The seed germination and seedling phytotoxicity of decabromodiphenyl ethane to tall fescue under citric acid amendment.

The novel brominated flame retardant decabromodiphenyl ethane (DBDPE) has biological toxicity, persistence, long-range migration and bioaccumulation ability. However, there is currently little research on the phytotoxicity of DBDPE in plants. The perennial herbaceous plant tall fescue (Festuca elata Keng ex E. B. Alexeev) was selected as the model organism for use in seed germination experiments, and the phytotoxicity of DBDPE in the soil of tall fescue was studied. The results indicated that DBDPE had a significant effect on the germination and growth of tall fescue seedlings. Citric acid reduced the stress caused by DBDPE in plants, effectively alleviating the phytotoxicity of DBDPE in tall fescue. The root vitality and protein content significantly increased after the application of citric acid, increasing by 74.93-183.90%, 146.44-147.67%, respectively. The contents of proline and soluble sugars significantly decreased after the application of citric acid, decreasing by 45.18-59.69% and 23.03%, respectively (P < 0.05). There was no significant difference in superoxide dismutase (SOD) or peroxidase (POD) activity in tall fescue seedlings, and the catalase (CAT) activity and malondialdehyde (MDA) content were significantly lower after the application of citric acid, decreasing by 64.62-67.91% and 29.10-49.80%, respectively (P < 0.05). Tall fescue seedlings bioaccumulated DBDPE, with biological concentration factors (BCFs) ranging from 4.28 to 18.38 and transfer factors (TFs) ranging from 0.43 to 0.54. This study provides theoretical support for the study of the toxicity of DBDPE to plants and offers a research foundation for exploring the phytoremediation of DBDPE-contaminated soil by tall fescue.

Regrettable Substitution? Organophosphate Flame Retardants and Macrophage Activity.

Certain immune cells exposed to a mixture of organophosphate esters showed changes in their function and biology. The mixture included chemicals detected in samples of house dust.

Adolescent exposure to tris(1,3-dichloro-2-propyl) phosphate (TCPP) induces reproductive toxicity in zebrafish through hypothalamic-pituitary-gonadal axis disruption.

Tris(1,3-dichloro-2-propyl) phosphate (TCPP), a prevalent organophosphorus flame retardant in aquatic environments, has raised significant concerns regarding its ecological risks. This study aims to explore the impacts of TCPP on the reproductive functions of zebrafish and delineate its gender-related toxic mechanisms. By assessing the effects on zebrafish of 10 mg/L TCPP exposure from 30 to 120 days post-fertilization (dpf), we thoroughly evaluated the reproductive capability and endocrine system alterations. Our findings indicated that TCPP exposure disrupted gender differentiation in zebrafish and markedly impaired their reproductive capacity, resulting in decreased egg laying and offspring development quality. Histological analyses of gonadal tissues showed an abnormal increase in immature oocytes in females and a reduction in mature sperm count and spermatogonial structure integrity in males, collectively leading to compromised embryo quality. Additionally, molecular docking results indicated that TCPP showed a strong affinity for estrogen receptors, and TCPP-treated zebrafish exhibited imbalanced sex hormones and increased estrogen receptor expression. Alterations in genes associated with the hypothalamic-pituitary-gonadal (HPG) axis and activation of the steroidogenesis pathway suggested that TCPP targets the HPG axis to regulate sex hormone homeostasis. Tamoxifen (TAM), as a competitive inhibitor of estrogen, exhibited a biphasic effect, as evidenced by the counteraction of TCPP-induced effects in both male and female zebrafish after TAM addition. Overall, our study underscored the gender-dependent reproductive toxicity of TCPP exposure in zebrafish, characterized by diminished reproductive capacity and hormonal disturbances, likely due to interference in the HPG axis and steroidogenesis pathways. These findings emphasize the critical need to consider gender differences in chemical risk assessments for ecosystems and highlight the importance of understanding the mechanisms underlying the effects of chemical pollutants on the reproductive health of aquatic species.

