TDCIPP Research Articles

Chlorinated organophosphorus flame retardants-induced mitochondrial abnormalities and the correlation with progesterone production in mLTC-1cells.

Environmental monitoring data have indicated that three chlorinated organophosphorus flame retardants (Cl-OPFRs), including tris(2-chloroethyl)-phosphate (TCEP), tris(2-chloropropyl)-phosphate (TCPP), and tris(1,3-dichloro-2-propyl)-phosphate (TDCPP) are the predominant chemicals in various environmental matrices and exhibit reproductive endocrine disrupting activities. Currently, mitochondrial abnormality is a new paradigm for evaluating chemical-mediated cell dysfunction. However, a comprehensive correlation between these two aspects of Cl-OPFRs remains unclear. In this research, the effects of TCEP, TCPP, and TDCPP on progesterone production and mitochondrial impairment were investigated by using mouse Leydig tumor cells (mLTC-1). The half maximal inhibitory concentration (IC50) values at 48h exposure indicated that the rank order of anti-androgenic activity was TDCPP>TCPP. Whereas, TCEP exhibited elevation of progesterone production. At concentrations close to IC50 of progesterone production by TCPP and TDCPP, the elevation of intracellular reactive oxygen species (ROS), depletion of mitochondrial membrane potential (MMP), reduction of cellular adenosine triphosphate (ATP) content, and alteration of mitochondrial structures was observed. In addition, the expression of main genes related to progesterone synthesis was dramatically down-regulated by TCPP and TDCPP treatments. These results imply that the inhibition effect of TCPP and TDCPP on progesterone production might be related to mitochondrial damage and down-regulated steroidogenic genes.

Toxic responses of freshwater microalgae Chlorella sorokiniana due to exposure of flame retardants

Flame retardants, such as Tetrabromobisphenol A (TBBPA), Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and tributyl phosphate (TBP), are frequently detected in surface water. However, the effects of FRs exposure on aquatic organisms especially freshwater microalgae are still unclear. In this study, the toxicities of TBBPA, TDCPP and TBP to microalgae Chlorella sorokiniana, in terms of growth inhibition, photosynthetic activity inhibition and oxidative damage, were investigated, and according ecological risks were assessed. The results showed that TBBPA, TDCPP and TBP had inhibitory effects on C. sorokiniana, with 96 h EC50 (concentration for 50% of maximal effect) values of 7.606, 41.794 and 49.996 mg/L, respectively. Fv/Fm decreased as the increase of exposure time under 15 mg/L TBBPA. Under 50 mg/L TDCPP and 80 mg/L TBP exposure, Fv/Fm decreased significantly after 24 h. However, Fv/Fm rose after 96 h, indicating that the damaged photosynthetic activity was reversible. The content of chlorophyll a decreased, as the increase of TBBPA concentration from 3 to 15 mg/L. However, chlorophyll a increased first and then decreased, as the increase of TDCPP and TBP concentrations from 0 to 50 mg/L and 0–80 mg/L, respectively. Results indicated that C. sorokiniana could use the phosphorus of TDCPP and TBP to ensure the production of chlorophyll a. The risen content of reactive oxygen species, malondialdehyde as well as superoxide dismutase activity indicated that exposure to FRs induced oxidative stress. Additionally, the risk quotients showed that tested FRs had ecological risks in natural waters or wastewaters. This study provides insights into the toxicological mechanisms of different FRs toward freshwater microalgae for better understanding of according environmental risks.

Pre- and post-natal exposure of children to organophosphate flame retardants: A nationwide survey in France.

