Chronic exposure to tris(1,3-dichloro-2-propyl) phosphate: Effects on intestinal microbiota and serum metabolism in rats.

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a widely used organophosphate ester that can adversely affect animal or human health. The intestinal microbiota is critical to human health. High-dose exposure to TDCIPP can markedly affect the intestinal ecosystem of mice, but the effects of long-term exposure to lower concentrations of TDCIPP on the intestinal flora and body metabolism remain unclear. In this study, TDCIPP was administered to Sprague-Dawley rats by gavage at a dose of 13.3 mg/kg bw/day for 90 days. TDCIPP increased the relative weight of the kidneys (P = 0.017), but had no effect on the relative weight of the heart, liver, spleen, lungs, testes, and ovaries (P > 0.05). 16 S rRNA gene sequencing revealed that long-term TDCIPP exposure affected the diversity, relative abundance, and functions of rat gut microbes. The serum metabolomics of the rats showed that TDCIPP can disrupt the serum metabolic profiles, result in the up-regulation of 26 metabolites and down-regulation of 3 metabolites, and affect multiple metabolic pathways in rat sera. In addition, the disturbed genera and metabolites were correlated. The functions of some disturbed gut microbes were consistent with the affected metabolic pathways in the sera, and these metabolic pathways were all associated with kidney disease, suggesting that TDCIPP may cause kidney injury in rats by affecting the intestinal flora and serum metabolism.

Compound-Specific Isotope Analysis Provides Direct Evidence for Identifying the Source of Residual Pesticides Diazinon and Procymidone in the Soil-Plant System.

Compound-specific isotope analysis stands as a promising tool for unveiling the behavior of pesticides in agricultural environments. Using the commercial formulations of persistent fungicide procymidone (PRO) and less persistent insecticide diazinon (DIA), respectively, we analyzed the concentration and carbon isotope composition (δ13C) of the residual pesticides through soil incubation experiments in a greenhouse (for 150 days) and lab conditions (for 50-70 days). Our results showed that the magnitude of δ13C variation depends on pesticide specificity, in which PRO in the soil exhibited little variation in δ13C values over the entire incubation times, while DIA demonstrated an increased δ13C value, with the extent of δ13C variability affected by different spiking concentrations, plant presence, and light conditions. Moreover, the pesticides extracted from soils were isotopically overlapped with those from crop lettuce. Ultimately, the isotope composition of pesticides could infer the degradation and translocation processes and might contribute to identifying the source(s) of pesticide formulation in agricultural fields.

The use of bispyridinium non-oxime analogues for the restoration of nerve agent impaired neuromuscular transmission in rat hemidiaphragms - Structure optimization.

Organophosphate pesticide poisoning challenges health care systems worldwide. Furthermore, nerve agents remain a continuous threat. The treatment options for organophosphate poisoning have virtually been unchanged for decades, relying on symptomatic treatment and the use of oximes to indirectly restore neuromuscular function. Hence, compounds targeting directly nicotinic acetylcholine receptors (nAChRs) might substantially improve treatment options. The current study investigated a series of bispyridinium analogues with a trimethylene or 2,2'-diethyloxy linker in a rat hemidiaphragm model, using indirect field stimulation. Methyl- and ethyl-substituted bispyridinium analogues restored neuromuscular function up to 37 ± 17% (MB419, a 3-methyl analogue) at a stimulation frequency of 20 Hz. The bispyridinium analogues with a 2- or 3-methyl group, or a 2- or 3-ethyl group, tended towards a higher restoration of neuromuscular function than those with a 4-methyl or 4-ethyl group, respectively. The current data can be used for future studies to optimize structure-based molecular modeling of compounds targeting the nAChR.

Acute intoxication with diisopropylfluorophosphate promotes cellular senescence in the adult male rat brain.

