Chlorpyrifos is widely used across the world as an organophosphate insecticide and frequently contaminates freshwater bodies through runoff from agricultural fields. In the laboratory, static bioassays were undertaken to examine differences in acute toxicity caused by exposure to the technical grade (94% a.i.) and an emulsifiable concentrate (20% EC) of chlorpyrifos to two species of freshwater fish, Labeo rohita and Mystus vittatus. The recovery of actual chlorpyrifos concentrations varied from 83% (technical grade, T) to 89% (emulsifiable concentrate, F) after two hours in water. The susceptibilities of the two fish species to the two types of chlorpyrifos varied. The 96-h LC50 values for T and F chlorpyrifos in L. rohita were 68 and 36 µg/L, respectively, and 120 and 62 µg/L in M. vittatus, respectively. As the exposure period was extended, the LC50 values gradually decreased. LC50 values between the technical grade and formulation were compared following the criteria of Mayer et al. (1986), Schmuck et al. (1994), APHA (1995), and Demetrio et al. (2014). It was concluded from the study that the emulsifiable concentrate (20% EC) of chlorpyrifos was more toxic than technical-grade chlorpyrifos.

The triggers of status epilepticus (SE) in non-epileptic patients can vary widely, from idiopathic causes to exposure to chemoconvulsants. Regardless of its etiology, prolonged SE can cause significant brain damage, commonly resulting in the development of epilepsy, which is often accompanied by increased anxiety. GABAA receptor (GABAAR)-mediated inhibition has a central role among the mechanisms underlying brain damage and the ensuing epilepsy and anxiety. During SE, calcium influx primarily via ionotropic glutamate receptors activates signaling cascades which trigger a rapid internalization of synaptic GABAARs; this weakens inhibition, exacerbating seizures and excitotoxicity. GABAergic interneurons are more susceptible to excitotoxic death than principal neurons. During the latent period of epileptogenesis, the aberrant reorganization in synaptic interactions that follow interneuronal loss in injured brain regions, leads to the formation of hyperexcitable, seizurogenic neuronal circuits, along with disturbances in brain oscillatory rhythms. Reduction in the spontaneous, rhythmic \"bursts\" of IPSCs in basolateral amygdala neurons is likely to play a central role in anxiogenesis. Protecting interneurons during SE is key to preventing both epilepsy and anxiety. Antiglutamatergic treatments, including antagonism of calcium-permeable AMPA receptors, can be expected to control seizures and reduce excitotoxicity not only by directly suppressing hyperexcitation, but also by counteracting the internalization of synaptic GABAARs. Benzodiazepines, as delayed treatment of SE, have low efficacy due to the reduction and dispersion of their targets (the synaptic GABAARs), but also because themselves contribute to further reduction of available GABAARs at the synapse; furthermore, benzodiazepines may be completely ineffective in the immature brain.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

Organophosphate esters (OPEs) serve as significant flame retardants and plasticizers in various petrochemical downstream products. The petrochemical industry could be a potential source of atmospheric OPEs, but their emissions from this industry are poorly understood. The present study revealed the spatial variation, emission, and atmospheric transport of traditional and novel OPEs (TOPEs and NOPEs, respectively) in atmospheric particulate matter (PM) across Hainan and Guangdong petrochemical complexes (HNPC and GDPC, respectively) in southern China. The total concentrations of TOPEs ranged from 232 to 46,002 pg/m3 and from 200 to 20,347 pg/m3 in the HNPC and GDPC, respectively, which were substantially higher than those of NOPEs (HNPC: 23.5-147 pg/m3, GDPC: 13.9-465 pg/m3). Enterprises involved in the production of downstream petrochemical products presented relatively high concentrations of OPEs, indicating evident emissions of these pollutants in the petrochemical industry. The correlations of PM-bound OPEs in the atmosphere are determined mainly by their coaddition to industrial products or their coexistence in technical mixtures. The annual emissions of TOPEs and NOPEs in the HNPC were 42.6 kg and 0.34 kg, respectively, and those in the GDPC were 116 kg and 1.85 kg, respectively. OPEs from the HNPC can reach Vietnam, Cambodia, and Guangxi Province, China, and those from the GDPC can reach Guangxi Province and Hunan Province via atmospheric transmission after 24 h of emission. The OPE concentrations reaching the receptor regions were generally less than 3.20 pg/m3. Risk assessment revealed that OPE inhalation exposure on two petrochemical complexes likely poses minor risks for people living in the study areas, but the risk resulting from two chlorinated OPEs should be noted since they are close to the threshold values. This study has implications for enhancing control measures for OPE emissions to reduce health risks related to the petrochemical industry.

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.

This study investigated the capability of electromembrane extraction (EME) as a general technique for peptides, by extracting complex pools of peptides comprising in total of 5953 different substances, varying in size from seven to 16 amino acids. Electromembrane extraction was conducted from a sample adjusted to pH 3.0 and utilized a liquid membrane consisting of 2-nitrophenyl octyl ether and carvacrol (1:1 w/w), containing 2% (w/w) di(2-ethylhexyl) phosphate. The acceptor phase was 50 mM phosphoric acid (pH 1.8), the extraction time was 45 min, and 10 V was used. High extraction efficiency, defined as a higher peptide signal in the acceptor than the sample after extraction, was achieved for 3706 different peptides. Extraction efficiencies were predominantly influenced by the hydrophobicity of the peptides and their net charge in the sample. Hydrophobic peptides were extracted with a net charge of +1, while hydrophilic peptides were extracted when the net charge was +2 or higher. A computational model based on machine learning was developed to predict the extractability of peptides based on peptide descriptors, including the grand average of hydropathy index and net charge at pH 3.0 (sample pH). This research shows that EME has general applicability for peptides and represents the first steps toward in silico prediction of extraction efficiency.