2-Ethylhexyl Diphenyl Phosphate Induces Autism Spectrum Disorder-Like Behaviors in Offspring Mice by Disrupting Postsynaptic Development.

As organophosphorus flame retardants (OPFRs) are constantly detected in human samples, the neurotoxicity of OPFRs is of concern. In this study, pregnant ICR mice were exposed to 2-ethylhexyl diphenyl phosphate (EHDPP) in drinking water from gestation to lactation to investigate its effects on autism spectrum disorder-like (ASD-like) behaviors in offspring. Serum EHDPP concentrations in dams in the 0.4, 2, and 10 mg/kg groups were 0.282 ± 0.051, 0.713 ± 0.115, and 0.974 ± 0.048 ng/mL, respectively, within the concentration range in humans. At the highest dose, EHDPP exposure induced ASD-like behaviors in both female and male offspring. Significant reductions in mature dendritic spines and structural damage to the postsynaptic density zone were noted in all but the lowest exposure groups, indicating postsynaptic membrane impairment. Mechanistically, EHDPP significantly downregulated disc large MAGUK scaffold protein 4 expression by inhibiting protein kinase B and type 1 insulin-like growth factor receptor phosphorylation. In the heterologous synapse formation assay in vivo, EHDPP significantly reduced the levels of postsynaptic density protein 95 expression in neurons at 1 µM. Overall, the study utilized in vitro and in vivo experiments to confirm that EHDPP damaged postsynaptic membrane formation and might increase the incidence of ASD in offspring.

Olfactory toxicity of tetrabromobisphenol A to the goldfish Carassius auratus.

Tetrabromobisphenol A (TBBPA) is one of the most extensively used brominated flame retardants and its increasing use in consumer products has raised concerns about its ecotoxicity. Given the ubiquity of TBBPA in aquatic environments, it is inevitable that these chemicals will enter the olfactory chambers of fish via water currents. Nevertheless, the olfactory toxicity of TBBPA to aquatic organisms and the underlying toxic mechanisms have yet to be elucidated. Therefore, we investigated the olfactory toxicity of TBBPA in the goldfish Carassius auratus, a model organism widely used in sensory biology. Results showed that exposure to TBBPA resulted in abnormal olfactory-mediated behaviors and diminished electro-olfactogram (EOG) responses, indicating reduced olfactory acuity. To uncover the underlying mechanisms of action, we examined the structural integrity of the olfactory epithelium (OE), expression levels of olfactory G protein-coupled receptors (GPCRs), enzymatic activities of ion transporters, and fluctuations in neurotransmitters. Additionally, comparative transcriptomic analysis was employed to investigate the molecular mechanisms further. Our study demonstrates for the first time that TBBPA at environmentally relevant levels can adversely affect the olfactory sensitivity of aquatic organisms by interfering with the transmission of aqueous stimuli to olfactory receptors, impeding the binding of odorants to their receptors, disrupting the olfactory signal transduction pathway, and ultimately affecting the generation of action potentials.

Maternal Exposure to Low-Dose BDE-47 Induced Weight Gain and Impaired Insulin Sensitivity in the Offspring.

Polybrominated diphenyl ethers (PBDEs), commonly used as synthetic flame retardants, are present in a variety of consumer products, including electronics, polyurethane foams, textiles, and building materials. Initial evidence from epidemiological and experimental studies suggests that maternal PBDE exposure may be associated with a higher BMI in children, with disturbance of energy metabolism and an increased risk of Type 2 diabetes. However, the causality between early exposure to real-life PBDE concentrations and increased weight as well as mechanisms underlying impaired metabolic pathways in the offspring remain elusive. Here, using a mouse model we examined the effect of maternal exposure to 2,2',4,4'-tetrabrominated diphenyl ether (BDE-47), the most abundant congener in human samples, on offspring weight gain and energy homeostasis using a mouse model. Maternal exposure to BDE-47 at low dose resulted in weight gain in female offspring together with an impaired glucose and insulin tolerance in both female and male mice. In vitro and in vivo data suggest increased adipogenesis induced by BDE-47, possibly mediated by DNA hypermethylation. Furthermore, mRNA data suggest that neuronal dysregulation of energy homeostasis, driven via a disturbed leptin signaling may contribute to the observed weight gain as well as impaired insulin and glucose tolerance.

