine-binding globulin (TBG)] and receptors [TRα ligand-binding domain (LBD) and TRβ-LBD] were determined by fluorescence competitive binding assays. Molecular docking was used to simulate the binding modes of the chemicals with the proteins. The cellular TR-disrupting potencies of chemicals were assessed by a GH3 cell proliferation assay. The intracellular concentrations of the chemicals were measured by high-performance liquid chromatography and mass spectrometry. Results: TBBPA mono-ether structural analogs bound to TTR with half maximal inhibitory concentrations ranging from 0.1μM to 1.0μM but did not bind to TBG. They also bound to both subtypes of TR-LBDs with 20% maximal inhibitory concentrations ranging from 4.0μM to 50.0μM. The docking results showed that the analogs fit into the ligand-binding pockets of TTR and TR-LBDs with binding modes similar to that of TBBPA. These compounds likely induced GH3 cell proliferation via TR [with the lowest effective concentrations (LOECs) ranging from 0.3μM to 2.5μM] and further enhanced TH-induced GH3 cell proliferation (with LOECs ranging from 0.3μM to 1.2μM). Compared with TBBPA, TBBPA-mono(2,3-dibromopropyl ether) showed a 4.18-fold higher GH3 cell proliferation effect and 105-fold higher cell membrane transportation ability. Conclusion: This study provided a possible mechanism underlying the difference in TTR or TR binding by novel TBBPA structural analogs. These compounds might exert TH system–disrupting effects by disrupting TH transport in circulation and TR activity in TH-responsive cells. https://doi.org/10.1289/EHP6498

The application and consumption of nanoparticles (NPs) inevitably result in the contamination of environmental water. The internalized NPs in unicellular organisms could travel to human bodies along food chains and raise health concerns. Current research failed to determine the characteristics of cellular uptake of NPs by unicellular organisms at extremely low concentration in the real environment. We here developed a label-free high-throughput mass cytometry method to investigate gold NP (AuNP) uptake in a unicellular organism (Tetrahymena thermophila) at the single-cell level. The limit of detection for Au is as low as to 6.67 × 10-18 g/cell, which equals ∼5.3 5 nm AuNPs. We demonstrated that active engulfment pathways were responsible for the cellular accumulation of AuNPs and T. thermophila could also eliminate the cellular AuNPs rapidly. The interaction between AuNPs and T. thermophila is highly dependent on the sizes of nanoparticles; i.e., the population of T. thermophila containing AuNPs decreased with the increment of the diameters of AuNPs when exposed to the same mass concentration. For each type of AuNP, distinct heterogeneous cellular uptake of AuNPs by T. thermophila was observed. Intriguingly, for 5 nm AuNP, even at 0.001 ng/mL, some T. thermophila cells could concentrate AuNPs, indicating a real environmental concern even when water was contaminated by only trace level of NPs. This method represents a promising tool for simultaneous determination of physiological status of cells together with the intracellular level of heavy metal or metallic NPs in study of biological effects.

Highlights • The COVID-19 patients had negative SARS-COV-2 RNA in EPS. • Serum SARS-CoV-2 IgM was positive in patients with positive pharyngeal RNA. • The inflammatory indictors were all elevated in COVID-19 patients., Due to the cellular entry of the novel coronavirus (SARS-CoV-2) modulated by angiotensin converting enzyme 2 (ACE2), the ACE2 bearing prostate is therefore hypothesized as a susceptible organ to COVID-19. To delineate whether the pathogenic SARS-CoV-2 of the coronavirus disease (COVID-19) could be detected in the expressed prostatic secretion (EPS), a total of ten male patients with confirmed COVID-19 were recruited. All patients were stratified into two groups: one group with positive nasopharyngeal swabbing SARS-CoV-2 within 3 days of the EPS taken day (PNS group, n = 3) and the other group with previously positive nasopharyngeal swabbing SARS-CoV-2 but turned negative before the taken day (PNNS group, n = 7). The COVID-19 patients showed elevated inflammatory indictors, i.e. C-reaction protein (3.28 (1.14, 33.33) mg/L), erythrocyte sedimentation rate (22.50 (8.00, 78.50) mm/h), and interleukin-6 (6.49 (4.96, 21.09) pg/ml). Serum IgM against SARS-CoV-2 was only positive in the PNS group, whereas serum IgG was positive for all patients. Furthermore, our data showed for the first time that none of the COVID-19 patients had positive SARS-CoV-2 RNA in EPS. To this end, this study found the negativity of SARS-CoV-2 in EPS and possibly exclude the sexual transmission of COVID-19.