The use of organophosphate flame retardants (OPFRs) has been on the rise ever since many brominated flame retardants were banned, back in the 2000s. The objectives of this study are to describe the pre- and post-natal exposure of children to OPFRs, and to explore their possible determinants. A total of 259 children aged 3.5years and 388 mothers from the French ELFE mother-child cohort were included. Both pre- and post-natal exposure to OPFRs were assessed, using OPFR concentrations in the hair of pregnant women (in 2011) and their 3.5-year-old children (in 2014-2015) for 15 OPFRs, of which 9 were detected in>20% hair samples. The highest geometric means for pre-natal exposure were 272ng/g for tris(1-chloro-2-propyl) phosphate (TCPP), 69.7ng/g for ng/g for triphenyl phosphate (TPP) and 54.4ng/g for tris(1,3-dichloro-2-propyl) phosphate (TDCPP). The highest geometric means for post-natal exposure were 249.6ng/g for TCPP, 85.3ng/g for TDCPP and 83.8ng/g for 2-ethylhexyl diphenyl phosphate (EHDPP). Correlations were found between both pre-natal exposures, and between pre-and post-natal exposures. No correlation was however found between pre-and post-natal exposures for any given OPFR. Pre-natal exposure to the 9 OPFRs was associated with pre-natal exposure to polybrominated diphenyl ethers 209 (BDE209), and 47 (BDE47). Maternal BMI was associated with pre-natal exposure to OPFRs other than TBEP. Home renovation work prior to birth was also associated with pre-natal exposure to OPFRs, with the exception of EHDPP, tris(2-butoxyethyl) phosphate (TBEP) and triethyl phosphate (TEP). Determinants of post-natal exposure appeared more disparate across OPFRs; although both the type of flooring in children's rooms and pre-natal exposure to polybrominated diphenyl ethers seem to be associated with post-natal exposure. Lastly, higher socioeconomic status appeared to be associated with lower exposure for several (though not all) OPFRs. The high prevalence of exposure to OPFRs suggests the need for studies to assess the health effects of OPFRs exposure, particularly on children.

The coupling between biological pump export and air-water exchange of organophosphate esters in a subtropical water environment

Organophosphate esters (OPEs) are well-known persistent organic pollutants with their ubiquitous environmental presence and adverse ecological and human health impacts. To study the transport and fate of OPEs in a subtropical environment, nine OPE compounds were analyzed in the gas phase (air samples), dissolved phase (water samples), and plankton samples collected over one year from or in the vicinity of an urban lake in Guangzhou, South China. The mean concentrations of ∑9OPEs were 2.93 ± 1.68 ng/m3 in the air, 455 ± 236 ng/L in the dissolved phase, 81.3 ± 41.2 ng/L in phytoplankton, and 4.79 ± 1.94 ng/L in zooplankton. Although the compositional profiles of OPEs varied among different media, tris (1-chloro-2-propyl) phosphate (TCPP) was the predominant OPE in most samples. Less hydrophobic OPEs such as TCPP and tris (2-chloroethyl) phosphate (TCEP) had lower bioaccumulation potential in the lake. The biological pump export played an important role in eliminating OPEs from the surface water, with fluxes ranging from 30.5 to 361 ng/m2/d. The more phytoplankton biomass in surface water, the greater the role of the biological pump. The fugacity fractions and air-water exchange fluxes suggested that TCPP and tris (1,3-dichloro-2-propyl) phosphate (TDCP) would enter the urban lake by gaseous deposition. Nevertheless, the lake acted as an important “secondary source” for TCEP and triphenyl phosphate (TPhP). The bio-pump might influence the air-water exchange processes of OPEs.

Organophosphorus flame retardant TDCPP induces neurotoxicity via mitophagy-related ferroptosis in vivo and in vitro

