Correlation of cholinesterase inhibition and toxicity in insects and mammals

Darlington, W. A.; Partos, R.D.; Ratts, K.W.

doi:10.1016/s0041-008x(71)80007-8

Cited by 27 publications

(6 citation statements)

References 8 publications

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“…Such differences in the sensitivity of ÁChE from different species to in vitro inhibition by organophosphorus agents have been documented in numerous comparative studies (2)(3)(4)(5)(6)(7)(8)(9). Correlations between the in vitro inhibition of AChE and the acute LD50 measured in vivo provide further evidence confirming the central role of the sensitivity of AChE as the principal determinant of acute toxicity of organophosphorus insecticides in various organisms (10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 59%

“…Once formed, the complex undergoes rapid nucleophilic substitution wherein the enzyme becomes irreversibly phosphorylated at the nucleophilic center, releasing the leaving group of the respective inhibitor. The centrality of the electronic properties of the phosphorus atom in distinguishing among inhibitor potency for a diverse array of structurally dissimilar organophosphorus agents is well documented (10,12,14,16,18).…”

Section: Introductionmentioning

confidence: 99%

“…Regardless, differences in sensitivity to inhibition by organophosphorus agents are a manifestation of differing kinetics involved in the interaction of the inhibitor with the active site of AChE, possibly reflecting distinct molecular features of the enzymes from different species. Structure-activity correlations have been employed to establish the principal physical-chemical properties responsible for discriminating between different organophosphorus inhibitors (5,10-12, [14][15][16][17][18][19]. However, since the association of organophosphorus compounds with AChE is dependent not only on the electrophilicity of the phosphorus atom of the inhibitor but also on the nucleophilic properties of the active site, species-related differences in the electronic properties of the esteratic subsite of AChE may account for the differences in the sensitivity of the enzyme to in vitro inhibition.…”

Section: Introductionmentioning

confidence: 99%

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Species specificity in the chemical mechanisms of organophosphorus anticholinesterase activity

Wallace¹,

Kemp

1991

Chem. Res. Toxicol.

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Structure-activity relationships reveal that the two principal determinants of anticholinesterase activity for various organophosphorus insecticides are steric hindrance and the electrophilic strength of the phosphorus atom. The objective of the present investigation was to distinguish between the molecular properties governing species-related differences in organophosphorus sensitivity by comparing the physical-chemical relationships for the inhibition of brain acetylcholinesterase isolated from rats, chickens, or rainbow trout. A homologous series of five dialkyl p-nitrophenyl phosphates consisting of methyl through n-butyl and isopropyl were synthesized and characterized both chemically and biologically. Structure-activity correlations revealed that whereas steric hindrance is the principal factor governing inhibitory potency for rats and hens, the electrophilicity of the phosphorus atom is the principal determinant of anticholinesterase activity in trout. The inductive effect of successive methylene substitutions on the phosphoryl group is reflected by 13C and 31P NMR spectroscopy which correlates with anticholinesterase activity in trout, but not in rats or hens. The results provide the first indication for species-related differences in the molecular regulation of anticholinesterase activity, suggesting that the trout enzyme possesses a relatively weak nucleophilic center within a dimensionally restricted esteratic subsite. Species-specific distinctions in the molecular properties governing anticholinesterase activity provide novel design strategies for improving the selectivity of toxic organophosphorus insecticides.

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Section: Introductionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Species specificity in the chemical mechanisms of organophosphorus anticholinesterase activity

Wallace¹,

Kemp

1991

Chem. Res. Toxicol.

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“…Whole fly homogenates were used to prepare the fly cholinesterase by a method previously described by Darlington et al (1971). Bovine erythrocyte cholinesterase was purchased from Sigma Chemical Co., St. Louis, Mo.…”

Section: M-acylamidophenyl and M-thioureidophenyl N-methylcarbamatesmentioning

confidence: 99%

Insecticidal and the anticholinesterase activity of m-acylamidophenyl and m-thioureidophenyl N-methylcarbamates