Acute intoxication with high levels of organophosphate (OP) cholinesterase inhibitors can cause cholinergic crisis, which is associated with acute, life-threatening parasympathomimetic symptoms, respiratory depression and seizures that can rapidly progress to status epilepticus (SE). Clinical and experimental data demonstrate that individuals who survive these acute neurotoxic effects often develop significant chronic morbidity, including behavioral deficits. The pathogenic mechanism(s) that link acute OP intoxication to chronic neurological deficits remain speculative. Cellular senescence has been linked to behavioral deficits associated with aging and neurodegenerative disease, but whether acute OP intoxication triggers cellular senescence in the brain has not been investigated. Here, we test this hypothesis in a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP). Adult male Sprague-Dawley rats were administered DFP (4 mg/kg, s.c.). Control animals were administered an equal volume (300 µL) of sterile phosphate-buffered saline (s.c.). Both groups were subsequently injected with atropine sulfate (2 mg/kg, i.m.) and 2-pralidoxime (25 mg/kg, i.m.). DFP triggered seizure activity within minutes that rapidly progressed to SE, as determined using behavioral seizure criteria. Brains were collected from animals at 1, 3, and 6 months post-exposure for immunohistochemical analyses of p16, a biomarker of cellular senescence. While there was no immunohistochemical evidence of cellular senescence at 1-month post-exposure, at 3- and 6-months post-exposure, p16 immunoreactivity was significantly increased in the CA3 and dentate gyrus of the hippocampus, amygdala, piriform cortex and thalamus, but not the CA1 region of the hippocampus or the somatosensory cortex. Co-localization of p16 immunoreactivity with cell-specific biomarkers, specifically, NeuN, GFAP, S100ß, IBA1 and CD31, revealed that p16 expression in the brain of DFP animals is neuron-specific. The spatial distribution of p16-immunopositive cells overlapped with expression of senescence associated ß-galactosidase and with degenerating neurons identified by FluoroJade-C (FJC) staining. The co-occurrence of p16 and FJC was positively correlated. This study implicates cellular senescence as a novel pathogenic mechanism underlying the chronic neurological deficits observed in individuals who survive OP-induced cholinergic crisis.

Determinants of urinary dialkyl phosphate metabolites in midlife women: the Study of Women's Health Across the Nation Multi-Pollutant Study (SWAN-MPS).

BACKGROUND: Biomonitoring data and determinants of urinary dialkylphosphate (DAP) metabolites, markers of organophosphate pesticides, in racially diverse, non-occupationally exposed populations are scarce. OBJECTIVE: This study evaluated urinary concentrations and potential determinants of DAP metabolites of organophosphate pesticides in a multi-site, multi-racial/ethnic cohort of women aged 45-56 years, the Study of Women's Health Across the Nation Multi-Pollutant Study (SWAN-MPS). METHODS: We analyzed 963 urine samples collected in 1999-2000, the baseline of SWAN-MPS for longitudinal studies, and quantified DAP metabolites, including dimethyl alkylphosphates (DMAPs): dimethylphosphate (DMP), dimethylthiophosphate (DMTP), dimethyldithiophosphate (DMDTP); and diethyl alkylphosphates (DEAPs): diethylphosphate (DEP), diethylthiophosphate (DETP), diethyldithiophosphate (DEDTP), using gas chromatography and triple quadrupole mass spectroscopy. Adjusted least squared geometric means (LSGMs) and 95% confidence intervals (CIs) were computed to compare DAP concentrations by socio-demographic, behavioral and dietary factors. RESULTS: The geometric means (geometric standard deviations) of total DAPs, DMAPs, and DEAPs were 141 (2.63) nmol/L, 102 (2.99) nmol/L, and 26.8 (2.46) nmol/L, respectively. Body mass index (BMI) was inversely associated with DMAPs and DEAPs: LSGM (95% CI) = 68.8 (55.7-84.9) and 21.0 (17.7-25.0) nmol/L for women with obesity vs. 102 (84.7-123) and 30.1 (25.7-35.1) nmol/L for women with normal/underweight, respectively. Fruit consumption was positively (74.9 (62.1-90.2) for less than 5-6 servings/week vs. 105 (84.8-130) nmol/L for 1 serving/day and more) whereas meat consumption was inversely associated with DMAPs (110 (95.0-128) for seldom vs. 82.3 (59.5-114) nmol/L for often consumption). Fresh apple consumption appears to be attributed to the DMAP differences. Alcohol consumption was positively associated with DEAPs (27.5 (23.1-32.7) for 2 drinks/week and more vs. 23.0 (20.0-26.6) nmol/L for less than 1 drink/month). Black women had higher concentrations of DEAPs compared with White women (27.3 (21.2-35.2) vs. 23.2 (20.2-26.7) nmol/L). IMPACT STATEMENT: Organophosphate pesticides (OPs) are synthetic chemicals and currently the most widely used type of insecticides. We examined multi-site, multi-ethnic cohort of midlife women in the U.S. that offers a unique opportunity to evaluate major determinants of OP exposure. We improved OP metabolite detection rates and obtained accurate concentrations using an improved analytical technique. Our findings suggest that consumptions of fruit, meat and alcohol are important determinants of OP exposure for midlife women. Higher concentrations of diethyl OP metabolites in Black women compared to White women, even after accounting for dietary intake, suggests additional, but unknown racial-ethnic differences that affect exposure.

