Identification of organic constituents on atmospheric particulate matter in the East Asian background air of free troposphere by GC×GC-TOFMS.

The presence of organic compounds on the particulate matter (PM) or aerosols can arise from the condensation of gaseous organic compounds on the existing aerosols, or from organic precursors to form secondary organic aerosols (SOA) through photochemistry. The objective of this study is to characterize organic constituents on aerosols relevant to their emission sources and the key compounds revealing the evolution of aerosols with the use of a novel analytical technique. A time-of-flight mass spectrometry (TOFMS) coupled with comprehensive two-dimensional gas chromatography (GC×GC) was developed using a flow type of modulator instead of a thermal type as a prelude to field applications without the need for cryogen. The methodology of GC×GC-TOFMS is discussed in this study in detail. Since the coarse PM (PM10-2.5) may exhibit with a relatively high OC content compared to PM2.5, the GC×GC results have been obtained by analyzing PM10 samples collected in parallel with OC/EC analysis of PM2.5 samples at the Lulin Atmospheric Background Station (LABS, 23.47°N, 120.87°E, 2862 m ASL) as the high-mountain background site in East Asia. We found that the organic analytes were in a majority in the range of 12-30 carbon numbers falling in the category of semi-volatile organic compounds (SVOCs) with 43 compounds of alcohol, aldehyde, ketone, and ester varieties if excluding alkanes. Intriguingly, trace amounts of plasticizers and phosphorus flame retardants such as phthalates (PAEs) and triphenyl phosphate (TPP) were also found, likely originating from regions involved in open burning of household solid waste in Southeast Asia or e-waste recycling in southern China and along the long-range transport route. Compounds such as these are unique to the specific sources, demonstrating the wide spread of these hazardous compounds in the environment.

Weight of evidence evaluation of the metabolism disrupting effects of triphenyl phosphate using an expert knowledge elicitation approach.

Identification of Endocrine-Disrupting Chemicals (EDCs) in a regulatory context requires a high level of evidence. However, lines of evidence (e.g. human, in vivo, in vitro or in silico) are heterogeneous and incomplete for quantifying evidence of the adverse effects and mechanisms involved. To date, for the regulatory appraisal of metabolism-disrupting chemicals (MDCs), no harmonised guidance to assess the weight of evidence has been developed at the EU or international level. To explore how to develop this, we applied a formal Expert Knowledge Elicitation (EKE) approach within the European GOLIATH project. EKE captures expert judgment in a quantitative manner and provides an estimate of uncertainty of the final opinion. As a proof of principle, we selected one suspected MDC -triphenyl phosphate (TPP) - based on its related adverse endpoints (obesity/adipogenicity) relevant to metabolic disruption and a putative Molecular Initiating Event (MIE): activation of peroxisome proliferator activated receptor gamma (PPARγ). We conducted a systematic literature review and assessed the quality of the lines of evidence with two independent groups of experts within GOLIATH, with the objective of categorising the metabolic disruption properties of TPP, by applying an EKE approach. Having followed the entire process separately, both groups arrived at the same conclusion, designating TPP as a "suspected MDC" with an overall quantitative agreement exceeding 85%, indicating robust reproducibility. The EKE method provides to be an important way to bring together scientists with diverse expertise and is recommended for future work in this area.

Recombinant AcMNPV-gp64-EGFP and synergist triphenyl phosphate, an effective combination against Spodoptera frugiperda.

OBJECTIVES: AcMNPV is a kind of microbial insecticide that can significantly relieve the resistance of Spodoptera frugiperda to chemical pesticides. TPP is a widely used synergist, which can reduce the use of pesticides by inhibiting carboxylesterase. It is emergently needed to develop a biological control way of Spodoptera frugiperda. RESULTS: GP64 mediates low-pH-triggered membrane fusion during entry by endocytosis and participates in AcMNPV particle budding. We explored the synergistic anti-insect activity of AcMNPV-gp64-EGFP and TPP. AcMNPV-gp64-EGFP could increase progeny virus proliferation and accelerate the transcription of 38k and vp39 genes. TPP could inhibit the carboxylesterase activity in the midgut of Spodoptera frugiperda larvae infected with AcMNPV-gp64-EGFP and enhance the virulence of AcMNPV-gp64-EGFP to Spodoptera frugiperda. CONCLUSIONS: TPP targeted carboxylesterase inhibition so that AcMNPV-gp64-EGFP could escape the antiviral response in insect hosts. It provided a novel strategy for the prevention of Spodoptera frugiperda.

The adverse outcome pathway (AOP) of estrogen interference effect induced by triphenyl phosphate (TPP): Integrated multi-omics and molecular dynamics approaches.