Tris(1-chloro-2-propyl) phosphate enhances the adverse effects of biodegradable polylactic acid microplastics on the mussel Mytilus coruscus.

Microplastics (MPs) and organophosphate flame retardants (OPFRs) have recently become ubiquitous and cumulative pollutants in the oceans. Since OPFRs are added to or adsorbed onto MPs as additives, it is necessary to study the composite contamination of OPFRs and MPs, with less focus on bio-based PLA. Therefore, this study focused on the ecotoxicity of the biodegradable MP polylactic acid (PLA) (5 µm, irregular fragments, 102 and 106 particles/L), and a representative OPFRs tris(1-chloro-2-propyl) phosphate (TCPP, 0.5 and 50 µg/L) at environmental and high concentrations. The mussel Mytilus coruscus was used as a standardised bioindicator for exposure experiments. The focus was on examining oxidative stress (catalase, CAT, superoxide dismutase, SOD, malondialdehyde, MDA), immune responses acid (phosphatase, ACP, alkaline phosphatase, AKP, lysozyme, LZM), neurotoxicity (acetylcholinesterase, AChE), energy metabolism (lactate dehydrogenase, LDH, succinate dehydrogenase, SDH, hexokinase, HK), and physiological indices (absorption efficiency, AE, excretion rate, ER, respiration rate, RR, condition index, CI) after 14 days exposure. The results of significantly increased oxidative stress and immune responses, and significantly disturbed energy metabolism and physiological activities, together with an integrated biomarker response (IBR) analysis, indicate that bio-based PLA MPs and TCPP could cause adverse effects on mussels. Meanwhile, TCPP interacted significantly with PLA, especially at environmental concentrations, resulting in more severe negative impacts on oxidative and immune stress, and neurotoxicity. The more severe adverse effects at environmental concentrations indicate higher ecological risks of PLA, TCPP and their combination in the real marine environment. Our study presents reliable data on the complex effects of bio-based MP PLA, TCPP and their combination on marine organisms and the environment.

1,2-bis(2,4,6-tribromophenoxy) ethane induces necroptosis via the co-competition of GAS5 and NUAK1 for miR-743a-5p in rat hepatocytes.

The brominated flame retardant 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE) widely used in manufacturing is inevitably released into the environment, resulting in the exposure of organisms to BTBPE. Therefore, it is particularly important to explore its toxic mechanism. The liver is one of the main accumulating organs of BTBPE, but the mechanism underlying BTBPE hepatotoxicity has not been thoroughly investigated. In our study, BTBPE was administered to Sprague-Dawley (SD) rats and rat hepatocytes (BRL cells) in vivo and in vitro, respectively, and HE staining, AO/EB staining, fluorescent probes, qPCR, immunofluorescence, and dual-luciferase reporter assays were performed. We investigated the mechanism of action of growth arrest-specific 5 (GAS5), miR-743a-5p, and NUAK family kinase 1 (NUAK1) in BTBPE-induced necroptosis from the perspective of competing endogenous RNAs (ceRNAs) using NUAK1 inhibitors, siRNAs, mimics, and overexpression plasmids. Our study showed that exposure to BTBPE caused necroptosis in the liver and BRL cells, accompanied by an oxidation-reduction imbalance and an inflammatory response. It is worth noting that NUAK1 is a newly discovered upstream regulatory target for necroptosis. In addition, miR-743a-5p was shown to inhibit necroptosis by targeting NUAK1 and down-regulating NUAK1. GAS5 upregulates NUAK1 expression by competitively binding to miR-743a-5p, thereby inducing necroptosis. This study demonstrated, for the first time, that the GAS5-miR-743a-5p-NUAK1 axis is involved in the regulation of necroptosis via ceRNAs. Thus, GAS5 and NUAK1 induce necroptosis by competitively binding to miR-743a-5p.

