Search Results (56)

This study presents an advanced analytical method for the simultaneous quantification of malondialdehyde (MDA), a biomarker of oxidative stress, and diphenyl phosphate (DPhP), a metabolite of the organophosphate flame retardant triphenyl phosphate (TPhP), in human urine. The method integrates hydrophilic interaction liquid chromatography (HILIC), a type of liquid chromatography suitable for polar compounds, for MDA separation, and an online restricted access material (RAM), a preconcentration column, for DPhP isolation, achieving high specificity and sensitivity. Validation with certified urine samples confirmed its robustness across diverse analyte concentrations and complex biological matrices. The optimized clean-up steps effectively minimized carryover, allowing for high-throughput analysis. Application to 72 urine samples revealed a significant positive correlation (ρ = 0.702, p-value = 1.9 × 10⁻⁷) between MDA and DPhP levels, supporting a potential link between oxidative stress and TPhP exposure. The subset analysis demonstrated a statistically significant moderate positive correlation in women (ρ = 0.622, p-value = 0.020), although this result should be interpreted with caution because of the limited sample size (N = 14). This method provides a powerful tool for biomonitoring oxidative stress and environmental contaminants, offering valuable insights into exposure-related health risks. Full article

Organophosphorus (OP) pesticides are a class of chemicals that are extensively used worldwide. The exposure to and use of organophosphates can be assessed by analyzing their metabolites and degradation products, such as dialkyl phosphate (DAP), dialkyl thiophosphate (DATP), and dialkyl dithiophosphate (DADTP). However, since these metabolites/hydrolysis products can result from the metabolism or breakdown of several organophosphorus pesticide families, they serve as nonspecific biomarkers and do not indicate the specific pesticide involved in exposure. In an earlier study, chemical derivatization using N-(2-(bromomethyl)benzyl)-N,N-diethylethanaminium bromide (CAX-B) was described to improve the signal intensity of numerous organophosphorus (OP) acids in liquid chromatography tandem mass spectrometry (LC-ESI-MS/MS) analysis. In the present study, CAX-B was employed to derivatize a set of seven phenolic compounds corresponding to the complementary portion of OP pesticides. The derivatization process using CAX-B was performed in acetonitrile with potassium carbonate at 50 °C for 30 min. LC-Orbitrap-ESI-MS/MS was used to analyze the resulting phenol derivatives and their fragmentation patterns were studied. Notably, the derivatized phenols were markedly more sensitive than the underivatized phenols when LC-ESI-MS/MS was used in MRM technique, without being affected by the sample matrix (soil or plant extracts). This derivatization technique aids in identifying OP pesticides, offers insights into their subfamily, and pinpoints a specific compound through the analysis of corresponding phenol derivative. Full article

In 2020, California banned the sale and agricultural use of chlorpyrifos, an organophosphate pesticide (OP) associated with neurotoxicity and other adverse health outcomes. We primarily assessed changes in chlorpyrifos associated with this policy and secondarily explored how other OP exposures changed. The participants were from California’s Central Valley, 18 years or older, and English- or Spanish-speaking. The surveys and urine samples were collected pre-ban (December 2020) and post-ban (February–April 2022). The urine samples were analyzed for a chlorpyrifos-specific metabolite (TCPy), six dialkyl phosphates (DEP, DMTP, DETP, DMDTP, DMP, DEDTP), and total DE and DM. The pre- and post-ban metabolite concentrations were compared via Wilcoxon signed-rank tests and natural log-transformed paired differences in linear mixed effects regression, adjusted for covariates. Forty-nine participants had repeated biomarker data. The mean age of the study population was 46.8 years (SD: 16), 61% female, 67% Spanish-speaking, 100% Hispanic/Latino(a), and 47% had less than a high school education. Six urinary metabolites (TCPy, DEP, DMP, DMTP, total DE and total DM) had sufficient variation for further analysis, while DMDTP, DEDTP, and DETP were undetected. The paired differences in adjusted models showed statistically significant increases in TCPy and DMP associated with the policy change (e.g., TCPy estimated ratio of geometric means: 4.53 (95% CI 2.66, 7.69)) Reductions in metabolites of chlorpyrifos exposure were not observed following California’s chlorpyrifos ban, suggesting ongoing exposure to chlorpyrifos from other sources. Full article