Numerous studies worldwide have evaluated pesticide residues detected in urine. This review serves as a contribution to this field by presenting an overview of scientific research studies published from 2001 to 2023, including details of study characteristics and research scope. Encompassing 72 papers, the review further delves into addressing key challenges in study design and method used such as sampling and analytical approaches, results adjustments, risk assessment, estimations, and results evaluation. The review explores urinary concentrations and detection frequency of metabolites of organophosphates and pyrethroids, as well as herbicides such as 2,4-D and glyphosate and their metabolites, across various studies. The association of the results with demographic and lifestyle variables were explored. While farmers generally have higher pesticide exposure, adopting organic farming practices can reduce the levels of pesticides detected in their urine. Residence close to agricultural areas has shown high exposure in some cases. Dietary exposure is especially high among people adopting a conventionally grown plant-rich dietary pattern. A higher detection level and frequency of detection are generally found in females and children compared to males. The implications of transitioning to organic and sustainable plant-rich diets for reducing pesticide exposure and potential health benefits for both adults and children require further investigation.

With the development of large numbers of novel organophosphate esters (OPEs) alternatives, it is imperative to screen and identify those with high priority. In this study, surface water, biofilms, and freshwater snails were collected from the flow-in rivers of Taihu Lake Basin, China. Screened by target, suspect, and nontarget analysis, 11 traditional and 14 novel OPEs were identified, of which 5 OPEs were first discovered in Taihu Lake Basin. The OPE concentrations in surface water ranged from 196 to 2568 ng/L, with the primary homologue tris(2,4-ditert-butylphenyl) phosphate (TDtBPP) being newly identified, which was likely derived from the transformation of tris(2,4-ditert-butylphenyl) phosphite. The majority of the newly identified OPEs displayed substantially higher bioaccumulation and biomagnification potentials in the biofilm-snail food chain than the traditional ones. Quantitative structure-property relationship models revealed both hydrophobicity and polarity influenced the bioaccumulation and biomagnification of the OPEs, while electrostatic attraction also had a contribution to the bioaccumulation in the biofilm. TDtBPP was determined as the utmost priority by toxicological priority index scheme, which integrated concentration, bioaccumulation, biomagnification, acute toxicity, and endocrine disrupting potential of the identified OPEs. These findings provide novel insights into the behaviors of OPEs and scientific bases for better management of high-risk pollutants in aquatic ecosystem.

As an important class of detoxifying enzymes, glutathione S-transferases (GSTs) are pivotal in decreasing insecticide toxicity to insects. Periplaneta americana GSTd1 (PaGSTd1) has been verified as a key enzyme in detoxifying pyrethroid insecticides, but its detoxification capability against a broader spectrum of insecticides has never been investigated. It is revealed that PaGSTd1 expression showed a rapid and significant increase upon exposure to various insecticides (organophosphates, neonicotinoids, and fipronil). Subsequent in vitro metabolic assays indicated that organophosphates, particularly chlorpyrifos-methyl, can be effectively metabolized by PaGSTd1. Further knockdown of PaGSTd1 via RNA interference significantly heightened the susceptibility of P. americana to chlorpyrifos-methyl, underscoring the enzyme\'s key role in detoxifying chlorpyrifos-methyl. Additionally, this study confirmed that PaGSTd1 cannot mitigate insecticide toxicity through countering oxidative stress. Collectively, these findings elucidate the involvement of PaGSTd1 in the detoxification processes for organophosphates, offering a comprehensive insight into the metabolic mechanisms mediated by GSTs in P. americana. This research provides a foundational understanding for managing GSTs-mediated metabolic resistance in this species, which is crucial for effective pest control strategies.

The aim was to study associations between dialkylphosphates (DAPs), organophosphate (OP) metabolites in urine, biomarkers of OP insecticide exposure, and respiratory symptoms among children in upper northern Thailand. We recruited junior high school children in randomly selected schools in four cities (N = 337), with repeated data collection in wet and dry seasons. Urine was collected and analyzed for six OP metabolites, with creatinine adjustment. Total DAP was expressed as sum of DAPs. Data on respiratory symptoms was collected by a standardized questionnaire. Associations were analyzed by multiple logistic regression. Totally 11.3 % lived in farm families. Total DAPs concentration was higher in dry season (p = 0.002) but did not differ between farm and non-farm children. Total DAPs in wet season was associated with current wheeze (p = 0.019), current asthma attacks (p = 0.012) and attacks of breathlessness in last 12 months (p = 0.021). Total DAPs in dry season was associated with current wheeze (p = 0.042), and associations between DAPs and respiratory symptoms were stronger for dimethylphosphate metabolites (DMPs) than for diethylphosphate metabolites (DEPs). DMPs are produced by certain OP pesticides. Biomass burning inside or outside the home, and dampness or mold at home, enhanced the association between total DAPs and attacks of breathlessness. In conclusion, OP pesticide exposure, measured as urinary DAPs, was higher in dry season and similar in farm and non-farm children. OPs exposure, especially to DMP related pesticides, can increase asthmatic symptoms, especially in wet season. Combined exposure to OP and smoke from biomass burning, or dampness and mold, can further increase the prevalence of attacks of breathlessness. There is a need to reduce OP insecticide and biomass smoke exposure among Thai children. Since different pesticides can be used in different seasons, studies on respiratory health effects of OPs pesticide exposure should be done in different seasons.