As a novel member of the two-dimensional nanomaterial family, mono- or few-layer black phosphorus (BP) with direct bandgap and high charge carrier mobility is promising in many applications such as microelectronic devices, photoelectronic devices, energy technologies, and catalysis agents. Due to its benign elemental composition (phosphorus), large surface area, electronic/photonic performances, and chemical/biological activities, BP has also demonstrated a great potential in biomedical applications including biosensing, photothermal/photodynamic therapies, controlled drug releases, and antibacterial uses. The nature of the BP-bio interface is comprised of dynamic contacts between nanomaterials (NMs) and biological systems, where BP and the biological system interact. The physicochemical interactions at the nano-bio interface play a critical role in the biological effects of NMs. In this review, we discuss the interface in the context of BP as a nanomaterial and its unique physicochemical properties that may affect its biological effects. Herein, we comprehensively reviewed the recent studies on the interactions between BP and biomolecules, cells, and animals and summarized various cellular responses, inflammatory/immunological effects, as well as other biological outcomes of BP depending on its own physical properties, exposure routes, and biodistribution. In addition, we also discussed the environmental behaviors and potential risks on environmental organisms of BP. Based on accumulating knowledge on the BP-bio interfaces, this review also summarizes various safer-by-design strategies to change the physicochemical properties including chemical stability and nano-bio interactions, which are critical in tuning the biological behaviors of BP. The better understanding of the biological activity of BP at BP-bio interfaces and corresponding methods to overcome the challenges would promote its future exploration in terms of bringing this new nanomaterial to practical applications.

With the potential continuous application of mono- or few-layered black phosphorus (BP) in electronic, photonic, therapeutic, and environmental fields, the possible side effects of BP on aquatic organisms after release into natural water are of great concern. We investigated the potential toxicity of BP on the unicellular organism, Tetrahymena thermophila. After the exposure for 8 h at 10 μg/mL, the reproduction of T. thermophila significantly decreased by 46.3%. Severe cell membrane and cilium damage were observed by scanning electron microscopy (SEM) upon treatment with BP. Based on bright-field microscopy and three-dimensional Raman imaging, we investigated the cellular uptake and translocation of BP within T. thermophila. It was observed that the engulfment of BP by T. thermophila was oral apparatus dependent, through which intracellular BP was then transported to the posterior end of T. thermophila by food vacuole packaging. Our study also revealed that BP induced the increase of intracellular reactive oxidant species and formed oxidative stress-dependent toxicity to T. thermophila. Our findings paved a way for better understanding the BP toxicityon aquatic organisms and its potential ecological risks.

Selenium (Se) is commonly recognized as a protective element with an antagonistic effect against mercury (Hg) toxicity. However, the mechanisms of this Hg–Se antagonism are complex and remain controversial. To gain insight into the Hg–Se antagonism, a type of unicellular eukaryotic protozoa (Tetrahymena malaccensis, T. malaccensis) was selected and individually or jointly exposed to two Hg and three Se species. We found that Se species showed different toxic effects on the proliferation of T. malaccensis with the toxicity following the order: selenite (Se(IV)) > selenomethionine (SeMeth) > selenate (Se(VI)). The Hg–Se antagonism in Tetrahymena was observed because the joint toxicity significantly decreased under co-exposure to highly toxic dosages of Hg and Se versus individual toxicity. Unlike Se(IV) and Se(VI), non-toxic dosage of SeMeth significantly decreased the Hg toxicity, revealing the influence of the Se species and dosages on the Hg–Se antagonism. Unexpectedly, inorganic divalent Hg (Hg2 +) and monomethylmercury (MeHg) also displayed detoxification towards extremely highly toxic dosages of Se, although their detoxifying efficiency was discrepant. These results suggested mutual Hg–Se detoxification in T. malaccensis, which was highly dependent on the dosages and species of both elements. As compared to other species, SeMeth and MeHg promoted the Hg–Se joint effects to a higher degree. Additionally, the Hg contents decreased for all the Hg–Se co-exposed groups, revealing a sequestering effect of Se towards Hg in T. malaccensis.

A novel, competitive, enzyme-linked immunosorbent assay (ELISA) was presented in this paper based on the inhibition of catalysis of AuNCs@BSA triggered by dissolved Ag+ for the detection of dibutyl phthalate (DBP). In the immunoassay system, numerous Ag+ was released from AgNPs (labelled on the second antibody, AgNPs@Ab2) in the presence of H2O2 after the competition step, preventing AuNCs@BSA from inducing a color change of 3,3',5,5'-tetramethylbenzidine (TMB) to blue. Due to the signal amplification by the principle, the sensitivity of the modified ELISA was improved with the low limit of detection (LOD) of 4.017μg/L for DBP, which was decreased 16 times relative to that using conventional ELISA with the same antibody. In addition, the established method showed satisfactory accuracy and reliability (recoveries, 85.75-117.73%; CV, 1.33-6.79%) in spike-recovery analysis. To the best of our knowledge, this is the first time that AuNCs@BSA has been used in ELISA as a peroxidase-like catalyst. Our method shows great potential for trace DBP detection from environmental and food samples.

