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Rural and Remote Health Jan 2020Organophosphates are a class of insecticides used globally by the agricultural industry for insect control. Acute consequences of organophosphate exposures are well... (Review)
Review
INTRODUCTION
Organophosphates are a class of insecticides used globally by the agricultural industry for insect control. Acute consequences of organophosphate exposures are well known, while there has been limited research on their long-term effects. The objective of this review was to discuss the health effects of chronic organophosphate exposure in farmers.
METHODS
Medline, Scopus and Web of Science were searched to find the relevant articles. Articles published only in English and until December 2018 were reviewed. The selected articles were then categorised as neurological (neurobehaviour, neurodevelopmental, neurological signs and symptoms) or non-neurological subheadings.
RESULTS
A total of 53 articles for neurological effects and 17 articles for non-neurological effects were identified. Chronic organophosphates exposure was associated with deficits in the neurobehaviour subsets of attention and short-term memory, increased incidence of neurodegenerative diseases and effects on peripheral nerves and neurodevelopment. However, research to support non-neurological effects such as respiratory symptoms, increased cancer risk, endocrine disruption, cardiac issues, chronic fatigue and infertility was limited.
CONCLUSION
Chronic organophosphate exposure was found to affect four of the five areas of described neurological effects in the literature. A large proportion of the research in this area was not methodologically strong, therefore few recommendations can be conclusively made. Future research is warranted to investigate the non-neurological effects of chronic exposure to ensure the occupational risks of low-level chronic exposure are clearly communicated to farmers and farm workers.
Topics: Agricultural Workers' Diseases; Farmers; Humans; Insecticides; Occupational Exposure; Organophosphates
PubMed: 31902214
DOI: 10.22605/RRH4508 -
Viruses May 2021Viral entry into host cells is a critical step in the viral life cycle. HIV-1 entry is mediated by the sole surface envelope glycoprotein Env and is initiated by the... (Review)
Review
Viral entry into host cells is a critical step in the viral life cycle. HIV-1 entry is mediated by the sole surface envelope glycoprotein Env and is initiated by the interaction between Env and the host receptor CD4. This interaction, referred to as the attachment step, has long been considered an attractive target for inhibitor discovery and development. Fostemsavir, recently approved by the FDA, represents the first-in-class drug in the attachment inhibitor class. This review focuses on the discovery of temsavir (the active compound of fostemsavir) and analogs, mechanistic studies that elucidated the mode of action, and structural studies that revealed atomic details of the interaction between HIV-1 Env and attachment inhibitors. Challenges associated with emerging resistance mutations to the attachment inhibitors and the development of next-generation attachment inhibitors are also highlighted.
Topics: Animals; Anti-HIV Agents; HIV Infections; HIV-1; Humans; Organophosphates; Piperazines; Virus Internalization
PubMed: 34066522
DOI: 10.3390/v13050843 -
Environmental Research Jun 2023Organophosphate esters (OPEs) are used as flame retardants and plasticizers in various consumer products. Limited prior research suggests sex-specific effects of...
Sex-specific effects of prenatal organophosphate ester (OPE) metabolite mixtures and adverse infant birth outcomes in the maternal and developmental risks from environmental and social stressors (MADRES) pregnancy cohort.
BACKGROUND
Organophosphate esters (OPEs) are used as flame retardants and plasticizers in various consumer products. Limited prior research suggests sex-specific effects of prenatal OPE exposures on fetal development. We evaluated overall and sex-specific associations between prenatal OPE exposures and gestational age (GA) at birth and birthweight for gestational age (BW for GA) z-scores among the predominately low-income, Hispanic MADRES cohort.
METHODS
Nine OPE metabolite concentrations were measured in 421 maternal urine samples collected during a third trimester visit (GA = 31.5 ± 2.0 weeks). We examined associations between single urinary OPE metabolites and GA at birth and BW for GA z-scores using linear regression models and Generalized Additive Models (GAMs) and effects from OPE mixtures using Bayesian Kernel Machine Regression (BKMR). We also assessed sex-specific differences in single metabolite analyses by evaluating statistical interactions and stratifying by sex.