Tris (1,3-dichloro-2-propyl) phosphate (TDCPP) has neurotoxicity, but its mechanism remains unclear. Evidence recently showed that ferroptosis might be associated with TDCPP-induced neurotoxicity. To explore the role and underlying mechanism of ferroptosis in TDCPP-induced neurotoxicity, the occurrence of ferroptosis was examined in mice and PC12 cells upon TDCPP exposure. The mechanism of TDCPP-induced ferroptosis was clarified in vitro combined with the RNA sequencing assay. The in vivo results showed that orally TDCPP exposure (100 mg/kg, 30 d) inhibited the learning and memory ability of mice, reduced hippocampus neurons, induced malondialdehyde (MDA) accumulation, and decreased glutathione (GSH) and superoxide dismutase (SOD) levels in the hippocampus. Moreover, TDCPP exposure (100 mg/kg, 30 d) altered the ferroptosis and autophagy-related protein abundances in the hippocampus. The in vitro results showed that TDCPP exposure (0, 5, 20, 50, 100, and 200 μM) for 24 h induced dose-dependent cell death in PC12 cells, and the cell death was ameliorated by the co-treatment with ferrostatin-1 (1 μM, 24 h). Similarly, TDCPP exposure (0, 50, 100, and 200 μM) for 24 h increased the levels of MDA and LPO, but decreased the reduced GSH in PC12 cells. Furthermore, TDCPP exposure (0, 50, 100, and 200 μM) for 24 h altered the ferroptosis and autophagy-related protein abundances in PC12 cells. The RNA-sequencing revealed that TDCPP exposure (100 μM, 24 h) induced mitophagy activation in SH-SY5Y cells. Meanwhile, the in vitro experiments confirmed that TDCPP exposure (0, 50, 100, and 200 μM) for 24 h increased abundances of mitophagy-related protein phosphatase and tensin homolog induced kinase 1(PINK1), Parkinson protein 2 E3 ubiquitin-protein ligase (PARKIN), inositol 1,4,5-trisphosphate receptor type 1 (IP3R1), and voltage-dependent anion channel 1 (VDAC1) in PC12 cells. Moreover, TDCPP treatment (100 μM, 24 h) increased the mitochondrial recruitment of PARKIN, decreased the mitochondrial membrane potential (MMP) level, and increased the Fe2+ level in mitochondria. In addition, decreased ATP levels and increased reactive oxygen species (ROS) levels were observed in PC12 cells upon TDCPP exposure (0, 50, 100, and 200 μM) for 24 h. In summary, ferroptosis was associated with TDCPP-induced neurotoxicity, and the mechanism might be related to PINK1/PARKIN-mediated mitophagy initiated by mitochondrial damage.

HRMS screening of organophosphate flame retardants and poly-/perfluorinated substances in dust from cars and trucks: Occurrence and human exposure implications

Time spent within vehicles' cabin has been largely increased during the last years. As a result, the assessment of indoor dust quality is meaningful since dust can be a source of numerous emerging contaminants associated with adverse effects in human health. To this end, fourteen cars and ten trucks from the city of Thessaloniki, Northern Greece were selected to assess the quality of vehicles' microenvironments. An HRMS-based strategy was deployed for the target and non-target analysis of the collected samples. The target approach aimed at the accurate mass screening of nine organophosphate flame retardants (OPFRs) and nine per-/polyfluorinated compounds (PFAS), revealing mean concentrations for the OPFRs varied from <MQL–3409 ng/g for tris(1,3-dichloro-2-propyl) phosphate (TDCP), while the PFASs were either not detected (<MDL) or detected below the quantification limit (<MQL). To exploit the advanced technology of HRMS, a non-target analysis (NTA) workflow was also designed and employed, allowing the identification of 17 non-targets (plasticizers, PPCPs, pesticides and industrial chemicals) at identification confidence levels from 3 to 1. The statistical analysis between the positive findings and vehicles' conditions evidenced a possible of association just for individual cases. Lastly, a preliminary evaluation of human exposure to the target analytes was applied with the view to assess the potential harmful effects. All values were < 1 indicating no special effects because of exposure to this concentration level.

Biphasic effects of typical chlorinated organophosphorus flame retardants on Microcystis aeruginosa

The potential accumulation of chlorinated organophosphorus flame retardants (Cl-OPFRs) in aquatic environments sparked interest in studying the effects of Cl-OPFRs on cyanobacterial blooms. In this work, two common Cl-OPFRs, tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and tris(2-chloroethyl) phosphate (TCEP), induced dose-dependent biphasic effect on bloom-forming M. aeruginosa. The hormetic response to low-dose Cl-OPFRs was associated with the upregulation of the type I NADH dehydrogenase (NDH-1) complex and its mediated cyclic electron transfer (CET) pathway, as reflected by a transient post-illumination increase in chlorophyll fluorescence, the dark reduction of P700+ and the change of NDH-1-related gene expression. The increased CET activity and carotenoid content jointly reduced the intracellular ROS production, facilitating cyanobacterial growth. Conversely, a higher concentration of both Cl-OPFRs induced severe inhibition of growth and photosynthetic oxygen-evolving activity through an imbalance between PSII and PSI. Toxic-dose Cl-OPFRs inhibited state transition and fixed cells into the State I with a higher PSII/PSI ratio, as indicated by chlorophyll fluorescence induction, 77 K fluorescence emission spectra and photosystem stoichiometry. The elevated PSII/PSI ratio created an imbalance between the two photosystems and eventually lead to ROS overproduction, which generate adverse effects on cell growth. This work provides important insights into the hormetic mechanism of Cl-OPFRs on Microcystis aeruginosa and their potential roles in harmful cyanobacteria blooms.