Pesticides are compounds of major use in agriculture worldwide. Nevertheless, many pesticide chemicals are classified as endocrine disruptors and potentially carcinogens. Farmers and farmworkers are particularly exposed and are at high risk of developing health-related impairments. In Morocco, the lack of awareness towards pesticide hazards and the inappropriate application of safety measures might increase the exposure as well as the risks of health concerns. In this paper, we present the framework of a study designed to assess pesticide exposure among Moroccan farmers and farmworkers and to evaluate potential health effects, namely endocrine and epigenetic impacts. Human biological monitoring will be conducted to determine pesticide levels in urine following the development and validation of sensitive chromatography methods (SPE, UPLC-MS/MS). Biomarkers of exposure include a set of parent and metabolite pesticide compounds (organophosphates, pyrethroids, triazines and urea-based pesticides). Thyroid and reproductive hormones (TSH, T₃, T₄, FSH and LH) as well as global and specific DNA methylation markers (5-mC, 5-hmC, N⁶-mA, THRB and LHR) are selected as biomarkers of effects. This provides guiding steps and methods to perform reliable exposure evaluation and health impact assessment. This study aims to expand the current knowledge on the endocrine and epigenetic risks related to pesticides, especially in low- and middle-income countries. Full article

The phosphorus-31 (³¹P) spectral modulus (PSM) is a measure of the metabolic status of cells, tissues, and organs. The PSM can be calculated from ³¹P nuclear magnetic resonance (³¹P NMR) spectra obtained from cell, tissue, or organ preparations. These ³¹P NMR spectra can be a measure of intact living cells, tissues, or organs, or appropriate biochemical extracts of such preparations. The ³¹P NMR spectrum is comprised of signals derived from organophosphate metabolites that resonate from 10 δ to −25 δ on the phosphorus chemical shift δ scale. The PSM is the ratio of the high-energy phosphate to that of the low-energy phosphate spectral integrals. These integrals may be conveniently grouped into high-energy and low-energy spectral regions, respectively, into ³¹P chemical shifts located between −0.13 δ to −25 δ and between 10 δ to −0.13 δ. High-energy phosphates are typically described as providing the energy necessary for the activity of cellular metabolism; chemically, they contain one or more phosphate anhydride bonds. This study demonstrates that, (1) in general, the higher the metabolic activity, the higher the PSM, and (2) the modulus calculation does not require a highly resolved ³¹P spectrum and can be calculated solely from the integral. The PSM was calculated among cells, tissues, and organs considered normal, diseased, and stressed. In diseased (mean 1.29 ± 0.73) and stressed (mean 1.23 ± 0.75) cells, tissues, and organs, PSM values are typically low or low relative to normal cells, tissues, or organs (mean 1.65 ± 0.90), following time-course measurements, in dynamic decline. The PSM is useful in determining the metabolic status of cells, tissues, or organs and can be employed as a calculable numeric assay for determining health status statically or over time. Calculation of the PSM can be carried out with spectra of low signal-to-noise; it relies on the minimal resolution required to detect an integral curve having a clear spectral integral inflection point at ca. −0.13 δ. Detection of an integral curve alone enables the calculation of a PSM even at levels of phosphorus concentration so low as to prevent detection of the individual or groups of metabolites, such as with in vivo or ex vivo cell, tissue, or organ determinations. This study (1) presents the foundations and fundamentals of the PSM, a living index of tissue metabolic health, and (2) demonstrates the use of spectral scan analysis in opening new vistas of biology and medicine for measuring the metabolic status of stressed and diseased tissues at a range of detectable levels for monitoring therapeutic interventions. Full article

Using NHANES data from 2003 to 2008, 2011 to 2012, and 2015 to 2020, we examined the relationship between urinary organophosphate pesticide (OPP) metabolites and the triglyceride glucose (TyG) index. The TyG index evaluates insulin resistance, a crucial factor in metabolic diseases. Linear regression analyzed urinary metabolites in relation to the TyG index and OPPs. An RCS (restricted cubic spline) model explored the nonlinear relationship of a single OPP metabolite to TyG. A weighted quantile regression and quantile-based g-computation assessed the impact of combined OPP exposure on the TyG index. XGBoost, Random Forest, Support Vector Machines, logistic regression, and SHapley Additive exPlanations models investigated the impact of OPPs on the TyG index and cardiovascular disease. Network toxicology identified CVD targets associated with OPPs. This study included 4429 participants based on specific criteria. Linear regression analysis indicated that diethyl thiophosphate was positively correlated with the TyG index. The positive correlation between OPP metabolites and the TyG index at low to moderate concentrations was confirmed by WQS and QGC analyses. The machine learning results aligned with traditional statistical findings. Network toxicology identified PTGS3, PPARG, HSP40AA1, and CXCL8 as targets influenced by OPPs. OPP exposure influences IR and cardiometabolic health, highlighting the importance of public health prevention. Full article