Distribution patterns and origins of organophosphate esters in soils from different climate systems on the Tibetan Plateau.

Organophosphate esters (OPEs) are extensively applied in various materials as flame retardants and plasticizers, and have high biological toxicity. OPEs are detected worldwide, even in distant polar regions and the Tibetan Plateau (TP). However, few studies have been performed to evaluate the distribution patterns and origins of OPEs in different climate systems on the TP. This study investigated the distribution characteristics, possible sources, and ecological risks of OPEs in soils from the different climate systems on the TP and its surroundings. The total concentrations of OPEs in soil varied from 468 to 17,451 pg g-1 dry weight, with greater concentrations in southeast Tibet (monsoon zone), followed by Qinghai (transition zone) and, finally, southern Xingjiang (westerly zone). OPE composition profiles also differed among the three areas with tri-n-butyl phosphate dominant in the westerly zone and tris(2-butoxyethyl) phosphate dominant in the Indian monsoon zone. Correlations between different compounds and altitude, soil organic carbon, or longitude varied in different climate zones, indicating that OPE distribution originates from both long-range atmospheric transport and local emissions. Ecological risk assessment showed that tris(2-chloroethyl) phosphate and tri-phenyl phosphate exhibited medium risks in soil at several sites in southeast Tibet. Considering the sensitivity and vulnerability of TP ecosystems to anthropogenic pollutants, the ecological risks potentially caused by OPEs in this region should be further assessed.

Associations between organophosphate esters and bone mineral density in adults in the United States: 2011-2018 NHANES.

BACKGROUND: Organophosphate esters (OPEs) are used extensively as flame retardants and plasticizers. Laboratory studies have shown that OPEs exhibit osteotoxicity by inhibiting osteoblast differentiation; however, little is known about how OPEs exposure is associated with bone health in humans. OBJECTIVES: We conducted a cross-sectional study to investigate the association between OPEs exposure and bone mineral density (BMD) in adults in the United States using data from the 2011-2018 National Health and Nutrition Examination Survey (NHANES). METHODS: Multivariate linear regression models were used to assess the association between concentrations of individual OPE metabolites and BMDs. We also used the Bayesian kernel machine regression (BKMR) and quantile g-computation (qgcomp) models to estimate joint associations between OPE mixture exposure and BMDs. All the analyses were stratified according to gender. RESULTS: A total of 3546 participants (median age, 40 years [IQR, 30-50 years]; 50.11% male) were included in this study. Five urinary OPE metabolites with a detection rate of > 50% were analyzed. After adjusting for the potential confounders, OPE metabolite concentrations were associated with decreased total-body BMD and lumbar spine BMD in males, although some associations only reached significance for bis(1-chloro-2-propyl) phosphate (BCPP), dibutyl phosphate (DBUP), and bis(2-chloroethyl) phosphate (BCEP) (ß = -0.013, 95% CI: -0.026, -0.001 for BCPP and total-body BMD; ß = -0.022, 95% CI: -0.043, -0.0001 for DBUP and lumbar spine BMD; ß=-0.018, 95% CI: -0.034, -0.002 for BCEP and lumbar spine BMD). OPE mixture exposure was also inversely associated with BMD in males, as demonstrated in the BMKR and qgcomp models. CONCLUSIONS: This study provides preliminary evidence that urinary OPE metabolite concentrations are inversely associated with BMD. The results also suggested that males were more vulnerable than females. However, further studies are required to confirm these findings.