Organophosphate flame retardant TDCPP: A risk factor for renal cancer?

Tris (1,3-dichloro-2-propyl) phosphate (TDCPP), a chlorinated organophosphate flame retardants(OPFRs), is widely used in a range of plastic foams, resins, and latexes. It can be detected in human tissues, including urine, and milk. Recent research has suggested that TDCPP has neurotoxic, reproductive, and potentially carcinogenic. In our study, we proposed a novel method for predicting the gene associated with tumor-compound interactions. We firstly used The Comparative Toxicogenomics Database (CTD) and downloaded potentially interactive genes about TDCPP in renal carcinoma. Gene expression data and the corresponding clinical information of the Kidney renal clear cell cancer (KIRC) patients were obtained from The Cancer Genome Atlas database (TCGA). Data from normal people in The Genotype‐Tissue Expression (GTEx) databases was used to supplement the calculations. After being predicted by PharmMapper database, and validated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, 25 genes were selected to construct protein-protein interaction network analysis. The prognostic value of these genes was evaluated with Kaplan-Meier analysis, and four interactive genes were selected. Gene set variation analysis and drug-target binding prediction proved the hub gene has a potential relationship with renal clear cell carcinoma. We then used the ChEA3 (Chip-X Enrichment Analysis, Version 3) database to predict the upstream of these interactive genes. Molecular docking was used to predict the binding of these transcription factors to TDCPP and interactive genes to TDCPP. Moreover, in cell lines and in vivo experiments demonstrated the cancer-promoting effect of TDCPP. The expression of the interactive genes was verified by qPCR and Western blot. Combining binding energy and qPCR results, we choose EPAS1 to verify its function in renal carcinoma cell lines. Our study provides a novel method to predict the potential interactive genes between TDCPP and renal cancer, which may reveal potential targets for the treatment and prevention of diseases.

Organelle specific fluorescent phenomics and transcriptomic profiling to evaluate cellular response to tris(1,3 dichloro 2 propyl)phosphate

Tris(1,3-dichloro-2-propyl)phosphate (TDCPP) has been suspected to cause toxicity invertebrates, but its phenotypic effects and the underlying regulatory mechanism have not been fully revealed. Generally, cellular responses tightly control and affect various phenotypes. The scope of the whole organism or cellular toxicological phenotyping, however, has been limited, and quantitative analysis methods using phenotype data have not been fully established. Here, we demonstrated that fluorescence imaging of sub-organelle-based phenomic analysis together with transcriptomic profiling can enable a comprehensive understanding of correlations between molecular and phenomic events. To reveal the cellular response to TDCPP exposure, we obtained three sub-organelle images as fluorescent phenotypes. Transcriptomic perturbation data were measured from the RNA-seq experiment, and both profiling results were analyzed together. Interestingly, organelle phenomic data showed a unique fluorescent intensity increase in the endoplasmic reticulum (ER), and pathway analysis using transcriptomic data also revealed that ER was significantly enriched in gene ontology terms. Following the series of analyses, RNA-seq data also revealed potential carcinogenic effects of TDCPP. Our multi-dimensional profiling approach for organophosphate chemicals can uniquely correlate phenotypic changes with transcriptomic perturbations.