Biomonitoring allows for the assessment of internal exposure to various pesticides and metabolites. Following PRISMA guidelines, this systematic review aims to summarise innovative biomonitoring techniques for assessing pesticide exposure in agricultural workers, their advantages and limitations, and their applicability. The search of the Medline/PubMed, ScienceDirect, Scopus, and Web of Science databases identified 14 articles dealing with new techniques for biomonitoring pesticide exposure in agricultural workers. These new methodologies have identified several biomarkers associated with exposure to organophosphates. Most of the included studies combine and/or improve traditional methods to overcome their limitations. This leads to more sensitive, specific, and precise techniques with lower detection and quantification limits. Therefore, it is necessary to thoroughly analyse and test new biomonitoring methods for assessing pesticide exposure. These techniques can complement qualitative risk assessments and aid in developing strategies to protect public health and the environment. Full article

Objectives: Growing evidence suggests a link between organophosphate insecticides and depression disorder. These chemicals are metabolized and subsequently expelled through the urinary tract. The present study aims to investigate whether dialkyl phosphate metabolites associate with depression score and severity among the general population. Methods: This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES). Depression was evaluated by the Patient Health Questionnaire-9 (PHQ-9). All urinary dialkyl phosphate metabolites were quantitatively analyzed. The survey’s complex design parameters and sampling weights were considered. Results: 3035 eligible individuals were included. The estimated prevalence of mild and major depression was 18.3% (95% confidence interval [CI]: 16.9–19.7%) and 9.9% (95% CI: 8.7–11.0%). For each incremental unit in the level of urinary dimethyl phosphate (DMP), individuals were found to have a higher depression score of 0.77 and a significantly increased odds ratio (OR) of 1.13 (95% CI: 1.12–1.13) for mild depression and 2.75 (95% CI: 2.74–2.76) for major depression. Conclusions: Our findings indicate positive and independent associations between urinary dialkyl phosphate metabolites and an elevated risk of depression among the general population. Full article

Evidence of the effects of postnatal exposure to organophosphates (OPs) on children’s neurodevelopment remains limited but crucial. This cross-sectional study evaluated exposure to OPs and neurobehavioral performance in 172 preschool children. Urinary dialkyl phosphate (DAP) metabolites, biomarkers for exposure to OPs, were measured. The neurobehavioral assessments included motor skills, memory, and cognitive function, measured using the Purdue pegboard test, digit span test, object memory test, and visual-motor integration. Multiple linear regression models were employed to explore the associations between urinary DAP metabolite levels and neurobehavioral performance, adjusting for potential confounders. Findings revealed that children of farming parents had higher urinary levels of dimethylphosphate (DMP) (Beta = 0.730, 95% CI = 0.138, 1.322, p value = 0.016) and diethylphosphate (DEP) (Beta = 0.668, 95% CI = 0.044, 1.291, p value = 0.036). Additionally, high fruit consumption correlated with increased urinary DEP levels (Beta = 0.398, 95% CI = 0.063, 0.733, p value = 0.020). Critically, elevated urinary DEP was associated with poorer fine motor coordination, affecting performance in the Purdue pegboard test for the dominant hand (Beta = −0.428, 95% CI = −0.661, −0.194, p value < 0.001), the preferred hand (Beta = −0.376, 95% CI = −0.603, −0.149, p value = 0.001), and both hands (Beta = −0.524, 95% CI = −0.773, −0.276, p value < 0.001). These findings highlight the role of parental occupation and diet in children’s OP exposure and suggest that OP exposure negatively impacts fine motor coordination. Targeted interventions, such as promoting organic diets, enhancing workplace safety, and ongoing biomonitoring, are vital to reduce neurodevelopmental risks for vulnerable populations. Full article