Malathion exposure may increase infertility risk among US Adults: Results from the 2015-2016 NHANES.

BACKGROUND AND PURPOSE: Organophosphate pesticides such as malathion are the most widely used pesticides. Despite endocrine-disrupting effects, there is a paucity of information regarding chronic exposure to non-persistent organopesticides such as malathion. The purpose of this study is to describe the exposure burden among U.S. residents as well as possible impacts on fertility. METHODS: Population-based data collected by the National Health and Nutrition Examination Survey (NHANES) between 2015 and 2016 were used to perform a retrospective analysis on urinary concentrations of malathion diacid. Samples were assessed from 1703 adult participants, statistically weighted to represent over 231 million individuals. General linear models were used to examine associations between exposure and reproductive health measures among pre-menopausal women. RESULTS: Detectable concentrations of malathion diacid were identified in 16.1 % (n = 254) of samples. Concentrations were higher among women who reported seeing a physician due to difficulties becoming pregnant (P < 0.001; r2 = 0.12) as well as among women who reported trying for at least a year to become pregnant (P < 0.001; r2 = 0.06). CONCLUSIONS: Exposure to malathion is associated with a history of reproductive health challenges among women.

Mixture toxicity study of two metal oxide nanoparticles and chlorpyrifos on Eisenia andrei earthworms.

Co-exposure soil studies of pollutants are necessary for an appropriate ecological risk assessment. Here, we examined the effects of two-component mixtures of metal oxide nanoparticles (ZnO NPs or goethite NPs) with the insecticide chlorpyrifos (CPF) under laboratory conditions in short-term artificial soil assays using Eisenia andrei earthworms. We characterized NPs and their mixtures by scanning electron microscopy, atomic force microscopy, dynamic light scattering and zeta potential, and evaluated effects on metal accumulation, oxidative stress enzymes, and neurotoxicity related biomarkers in single and combined toxicity assays. Exposure to ZnO NPs increased Zn levels compared to control in single and combined exposure (ZnO NPs + CPF) at 72 h and 7 days, respectively. In contrast, there was no indication of Fe increase in organisms exposed to goethite NPs. One of the most notable effects on oxidative stress biomarkers was produced by single exposure to goethite NPs, showing that the worms were more sensitive to goethite NPs than to ZnO NPs. Acetylcholinesterase and carboxylesterase activities indicated that ZnO NPs alone were not neurotoxic to earthworms, but similar degrees of inhibition were observed after single CPF and ZnO NPs + CPF exposure. Differences between single and combined exposure were found for catalase and superoxide dismutase (goethite NPs) and for glutathione S-transferase (ZnO NPs) activities, mostly at 72 h. These findings suggest a necessity to evaluate mixtures of NPs with co-existing contaminants in soil, and that the nature of metal oxide NPs and exposure time are relevant factors to be considered when assessing combined toxicity, as it may have an impact on ecotoxicological risk assessment.

Spatiotemporal patterns and deposition of organophosphate esters (OPEs) in air, foliage and litter in a subtropical forest of South China.