Occurrence and distribution of organophosphate flame retardants in seawater and sediment from coastal areas of the East China and Yellow Seas

Organophosphates (OPEs) are manmade organic pollutants that are widely used as flame retardants, plasticizers, and antifoaming and hydraulic agents. In this study, seven OPEs in seawater and sediment from the Yellow Sea and East China Sea were determined to study the distribution and diffusion behavior, and to evaluate the environmental risks. The ΣOPEs in the seawater and sediments ranged from below the method detection limit (<MDL) to 497.40 ng/L and from < MDL to 66.50 ng/g dw, respectively. Tri-n-butyl phosphate (TnBP), tris-(1, 3-Dichloro-2-Propyl) phosphate (TDCPP), and tri-meta-cresyl phosphate (TmCP) were the dominant OPEs in the seawater and sediments. OPEs were mainly distributed in coastal areas and the South Yellow Sea, indicating that they are mainly affected by land-based pollution and ocean currents. Fugacity analysis shows that tri-para-cresyl phosphate (TpCP) was in a state of equilibrium, while TDCPP, TnBP, and TmCP other OPEs tended to diffuse from sediment to water. The diffusion behavior of OPEs is mainly affected by their chemical properties. Hazard quotient (HQ) values of TmCP and TpCP in sediment samples were >1.0, indicating high ecological risks to aquatic organisms.

Terrigenous export and ocean currents' diffusion of organophosphorus flame retardants along China's adjacent seas

High demands for but strict regulatory measures on Organophosphorus Flame Retardants (OPFRs) have resulted in mainland China transitioning from the region that imports OPRFs to one that exports these substances. Simultaneously, large quantities of terrigenous OPFRs have been exported to adjacent seas by the major river systems, particularly the Yangtze River. This study examined the presence of ten OPFRs in China's adjacent seas. High levels of OPFRs were observed in seas south of mainland China, with Tris (2-chloroethyl) phosphate (TCEP) and Tris (1,3-dichloro-2-propyl) phosphate (TDCPP) dominant. The terrigenous OPFRs were redistributed by the ocean surface currents, with OPFRs tending to accumulate in regions with lower current speed. The producers of OPFRs are mainly distributed along the Haihe, Yellow, and Yangtze river systems. The application of OPFRs to electric vehicle charging stations, charging connectors, and 5G infrastructure in the Chinese mainland will likely drive rapid growth in OPFR related industry in the future. The diffusion trend map of OPFR indicated that the Bohai Sea and the central northern Yellow Sea are at high risk of ecological damage in the spring. The offshore region of the north of the South China Sea tended to aggregate more OPFRs in summer. Regions of the OPFR aggregation effect were at a higher risk of ecological damage.

Organophosphorus Flame Retardant TDCPP Displays Genotoxic and Carcinogenic Risks in Human Liver Cells.

Tris(1,3-Dichloro-2-propyl)phosphate (TDCPP) is an organophosphorus flame retardant (OPFR) widely used in a variety of consumer products (plastics, furniture, paints, foams, and electronics). Scientific evidence has affirmed the toxicological effects of TDCPP in in vitro and in vivo test models; however, its genotoxicity and carcinogenic effects in human cells are still obscure. Herein, we present genotoxic and carcinogenic properties of TDCPP in human liver cells (HepG2). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and neutral red uptake (NRU) assays demonstrated survival reduction in HepG2 cells after 3 days of exposure at higher concentrations (100–400 μM) of TDCPP. Comet assay and flow cytometric cell cycle experiments showed DNA damage and apoptosis in HepG2 cells after 3 days of TDCPP exposure. TDCPP treatment incremented the intracellular reactive oxygen species (ROS), nitric oxide (NO), Ca2+ influx, and esterase level in exposed cells. HepG2 mitochondrial membrane potential (ΔΨm) significantly declined and cytoplasmic localization of P53, caspase 3, and caspase 9 increased after TDCPP exposure. qPCR array quantification of the human cancer pathway revealed the upregulation of 11 genes and downregulation of two genes in TDCPP-exposed HepG2 cells. Overall, this is the first study to explicitly validate the fact that TDCPP bears the genotoxic, hepatotoxic, and carcinogenic potential, which may jeopardize human health.