Sacher¹,

Olin²

1972

J. Agric. Food Chem.

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SACHER, OLINand only one sample of 2,4-D contained measurable amounts of the hexa isomers. The hexa isomers present presumably were there because of tetrachlorophenol impurities which condensed with each other. Higher dioxins were found in some samples of several other pesticides, including erbon, tetradifon, ronnel, sesone, and DMPA.The dioxin content of the 20 chlorophenol samples is also presented in Table 111. No TCDD was detected in any sample at levels above 0.5 ppm. However, the higher dioxins were plentiful. Trichlorophenol contained only small amounts of hexachlorodibenzo-p-dioxin and no sample contained over 10 ppm. Tetrachlorophenol contained less than 100 ppm of hexa-, hepta-, and octachlorodibenzo-p-dioxins, while six of 20 pentachlorophenol samples contained over 100 ppm of the hepta-and octachlorodibenzo-p-dioxin isomers. An infrared spectrum of a pentachlorophenol extract is presented in Figure 2. It is quite obvious that the extract contains octachlorodibenzo-p-dioxin when the spectrum is compared to the standard octachlorodibenzo-p-dioxin spectrum. Analysis by ec-gc indicated both hepta-and octachlorodioxins were present in the sample. This may account for the peak broadening. The reason for the high amounts of dioxin in chlorophenol is probably due to heat treatment during synthesis. As chlorination of phenol proceeds past the dichlorophenol stage, heat must be supplied in order to keep the reaction mixture in a melt condition. Since heat is being supplied in the presence of chlorophenols, the formation of higher chlorinated dibenzo-p-dioxins might be expected. The rate and time of melt heating probably governs the formation and amounts of the various dioxin isomers. If the chlorination temperature is raised too high too quickly, the lower chlorinated dioxins may be formed since the lower chlorophenols would be present and available for reaction with each other. If the temperature is raised too high after nearly all chlorophenol is in the penta form, octachlorodibenzo-p-dioxin would be the predominant impurity formed.In conclusion, TCDD has been present at levels above 0.5 ppm in the past, but was less than 0.5 ppm in the current production samples examined. Higher chlorodioxins are present predominantly in chlorophenols with the highest amounts present in pentachlorophenol. Thirty-eight percent of all samples examined contained at least one chlorodioxin, with many containing more than one.Fifty-nine new N-methyl and N,N-dimethylcarba-gized effectively by 2,3-methylenedioxynaphthalene. mates were synthesized and tested as insecticides Structure-activity correlation revealed that maximal and as inhibitors of fly and bovine cholinesterases.anticholinesterase activity is associated with a In spite of the high anticholinesterase activity ex-definite size of the alkyl substituent on the amide hibited by many of these compounds, only few or the thiourea grouping. In all series tested, chemicals have shown insecticidal activity. Fur-alkyl substituent with four to six carbon atoms thermore, these compo...

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“…Organophosphorous (OP) insecticides are widely used in the control of insect pests. OPs are not very persistent in soil and they are known to be considerably toxic in that they inhibit a number of hydrolytic enzymes and have neurotoxic action in insects and mammals [8] [9].…”

Section: Introductionmentioning

confidence: 99%

Bioavailability of Chlorpyrifos in Wheat Plants (<i>Triticum aestivun</i>)

Copaja

Vergara²,

Bravo³

2014

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Adsorption processes of chlorpyrifos in two Chilean agro soils (Calera: C; San Esteban: SE) in relation with the bioaccumulation in wheat plants (Triticum aestivun) were studied. RP-HPLC method was developed to determine the chlorpyrifos content in soils, roots and seedling tissues. The two soils showed high adsorption capacity (C = 78%, SE = 92%). The values are not in relation with the contents of organic matter (C = 3.9% and SE = 2.0%) and clay (C = 12.7% and SE = 10.1%) determined in the soils. Persistence and mobility of chlorpyrifos in the soils were estimated from halflife values (Csoil = 23 d, SEsoil = 14 d) and the Guss index (Csoil = 0.89, SEsoil = 0.25) respectively. These values are in the range of non-leaching compounds, and suggest that there should be no pollutant in the ground water. Wheat plants grown in both soils incubated with chlorpyrifos bioaccumulate residues in roots and seedling tissues. Root tissues showed the greatest contents (C = 22.3 mg/k. f. wt; SE = 51.8 mg/kg. f. wt.). Germination and growth of wheat young plants were not inhibited for the contents in the tissues. A relation between the levels of chlorpyrifos residues in the soils and the bioaccumulation in wheat tissues was estimated from the BAI parameter. Values showed that the bioaccumulation is dependent on the residues contents in soils. These results suggest that bioavailability of chlorpyrifos in wheat plants may be a harmful pollutant for mammals if it remains stable at all growth stage of the plant. Further research should be considered to see if bioavailability in forage and/or grain can occur.

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Correlation of cholinesterase inhibition and toxicity in insects and mammals

Cited by 27 publications

References 8 publications

Species specificity in the chemical mechanisms of organophosphorus anticholinesterase activity

Species specificity in the chemical mechanisms of organophosphorus anticholinesterase activity

Insecticidal and the anticholinesterase activity of m-acylamidophenyl and m-thioureidophenyl N-methylcarbamates

Bioavailability of Chlorpyrifos in Wheat Plants (<i>Triticum aestivun</i>)

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Correlation of cholinesterase inhibition and toxicity in insects and mammals

Cited by 27 publications

References 8 publications

Species specificity in the chemical mechanisms of organophosphorus anticholinesterase activity

Species specificity in the chemical mechanisms of organophosphorus anticholinesterase activity

Insecticidal and the anticholinesterase activity of m-acylamidophenyl and m-thioureidophenyl N-methylcarbamates

Bioavailability of Chlorpyrifos in Wheat Plants (&lt;i&gt;Triticum aestivun&lt;/i&gt;)

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Bioavailability of Chlorpyrifos in Wheat Plants (<i>Triticum aestivun</i>)