Recent studies revealed the un-negligible impact of airborne organophosphate esters (OPEs) on phosphorus (P)-limited ecosystems. Subtropical forests, the global prevalence P-limited ecosystems, contain canopy structures that can effectively sequester OPEs from the atmosphere. However, little is known about the behavior and fate of OPEs in subtropical forest ecosystem, and the impact on the P cycling in this ecosystem. OPE concentrations in the understory air (at two heights), foliage, and litterfall were investigated in a subtropical forest in southern China. The median ∑OPE concentrations were 3149 and 2489 pg/m3 in the upper and bottom air, respectively. Foliage exhibited higher ∑OPE concentrations (median = 386 ng/g dry weight (dw)) compared to litter (median = 267 ng/g dw). The air OPE concentrations were ordered by broadleaved forest > mixed forest > coniferous forest, which corresponds to the results of canopy coverage or leaf area index. The spatial variation of OPEs in foliage and litter was likely caused by the leaf surface functional traits. Higher OPE concentrations were found in the wet season for understory air while in the dry season for foliage and litter, which were attributed to the changes in emission sources and meteorological conditions, respectively. The inverse temporal variation suggests the un-equilibrium partitioning of OPEs between leaf and air. The OPE concentrations during the litter-incubation presented similar temporal trends with those in foliage and litter, indicating the strong interaction of OPEs between the litter layer and the near-soil air, and the efficient buffer of litter layer played in the OPEs partitioning between soil and air. The median OPEs-associated P deposition fluxes through litterfall were 270, 186, and 249 µg P/m2·yr in the broadleaved, mixed, and coniferous forests, respectively. Although the fluxes accounted for approximately 0.2% of the total atmospheric P deposition, their significance to this P-limited ecosystem may not be negligible.

Estimated daily intake and cumulative risk assessment of organophosphate esters and associations with DNA damage among e-waste workers in Hong Kong.

Organophosphate esters (OPEs) are extensively used as additives in various products, including electronic equipment, which becomes e-waste when obsolete. Nevertheless, no study has evaluated OPEs exposure levels and the related health risks among e-waste workers in Hong Kong. Therefore, 201 first-spot morning urine samples were collected from 101 e-waste workers and 100 office workers to compare eight urinary OPE metabolites (mOPEs) levels in these groups. The concentrations of six mOPEs were similar in e-waste workers and office workers, except for significantly higher levels of diphenyl phosphate (DPHP) in e-waste workers and bis(1-chloro-2propyl) phosphate (BCIPP) in office workers. Spearman correlation analysis showed that most non-chlorinated mOPEs were correlated with each other in e-waste workers (i.e., nine out of ten pairs, including di-p-cresyl phosphate (DpCP) and di-o-cresyl phosphate (DoCP), DpCP and bis(2-butoxyethyl) phosphate (BBOEP), DpCP and DPHP, DpCP and dibutyl phosphate (DBP), DoCP and BBOEP, DoCP and DPHP, DoCP and DBP, BBOEP and DPHP, DPHP and DBP), indicating that handling e-waste could be the exposure source of specific OPEs. The median values of estimated daily intake (EDI) and hazard quotient (HQ) suggested that the health risks from OPEs exposures were under the recommended thresholds. However, linear regression models, Quantile g-computation, and Bayesian kernel machine regression found that urinary mOPEs elevated 8-hydroxy-2-deoxyguanosine (8-OhdG) levels individually or as a mixture, in which DPHP contributed prominently. In conclusion, although e-waste might not elevate the internal OPEs levels among the participating Hong Kong e-waste workers, attention should be paid to the potential DNA damage stimulated by OPEs under the currently recommended thresholds.

Cholesterol Oxime Olesoxime Assessed as a Potential Ligand of Human Cholinesterases.