Similarities and differences among the responses to three chlorinated organophosphate esters in earthworm: Evidences from biomarkers, transcriptomics and metabolomics

The wide use of chlorinated organophosphate esters (Cl-OPEs) as additive flame retardants has aroused concern about their potential risks on ecosystem and human health. However, knowledge about the toxicity of Cl-OPEs on soil organisms remains limited. In this study, earthworms, Eisenia fetida, were exposed to three representative Cl-OPEs, i.e., tris(2-chloroethyl) phosphate (TCEP), tris(2-chloro-1-methylethyl) phosphate (TCPP), and tris(1,3-dichloro-2-propyl) phosphate (TDCPP) in artificial soil. Using a combination of biochemical indicators (biomarkers), transcriptomics, and metabolomics, we compared the Cl-OPE-induced toxicity to E. fetida and provide new insight into the related molecular mechanism. All three Cl-OPEs elicited immune defense by the earthworms, as evidenced by increased acid phosphatase and alkaline phosphatase activities, and the genes involved in immune-related pathways (e.g., lysosomal and interleukin-17 signaling pathways). Furthermore, no effects on acetylcholinesterase activity were observed among the three Cl-OPEs. However, the TCPP and TDCPP treatments significantly decreased the neurotransmitter serotonin, suggesting the potential neurotoxicity of Cl-OPEs. Although TCEP affected the genes involved in carbohydrate and amino acid metabolism, the changes in the corresponding metabolites were not statistically significant. In contrast, exposure to TCPP and TDCPP induced oxidative stress, and affected xenobiotic metabolism and energy metabolism, leading to the decreased body weight in E. fetida. Based on these toxic effects, TCPP and TDCPP were more severely toxic than TCEP, despite their structural similarity. Given that the use of TCEP has been tightly regulated, our results suggest the potentially toxic effects of TCPP and TDCPP should not be ignored in future risk assessments of flame retardants.

Tris(1,3-dichloro-2-propyl) phosphate reduces longevity through a specific microRNA-mediated DAF-16/FoxO in an unconventional insulin/insulin-like growth factor‑1 signaling pathway

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) has received concerns due to its frequent detection in environmental media and biological samples. Our previous study has indicated TDCPP reduced the lifespan of Caenorhabditis elegans (C. elegans) by triggering an unconventional insulin/insulin-like growth factor signaling (IIS) pathway. This study continued to investigate the possible deleterious effects of TDCPP relating to longevity regulation signal pathways and biological processes. Specifically, this study uniquely performed small RNA transcriptome sequencing (RNA-seq), focusing on the underlying mechanisms of TDCPP-reduced the longevity of C. elegans in-depth in microRNAs (miRNAs). Based on Small RNA-seq results and transcript levels of mRNA involved in the unconventional IIS pathway, a small interaction network of miRNAs-mRNAs following TDCPP exposure in C. elegans was preliminarily established. Among them, up-regulated miR-48 and miR-84 (let-7 family members) silence the mRNA of daf-16 (the crucial member of the FoxO family and pivotal regulator in longevity) via post-transcription and translation dampening abilities, further inhibit its downstream target metallothionein-1 (mtl-1), and ultimately contributed to the reduction of nematode longevity and locomotion behaviors. Meanwhile, the high binding affinities of TDCPP with miRNAs cel-miR-48–5p and cel-miR-84–5p strongly support their participation in the regulation of nematode mobility and longevity. These findings provide a comprehensive analysis of TDCPP-reduced longevity from the perspective of miRNAs.

Occurrence and dry deposition of organophosphate esters in atmospheric particles above the Bohai Sea and northern Yellow Sea, China

Levels of eleven organophosphate esters (OPEs) were measured in particle phase atmospheric samples collected at Bohai Sea and northern Yellow Sea in China. The concentration of ∑11OPEs in atmospheric particles ranged from 426 to 3933 pg/m3, with the mean concentration of 1412 pg/m3. Tris(1-chloro-2-propyl) phosphate (TCPP) and triphenyl-phosphine oxide (TPPO) were the most abundant OPE congeners measured, and the individual concentrations of trimethyl phosphate (TMP), tri-iso-butyl phosphate (TiBP), tri-n-butyl phosphate (TnBP), tris(1,3-dichloro-2-propyl) phosphate (TDCP), triphenyl phosphate (TPhP), 2-ethylhexyl diphenyl phosphate (EHDPP), TPPO and tri-m-cresyl phosphate (TMTP) in atmospheric particles above the Bohai Sea were higher than those above the northern Yellow Sea. The estimated atmospheric dry deposition fluxes ranged from 202 to 1869 ng/m2/day. Up to 18.3 ± 12.5 ton/year of OPEs can be loaded to the Bohai Sea.