Adenosine triphosphate (ATP) has a high intracellular millimolar concentration (ca. 2.4 mM) throughout the phylogenetic spectrum of eukaryotes, archaea, and prokaryotes. In addition, the function of ATP as a hydrotrope in the prevention of protein aggregation and maintenance of protein solubilization is essential to cellular, tissue, and organ homeostasis. The ³¹P spectral modulus (PSM) is a measure of the health status of cell, tissue, and organ systems, as well as of ATP, and it is based on in vivo ³¹P nuclear magnetic resonance (³¹P NMR) spectra. The PSM is calculated by dividing the area of the ³¹P NMR integral curve representing the high-energy phosphates by that of the low-energy phosphates. Unlike the difficulties encountered in measuring organophosphates such as ATP or any other phosphorylated metabolites in a conventional ³¹P NMR spectrum or in processed tissue samples, in vivo PSM measurements are possible with NMR surface-coil technology. The PSM does not rely on the resolution of individual metabolite signals but uses the total area derived from each of the NMR integral curves of the above-described spectral regions. Calculation is based on a simple ratio of the high- and low-energy phosphate bands, which are conveniently arranged in the high- and low-field portions of the ³¹P NMR spectrum. In practice, there is essentially no signal overlap between these two regions, with the dividing point being ca. −3 δ. ATP is the principal contributor to the maintenance of an elevated PSM that is typically observed in healthy systems. The purpose of this study is to demonstrate that (1) in general, the higher the metabolic activity, the higher the ³¹P spectral modulus, and (2) the modulus calculation does not require highly resolved ³¹P spectral signals and thus can even be used with reduced signal-to-noise spectra such as those detected as a result of in vivo analyses or those that may be obtained during a clinical MRI examination. With increasing metabolic stress or maturation of metabolic disease in cells, tissues, or organ systems, the PSM index declines; alternatively, with decreasing stress or resolution of disease states, the PSM increases. The PSM can serve to monitor normal homeostasis as a diagnostic tool and may be used to monitor disease processes with and without interventional treatment. Full article

Background: Organophosphate flame retardants (OPFRs) are compounds with a wide range of industrial and commercial applications and are mainly used as flame retardants and plasticizers. The global consumption of OPFRs has risen rapidly in recent decades, and they have been widely detected in environmental media. Unfortunately, OPFRs have been associated with many adverse health outcomes. The issue of the health risks of OPFRs is attracting increasing attention. Therefore, there is a need to review the current state of research and trends in this field to help researchers and policymakers quickly understand the field, identify new research directions, and allocate appropriate resources for further development of the OPFR health risk research field. Methods: This study statistically analyzed 1162 relevant publications included in the Web of Science Core Collection from 2003–2023. The internal and external features of the literature, such as publication trends, countries, authors, journals, and keywords, were quantitatively analyzed and visually presented to identify the research hotspots, compositions, and paradigms of the field and to horizontally and vertically analyze the development trends and structural evolution of the field. Results: The development of the field can be divided into three stages, and the field entered a period of rapid development in 2016. China (649 papers) is the most prolific country, followed by the United States (188 papers). The authors STAPLETON HM and WANG Y have the highest combined impact. International collaboration between countries and researchers still needs to be strengthened. Science of The Total Environment is the most frequently published journal (162 papers), and Environmental Science and Technology is the most frequently cited journal (5285 citations). Endocrine disruption, developmental toxicity, and neurotoxicity are the health effects of greatest interest. Conclusions: Future research is expected to be multidisciplinary, and research hotspots may involve a comprehensive assessment of OPFR exposure in the population, exploration of the mechanisms of endocrine-disrupting effects and in vivo metabolic processes, and examination of the health effects of OPFR metabolites. Full article

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. Full article

As emerging pollutants, organophosphate esters (OPEs) have been reported in coastal environments worldwide. Nevertheless, information on the occurrence and ecological risks of OPEs, especially the related transformation products, in mangrove wetlands is scarce. For the first time, the coexistence and distribution of OP triesters and their transformation products in three mangrove wetlands in the Beibu Gulf were investigated using ultrasonication and solid-phase extraction, followed by UHPLC-MS/MS detection. The studied OPEs widely existed in all the sampling sites, with the total concentrations ranging from 6.43 ng/g dry weight (dw) to 39.96 ng/g dw and from 3.33 ng/g dw to 22.50 ng/g dw for the OP triesters and transformation products, respectively. Mangrove wetlands tend to retain more OPEs than the surrounding coastal environment. Pearson correlation analysis revealed that the TOC was not the sole factor in determining the OPEs’ distribution, and degradation was not the main source of the transformation products in mangrove sediments in the Beibu Gulf. The ecological risks of selected OPEs for different organisms were also assessed, revealing a medium to high risk posed by OP diesters to organisms. The levels or coexistence of OPEs and their metabolites in mangroves need constant monitoring, and more toxicity data should be further studied to assess the effect on normal aquatic organisms. Full article

