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Environmental Health Perspectives Apr 2021Inhibition of acetylcholinesterase (AChE), a biomarker of organophosphorous and carbamate exposure in environmental and occupational human health, has been commonly used...
BACKGROUND
Inhibition of acetylcholinesterase (AChE), a biomarker of organophosphorous and carbamate exposure in environmental and occupational human health, has been commonly used to identify potential safety liabilities. So far, many environmental chemicals, including drug candidates, food additives, and industrial chemicals, have not been thoroughly evaluated for their inhibitory effects on AChE activity. AChE inhibitors can have therapeutic applications (e.g., tacrine and donepezil) or neurotoxic consequences (e.g., insecticides and nerve agents).
OBJECTIVES
The objective of the current study was to identify environmental chemicals that inhibit AChE activity using and models.
METHODS
To identify AChE inhibitors rapidly and efficiently, we have screened the Toxicology in the 21st Century (Tox21) 10K compound library in a quantitative high-throughput screening (qHTS) platform by using the homogenous cell-based AChE inhibition assay and enzyme-based AChE inhibition assays (with or without microsomes). AChE inhibitors identified from the primary screening were further tested in monolayer or spheroid formed by SH-SY5Y and neural stem cell models. The inhibition and binding modes of these identified compounds were studied with time-dependent enzyme-based AChE inhibition assay and molecular docking, respectively.
RESULTS
A group of known AChE inhibitors, such as donepezil, ambenonium dichloride, and tacrine hydrochloride, as well as many previously unreported AChE inhibitors, such as chelerythrine chloride and cilostazol, were identified in this study. Many of these compounds, such as pyrazophos, phosalone, and triazophos, needed metabolic activation. This study identified both reversible (e.g., donepezil and tacrine) and irreversible inhibitors (e.g., chlorpyrifos and bromophos-ethyl). Molecular docking analyses were performed to explain the relative inhibitory potency of selected compounds.
CONCLUSIONS
Our tiered qHTS approach allowed us to generate a robust and reliable data set to evaluate large sets of environmental compounds for their AChE inhibitory activity. https://doi.org/10.1289/EHP6993.
Topics: Acetylcholinesterase; Cholinesterase Inhibitors; Humans; Insecticides; Molecular Docking Simulation
PubMed: 33844597
DOI: 10.1289/EHP6993 -
Bulletin of the World Health... 1966In a continuation of the World Health Organization's collaborative scheme for testing new insecticides against malaria vectors, field trials were carried out during 1965... (Comparative Study)
Comparative Study
In a continuation of the World Health Organization's collaborative scheme for testing new insecticides against malaria vectors, field trials were carried out during 1965 in the forest belt of Western Nigeria near Lagos and in the Guinea savanna belt of Northern Nigeria near Kaduna, using bromophos residual spray and cheesecloth impregnated with Bayer 39007; Schering 34615 was applied as a residual spray in Lagos. Although bromophos appeared to be effective for at least five months after spraying in the Lagos area, the desired control was obtained for only one month in the Kaduna area; these differences appear to be due to differences in environmental conditions and to the ecology of Anopheles gambiae. Schering 34615 was also effective for up to five months in Lagos and was definitely superior to bromophos. Cheesecloth impregnated with Bayer 39007 gave good control of mosquitos for two and for three months in Kaduna and Lagos, respectively, but because the walls of the treated huts were only partly covered, some mosquitos avoided contact with the cloth. It is suggested that, because of the reduced toxic hazards, cheesecloth treatments may be feasible with potentially effective insecticides that are too toxic to spray.
Topics: Anopheles; Insecticides; Malaria; Mosquito Control; Nigeria
PubMed: 5297804
DOI: No ID Found -
The Science of the Total Environment Feb 2024Widespread use of pesticides globally has led to serious concerns about environmental contamination, particularly with regard to aquatic and soil ecosystems. This work...