Olesoxime, a cholesterol derivative with an oxime group, possesses the ability to cross the blood-brain barrier, and has demonstrated excellent safety and tolerability properties in clinical research. These characteristics indicate it may serve as a centrally active ligand of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), whose disruption of activity with organophosphate compounds (OP) leads to uncontrolled excitation and potentially life-threatening symptoms. To evaluate olesoxime as a binding ligand and reactivator of human AChE and BChE, we conducted in vitro kinetic studies with the active metabolite of insecticide parathion, paraoxon, and the warfare nerve agents sarin, cyclosarin, tabun, and VX. Our results showed that both enzymes possessed a binding affinity for olesoxime in the mid-micromolar range, higher than the antidotes in use (i.e., 2-PAM, HI-6, etc.). While olesoxime showed a weak ability to reactivate AChE, cyclosarin-inhibited BChE was reactivated with an overall reactivation rate constant comparable to that of standard oxime HI-6. Moreover, in combination with the oxime 2-PAM, the reactivation maximum increased by 10-30% for cyclosarin- and sarin-inhibited BChE. Molecular modeling revealed productive interactions between olesoxime and BChE, highlighting olesoxime as a potentially BChE-targeted therapy. Moreover, it might be added to OP poisoning treatment to increase the efficacy of BChE reactivation, and its cholesterol scaffold could provide a basis for the development of novel oxime antidotes.

Flame Retardant Exposure in Vehicles Is Influenced by Use in Seat Foam and Temperature.

Flame retardants (FRs) are added to vehicles to meet flammability standards, such as US Federal Motor Vehicle Safety Standard FMVSS 302. However, an understanding of which FRs are being used, sources in the vehicle, and implications for human exposure is lacking. US participants (n = 101) owning a vehicle of model year 2015 or newer hung a silicone passive sampler on their rearview mirror for 7 days. Fifty-one of 101 participants collected a foam sample from a vehicle seat. Organophosphate esters (OPEs) were the most frequently detected FR class in the passive samplers. Among these, tris(1-chloro-isopropyl) phosphate (TCIPP) had a 99% detection frequency and was measured at levels ranging from 0.2 to 11,600 ng/g of sampler. TCIPP was also the dominant FR detected in the vehicle seat foam. Sampler FR concentrations were significantly correlated with average ambient temperature and were 2-5 times higher in the summer compared to winter. The presence of TCIPP in foam resulted in ∼4 times higher median air sampler concentrations in winter and ∼9 times higher in summer. These results suggest that FRs used in vehicle interiors, such as in seat foam, are a source of OPE exposure, which is increased in warmer temperatures.

Exposure to resorcinol bis (diphenyl phosphate) induces colonization of alien microorganisms with potential impacts on the gut microbiota and metabolic disruption in male zebrafish.

Organophosphate esters (OPEs) have been demonstrated to induce various forms of toxicity in aquatic organisms. However, a scarcity of evidence impedes the conclusive determination of whether OPEs manifest sex-dependent toxic effects. Here, we investigated the effects of tris (1-chloro-2-propyl) phosphate (TCPP) and resorcinol bis (diphenyl phosphate) (RDP) on the intestines of both female and male zebrafish. The results indicated that, in comparison to TCPP, RDP induced more pronounced intestinal microstructural damage and oxidative stress, particularly in male zebrafish. 16S rRNA sequencing and metabolomics revealed significant alterations in the species richness and oxidative stress-related metabolites in the intestinal microbiota of zebrafish under exposure to both TCPP and RDP, manifesting gender-specific effects. Based on differential species analysis, we defined invasive species and applied invasion theory to analyze the reasons for changes in the male fish intestinal community. Correlation analysis demonstrated that alien species may have potential effects on metabolism. Overall, this study reveals a pronounced gender-dependent impact on both the intestinal microbiota and metabolic disruptions of zebrafish due to OPEs exposure and offers a novel perspective on the influence of pollutants on intestinal microbial communities and metabolism.

Baseline physiological data from anesthetized pigs in a VX intoxication model.