Inorganic divalent mercury complexes (Hg2+) and monomethylmercury complexes (MeHg) are the main mercury species in aquatic systems and their toxicity to aquatic organisms is of great concern. Tetrahymena is a type of unicellular eukaryotic protozoa located at the bottom of food chain that plays a fundamental role in the biomagnification of mercury. In this work, the dynamic accumulation properties, toxicological characteristics and mechanisms of Hg2+ and MeHg in five Tetrahymena species were evaluated in detail. The results showed that both Hg2+ and MeHg were ingested and exhibited inhibitory effects on the proliferation or survival of Tetrahymena species. However, the ingestion rate of MeHg was significantly higher than that of Hg2+. The mechanisms responsible for the toxicity of MeHg and Hg2+ were different, although both chemicals altered mitochondrial membrane potential (MMP). MeHg disrupted the integrity of membranes while Hg2+ had detrimental effects on Tetrahymena as a result of the increased generation of reactive oxygen species (ROS). In addition, the five Tetrahymena species showed different capacities in accumulating Hg2+ and MeHg, with T. corlissi exhibiting the highest accumulations. The study also found significant growth-promoting effect on T. corlissi under low concentration exposure (0.003 and 0.01μg Hg/mL (15 and 50nM)), suggesting different effect and mechanism that should be more closely examined when assessing the bioaccumulation and toxicity of mercury in aquatic ecosystems.

Bisphenol A (BPA) and its analogs (bisphenol F, BPF; bisphenol AF, BPAF; bisphenol S, BPS; and tetrabromobisphenol A, TBBPA) are transported by blood and bind estrogen receptors of target organs or cells. They were confirmed to bind human serum albumin (HSA) in blood, and the binding constants of BPA (5.14 × 103 M−1), BPF (1.05 × 104 M−1), and BPS (7.89 × 103 M−1) determined via equilibrium dialysis shows moderate binding ability with multiple binding sites. The HSA-water partition coefficients (log KHW > 3) are greater than their octanol-water distribution coefficients, and may follow the order: TBBPA > BPAF > BPA (3.75) > BPF (3.61) > BPS (3.27). Functional groups and substitutions of bisphenols (BPs) determine the fluorescence quenching of Trp214 in HSA. The effects follow: TBBPA (4.41 × 1014 M−1 s−1) » BPS (4.08 × 1012 M−1 s−1) > BPAF (1.20 × 1012 M−1 s−1) > BPF (3.06 × 1011 M−1 s−1) ≈ BPA (4.47 × 1011 M−1 s−1), which is in line with the molecular docking results. In this process, the enzymatic characteristics of HSA were changed simultaneously, as evidenced by decreased Km and Vmax except for BPS (increased Km and Vmax) and increased catalytic efficiency, which may improve the hydrolysis of other drugs. However, the native conformation of the protein underwent locally adaptive changes due to the reversible binding. Overall, these data provide a mechanistic explanation for the transport of BPs in human blood, which may affect their retention and toxicity.

Black phosphorus nanosheets (BPs) belong to a type of two-dimensional layered materials and have garnered significant attention due to their diverse potential in nanomedical applications. Until recently, BPs have been increasingly applied in the biomedical field due to their excellent physical and chemical properties, as well as good biocompatibility. However, there has not been much concern about their potential toxic effects or biological effects on physiological systems. Herein, we found that BPs induced a reversible inflammatory response in mice, and then the detailed multifactorial inflammatory effects were studied among mouse macrophages. The treatment with BPs can induce higher levels of reactive oxygen species (ROS) in mouse bone marrow-derived macrophages (BMDMs), leading to significant changes in cell survival rate, apoptosis, and inflammatory cytokines. The molecular levels of nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and nitric oxide (NO) in the treated cells were evaluated. The results indicated a significant increase in the expression of these molecules, suggesting an expansion of inflammatory reactions. The protein expression of heme oxygenase-1 (HO-1) molecules was decreased in BP-treated groups of cells, which indicates that BPs may inhibit anti-inflammatory effects of cells, leading to aggravation of inflammation. These findings provide evidence for biointeractions of BPs in physiological systems and may be helpful for the safe use of BP-based therapies.

With the potential biomedical applications of nanomaterials such as silver nanoparticles (SNPs), nanotoxicity concerns are growing, and the importance of NP and protein interactions is far from being addressed enough. Here, we identified the major binding protein on SNPs in blood as human serum albumin (HSA) using polyacrylamide gel electrophoresis and liquid chromatography-mass spectrometry/mass spectrometry. By comparing with the previous methods, we emphasized surface area concentration as a new dose metric to address the importance of NP curvature. SNPs interacted with cysteine and cystine, disrupting the secondary structure and conformation of HSA, and this tendency became stronger on small SNPs than large ones. The protein corona significantly alleviated the toxicity and decreased SNPs' internalization in a particle size-dependent manner, where more significant inhibition effects occurred on larger particles at the same area concentration. These findings may shed light on nanotoxicity and also the design of safe nanomaterials by a comprehensive preconsideration of the metrological method.