Widespread use of pesticides globally has led to serious concerns about environmental contamination, particularly with regard to aquatic and soil ecosystems. This work involved investigating concentrations of 64 pesticides in surface-water and soil samples collected in four provinces along the Mekong River in Cambodia during the dry and rainy seasons (276 samples in total), and conducting semi-structured interviews with local farmers about pesticide use. Furthermore, an ecological risk assessment of the detected pesticides was performed. In total, 56 pesticides were detected in surface water and 43 in soil, with individual pesticides reaching maximum concentrations of 1300 ng/L in the surface-water samples (tebufenozide) and 1100 ng/g dry weight in the soil samples (bromophos-ethyl). The semi-structured interviews made it quite evident that the instructions that farmers are provided regarding the use of pesticides are rudimentary, and that overuse is common. The perceived effect of pesticides was seen as an end-point, and there was a limited process of optimally matching pesticides to pests and crops. Several pesticides were used regularly on the same crop, and the period between application and harvest varied. Risk analysis showed that bromophos-ethyl, dichlorvos, and iprobenfos presented a very high risk to aquatic organisms in both the dry and rainy seasons, with risk quotient values of 850 for both seasons, and of 67 in the dry season and 78 in the rainy season for bromophos-ethyl, and 49 in the dry season and 16 in the rainy season for dichlorvos. Overall, this work highlights the occurrence of pesticide residues in surface water and soil along the Mekong River in Cambodia, and emphasizes the urgent need for monitoring and improving pesticide practices and regulations in the region.
Topics: Rivers; Water; Soil; Dichlorvos; Cambodia; Ecosystem; Environmental Monitoring; Water Pollutants, Chemical; Pesticides; Pesticide Residues; Organothiophosphates
PubMed: 38104830
DOI: 10.1016/j.scitotenv.2023.169312 -
Saudi Journal of Biological Sciences Jan 2021larvae obtained from different types of agricultural and non-agricultural localities in Peninsular Malaysia were subjected to several larvicides at World Health...
larvae obtained from different types of agricultural and non-agricultural localities in Peninsular Malaysia were subjected to several larvicides at World Health Organization (WHO) recommended dosages. Upon 24 h of WHO larval bioassay using two organochlorines and six organophosphates, high resistance against dichlorodiphenyltrichloroethane (DDT), temephos, chlorpyrifos and bromophos were demonstrated among all larval populations. larvae from both paddy growing areas (92.33% mortality) and rubber estates (97.00% mortality) were moderately resistant to dieldrin while only larvae from dengue prone residential areas (89.00% mortality) showed high resistance against dieldrin. All larval populations also developed either incipient or high resistance to both malathion (33.67%-95.33% mortality) and fenitrothion (73.00%-92.67% mortality). Only larvae from fogging-free residential areas that were tolerant to fenthion (97.33% mortality), whereas larvae from dengue prone residential areas were highly resistant to the same organophosphate (88.33% mortality). Cross resistance between intraclass and interclass larvicides of organochlorines and organophosphates were also exhibited in this study. The present study provided baseline data on various susceptibility levels of larval populations from different types of agricultural and non-agricultural localities against organochlorines and organophosphates at WHO recommended dosages. Nevertheless, further susceptibility investigations are suggested using revised doses of larvicides established from the local reference strain of to prevent the underestimation or overestimation of insecticide resistance level among field strains of larvae.
PubMed: 33424394
DOI: 10.1016/j.sjbs.2020.11.040 -
Revista de Salud Publica (Bogota,... Aug 2016Objective Large quantities of pesticides are used in rice crops. The aim of this study is to characterize how farmers are exposed to pesticides and subsequent poisoning....