Over the past fifty years, swine models have been used for organophosphorus intoxication studies. Among these studies and others on the swine model in general, some physiological data, especially cholinesterase activity highly impacted by organophosphorus compounds like nerve agent VX, still need to be completed. To support and compare our model to others, we have published the experimental protocol, the physiological values of 31 juvenile anesthetized pigs, and the 6h-follow-up of six supplementary anesthetized control animals and 7 VX-intoxicated pigs. We reported hemodynamics and respiratory parameters, blood levels in several biochemical parameters, blood gas, and complete blood count and compared them to the literature. We also focused on tissue and blood cholinesterase activities and detailed them for acetylcholinesterase and butyrylcholinesterase. After establishing a broad physiological data set consistent with the literature, we reported several cardio-respiratory parameters that seem more affected by an organophosphate intoxication, like heart rate, arterial blood pressure, cardiac output, and respiratory rate. Within the blood, oxygen saturation (SpO2), lactatemia, base excess, and glycemia can also be measured and associated with the other parameters to evaluate the life-threatening status. This swine model is currently used to develop and evaluate medical countermeasures against organophosphate nerve agent intoxications.

Exposure to organophosphate esters and maternal-child health.

Organophosphate esters (OPEs) are a class of chemicals now widely used as flame retardants and plasticizers after the phase-out of polybrominated diphenyl ethers (PBDEs). However, OPEs carry their own risk of developmental toxicity, which poses concern for recent birth cohorts as they have become ubiquitous in the environment. In this review, we summarize the literature evaluating the association between OPE exposure and maternal, perinatal, and child health outcomes. We included original articles investigating associations of OPE exposure with any health outcome on pregnant women, newborns, children, and adolescents. We found 48 articles on this topic. Of these, five addressed maternal health and pregnancy outcomes, 24 evaluated prenatal OPE exposure and child health, 18 evaluated childhood OPE exposure and child/adolescent health, and one article evaluated both prenatal and childhood OPE exposure. These studies suggest that OPE exposure is possibly associated with a wide range of adverse health outcomes, including pregnancy loss, altered gestational duration and smaller birthweight, maternal and neonatal thyroid dysfunction, child metabolic dysregulation and abnormal growth, impaired neurodevelopment, and changes in immune response. Many of the reported outcomes associated with OPE exposure varied by child sex. Findings also varied substantially by OPE metabolite and exposure time. The OPEs most frequently measured, detected, and found to be associated with health outcomes were triphenyl phosphate (TPHP, metabolized to DPHP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP, metabolized to BDCIPP). The extensive range of health outcomes associated with OPEs raises concern about their growing use in consumer products; however, these findings should be interpreted considering the limitations of these epidemiological studies, such as possible exposure misclassification, lack of generalizability, insufficient adjustment for covariates, and failure to consider chemical exposures as a mixture.

Organophosphate pesticide residue impact on water quality and changes in macroinvertebrate community in an Afrotropical stream flowing through farmlands.

River Chanchaga has experienced significant agricultural practices around its catchment, which involved the indiscriminate use of pesticides. However, residents of the study area are not well aware of the negative impact of pesticides on water quality and macroinvertebrates. In this study, the first report on the influence of organophosphate pesticide contamination on the abundance of the macroinvertebrate community was provided. Sampling for the determination of organophosphate pesticide residues was carried out during the peak of the two seasons, while macroinvertebrates and physicochemical variables were observed for 6 months. We examined 11 organophosphate pesticide residues using gas chromatography coupled with mass spectrometry, 12 water quality variables, and 625 macroinvertebrate individuals. The concentration of recorded organophosphate pesticide residues ranged from 0.01 to 0.52 µg/L. From the Canonical Correspondence Analysis plot, malathion, chlorine, and paraffin show a positive correlation with Unima sp., Hydrocanthus sp., Chironomus sp., and Potadoma sp. At station 3, depth shows a positive correlation with Biomphalaria sp. and Zyxomma sp., indicating poor water quality as most of these macroinvertebrates are indicators of water pollution. Diuron and carbofuran show a negative correlation with Lestes sp. and Pseudocloeon sp., and these are pollution-sensitive macroinvertebrates. The total mean concentration of organophosphate pesticide residues was above international drinking water standards set by the World Health Organization except for paraffin, chlorpyrifos, and diuron. In conclusion, the observations recorded from this research are useful in managing pesticide applications around the river catchment.