TDMPP activation of estrogen receptor 2a regulates smc2 and p53 signaling to interfere with liver development in zebrafish (Danio rerio).

Tris (2,6-dimethylphenyl) phosphate (TDMPP), a novel organic phosphorus flame retardant (OPFR), has been found to have estrogenic activity. Estrogens are critical in regulating various biological responses during liver development. However, the effects of TDMPP on zebrafish liver development remain largely unexplored. Here, we utilized a chemical genetic screening approach to assess the estrogenic effects of TDMPP on liver development and to elucidate the underlying molecular mechanism. Our findings revealed that zebrafish larvae exposed to environmentally relevant concentrations of TDMPP (0.05 and 0.5 µM) exhibited concentration-dependent liver impairments, including reduced liver size, histopathological changes, and hepatocyte apoptosis. In addition, E2 caused similar adverse effects to TDMPP, but the pharmacological blockade of estrogen synthesis alleviated the effects on liver development. Chemical inhibitors and morpholino knockdown assays indicated that the reduction of esr2a blocked TDMPP-induced liver impairments, which was further confirmed in the esr2a-/- mutant line. Subsequently, transcriptomic analysis showed that the estrogen receptor activated by TDMPP inhibited the expression of smc2, which was linked to the suppression of liver development through p53 activation. Consistently, overexpression of smc2 and inhibition of p53 evidently rescued hepatic damages induced by TDMPP. Taken together, the above findings identified esr2a, downstream smc2, and p53 as important regulators for the estrogenic effects of TDMPP on liver development. Our work fills crucial gaps in the current knowledge of TDMPP's hepatotoxicity, providing new insights into the adverse effects of TDMPP and the molecular mechanisms of action. These findings underscore the need for further ecological risk assessment and regulatory considerations.

Life-time exposure to decabromodiphenyl ethane (DBDPE) caused transgenerational epigenetic alterations of thyroid endocrine system in zebrafish.

Because of its ubiquitous occurrence in the environment, decabromodiphenyl ethane (DBDPE), a novel brominated flame retardant, has been widely concerned. However, its transgenerational thyroid disrupting potential and intricate mechanism are barely explored. Therefore, zebrafish embryos were exposed to environmentally relevant concentrations of DBDPE (0, 0.1, 1 and 10 nM) until sexual maturity. The results indicated that life-time exposure to DBDPE caused anxiety-like behavior in unexposed offspring. Furthermore, the changing of thyroid hormones as well as transcriptional and DNA methylation level in the promoter region of related genes were evaluated. The thyroid disruptions observed in F1 larvae were primarily attributed to excessive transfer of thyroid hormone from F0 adults to F1 eggs. Conversely, the disruptions in F2 larvae were likely due to inherited epigenetic changes, specifically hypomethylation of crh and hypermethylation of ugt1ab, passed down from the F1 generation. Additionally, our results revealed sex-specific responses of the hypothalamic-pituitary-thyroid (HPT) axis in adult zebrafish. Furthermore, thyroid disruptions observed in unexposed offspring were more likely inherited from their mothers. The current results prompted our in-depth understanding of the multi- and transgenerational toxicity by DBDPE, and also highlighted the need to consider their adverse effects on persistent and inheritable epigenetic changes in future research on emerging pollutants.

Visual toxicity in zebrafish larvae following exposure to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), triphenyl phosphate (TPhP), and isopropyl phenyl diphenyl phosphate (IPPP).

TPhP and IPPP, alternatives to PBDEs as flame retardants, have been studied for their developmental toxicity, but their visual toxicities are less understood. In this study, zebrafish larvae were exploited to evaluate the potential ocular impairments following exposure to BDE-47, TPhP, and IPPP. The results revealed a range of ocular abnormalities, including malformation, vascular issues within the eyes, and histopathological changes in the retina. Notably, the visually mediated behavioral changes were primarily observed in IPPP and TPhP, indicating that they caused more severe eye malformations and vision impairment than BDE-47. Molecular docking and MD simulations showed stronger binding affinity of TPhP and IPPP to RAR and RBP receptors. Elevated ROS and T3 levels induced by these compounds led to apoptosis in larvae eyes, and increased GABA levels induced by TPhP and IPPP hindered retinal repair. In summary, our results indicate TPhP and IPPP exhibit severer visual toxicity than BDE-47, affecting eye development and visually guided behaviors. The underlying mechanism involves disruptions in RA signaling, retinal neurotransmitters imbalance, thyroid hormones up-regulation, and apoptosis in larvae eyes. This work highlights novel insights into the need for cautious use of these flame retardants due to their potential biological hazards, thereby offering valuable guidance for their safer applications.