Organophosphate ester plasticizers in edible fish from the Mediterranean Sea: Marine pollution and human exposure

Concentrations of organophosphate esters (OPEs) plasticizers were analysed in the present study. Fifty-five fish samples belonging to three highly commercial species, European sardine (Sardina pilchardus), European anchovy (Engraulis encrasicolus), and European hake (Merluccius merluccius), were taken from the Western Mediterranean Sea. OPEs were detected in all individuals, except for two hake samples, with concentrations between 0.38 and 73.4 ng/g wet weight (ww). Sardines presented the highest mean value with 20.5 ± 20.1 ng/g ww, followed by anchovies with 14.1 ± 8.91 ng/g ww and hake with 2.48 ± 1.76 ng/g ww. The lowest OPE concentrations found in hake, which is a partial predator of anchovy and sardine, and the higher δ15N values (as a proxy of trophic position), may indicate the absence of OPEs biomagnification. Eleven out of thirteen tested OPEs compounds were detected, being diphenyl cresyl phosphate (DCP) one of the most frequently detected in all the species. The highest concentration values were obtained for tris(1,3-dichloro-2-propyl) phosphate (TDClPP), trihexyl phosphate (THP), and tris(2-butoxyethyl) phosphate (TBOEP), for sardines, anchovies, and hakes, respectively. The human health risk associated with the consumption of these fish species showing that their individual consumption would not pose a considerable threat to public health regarding OPE intake.

Phosphorus Deficiency Promoted Hydrolysis of Organophosphate Esters in Plants: Mechanisms and Transformation Pathways.

The biotransformation of organophosphate esters (OPEs) in white lupin (Lupinus albus) and wheat (Triticum aestivum L.) was investigated in hydroponic experiments with different phosphorus (P)-containing conditions. The hydrolysis rates of OPEs followed the order of triphenyl phosphate (TPHP) > tri-n-butyl phosphate (TnBP) > tris(1,3-dichloro-2-propyl) phosphate (TDCPP). Hydrolysis of OPEs was accelerated at P-deficient conditions, and faster hydrolysis took place in white lupin than in wheat. Coincidingly, the production of acid phosphatase (ACP) in both plants was promoted, and much higher intracellular and extracellular ACPs were observed in white lupin under P-deficient conditions. In vitro experiments revealed that ACP was a key enzyme to hydrolyze OPEs. The hydrolysis rates of OPEs were significantly correlated with the Hirshfeld charges, calculated by density functional theory, of the oxygen atom in the single P-O bond. Using ultra-high-performance liquid chromatography coupled with Orbitrap Fusion mass spectrometer, 30 metabolites were successfully identified. Some of these metabolites, such as sulfate-conjugated products, hydration of cysteine-conjugated products of TPHP, and reductively dechlorinated metabolites of TDCPP, were observed for the first time in plants. It is noteworthy that OPEs may transform into many hydroxylated metabolites, and special attention should be paid to their potential environmental effects.

Screening ecological risk of pesticides and emerging contaminants under data limited conditions – Case study modeling urban and agricultural watersheds with OrganoFate

The increasing number of chemicals used by society requires accessible, easy to implement tools to perform screening-level ecological risk assessments. However, field data to calibrate and validate screening tools is challenging to obtain for many watersheds. Thus, the evaluation must be done under data limited conditions. Here we employ a fate and transport model, OrganoFate, to predict environmental concentrations of contaminants of emerging concern (CECs) as well as a number of pesticides. CECs evaluated include antibacterial compounds sulfamethoxazole and triclocarban and a flame-retardant tris(1,3-dichloro-2-propyl)phosphate (TDCPP). We also evaluated widely used pesticides chlorpyrifos, bifenthrin and esfenvalerate. We predict concentrations of the contaminants in high-risk watersheds which were dominated by either urban or agricultural development and have small aquatic compartments. Screening-level predictions were in good agreement with observed concentrations in surface water and sediment. Maximum predicted concentrations were close to the highest observed concentrations for CECs, only ~0.1 μg/L greater for sulfamethoxazole and triclocarban concentrations, and for TDCPP <5 μg/L higher. ChemFate was also employed to screen possible aquatic health impacts. Results demonstrated possible CEC aquatic health risk for TDCPP and triclocarban (risk quotients of 0.9 and 1.1 respectively). For pesticides, exceedance of effect (EC50) and lethal (LC50) endpoints was predicted for various taxonomic groups which include aquatic invertebrates, fish, amphibians, and benthic organisms.