Black phosphorus nanosheets (BPs) have exhibited great potential for various applications including biomedicine, thus their potential side effects and corresponding improvement strategy deserve investigation. Here, in vitro and in vivo biological effects of BPs with and without titanium sulfonate ligand (TiL4) modification are investigated. Comparing to bare BPs, BPs with TiL4 modification (TiL4@BPs) can efficiently escape from macrophages uptake, and reduce the cytotoxicity and proinflammation. When intravenously injected into mice, bare BPs trigger significant inflammatory responses, including an increase in peripheral neutrophils accompanied by elevation of a group of inflammatory cytokines, while TiL4@BPs exhibit no such adverse immune responses. The corresponding mechanisms are also discussed. These findings may not only guide the applications of BPs, but also propose an efficient strategy to further improve the biocompatibility of BPs.

Tetrabromobisphenol A bis(2-hydroxyethyl) ether (TBBPA DHEE), as one of the TBBPA derivatives, is frequently applied as a flame retardant. To date, however, little evidence has been gathered regarding its environmental behavior and fate. This is mainly attributed to the lack of an analytical approach available to measure it. Mass spectrometry cannot determine levels of TBBPA DHEE. LC-MS could not ionize TBBPA DHEE to yield enough fragments, while GC-MS could not be applied for the analysis either, due to the thermal degradation of TBBPA DHEE. We here designed a novel hapten, then conjugated it with a carrier protein and produced a type of polyclonal antibody capable of recognizing TBBPA DHEE. Based on this approach, a sensitive and high-throughput indirect competitive enzyme-linked immunosorbent assay (ELISA) was established. The respective detection limit (LOD, based on 90% B/B0) and IC50 calculated from the standard curve were 0.702 and 9.868 ng/mL for TBBPA DHEE. And the established method showed good tolerance to various matrix interferents. Using our ELISA, we measured the concentrations of these substances from environmental water samples with no pretreatment other than filtration. We found the presence of TBBPA DHEE in environmental water samples collected in Jiangsu province, and the detected concentrations ranging from 1.5 to 7.7 ng/mL. Our proposed method here could be applied to completely and systematically investigate TBBPA DHEE and TBBPA MHEE concentrations in environmental samples.

In contrast to the extensive investigation already conducted on tetrabromobisphenol A (TBBPA), the metabolism of TBBPA derivatives is still largely unknown. In this paper, we characterized unknown brominated compounds detected in 84 soil samples collected from sites around three brominated flame retardant production plants to determine possible transformation products of TBBPA derivatives. In addition to tribromobisphenol A (TriBBPA), dibromobisphenol A (DBBPA), and TBBPA, six novel transformation products, TriBBPA mono(allyl ether) (TriBBPA-MAE), DBBPA-MAE, hydroxyl TriBBPA-MAE, TBBPA mono(2-bromo-3-hydroxypropyl ether) (TBBPA-MBHPE), TBBPA mono(2,3-dihydroxypropyl ether) (TBBPA-MDHPE), and TBBPA mono(3-hydroxypropyl ether) (TBBPA-MHPE) were identified. The detection frequencies of these identified chemicals in soil samples ranged from 17% to 89%, indicating the widespread presence of the transformation products. To uncover the possible TBBPA derivative transformation pathways involved, super-reduced vitamin B12 (cyanocobalamin, (CCAs)) was used to treat TBBPA derivative and transformation products in this process were characterized. To our knowledge, this is the first study examining the transformation of TBBPA derivatives and the first to report several novel associated TBBPA and bisphenol A derivatives as transformation products. Our research suggests that ether bond breakage and debromination contribute to the transformation of TBBPA derivatives and the existence of the novel transformation products. These data provide new insights into the fate of TBBPA derivatives in environmental compartments.

Blood is the transmission medium for metal contaminants to and from bodily organs; as such, it can provide useful and reliable information about their bio-kinetics as they're distributed throughout the body. Metals can interact with endogenous proteins present in the blood, and these metal-protein complexes often dictate the fates of the introduced metals. The aim of this study was to investigate cadmium-binding protein characteristics in normal human plasma. Cadmium-binding plasma proteins in two different groups: normal human plasma (n = 29), and normal paired maternal and fetal umbilical cord plasmas (n = 3), were analyzed. In order to detect cadmium-binding plasma proteins present in low concentrations, blood plasma samples were first depleted of their two most abundant proteins - albumin and immunoglobulin G. Both the crude and depleted plasma samples were analyzed using column gel electrophoresis in conjunction with Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). One cadmium-binding protein was detected in 11 of 29 normal plasma samples and all three paired maternal and cord plasma samples. This protein was further identified as apolipoprotein A-I by high-resolution mass spectrometry. To the best of our knowledge, this is the first study to reveal cadmium-binding proteins in real human blood plasma, which is extremely critical to our understanding of cadmium transportation and accumulation in human blood.