Triphenyl phosphate (TPP) has been detected with increasing frequency in various biota and environmental media, and it has been confirmed that G protein-coupled estrogen receptor (GPER) was involved in the estrogenic activity of TPP. Therefore, it is necessary to link the estrogen-interfering effects and possible mechanisms of action of TPP with the molecular initiation event (MIE) to improve its adverse outcome pathway framework. In this study, transcriptomic and proteomic methods were used to analyze the estrogen interference effect of TPP mediated by GPER, and the causal relationship was supplemented by molecular dynamics simulation and fluorescence analysis. The omics results showed that TPP could regulate the response of key GPER signaling factors and the activation of downstream pathways including PI3K-Akt signaling pathway, MAPK signaling pathway, and estrogen signaling pathway. The similar activation effect of TPP and agonist G1 change of GPER was proved by molecular dynamics simulation. After TPP binding, the conformation of GPER will change from the inactive to active state. Therefore, TPP may affect cell proliferation, metastasis, and apoptosis and regulate gene transcription and kinase activity, leading to abnormal immune function and other estrogen-dependent cell processes and cancer through GPER, ultimately causing the estrogen interference effect.

New insights into the mechanism of hepatocyte apoptosis induced by typical organophosphate ester: An integrated in vitro and in silico approach.

Apoptosis is one of the typical features of liver diseases, therefore molecular targets of hepatic apoptosis and regulatory mechanisms need to be further investigated. The caspases play important functions in the execution of apoptosis and many studies have focused on classical caspase-dependent cell death pathways. However, other types of cell death pathways (such as mitochondrial poly (ADP-ribose) polymerase-1 (PARP1) pathway) are suggested to be also as important as the caspase-mediated pathways in reflection of early toxic effects in hepatocytes, which requires additional research. In this work, an approach integrated in silico and in vitro was used to investigate the underlying toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway induced by triphenyl phosphate (TPP). Docking view showed that TPP could interact with helix αJ to affect the activation of PARP1 as a molecular initial event. In vitro assays suggested some biochemical events downstream of PARP1 activation, such as mitochondrial injury, apoptosis inducing factor (AIF) release, reactive oxygen species (ROS) production, and DNA damage. Moreover, the apoptosis was alleviated when cells were pretreated with PJ34 hydrochloride (PARP1 inhibitor), suggesting the mitochondrial PARP1 dependent pathway played a pivotal role in L02 cells apoptosis. This study indicated that PARP1 was an important molecular target in this process. And it also helped to understand the mechanism of hepatocytes apoptosis, early hepatic toxicity, and even liver diseases.

Transcriptomic, proteomic and metabolomic profiling unravel the mechanisms of hepatotoxicity pathway induced by triphenyl phosphate (TPP).

Triphenyl phosphate (TPP) has been found in various environmental media and in biota suggesting widespread human exposure. However, there is still insufficient information on the hepatotoxicity mechanisms of health risk exposed to TPP. In this study, TPP could induce human normal liver cell (L02) apoptosis, injury cell ultrastructure and elevate the levels of reactive oxygen species (ROS). The integrated multi-omic (transcriptomic, proteomic, and metabolomic) analysis was used to further investigate the mechanisms. Transcriptomic analysis revealed that TPP exposure markedly affected cell apoptosis, oncogene activation, REDOX homeostasis, DNA damage and repair. Additionally, proteomic analysis found that the related proteins associated with apoptosis, oxidative stress, metabolism and membrane structure were affected. And metabolomic analysis verified that the related metabolic pathways, such as glycolysis, citrate cycle, oxidative phosphorylation, lipid and protein metabolism, were also significantly disrupted. Based on the multi-omic results, a hypothesized network was constructed to discover the key molecular events in response to TPP and illustrate the mechanism of TPP-induced hepatotoxicity in L02 cells. Therefore, molecular responses could be elucidated at multiple biological levels, and multi-omic analysis could provide scientific tools for exploring potential mechanisms of toxicity and chemical risk assessment.

Toxicological effects of graphene on mussel Mytilus galloprovincialis hemocytes after individual and combined exposure with triphenyl phosphate.

Graphene nanoparticles are increasingly released into the aquatic environment with the growth of production. However, there are rare investigations focusing on the interaction of nanoparticles with other contaminants. Triphenyl phosphate (TPP) is a frequently detected organophosphate flame retardant in the environment. This study aimed to assess the joint effects of graphene and TPP on Mytilus galloprovincialis hemocytes. Oxidative stress could be induced by graphene and TPP in mussel hemocytes, which could further cause apoptosis, DNA damage and decrease in the lysosomal membrane stability (LMS). Moreover, hemocytes could internalize graphene, thereby resulting in oxidative stress. The oxidative stress and DNA damage in hemocytes were increased in the graphene-exposed group, but significantly reduced after combined exposure of graphene and TPP. The up-regulated genes, including NF-κB, Bcl-2 and Ras, were mainly associated with reduced apoptosis and DNA damage after co-exposure to graphene and TPP.

Combinatorial immune and stress response, cytoskeleton and signal transduction effects of graphene and triphenyl phosphate (TPP) in mussel Mytilus galloprovincialis.