Objective Large quantities of pesticides are used in rice crops. The aim of this study is to characterize how farmers are exposed to pesticides and subsequent poisoning. Materials and Methods A multilevel (individual and community) multi-method study, which included ethnographic and survey methods, as well as measurement of pesticides in water and human samples, was performed. Results The production process is described and the main risk factors are presented. Pesticides are considered the greatest danger at work and at their homes. Workers have poor working conditions and are not protected by the system of occupational risks. Azinphos-methyl, endosulfan, β-BHC, bromophos-methyl, bromophos-ethyl and 2,4- DDT were found in water samples. The survey included 381 workers with mild (12.86 %), moderate (67.98 %) and severe (5.51 %) poisonings respectively. Severe cases presented lower levels of education, lower levels of health care access to the contributory regimen of the Colombian social security system and higher incidence of cardiovascular disease, diabetes, herpes or other viral infections. Conclusion There are precarious working conditions that favor exposure to pesticides correlated to the exclusion of farmers from the occupational risk system, to poverty and to poor education. It is urgent to include these workers to the system of occupational risk system and to improve their living conditions, thus reducing unsafe practices when handling pesticides.
Topics: Agricultural Workers' Diseases; Agriculture; Colombia; Crops, Agricultural; Farmers; Humans; Occupational Exposure; Oryza; Pesticides; Qualitative Research; Socioeconomic Factors; Water Pollutants, Chemical
PubMed: 28453066
DOI: 10.15446/rsap.v18n4.52617 -
Bulletin of Environmental Contamination... May 2015In a Belgian pilot study honey bee wax combs from ten hives were analyzed on the presence of almost 300 organochlorine and organophosphorous compounds by LC-MS/MS and...
In a Belgian pilot study honey bee wax combs from ten hives were analyzed on the presence of almost 300 organochlorine and organophosphorous compounds by LC-MS/MS and GC-MS/MS. Traces of 18 pesticides were found and not a single sample was free of residues. The number of residues found per sample ranged from 3 to 13, and the pesticides found could be categorized as (1) pesticides for solely apicultural (veterinary) application, (2) pesticides for solely agricultural (crop protection) application, (3) pesticides for mixed agricultural and apicultural (veterinary) application. The frequencies and quantities of some environmental pollutants bear us high concerns. Most alarming was the detection of lindane (gamma-HCH) and dichlorodiphenyltrichloroethane (including its breakdown product dichlorodiphenyldichloroethylene), two insecticides that are banned in Europe. The present comprehensive residue analysis, however, also reveals residues of pesticides never found in beeswax before, i.e. DEET, propargite and bromophos.
Topics: Agriculture; Animals; Bees; Belgium; Chromatography, Liquid; Environmental Monitoring; Environmental Pollutants; Hexachlorocyclohexane; Hydrocarbons, Chlorinated; Insecticides; Mass Spectrometry; Pesticides; Pilot Projects; Tandem Mass Spectrometry; Waxes
PubMed: 25749505
DOI: 10.1007/s00128-015-1511-y -
Scandinavian Journal of Work,... Sep 1978Neurophysiological investigations and determinations of cholinesterase activity on plasma and erythrocytes were carried out on 11 Swedish spraymen exposed to bromophos,...
Neurophysiological investigations and determinations of cholinesterase activity on plasma and erythrocytes were carried out on 11 Swedish spraymen exposed to bromophos, diazinon, dursbane, and malathion. Plasma cholinesterase activity was significantly reduced after work, while erythrocyte cholinesterase activity was unchanged. In none of the workers with a decreased plasma cholinesterase activity after work could any related acute neuromuscular disturbance be detected when the men were tested with repetitive nerve stimulation and with single fiber electromyography. Signs of subclinical neuropathy were present as a slight reduction in sensory conduction velocity and increased fiber density in some workers.
Topics: Action Potentials; Air Pollutants; Air Pollutants, Occupational; Cholinesterases; Electric Stimulation; Electromyography; Environmental Exposure; Erythrocytes; Evoked Potentials; Insecticides; Neuromuscular Junction; Organophosphorus Compounds; Synaptic Transmission
PubMed: 212825
DOI: 10.5271/sjweh.2709 -
Environmental Science and Pollution... Feb 2013Pesticides that contain a halogen functional group have been destructed by means of detonative combustion. The following compounds were examined: (1)...