Phenotypic and Functional Outcomes in Macrophages Exposed to an Environmentally Relevant Mixture of Organophosphate Esters in Vitro.

BACKGROUND: Organophosphate esters (OPEs) are flame retardants and plasticizers used in consumer products. OPEs are found ubiquitously throughout the environment with high concentrations in indoor house dust. Exposure to individual OPEs is associated with immune dysfunction, particularly in macrophages. However, OPEs exist as complex mixtures and the effects of environmentally relevant mixtures on the immune system have not been investigated. OBJECTIVES: The objectives of this study were to evaluate the toxicity of an environmentally relevant mixture of OPEs that models Canadian house dust on macrophages using phenotypic and functional assessments in vitro. METHODS: High-content live-cell fluorescent imaging for phenotypic biomarkers of toxicity in THP-1 macrophages treated with the OPE mixture was undertaken. We used confocal microscopy and cholesterol analysis to validate and expand on the observed OPE-induced lipid phenotype. Then, we used flow cytometry and live-cell imaging to conduct functional tests and uncover mechanisms of OPE-induced phagocytic suppression. Finally, we validated our THP-1 findings in human primary peripheral blood mononuclear cells (hPBMC) derived macrophages. RESULTS: Exposure to non-cytotoxic dilutions of the OPE mixture resulted in higher oxidative stress and disrupted lysosome and lipid homeostasis in THP-1 and primary macrophages. We further observed that phagocytosis of apoptotic cells in THP-1 and primary macrophages was lower in OPE-exposed cells vs. controls. In THP-1 macrophages, phagocytosis of both Gram-positive and Gram-negative bacteria was also lower in OPE-exposed cells vs. controls. Additionally, the OPE mixture altered the expression of phagocytic receptors linked to the recognition of phosphatidylserine and pathogen-associated molecular patterns. DISCUSSION: The results of this in vitro study suggested that exposure to an environmentally relevant mixture of OPEs resulted in higher lipid retention in macrophages and poor efferocytic response. These effects could translate to enhanced foam cell generation resulting in higher cardiovascular mortality. Furthermore, bacterial phagocytosis was lower in OPE-exposed macrophages in an in vitro setting, which may indicate the potential for reduced bacterial clearance in models of infections. Taken together, our data provide strong evidence that mixtures of OPEs can influence the biology of macrophages and offer new mechanistic insights into the impact of OPE mixtures on the immune system. https://doi.org/10.1289/EHP13869.

2-ethylhexyl diphenyl phosphate exposure induces duodenal inflammatory injury through oxidative stress in chickens.

2-ethylhexyl diphenyl phosphate (EHDPHP) is a widely used organophosphorus flame retardant and plasticizer, which is commonly found in the environment. EHDPHP not only potentially harms the environment but also causes different degrees of damage to the organism. In this study, the duodenum of chicks was selected as the potential toxic target organ to explore the mechanism of duodenal injury induced by EHDPHP exposure. Ninety one-day-old healthy male chicks were selected and randomly divided into C1(control group), C2(solvent control group), L(800 mg/kg), M(1600 mg/kg), H(3200 mg/kg) according to different doses of EHDPHP after one week of environmental adaptation. The chicks were given continuous gavage for 14 d, 28 d, and 42 d. It was found that constant exposure to EHDPHP caused an increase in duodenal MDA content, a decrease in P-gp, SOD, GSH-Px activities, and a decrease in duodenal mucosal immune factor (sIgA, GSH-Px). The expression of sIgM and mucosal link proteins (CLDN, OCLN, ZO-1, JAM) decreased, and the expression of the inflammatory protein (NF-κB, COX2) in duodenal tissues was up-regulated. The results showed that continuous exposure to EHDPHP could cause duodenal oxidative stress, inflammation, and mucosal barrier damage in chicks, which provided a basis for studying the mechanism of toxic damage caused by EHDPHP in poultry.