Owing to its unique surface properties, graphene can absorb environmental pollutants, thereby affecting their environmental behavior. Triphenyl phosphate (TPP) is a highly produced flame retardant. However, the toxicities of graphene and its combinations with contaminants remain largely unexplored. In this work, we investigated the toxicological effects of graphene and TPP to mussel Mytilus galloprovincialis. Results indicated that graphene could damage the digestive gland tissues, but no significant changes were found in the graphene + TPP co-exposure group. There was a significant decrease in the content of GSH and the activities of GST and CAT in the co-exposure group compared to that in graphene-exposed group. It seemed that the adsorption of TPP on graphene could inhibit the surface activity of graphene and thus reduced its tissue damage and oxidative stress in mussels. Expression levels of stress response (MyD88a), cytoskeleton (MHC1, PMyo and TMyo) and reproductive (CP450 and HSD) genes were up-regulated in the graphene-exposed group, but significantly down-regulated after combined exposure of graphene and TPP. Furthermore, PPI analysis proved that the interactions of HSP90AA1 with UNC45B and FKBP4/5/6/L contributed to the toxicity caused by the combined exposure. Because of the potential toxicity of graphene and TPP, government administrators should consider its risks prior to the widespread environmental exposure.

Characterization and monitoring of deltamethrin-resistance in Anopheles culicifacies in the presence of a long-lasting insecticide-treated net intervention.

BACKGROUND: Deltamethrin-impregnated, long-lasting insecticidal nets (LLINs) were distributed in the study area from November 2014 to January 2015 to evaluate their impact on malaria transmission in the presence of insecticide-resistant vectors. Studies were carried out in 16 selected clusters in Keshkal sub-district, Chhattisgarh State, India to monitor and characterize deltamethrin resistance in Anopheles culicifacies sensu lato. RESULTS: Deltamethrin susceptibility of An. culicifacies decreased in a post-LLIN survey compared to a pre-LLIN survey and was not significant (p > 0.05) while, the knockdown values showed significant increase (p < 0.05). Pre-exposure to piperonyl butoxide, triphenyl phosphate showed synergism against deltamethrin (p < 0.001). Biochemical assays showed significantly (p < 0.05) elevated monooxygenases in 3 of 5 clusters in post-LLIN survey-I that increased to 10 of 11 clusters in post-LLIN survey-II, while esterases were found significantly elevated in all clusters and both enzymes were involved in conferring pyrethroid resistance, not discounting the involvement of kdr (L1014L/S) gene that was heterozygous and at low frequency (4-5%). CONCLUSION: This field study, in a tribal district of India, after distribution of deltamethrin-impregnated LLINs showed decrease in deltamethrin susceptibility in An. culicifacies, a major vector of malaria in this study area and in India. Results indicated development of resistance as imminent with the increase in insecticide selection pressure. There is an urgent need to develop new vector control tools, with insecticide classes having novel mechanisms of resistance, to avoid or delay the onset of resistance. Regular insecticide resistance monitoring and mechanistic studies should be the priority for the malaria control programmes to suggest strategies for insecticide resistance management. The global commitment to eliminate malaria by 2030 needs various efforts that include development of combination vector control products and interventions and few are becoming available.

Urinary metabolites of organophosphate flame retardants and their variability in pregnant women.

Organophosphate flame retardants (OPFRs) are commonly added to consumer products to reduce their flammability. Based on levels of OPFRs in indoor environments, human exposure is likely chronic and ubiquitous. Animal studies suggest that exposure to some OPFRs may result in adverse health impacts, particularly for Tris (1,3-dichloropropyl) phosphate (TDCPP); however, human data on the impacts of exposure to OPFRs are lacking. To design human studies, more information is needed on the stability of measured OPFRs in human samples over time. In this study, we sought to assess the degree of temporal variability of urinary TDCPP and triphenyl phosphate (TPP) metabolites throughout pregnancy in a cohort of women from central North Carolina. Eight pregnant women provided multiple urine samples: 3 during the 18th week of pregnancy, 1 during the 28th week, and 1 shortly after the child's birth. Bis (1,3-dichloropropyl) phosphate (BDCPP) and diphenyl phosphate (DPP), the respective metabolites of TDCPP and TPP, were measured in urine samples using liquid chromatography-tandem mass spectrometry. BDCPP and DPP were each detected in 38 of 39 urine samples and were not normally distributed. Geometric mean BDCPP and DPP concentrations were 1.3ng/mL (interquartile range (IQR): 0.8, 2.7ng/mL) and 1.9ng/mL (IQR: 0.9, 3.5ng/mL), respectively. BDCPP and DPP were moderately to strongly reliable over one week (intraclass correlation coefficient (ICC)=0.5; 95% confidence interval (CI): 0.4, 0.7 and ICC=0.7; 95% CI: 0.5, 0.8, respectively), and over the entire pregnancy (ICC=0.5 95% CI: 0.3, 0.7 and ICC=0.6; 95% CI: 0.4, 0.7, respectively). These data suggest that exposures to TDCPP and TPP are widespread and variable for pregnant women, and that a single measure of BDCPP or DPP, taken in the second trimester, likely captures information on the rank order of exposure throughout pregnancy.