Safety concerns have been raised with regard to silver nanowires (AgNWs) because of their extensive applications. Recently, ultralong AgNWs have shown physical properties superior to those of short AgNWs. However, little is known about their toxicity and potential risks. In this study, we demonstrated a series of ultralong AgNWs-induced biological effects in human lung cancer epithelial cells (A549). Ultralong AgNWs treatments induced ROS generation, mitochondria-mediated apoptosis, and self-protective autophagy at nonlethal concentrations. In contrast to some previous reports, apoptosis was found not to correlate with the reduction of intracellular ROS. Measuring the processing of ROS generation, apoptosis and autophagy, we demonstrated that ROS not only enhance mitochondrial damage, but also raise protective autophagic flux in ultralong AgNW-treated cells. Moreover, ultralong AgNWs were found to be internalized into the cytoplasm of the epithelial cells. This study not only investigates ultralong AgNWs-induced cytotoxicity but also pinpoints ROS as a key signal in mechanisms of their toxicity.

Asbestos fiber has been associated with mesothelioma and lung cancer. However, the carcinogenic risks of other fiber nanomaterials with morphological similarities to asbestos have not been fully studied. Ultra-long silver nanowires (AgNWs) are increasingly used fiber-shaped nanomaterials with a high aspect ratio, but very few studies have investigated their health risks. Here, proliferation abnormalities of lung epithelial cells induced by ultra-long AgNWs were investigated. Ultra-long AgNW treatment induced dose- and diameter-dependent increase in the ratio of multinucleated cells. Further, proteins involved in mitosis and cytokinesis, including Aurora A, p-Histone 3 (ser10), RhoA, p-MLC, and myosin IIb, were significantly upregulated after an ultra-long AgNW treatment, leading to mitotic abnormalities and cytokinetic failure. Meanwhile, exposure to ultra-long AgNWs induced cell cycle arrest. Interestingly, a series of experiments demonstrated that ROS generation and Ag+ release were not responsible for the multinucleation induced by ultra-long AgNWs, but ultra-long AgNWs in the intercellular bridge might obstruct the contractile ring and inhibit abscission of the cytokinetic furrow by direct physical contact. Altogether, our findings indicate that ultra-long AgNWs can induce chromosomal instability, which has important consequences for the safety of ultra-long AgNWs to human health.

Selective adsorption via the size matching effect is one of the most effective strategies for separating and analyzing low levels of organic molecules. Herein, multicomponent covalent organic frameworks (MC-COFs) with tunable pore sizes are constructed by using one knot (1,3,5-triformylphloroglucinol, Tp) and two organic linkers (p-phenylenediamine, Pa; benzidine, BD). The pore sizes of the MC-COFs composed of TpPaBDX (X = [BD]/([Pa] + [BD]) × 100 = 0, 25, 50, 75, and 100) range from 0.5–1.5 to 0.5–2.2 nm due to variations in the initial organic linker ratios. When coupling TpPaBDX-based solid-phase microextraction (SPME) with constant flow desorption ionization mass spectrometry (CFDI-MS), these MC-COFs feature better selective adsorption performance for tetrabromobisphenol A (TBBPA) derivatives than TpPa with a smaller pore size, TpBD with a larger pore size and even some commercial fibers (e.g., polydimethylsiloxane/divinylbenzene (PDMS/DVB)-, polyacrylate (PA)- and PDMS-coated fibers). The improved method involving MC-COF TpPaBD50 also presents favorable stability with relative standard deviations (RSD, 1 μg L−1) for single fibers of 5.5–7.9% (n = 7) and fiber-to-fiber of 6.6–7.8% (n = 7). Due to the decreased limits of detection and quantification (0.5–12 and 1.6–40 ng L−1), and reduced separation and detection time (7 min), ultratrace levels of TBBPA derivatives in real water samples are successfully detected. The proposed method shows great potential for the rapid tracing of the distribution, transportation and transformation of TBBPA derivatives to better understand their ecotoxicological effects in environmental media.

Tetrabromobisphenol A (TBBPA) is the most widely used brominated flame retardant. TBBPA and its alternative, tetrabromobisphenol S (TBBPS), are the reactive chemicals used to produce TBBPA/S derivatives. The manufacturing and application of TBBPA/S derivatives may result in their accumulation in environmental compartments and may cause risks to environmental safety and human health. To investigate the occurrence and transformation products of TBBPA/S and TBBPA/S derivatives, it is imperative to develop effective sample preparation and sensitive analytical methods for various environmental matrices. In this paper, we summarize the techniques for analysis of TBBPA/S and their derivatives. We also critically review methodologies for the identification of unknown metabolites transformed from these chemicals. In the perspective section, we discuss trends in analytical strategies for studying emerging TBBPA/S derivatives.