Mechanistic insights into cadmium exacerbating 2-Ethylhexyl diphenyl phosphate-induced human keratinocyte toxicity: Oxidative damage, cell apoptosis, and tight junction disruption.

Organophosphate flame retardants 2-ethylhexyldiphenyl phosphate (EHDPP) and cadmium (Cd) are ubiquitous in environmental matrices, and dermal absorption is a major human exposure pathway. However, their detrimental effects on the human epidermis remain largely unknown. In this study, human keratinocytes (HaCaT cells) were employed to examine the toxicity and underlying mechanisms of co-exposure to EHDPP and Cd. Their influence on cell morphology and viability, oxidative damage, apoptosis, and tight junction were determined. The results showed that co-exposure decreased cell viability by >40 %, induced a higher level of oxidative damage by increasing the generation of reactive oxygen species (1.3 folds) and inhibited CAT (79 %) and GPX (90 %) activities. Moreover, Cd exacerbated EHDPP-induced mitochondrial disorder and cellular apoptosis, which was evidenced by a reduction in mitochondrial membrane potential and an elevation of cyt-c and Caspase-3 mRNA expression. In addition, greater loss of ZO-1 immunoreactivity at cellular boundaries was observed after co-exposure, indicating skin epithelial barrier function disruption, which may increase the human bioavailability of contaminants via the dermal absorption pathway. Taken together, oxidative damage, cell apoptosis, and tight junction disruption played a crucial role in EHDPP + Cd triggered cytotoxicity in HaCaT cells. The detrimental effects of EHDPP + Cd co-exposure were greater than individual exposure, suggesting the current health risk assessment or adverse effects evaluation of individual exposure may underestimate their perniciousness. Our data imply the importance of considering the combined exposure to accurately assess their health implication.

Triphenyl Phosphate Alters Methyltransferase Expression and Induces Genome-Wide Aberrant DNA Methylation in Zebrafish Larvae.

Emerging environmental contaminants, organophosphate flame retardants (OPFRs), pose significant threats to ecosystems and human health. Despite numerous studies reporting the toxic effects of OPFRs, research on their epigenetic alterations remains limited. In this study, we investigated the effects of exposure to 2-ethylhexyl diphenyl phosphate (EHDPP), tricresyl phosphate (TMPP), and triphenyl phosphate (TPHP) on DNA methylation patterns during zebrafish embryonic development. We assessed general toxicity and morphological changes, measured global DNA methylation and hydroxymethylation levels, and evaluated DNA methyltransferase (DNMT) enzyme activity, as well as mRNA expression of DNMTs and ten-eleven translocation (TET) methylcytosine dioxygenase genes. Additionally, we analyzed genome-wide methylation patterns in zebrafish larvae using reduced-representation bisulfite sequencing. Our morphological assessment revealed no general toxicity, but a statistically significant yet subtle decrease in body length following exposure to TMPP and EHDPP, along with a reduction in head height after TPHP exposure, was observed. Eye diameter and head width were unaffected by any of the OPFRs. There were no significant changes in global DNA methylation levels in any exposure group, and TMPP showed no clear effect on DNMT expression. However, EHDPP significantly decreased only DNMT1 expression, while TPHP exposure reduced the expression of several DNMT orthologues and TETs in zebrafish larvae, leading to genome-wide aberrant DNA methylation. Differential methylation occurred primarily in introns (43%) and intergenic regions (37%), with 9% and 10% occurring in exons and promoter regions, respectively. Pathway enrichment analysis of differentially methylated region-associated genes indicated that TPHP exposure enhanced several biological and molecular functions corresponding to metabolism and neurological development. KEGG enrichment analysis further revealed TPHP-mediated potential effects on several signaling pathways including TGFß, cytokine, and insulin signaling. This study identifies specific changes in DNA methylation in zebrafish larvae after TPHP exposure and brings novel insights into the epigenetic mode of action of TPHP.