RESULTS
We did not find significant associations between individual OPE metabolites and birth outcomes in the full infant sample; however, we found that higher bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) was associated with earlier GA at birth among male infants (p = 0.04), and a nonlinear, inverted U-shape association between the sum of dibutyl phosphate and di-isobutyl phosphate (DNBP + DIBP) and GA at birth among female infants (p = 0.03). In mixtures analysis, higher OPE metabolite mixture exposures was associated with lower GA at birth, which was primarily driven by female infants. No associations were observed between OPE mixtures and BW for GA z-scores.
CONCLUSION
Higher BDCIPP and DNBP + DIBP concentrations were associated with earlier GA at birth among male and female infants, respectively. Higher exposure to OPE mixtures was associated with earlier GA at birth, particularly among female infants. However, we saw no associations between prenatal OPEs and BW for GA. Our results suggest sex-specific impacts of prenatal OPE exposures on GA at birth.
Topics: Pregnancy; Infant, Newborn; Humans; Male; Infant; Female; Bayes Theorem; Organophosphates; Phosphates; Flame Retardants; Esters
PubMed: 36934865
DOI: 10.1016/j.envres.2023.115703 -
Chemical Communications (Cambridge,... Mar 2022A new supramolecular approach to broad spectrum antivirals utilizes host guest chemistry between molecular tweezers and lysine/arginine as well as choline. Basic amino... (Review)
Review
A new supramolecular approach to broad spectrum antivirals utilizes host guest chemistry between molecular tweezers and lysine/arginine as well as choline. Basic amino acids in amyloid-forming SEVI peptides (semen-derived enhancers of viral infection) are included inside the tweezer cavity leading to disaggregation and neutralization of the fibrils, which lose their ability to enhance HIV-1/HIV-2 infection. Lipid head groups contain the trimethylammonium cation of choline; this is likewise bound by molecular tweezers, which dock onto viral membranes and thus greatly enhance their surface tension. Disruption of the envelope in turn leads to total loss of infectiosity (ZIKA, Ebola, Influenza). This complexation event also seems to be the structural basis for an effective inihibition of cell-to-cell spread in Herpes viruses. The article describes the discovery of novel molecular recognition motifs and the development of powerful antiviral agents based on these host guest systems. It explains the general underlying mechanisms of antiviral action and points to future optimization and application as therapeutic agents.
Topics: Amyloidosis; Antiviral Agents; Bridged-Ring Compounds; Humans; Organophosphates; Viral Envelope; Viruses
PubMed: 35170594
DOI: 10.1039/d1cc06737k -
Chemosphere Dec 2022Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers worldwide. Therefore, the potentially deleterious effect of OPE on human beings...
Association of organophosphate ester exposure with cardiovascular disease among US adults: Cross-sectional findings from the 2011-2018 National Health and Nutrition Examination Survey.
Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers worldwide. Therefore, the potentially deleterious effect of OPE on human beings deserves extensive attention. The primary objective of this present study was to untangle the relationship between OPE exposure and cardiovascular disease (CVD) among general population. Detailed information about participants' baseline characteristics, involving socioeconomic data, demographic data and key covariates was obtained from National Health and Nutrition Examination Survey (NHANES) 2011-2018. Multivariate logistic regression models with adjustment for prior-determined covariates were utilized to examine the relationship between various OPEs and CVD among US adults and calculate odd ratios (ORs) and corresponding confidence intervals (CIs). Two multi-pollutant statistical strategies (weighted quantile sum regression and Bayesian kernel machine regression) were employed to investigate the joint effect of OPE mixture on CVD. A total of 5067 participants were included in this study. In completely-adjusted logistic model, the highest tertiles of OPE metabolites were positively associated with CVD risk, while the relationships did not reach statistical significance. The weighted quantile sum (WQS) index was significantly correlated with increased prevalence of CVD (adjusted OR: 1.25; CI: 1.02, 1.53, p value = 0.032) and Diphenyl phosphate (DPHP) was the greatest contributor (31.38%). The BKMR also indicated that mixed OPE exposure associated with an increased risk of CVD. Taken together, the present study demonstrated that there were possible links between OPE exposures and increased risk of CVD, while the relationships did not reach statistical significance. Our study provided the suggestive evidence that cumulative effect of OPE mixtures on CVD. DPHP may be a major driver of this positive association. Given the limitation of cross-sectional design and relatively limited kinds of OPE metabolites, further studies are warranted to longitudinally evaluate the potential effect of a wider range of OPEs on CVD or cardiac metabolism.