Characterizing exposures to flame retardants, dioxins, and furans among firefighters responding to controlled residential fires.

Firefighters may encounter items containing flame retardants (FRs), including organophosphate flame retardants (OPFRs) and polybrominated diphenyl ethers (PBDEs), during structure fires. This study utilized biological monitoring to characterize FR exposures in 36 firefighters assigned to interior, exterior, and overhaul job assignments, before and after responding to controlled residential fire scenarios. Firefighters provided four urine samples (pre-fire and 3-h, 6-h, and 12-h post-fire) and two serum samples (pre-fire and approximately 23-h post-fire). Urine samples were analyzed for OPFR metabolites, while serum samples were analyzed for PBDEs, brominated and chlorinated furans, and chlorinated dioxins. Urinary concentrations of diphenyl phosphate (DPhP), a metabolite of triphenyl phosphate (TPhP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), a metabolite of tris(1,3-dichloro-2-propyl) phosphate (TDCPP), and bis(2-chloroethyl) phosphate (BCEtP), a metabolite of tris(2-chloroethyl) phosphate (TCEP), increased from pre-fire to 3-hr and 6-hr post-fire collection, but only the DPhP increase was statistically significant at a 0.05 level. The 3-hr and 6-hr post-fire concentrations of DPhP and BDCPP, as well as the pre-fire concentration of BDCPP, were statistically significantly higher than general population levels. BDCPP pre-fire concentrations were statistically significantly higher in firefighters who previously participated in a scenario (within the past 12 days) than those who were responding to their first scenario as part of the study. Similarly, firefighters previously assigned to interior job assignments had higher pre-fire concentrations of BDCPP than those previously assigned to exterior job assignments. Pre-fire serum concentrations of 2,3,4,7,8-pentachlorodibenzofuran (23478-PeCDF), a known human carcinogen, were also statistically significantly above the general population levels. Of the PBDEs quantified, only decabromodiphenyl ether (BDE-209) pre- and post-fire serum concentrations were statistically significantly higher than the general population. These results suggest firefighters absorbed certain FRs while responding to fire scenarios.

Cytotoxicity, mitochondrial impairment, DNA damage and associated mechanisms induced by tris(1,3-dichloro-2-propyl) phosphate and tris(2-butoxyethyl) phosphate in A549 cells

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and tris(2-butoxyethyl) phosphate (TBOEP), two of the most widely applied phosphorus-containing flame retardants (PFRs), have been shown to have adverse effects in different organisms, but their underlying toxicity mechanism remains to be elucidated. In the present study, the toxicological effects of TDCPP and TBOEP on human lung carcinoma (A549) cells and their associated mechanisms were investigated at the cellular, organelle and transcriptional levels. Cell Counting Kit-8 assay results showed that TDCPP and TBOEP reduced cell viability in a concentration-dependent manner. High-content screening assays showed that both PFRs caused mitochondrial impairment at the organelle level, decreasing the mitochondrial membrane potential and increasing the mitochondrial mass, and leading to increased cell cycle arrest-associated DNA damage that decreased the ratio of cells in S phase and increased the DNA content. In addition, oxidative stress was identified as a possible initial mechanistic process underlying PFR-induced cytotoxicity and mitochondrial impairment, as evidenced by intracellular reactive oxygen species and mitochondrial superoxide overproduction from environmentally relevant concentrations. Furthermore, p53 activation was shown to be involved in regulating DNA damage after A549 cell exposure to TDCPP and TBOEP. Quantitative PCR analyses showed that TDCPP and TBOEP triggered p53/p21-mediated cell cycle arrest pathways, indicating that these PFRs can activate p53, and promote associated functional repair. However, the p53/bax-mediated apoptosis pathway was not activated following exposure to PFRs at specific concentrations. Our results showed that TDCPP and TBOEP can cause cytotoxicity, mitochondrial impairment and cell cycle arrest-associated DNA damage in A549 cells, suggesting that oxidative stress is the initial molecular event by which these adverse outcomes are induced.