In vitro impacts of polystyrene microplastics and environmental pollutants on ethoxyresorufin-O-deethylase and glutathione S-transferase activity in Mossambica tilapia.

Microplastic (MP) pollution is a potential threat to marine organisms. In vitro toxicity of MPs and other pollutants, such as pharmaceutically active compounds (PhACs) and brominated flame retardants (BFRs), has been understudied. This study aimed to investigate the effects of polystyrene microplastics (PS-MPs) with different particle sizes on two biomarkers: ethoxyresorufin-O-deethylase (EROD) and glutathione S-transferase (GST) in tilapia liver homogenates. The study also examined the combined effects of PS-MPs with various environmental contaminants, including three metal ions (Cu2+, Zn2+, Pb2+), three BFRs, and six PhACs. PS-MPs alone had no remarkable effects on the two biomarkers at the selected concentrations. However, PS-MPs combined with other pollutants significantly affected the two biomarkers in most situations. For EROD activity, PS + metal ions (except Zn2+ at 1000 µg/L), PS + BFRs (except decabromodiphenyl oxide (BDE-209)) or PS+ trimethoprim (TMP) significantly inhibited activity values, whereas PS+ 4-acetaminophen (AMP) induced EROD activity. For GST, PS together with most tested pollutants (except PS+ ibuprofen (IBF)) greatly decreased the activities. Accordingly, future research should focus on combined toxicity of mixtures to set more reasonable environmental safety evaluation standards.

Physiological and transcriptomic changes of zebrafish (Danio rerio) in response to Isopropylate Triphenyl Phosphate (IPPP) exposure.

Isopropylate Triphenyl Phosphate (IPPP), a novel organophosphorus flame retardant, has become a widespread environmental pollutant. However, the toxic effects and mechanisms of IPPP remain unclear. In this study, we evaluated the neurodevelopmental toxicity effects of IPPP on zebrafish embryonic development, neurobehavior, and physiological and transcriptomic changes. The results showed that IPPP induced adverse developments such as low survival rates and hatching rates, decreased body length and eye distance, and also led to increased heart rates and embryonic malformation rates. The developmental defects mainly included typical pericardial edema, eye deformities, and a reduction in the number of newborn neurons. Mitochondrial energy metabolism disorders and apoptosis of cardiomyocytes may be responsible for heart malformation. Behavioral results showed that IPPP caused abnormal changes in swimming speed, total swimming distance and trajectory, and showed a low-dose effect. In addition, the decreased activity of neurotransmitters such as acetylcholinesterase (AchE) and dopamine (DA), and the changes in genes related to the central nervous system (CNS) and metabolism pathway may be the causes of neurodevelopmental toxicity of IPPP. Meanwhile, IPPP induced oxidative stress and apoptosis, and changed the ATPase activity of zebrafish larvae by altering nuclear factor erythroid2-related factor 2 (Nrf2) and mitochondrial signaling pathways, respectively. Transcriptome sequencing results indicated that Cytochrome P450 and drug metabolism, Energy metabolism-related pathways, Glutathione metabolism, Retinoid acid (RA) and REDOX signaling pathways were significantly enriched, and most of the genes in these pathways were up-regulated after IPPP treatment, which may be new targets for IPPP-induced neurodevelopment. In summary, the results of this study provide an important reference for a comprehensive assessment of the toxic effects and health risks of the new pollutant IPPP.

Structure-dependent destructive adsorption of organophosphate flame retardants on lipid membranes.