Topics: Adult; Bayes Theorem; Biphenyl Compounds; Cardiovascular Diseases; Cross-Sectional Studies; Environmental Pollutants; Esters; Flame Retardants; Humans; Nutrition Surveys; Organophosphates; Phosphates; Plasticizers
PubMed: 36115470
DOI: 10.1016/j.chemosphere.2022.136428 -
Pharmaceutical Research May 2020Hemolysis is a serious side effect of antitumor alkylphospholipids (APLs) that limits dose levels and is a constraint in their use in therapeutic regimen. Nine prodrugs...
PURPOSE
Hemolysis is a serious side effect of antitumor alkylphospholipids (APLs) that limits dose levels and is a constraint in their use in therapeutic regimen. Nine prodrugs of promising APLs (miltefosine, perifosine, and erufosine) were synthesized so as to decrease their membrane activity and improve their toxicity profile while preserving their antineoplastic potency.
METHODS
The synthesis of the pro-APLs was straightforwardly achieved in one step starting from the parent APLs. The critical aggregation concentration of the prodrugs, their hydrolytic stability under various pH conditions, their blood compatibility and cytotoxicity in three different cell lines were determined and compared to those of the parent antitumor lipids.
RESULTS
The APL prodrugs display antitumor activity which is similar to that of the parent alkylphospholipids but without associated hemolytic toxicity.
CONCLUSION
The pro-APL compounds may be considered as intravenously injectable derivatives of APLs. They could thus address one of the major issues met in cancer therapies involving antitumor lipids and restricting their utilization to oral and topical administration because of limited maximum tolerated dose.
Topics: Administration, Intravenous; Antineoplastic Agents; Cell Line, Tumor; Drug Screening Assays, Antitumor; Drug Stability; Hemolysis; Humans; Maximum Tolerated Dose; Neoplasms; Organophosphates; Phosphorylcholine; Prodrugs; Quaternary Ammonium Compounds
PubMed: 32462253
DOI: 10.1007/s11095-020-02830-y -
The Science of the Total Environment Jun 2022Organophosphate esters (OPEs) have been extensively used as flame retardants and/or plasticizers and they found to be ubiquitous in various environmental matrices along...
Organophosphate esters and their diester metabolites in infant formulas and baby supplementary foods collected in Beijing, China: Occurrence and the implications for infant exposure.
Organophosphate esters (OPEs) have been extensively used as flame retardants and/or plasticizers and they found to be ubiquitous in various environmental matrices along with the gradual phase-out of brominated flame retardants (BFRs). Moreover, their main metabolites, organophosphate di-esters (di-OPEs), were also frequently detected. However, few studies focused on the occurrence of OPEs and di-OPEs in foods. In this study, fourteen OPEs and five di-OPEs were measured in infant formula and baby supplementary food (BSF) collected in Beijing, China. Most OPEs and di-OPEs presented high detection frequencies, which indicated their ubiquity in baby foods. The concentrations of ∑OPEs in the 75 infant formula samples ranged from 0.79 to 159 ng/g, with a median of 23.2 ng/g, and in which triphenyl phosphate (TPhP) was the most abundant compound. The concentrations of ∑OPEs in the 32 BSF samples were 4.42-115 ng/g (median: 19.5 ng/g), and tri(3-chloropropyl) phosphate (TCIPP) was predominant. Moreover, no significant difference was observed between OPE levels in infant formula and BSF. The median concentrations of Σdi-OPEs in infant formula and BSF were 3.39 and 5.43 ng/g, respectively. However, no significantly correlation was observed between concentrations of di-OPEs and their parent compounds, which indicated they have different sources. The median estimated dietary intakes (EDIs) of the ∑OPEs were from 165 to 383 ng/kg bodyweight (bw)/day for infants via infant formula feeding, and were from 429 to 470 ng/kg bw/day via BSF feeding. A comparison to corresponding reference dose (RfD) suggested that dietary intakes of OPEs to Beijing infants via formula/BSF consumption were still unable to cause significant health concerns. However, EDIs of OPEs for infants were found to be significantly higher than that for Chinese adults, and dietary intake might be the predominant OPE intake pathway for infants. To our knowledge, this is the first study to investigate OPEs and their metabolites in baby foods.