The waste of electrical and electronic equipment (WEEE) is generally considered a secondary raw material for the recovery of valuable components. However, emerging issues regarding the impact of suspended particles arising from WEEE recycling operations are a concern. It was recently demonstrated that samples from three different WEEE plants were rich in organophosphate flame retardants (OPFRs). Since exposure to a xenobiotic can lead to its biotransformation through human metabolism routes, in the present study, the metabolism of eight OPFRs of interest in our sampling campaign (triphenyl phosphate (TPhP), tri-m-tolyl phosphate (TMTP), ethylhexyl diphenyl phosphate (EHDPhP), tributoxyethyl phosphate (TBOEP), diphenyl phosphate (DPhP), trichloroethyl phosphate (TCEP), tris(1,3-dichloropropan-2-yl) phosphate (TDClPP) and bisphenol A bis(diphenyl phosphate) (BDP)) was investigated. Their metabolism was studied at different time points in three matrices: human liver microsomes, human hepatocytes and human skin microsomes. This study, which was run using a common experimental setting, allowed easy comparison of results for each OPFR of interest, and a comparison with other data in the literature was performed. In particular, a number of metabolites not previously described were detected, and for the first time, it was shown that TPhP could be metabolized in human skin microsomes. Full article

The knowledge of the effects of organophosphate flame retardants on children’s neurodevelopment is limited. The purpose of the present research is to evaluate the association between exposure to organophosphate flame retardants and children’s neurodevelopment in two European cohorts involved in the Human Biomonitoring Initiative Aligned Studies. The participants were school-aged children belonging to the Odense Child Cohort (Denmark) and the PCB cohort (Slovakia). In each cohort, the children’s neurodevelopment was assessed through the Full-Scale Intelligence Quotient score of the Wechsler Intelligence Scale for Children, using two different editions. The children’s urine samples, collected at one point in time, were analyzed for several metabolites of organophosphate flame retardants. The association between neurodevelopment and each organophosphate flame retardant metabolite was explored by applying separate multiple linear regressions based on the approach of MM-estimation in each cohort. In the Danish cohort, the mean ± standard deviation for the neurodevelopment score was 98 ± 12; the geometric mean (95% confidence interval (95% CI)) of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) standardized by creatinine (crt) was 0.52 µg/g crt (95% CI = 0.49; 0.60), while that of diphenyl phosphate (DPHP) standardized by crt was 1.44 µg/g crt (95% CI = 1.31; 1.58). The neurodevelopment score showed a small, negative, statistically imprecise trend with BDCIPP standardized by crt (β = −1.30; 95%CI = −2.72; 0.11; p-value = 0.07) and no clear association with DPHP standardized by crt (β = −0.98; 95%CI = −2.96; 0.99; p-value = 0.33). The neurodevelopment score showed a negative trend with BDCIPP (β = −1.42; 95% CI = −2.70; −0.06; p-value = 0.04) and no clear association with DPHP (β = −1.09; 95% CI = −2.87; 0.68; p-value = 0.23). In the Slovakian cohort, the mean ± standard deviation for the neurodevelopment score was 81 ± 15; the geometric mean of BDCIPP standardized by crt was 0.18 µg/g crt (95% CI = 0.16; 0.20), while that of DPHP standardized by crt was 2.24 µg/g crt (95% CI = 2.00; 3.52). The association of the neurodevelopment score with BDCIPP standardized by crt was −0.49 (95%CI = −1.85; 0.87; p-value = 0.48), and with DPHP standardized by crt it was −0.35 (95%CI = −1.90; 1.20; p-value = 0.66). No clear associations were observed between the neurodevelopment score and BDCIPP/DPHP concentrations that were not standardized by crt. No clear associations were observed with bis(1-chloro-2-propyl) phosphate (BCIPP) in either cohort, due to the low detection frequency of this compound. In conclusion, this study provides only limited evidence of an inverse association between neurodevelopment and exposure to BDCIPP and DPHP. The timing of exposure and effect modification of other organophosphate flame retardant metabolites and other substances should be the subject of further investigations that address this scientific hypothesis. Full article