Pesticides that contain a halogen functional group have been destructed by means of detonative combustion. The following compounds were examined: (1) atrazine-2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine-herbicide; (2) bromophos-O,4-bromo-2,5-dichlorophenyl O,O-dimethyl phosphorothioate-insecticide; (3) chloridazon-5-amino-4-chloro-2-phenylopyridazin-3(2H)-one-herbicide; (4) linuron-3-(3,4-dichlorophenyl)-1-metoxy-1-methylurea-herbicide; (5) metoxychlor-1,1,1-trichloro-2,2-bis(4-metoxyphenyl)ethane-insecticide and acaricide; and (6) trichlorfon-dimethyl 2,2,2-trichloro-1-hydroxyethylphosphonate-insecticide. Explosive material has been produced on the basis of ammonium nitrate, which served as an oxidizer while the pesticides were used as fuels. Composition of the explosive was adjusted in such a way as to respect thermodynamic parameters. Detonative decomposition of the mixtures has been carried out in shot-holes pre-drilled in soil. Efficiency of the pesticide decomposition has been examined with gas chromatography in order to determine pesticides residues in the environment. It was found that for some, the amount of pesticides in some compounds in the analyzed samples after decomposition was below the determination threshold of the applied method.
Topics: Atrazine; Chromatography, Gas; Explosive Agents; Linuron; Methoxychlor; Nitrates; Organothiophosphates; Pesticide Residues; Pesticides; Pyridazines; Soil Pollutants; Trichlorfon
PubMed: 23128990
DOI: 10.1007/s11356-012-1277-2 -
Bulletin of the World Health... 1972New insecticides have been evaluated for toxicity to tsetse flies and compared with organochlorine compounds currently in use. The most toxic compounds and their...
New insecticides have been evaluated for toxicity to tsetse flies and compared with organochlorine compounds currently in use. The most toxic compounds and their estimated median lethal doses in nanograms per fly by topical application in solution to teneral Glossina austeni were: resmethrin 4, fenthion 8, dieldrin 10, propoxur 12, chlorfenvinphos 12, tetrachlorvinphos 20, and dichlorvos 20. There was little variation in the susceptibility of teneral male and female flies, young fed flies, and fed stud males with all the compounds tested (dieldrin, resmethrin, tetrachlorvinphos, bromophos, and propoxur) and increased tolerance in old fed pregnant flies occurred only with dieldrin and resmethrin. There was also little variation in the susceptibility of teneral flies of the two species G. austeni and G. morsitans. In contact toxicity tests with water dispersible powder deposits on plywood, propoxur was highly active initially but lost its effectiveness after only a few weeks, whereas tetrachlorvinphos was less active initially but more persistent.
Topics: Animals; Carbamates; Hydrocarbons, Halogenated; Insect Control; Insecticides; Organophosphorus Compounds; Powders; Solutions; Structure-Activity Relationship; Tsetse Flies
PubMed: 4537853
DOI: No ID Found -
Bulletin of the World Health... 1970The effects of changes in structure upon toxicity to adult mosquitos and upon physical properties which are important in determining contact effectiveness and residual...
The effects of changes in structure upon toxicity to adult mosquitos and upon physical properties which are important in determining contact effectiveness and residual activity are described for a group of O,O-dialkyl O-halogenated-phenyl phosphates, phosphorothionates and phosphamido(thio)ates. This group includes such established insecticides as fenchlorphos, bromophos and iodofenphos.
Topics: Animals; Chemical Phenomena; Chemistry; Culicidae; Esters; Female; Hydrocarbons, Halogenated; Insecticides; Mosquito Control; Phosphorus
PubMed: 4392938
DOI: No ID Found