Topics: Beijing; China; Environmental Monitoring; Esters; Flame Retardants; Humans; Infant Formula; Organophosphates
PubMed: 35247416
DOI: 10.1016/j.scitotenv.2022.154272 -
Molecular Informatics Aug 2019In March 2018 the term Novichok (Hoвичoκ) became publically known following an attempted murder of a former Russian spy in Salisbury, UK. Novichok is the name of a...
In March 2018 the term Novichok (Hoвичoκ) became publically known following an attempted murder of a former Russian spy in Salisbury, UK. Novichok is the name of a group of nerve agents secretly produced by Russia in the later stages of the Cold War. These compounds were never declared under the Chemical Weapons Convention and very little is known about the actual identity and characteristics of these compounds. Structures of some of the Novichoks have been reported by a former Russian chemist, Vil Mirzayanov, previously working at the Russian State Scientific Research Institute of Organic Chemistry and Technology (GOSNIIOKhT). It was in this context claimed that at least two compounds of the Novichok family, known as Novichok-5 and Novichok-7 were 5-8 times more potent than the hitherto most toxic nerve agent, VX. The present study elucidates, applying a series of QSAR models toxicity, skin permeation, pharmacokinetic aspects as well as the environmental fate of a series of Novichoks. Virtually the results from the different studies related to human health point in the same direction, i. e., the Novichoks are significantly less toxic than VX and the skin permeation much lower and less efficient than observed for VX. Hence, the claim by Mirzayanov could not be substantiated.
Topics: Humans; Models, Molecular; Molecular Structure; Nerve Agents; Organophosphates; Quantitative Structure-Activity Relationship; Skin; Solubility
PubMed: 30474294
DOI: 10.1002/minf.201800106 -
Toxicology Jan 2023This article reviews available data regarding the possible association of organophosphorus (OP) pesticides with neurological disorders such as dementia, attention... (Review)
Review
This article reviews available data regarding the possible association of organophosphorus (OP) pesticides with neurological disorders such as dementia, attention deficit hyperactivity disorder, neurodevelopment, autism, cognitive development, Parkinson's disease and chronic organophosphate-induced neuropsychiatric disorder. These effects mainly develop after repeated (chronic) human exposure to low doses of OP. In addition, three well defined neurotoxic effects in humans caused by single doses of OP compounds are discussed. Those effects are the cholinergic syndrome, the intermediate syndrome and organophosphate-induced delayed polyneuropathy. Usually, the poisoning can be avoided by an improved administrative control, limited access to OP pesticides, efficient measures of personal protection and education of OP pesticide applicators and medical staff.
Topics: Humans; Pesticides; Organophosphorus Compounds; Neurotoxicity Syndromes; Attention Deficit Disorder with Hyperactivity; Organophosphates
PubMed: 36543276
DOI: 10.1016/j.tox.2022.153407 -
Journal of Hazardous Materials Oct 2023The impact of primary metabolites of organophosphate triesters (tri-OPEs), namely, organophosphate diesters (di-OPEs), on the ecology, environment, and humans cannot be... (Review)
Review
The impact of primary metabolites of organophosphate triesters (tri-OPEs), namely, organophosphate diesters (di-OPEs), on the ecology, environment, and humans cannot be ignored. While extensive studies have been conducted on tri-OPEs, research on the environmental occurrence, toxicity, and health risks of di-OPEs is still in the preliminary stage. Understanding the current research status of di-OPEs is crucial for directing future investigations on the production, distribution, and risks associated with environmental organophosphate esters (OPEs). This paper specifically reviews the metabolization process from tri-OPEs to di-OPEs and the occurrence of di-OPEs in environmental media and organisms, proposes typical di-OPEs in different media, and classifies their toxicological and epidemiological findings. Through a comprehensive analysis, six di-OPEs were identified as typical di-OPEs that require prioritized research. These include di-n-butyl phosphate (DNBP), bis(2-butoxyethyl) phosphate (BBOEP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis(2-chloroethyl) phosphate (BCEP), bis(1-chloro-2-propyl) phosphate (BCIPP), and diphenyl phosphate (DPHP). This review provides new insights for subsequent toxicological studies on these typical di-OPEs, aiming to improve our understanding of their current status and provide guidance and ideas for research on the toxicity and health risks of di-OPEs. Ultimately, this review aims to enhance the risk warning system of environmental OPEs.
Topics: Humans; Phosphates; Epidemiologic Studies; Ecology; Organophosphates
PubMed: 37683352
DOI: 10.1016/j.jhazmat.2023.132426