The widespread use of organophosphate flame retardants (OPFRs), a serious type of pervasive environmental contaminants, has led to a global concern regarding their diverse toxicities to living beings. Using a combination of experimental and theoretical approaches, we systematically studied the adsorption, accumulation, and influence of a series of OPFRs on the lipid membranes of bacteria and cells. Our results revealed that OPFRs can aggregate in lipid membranes, leading to the destruction of membrane integrity. During this process, the molecular structure of the OPFRs is a dominant factor that significantly influences the strength of their interaction with the lipid membrane, resulting in varying degrees of biotoxicity. Triphenyl phosphate (TPHP), owing to its large molecular size and strong hydrophobicity, causes severe membrane disruption through the formation of nanoclusters. The corresponding severe toxicity originates from the phase transitions of the lipid membranes. In contrast, smaller OPFRs such as triethyl phosphate (TEP) and tris(2-chloroethyl) phosphate (TCEP) have weaker hydrophobicity and induce minimal membrane disturbance and ineffective damage. In vivo, gavage of TPHP induced more severe barrier damage and inflammatory infiltration in mice than TEP or TCEP, confirming the higher toxicity of TPHP. Overall, our study elucidates the structure-dependent adsorption of OPFRs onto lipid membranes, highlighting their destructive interactions with membranes as the origin of OPFR toxicity.

Cytotoxicity evaluation of organophosphorus flame retardants using electrochemical biosensors and elucidation of associated toxic mechanisms.

In recent years, organophosphorus flame retardants (OPFRs) have been widely used as substitutes for brominated flame retardants with excellent properties, and their initial toxicological effects on the water ecosystem and human health have gradually emerged. However, to date, research on the cytotoxicity and health risks of OPFRs is still limited. Therefore, this study aims to systematically explore the cytotoxic effects and toxic mechanisms of OPFRs on cells. Human liver cancer (HepG2) cells were adopted as an ideal model for toxicity evaluation due to their rapid growth and metabolism. This study proposes a sensitive electrochemical cell-based sensor constructed on a graphitized multi-walled carbon nanotube/ionic liquid/gold nanoparticle-modified electrode. The sensor was used to detect the cytotoxicity of tri(2-butylxyethyl) phosphate (TBEP), tributyl phosphate (TnBP), triphenyl phosphate (TPhP), tri(1,3-dichloro-2-propyl) phosphate (TDCIPP), tri(2-chloropropyl) phosphate (TCPP) and tri(2-chloroethyl) phosphate (TCEP) in the liquid medium, providing insight into their toxicity in water environments. The half-maximal inhibitory concentration (IC50) of TBEP, TnBP, TPhP, TDCIPP, TCPP and TCEP on HepG2 cells were 179.4, 194.9, 219.8, 339.4, 511.8 and 859.0 µM, respectively. Additionally, the cytotoxic mechanism of six OPFRs was discussed from the perspective of oxidative stress and apoptosis, and four indexes were correlated with toxicity. Furthermore, transcriptome sequencing was conducted, followed by a thorough analysis of the obtained sequencing results. This analysis demonstrated a significant enrichment of the p53 and PPAR pathways, both of which are closely associated with oxidative stress and apoptosis. This study presents a simplified and efficient technique for conducting in vitro toxicity studies on organophosphorus flame retardants in a water environment. Moreover, it establishes a scientific foundation for further investigation into the mechanisms of cytotoxicity associated with these compounds.

[Research progress on the developmental toxicity and mechanism of brominated flame retardants during pregnancy exposure on offspring].

Brominated flame retardants (BFRs) are a kind of brominated compounds widely used in electronic and electrical appliances, textiles, construction materials and other industrial products to improve the flame retardant property. Because of its strong chemical stability, environmental persistence, long-distance transmission, biological accumulation, the exposure of humans and organisms in the ecosystem is increasing, and its potential biological effects are of great concern. Now BFRs can be detected in breast milk, serum, placenta and cord blood. Studies have shown that exposure to BFRs during pregnancy can lead to adverse birth outcomes such as low birth weight, malformation, gestational age changes and impairment of neurobehavioral development. This article summarizes the pollution and population exposure of three traditional BFRs, polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA), as well as the impact and mechanism of prenatal exposure on offspring birth outcomes and growth and development. It explores the harm of prenatal exposure to BFRs to offspring and proposes preventive measures for occupational populations for reference.