With the wide application of nanosilver or silver nanoparticles (AgNPs) in a diverse spectrum of fields, the environmental exposure of this kind of nanomaterial has become inevitable. Lots of attention was paid to its potential adverse effects based on multiple experimental models; nevertheless, the translocation, distribution, and possible biotransformation of nanosilver in organisms are the essential prerequisites for its biological effects. This work focused on this point and provided a comprehensive review of the behavior of nanosilver in multiple mammals, in view of its administration routes, biouptake, translocation, biodistribution, bioaccumulation, biotransformation, elimination, and retention. The regulatory factors for the bioavailability of nanosilver included the characteristics of the nanoparticle per se and the ambient condition. This review brings insights on the biological processes of nanosilver and may help explain its potential effects on mammals, including human beings.

Tetrabromobisphenol-A/S (TBBPA/S) analogs have raised substantial concern because of their adverse effects and potential bioaccumulative properties, such as TBBPA bis(allyl ether) (TBBPA-BAE) and TBBPA bis(2,3-dibromopropyl ether) (TBBPA-BDBPE). In this study, a comprehensive method for simultaneous determination of TBBPA/S and nine novel analogs, including TBBPA-BAE, TBBPA-BDBPE, TBBPS-BDBPE, TBBPA mono(allyl ether) (TBBPA-MAE), TBBPA mono(2-bromoallyl ether) (TBBPA-MBAE), TBBPA mono(2,3-dibromopropyl ether) (TBBPA-MDBPE), TBBPS-MAE, TBBPS-MBAE, and TBBPS-MDBPE in biological samples was developed. The distribution patterns and trophic transfer properties of TBBPA/S and analogs in various biological samples collected from the Chinese Bohai Sea were then studied in detail. For the first time, TBBPA-MBAE and TBBPS-BDBPE were detected in biological samples and TBBPA-MBAE was identified as a byproduct. The concentrations of TBBPA and analogs ranged from ND (not detected or below the method detection limit) to 2782.8 ng/g lipid weight (lw), and for TBBPS and analogs ranged from ND to 927.8 ng/g lw. High detection frequencies (86%) for TBBPA, TBBPS and TBBPA-MAE, TBBPA-MDBPE, TBBPS-MAE, TBBPS-MBAE, and TBBPS-MDBPE were obtained. Meanwhile, TBBPA, TBBPS, and these five analogs displayed trophic dilution tendencies due to significantly negative correlations between trophic levels and lipid-corrected concentrations together with the trophic magnification factors (from 0.31 to 0.55). The results also indicated the novel TBBPA-MAE, TBBPA-MBAE, TBBPA-MDBPE, TBBPS-MAE, TBBPS-MBAE, and TBBPS-MDBPE could be generated not only as byproducts, but also as the probable transformation products of commercial TBBPA/S derivatives.

The emergence of a novel coronavirus named SARS-CoV-2 during December 2019, has caused the global outbreak of coronavirus disease 2019 (COVID-19), which is officially announced to be a pandemic by the World Health Organization (WHO). The increasing burden from this pandemic is seriously affecting everyone’s life, and threating the global public health. Understanding the transmission, survival, and evolution of the virus in the environment will assist in the prevention, control, treatment, and eradication of its infection. Herein, we aimed to elucidate the environmental impacts on the transmission and evolution of SARS-CoV-2, based on briefly introducing this respiratory virus. Future research objectives for the prevention and control of these contagious viruses and their related diseases are highlighted from the perspective of environmental science. This review should be of great help to prevent and control the epidemics caused by emerging respiratory coronaviruses (CoVs)., Graphical abstract Image 1, Highlights • Several environmental factors are involved in the transmission of respiratory CoVs. • Genetic factors and human activities can affect the evolution of respiratory CoVs. • Understanding environmental impacts on transmission and evolution of SARS-CoV-2 is of great importance., Summary: More knowledge on the transmission and evolution of SARS-CoV-2 in the environment is urgently needed.