Global responses to tris(1-chloro-2-propyl) phosphate and tris(2-butoxyethyl) phosphate in Escherichia coli: Evidences from biomarkers, and metabolic disturbance using GC-MS and LC-MS metabolomics analyses.

Tris(1-chloro-2-propyl) phosphate (TCPP) and tris(2-butoxyethyl) phosphate (TBEP) as pollutants of emerging concern have aroused the rising attention due to their potential risks on aquatic ecosystem and public health. Nevertheless, there is a lack of toxicological mechanisms exploration of TCPP and TBEP at molecular levels. Herein, the toxicity effects and molecular mechanism of them were fully researched and summarized on Escherichia coli (E.coli). Acute exposure to them significantly activated antioxidant defense system and caused lipid peroxidation, as proved by the changes of antioxidant enzymes and MDA. The ROS overload resulted in the drop of membrane potential as well as the downregulated synthesis of ATPase, endorsing that E. coli cytotoxicity was ascribed to oxidative stress damage induced by TCPP and TBEP. The combination of GC-MS and LC-MS based metabolomics validated that TCPP and TBEP induced metabolic reprogramming in E.coli. More specifically, the responsive metabolites in carbohydrate metabolism, lipids metabolism, nucleotide metabolism, amino acid metabolism, and organic acids metabolism were significantly disturbed by TCPP and TBEP, confirming the negative effects on metabolic functions and key bioprocesses. Additionally, several biomarkers including PE(16:1(5Z)/15:0), PA(17:1(9Z)/18:2(9Z,12Z)), PE(19:1(9Z)/0:0), and LysoPE(0:0/18:1(11Z)) were remarkably upregulated, verifying that the protection of cellular membrane was conducted by regulating the expression of lipids-associated metabolites. Collectively, this work sheds new light on the potential molecular toxicity mechanism of TCPP and TBEP on aquatic organisms, and these findings using GC-MS and LC-MS metabolomics generate a fresh insight into assessing the effects of OPFRs on target and non-target aquatic organisms.

Temporal trends of plastic additive contents in sediment cores of three French rivers (Loire, Meuse and Moselle) over the last decades.

Sediment cores from three major French watersheds (Loire, Meuse and Moselle) have been dated by 137Cs and 210Pbxs from 1910 (Loire), 1947 (Meuse) and 1930 (Moselle) until the present in order to reconstruct trajectories of plastic additive contaminants including nine phthalate esters (PAEs) and seven organophosphate esters (OPEs), measured by gas chromatography-mass spectrometer (GC-MS-MS). Historical levels of ∑PAEs were higher than those of ∑OPEs in the Loire and the Moselle sediments, while ∑PAEs and ∑OPEs contents were of the same order of magnitude in the Meuse sediments. Although increases in concentrations do not evolve linearly, our results clearly indicate an increase in OPEs and PAEs concentrations from the 1950-1970 period onwards, compared with the first half of the 20th century. Our results show that, ∑OPE contents increase gradually over time in the Loire and Meuse rivers but evolve more randomly in the Moselle River. Trajectories of ∑PAEs depend on the river and no generality can be established, suggesting sedimentary reworking and/or local contamination. Data from this study allowed comparisons of contents of ∑OPEs and ∑PAEs between rivers, with ∑OPE concentrations in the Moselle River > Meuse River > Loire River, and concentrations of ∑PAEs in the Loire River > Moselle River > Meuse River. Among all PAEs, di(2-ethylhexyl) phthalate (DEHP) was the most abundant in all sediment samples, followed by diisobutyl phthalate (DiBP). Tris (2-chloroisopropyl) phosphate (TCPP) was the most abundant OPE in sediments of the three rivers. In addition, strong positive Pearson correlations were observed between organic matter (OM) parameters and OPE concentrations, and to a lesser extent, between OM parameters and PAE concentrations. This is particularly true for the Moselle River and for the Loire River, but less so for the Meuse River.