Environmental distribution and concentration of tetrabromobisphenol A bis- (2-hydroxyethyl) ether (TBBPA-DHEE) and tetrabromobisphenol A mono- (hydroxyethyl) ether (TBBPA-MHEE), are obscure due to the lack of available analytical methods. Here two novel immunoassays were established to systematically investigate their distributions in Taizhou, Eastern China. Five monoclonal antibodies against pollutants were generated with two designed haptens through animal immunization. After matched with different coating antigens/antibodies, ELISAs were established (LOD for TBBPA-DHEE, 0.12 ng/mL, based on OVA-M3/mAb-D4G6; LOD for TBBPA-MHEE, 0.79 ng/mL, based on OVA-M3/mAb-D2G6) and applied for investigation of their occurrences at a typical e-waste recycling area after 2-year samples collection, where the total 33 water, 32 soil and 16 biological samples were collected with the highest concentrations of 3.46 ng/mL, 2.76 ng/g (dry weight, dw) and 5.01 ng/g (dw), respectively. Meanwhile, our study also indicated that at the centralizing e-waste recycling sites the serious pollution for both chemicals still existed despite of various efforts. Besides, obvious improvements were observed at an abandoned e-waste recycling region treated and remedied for many years by the local Chinese government. These findings highlight the importance of policy decisions in treatment of pollutants to reduce organic pollutant-related health risks.

Widespread environmental contamination of legacy long-chain poly- and per-fluoroalkyl substances (PFASs) has triggered chemical regulatory action and a global transitioning to alternative PFASs. More than 5000 PFASs are now recognized on various lists, but few have been monitored despite ample evidence of unidentified organic fluorine in human and environmental samples. Nevertheless, our review of the literature indicates that nontarget analytical methods based on high-resolution mass spectrometry have been used to discover more than 750 PFASs, belonging to more than 130 diverse classes, in strategically selected environmental samples, biofluids or commercial products. Among these reports, we summarize the analytical and data-processing strategies for nontarget PFAS discovery, identify knowledge gaps and propose new areas for method development. Discovery of emerging PFASs before they are global contaminants could mitigate future contamination if strategic techniques can be developed to prioritize some of these substances for synthesis and confirmation, further monitoring, source elucidation and hazard characterization.

Mercury-binding protein profiles in rat plasma at different levels of mercury exposure in vitro and in vivo were systematically investigated using column gel electrophoresis coupled with inductively coupled plasma-mass spectrometry. The current finding provided various protein candidates that may play critical roles in mercury binding and transporting in plasma.

Organotin compounds (OTs) are used in a range of industrial products, such as antifouling paints, agricultural pesticides and stabilizers. Owing to potential endocrine-disrupting effects, human exposure to such compounds is a concern. Nevertheless, little is known about the adverse effect of OTs on adrenocortical function in organisms. In this study, the human adrenocortical carcinoma cell (H295R) model was used to investigate effects of OTs on steroidogenesis and potential causes for such endocrine disruption was examined. H295R cells were exposed to several commonly used OTs, including triphenyltin (TPT), tributyltin (TBT), dibutyltin (DBT), and monobutyltin (MBT), and the production level of steroid hormones were quantified. TPT and TBT decreased the production levels of 17β-estradiol, aldosterone, and cortisol, but increased that of testosterone. Furthermore, the expression levels of ten major steroidogenic genes (HMGR, StAR, CYP11A1, 3βHSD2, CYP17, CYP19A1, CYP21, CYP11B1, CYP11B2, and 17βHSD) were examined and both up-regulation of CYP11B2 and down-regulation of StAR, 3βHSD2, CYP19A1, CYP21 and CYP11B1 by TPT and TBT were observed. Intracellular levels of ATP and cyclic adenosine monophosphate (cAMP) and the activity of adenylate cyclase (AC) decreased in the H295R cells treated with TPT and TBT. No obvious changes in H295R were found with the treatment of DBT and MBT. These results suggest that OTs may stimulate steroidogenesis in vitro via inhibition of cAMP signaling pathway.

The neurotoxic effects of methylmercury (MeHg) have been intensively studied. However, the molecular mechanisms responsible for the neurotoxicity of MeHg are not fully understood. To decipher these mechanisms, proteomic and high-throughput mRNA sequencing (RNA-seq) technique were utilized, comprehensively evaluating the cellular responses of human neuroblastoma SK-N-SH cells to MeHg exposure. Proteomic results revealed that MeHg exposure interfered with RNA splicing via splicesome, along with the known molecular mechanisms of mercury-related neurotoxicity (e.g. oxidative stress, protein folding, immune system processes, and cytoskeletal organization). The effects of MeHg on RNA splicing were further verified using RNA-seq. Compared to control, a total of 658 aberrant RNA alternative splicing (AS) events were observed after MeHg exposure. Proteomics and RNA-seq results also demonstrated that mercury chloride (HgCl2) influenced the expression levels of several RNA splicing related proteins and 676 AS events compared to control. These results suggested that RNA splicing could be a new molecular mechanism involved in MeHg and HgCl2 neurotoxicity.

Per- and polyfluoroalkyl substances (PFASs) are a global concern because of their ubiquitous occurrence and high persistence in human blood, and increasing amounts of unidentified fluorinated compounds are now becoming new exposure issues. This study aims to investigate the structure-related effects of PFASs on the activation of the plasma kallikrein-kinin system (KKS). The effects of 20 PFASs and the related long-chain aliphatic compounds were screened, and their binding affinities for the initial zymogen, Hagmen factor XII (FXII) in the KKS, were evaluated by molecular docking analysis. PFASs were demonstrated to activate the KKS in a structure-dependent mode. More specifically, PFASs with longer carbon chain length, higher fluorine atom substitution degree, and terminal acid group exhibited relatively higher activities in activating the KKS. The binding affinities of PFASs with FXII determined their capabilities for inducing KKS activation. The alternative binding modes of PFASs with FXII, together with van der Waals and hydrogen bonds, specifically accommodated the distinctive chemical structures. To our knowledge, PFASs, for the first time, were found to induce the activation of the KKS in plasma, and their chemical structure-related effects would be extremely important for risk assessment on emerging PFASs in addition to the listing in Stockholm Convention.

Gold nanorods (GNRs) are a unique class of metal nanostructures that have attractive potentials in biomedical applications, and the concern on their biological safety is concomitantly increasing. Hemocompatibility is extremely important as their contact with blood circulation is unavoidable during in vivo delivery. Herein, two kinds of GNRs coated with hexadecyltrimethylammonium bromide (C‐GNRs) or poly(sodium‐p‐styrenesulfonate) are used to test their potential toxicological effects in blood. C‐GNRs with positive surface charges efficiently induce hemolysis when encountering erythrocytes. Cellular internalization of C‐GNRs is found, and they subsequently bind with hemoglobin, forming bioconjugates. The interaction between hemoglobin and C‐GNR (stoichiometry 32.7:1) is regulated by electrostatic forces. Chromophores like tryptophan (Trp) are found to interact with C‐GNRs, causing enhancement in fluorescence intensity. The conformation of protein is partially altered, evidenced by decrease in α‐helical, increase in β‐sheet and random coil of hemoglobin. Although C‐GNRs do not essentially decrease oxygen binding capacity of hemoglobin, they hamper oxygen release from the protein. Heme, the oxygen binding unit, releases from hemoglobin upon C‐GNR treatment, which could contribute to C‐GNR‐induced hemolysis. This study demonstrates the hematological effects of GNRs, revealing their potential risk in biomedical applications.

Paired serum and urine samples were collected from workers in a fluorochemical plant from 2008 to 2012 (n = 302) to investigate the level, temporal trends, and half-lives of PFAAs in workers of a fluorochemical plant. High levels of perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), and perfluorooctanesulfonate (PFOS) were detected in serum with median concentrations of 764, 427, and 1725 ng mL−1, respectively. The half-lives of PFAAs in workers were estimated by daily clearance rates and annual decline rates of PFAAs in serum by a first-order model. The geometric mean and median value for PFHxS, PFOA, and PFOS were 14.7 and 11.7, 4.1 and 4.0, 32.6 and 21.6 years, respectively, by the daily clearance rates, and they were 3.6, 1.7, and 1.9 years estimated by annual decline rates. The half-lives estimated by the limited clearance route information could be considered as the upper limits for PFAAs, however, the huge difference between two estimated approaches indicated that there were other important elimination pathways of PFAAs other than renal clearance in human. The half-lives estimated by annual decline rates in the present study were the shortest values ever reported, and the intrinsic half-lives might even shorter due to the high levels of ongoing exposure to PFAAs.

Tetrabromobisphenol A (TBBPA) can cause diverse adverse effects including neurotoxicity. Emerging TBBPA derivatives, with high structure similarity to the parent compound, are now being concerned. In this study, the potential neurotoxicities of four TBBPA derivatives and their parent compound were studied by cell viability inhibition in rat pheochromocytoma cells (PC12) and the corresponding molecular mechanisms were investigated. The cellular toxicity was correlated with the chemical hydrophobicity. Tetrabromobisphenol A bis(2-hydroxyethyl ether) (TBBPA-BHEE) exhibited the highest cellular toxicity to PC12 due to its lowest hydrophobicity among these 5 tested compounds. Further experiments showed that TBBPA-BHEE disturbed dopamine (DA) secretion and altered acetylcholinesterase (AChE) enzymatic activity in PC12 cells. The molecular mechanism study indicated that TBBPA-BHEE induced cellular toxicity to PC12 cells through ROS-mediated caspase activation to a large extent, which was partially attenuated by the anti-oxidation of Vitamin E. Moreover, in contrast to TBBPA, the occurrence of TBBPA-BHEE toxicity to PC12 was not attributed to activation of mitogen-activated protein kinases (MAPKs) or thyroid hormone (TH) signaling pathway. These findings suggest TBBPA derivatives, especially TBBPA-BHEE, as potential neurotoxins need urgent attention.