Studies on Organophosphorus Insecticides

Various insecticides belonging to the O-alkyl-O-(subst. phenyl) phenylphosphonothioate family were prepared and their biological activities studied. Besides O-ethyl-O-(4-nitrophenyl) phenylphosphonothioate, which is utilized in these days, another compound, O-ethyl-O-(4-cyanophenyl) phenylphosphonothioate, proved to have excellent properties as an insecticide.

In our previous paper, it was reported that O,O-dimethyl-O-(4-cyanophenyl) phosphorothioate (S-4084) has only a low toxicity towards mammals though possessing a high activity towards rice stem borers. In this paper, the chemical and biological properties of S-4084 and its phenylphosphonothioate derivative (S-4087) will be reported in detail. It should especially be noted that S-4084 had a higher activity towards rice stem borers than S-4087 by topical or pot test in a room or in a green-house, but by field test S-4087 was stronger than S-4084.     

Studies on the Organophosphorus Insecticides

The reaction of O,O-dialkyl phosphorochloridates or phosphorochloridothioates with sodium salts of benzoylacetone and the reaction of trialkyl phosphites with α-chloro-benzoylacetone or acetophenone were attempted with a view to prepare the low toxic phosphorus insecticides containing acyl-vinyl group. It was found that the products did not have a phosphonate-form but a phosphorate-form and the phenyl-acyl-vinyl group had linkage with phosphorus atom by the enol-form of next carbonyl group of the phenyl-group.     

Studies on the Organophosphorus Insecticides

During the course of an investigation of organophosphorus insecticides, the reactions of trialkyl phosphites with ethyl or phenyl trichloroacetate, diethyl monochloro- or dichloromalonate and ethyl chlorocyanoacetate were attempted. It was cleared that the above reaction did not belong to the Arbuzov reaction but to the Perkow reaction and the products had the phosphorate forms and the carbonyl group of the carboxylic acid linked with phosphorus atom by the enol-form.     

Studies on the Organophosphorus Insecticides

During an investigation of organophosphorus insectiside, the present author found that the reactions of O,O-dialkyl phosphorochloridate or O,O-dialkyl phosphorochloridothioates with sodium salts of β-keto-esters or nitriles give new phosphoroates or phosphorothioates containg phenylacrylate or phenylacrylonitrile radicals, but do not give phosphonates.

The reactions of trialkylphosphites with α-halo- or α,α-dihalo-phenyl-β-keto-esters or nitrils also gave phosphoroates. Some phosphoroates prepared by this methods have high insecticidal activity.     

Studies on the Organophosphorus Insecticides

During the course of investigation on organophosphorus insecticides, many organophosphorus compounds having methyl-, methyl-chloro-, methyl-nitro-, methyl-cyano-, methyl-thiocyano-, methoxy-nitro-, acyloxy-nitro-, and chloro-cyano-phenyl groups were prepared and their biological activities tested. As the results of these studies, two compounds were found as new low toxic organophosphorus insecticides, namely, O,O-dimethyl-O- (3-methyl-4-nitro-phenyl) and O,O-dimethyl-O- (4-cyanophenyl) phosphorothioates.     

Poisoning with Organophosphorus Insecticides

Because of an increasing incidence of poisoning with the newer organophosphorus anticholinesterase insecticides, these compounds have been reviewed in terms of their history and pharmacology, relationship with other drugs, factors affecting toxicity, mechanism of action, toxic signs and treatment. The modern organophosphorus pesticide requires metabolic conversion before toxicity develops. Insects have a greater propensity for this conversion than humans. Nevertheless, this conversion does occur in humans and can be potentiated by other drugs. Toxicity also varies with age, sex, route and frequency of administration, and previous exposure. The mechanism of toxicity is inhibition of acetylcholinesterase, causing an intoxicating build-up of acetylcholine. Signs and symptoms consist of the clinical manifestations of unopposed parasympathetic and central activity. Treatment must be initiated early. Respiration must be maintained and the effects of acetylcholine must be counteracted by massive doses of atropine. Metaraminol enhances the antagonistic action of atropine against acetylcholine and may also be given. Once acetylcholinesterase is inactivated, restoration is slow. Recovery can be accelerated by enzyme reactivators like the oxime compounds. Pyridine aldoxime (Pralidoxime, Protopam, P₂S and 2-PAM) can be given in combination with atropine and metaraminol (AMP therapy) and may be the treatment of choice.     

Studies on Organic Insecticides

An improved synthesis of nereistoxin, 4-dimethylamino-1, 2-dithiolane (Ia), has been achieved in a 3-step sequence starting from 1, 3-bis (benzylthio)-2-propanone (IIa) or 2-phenyl-1, 3-dithian-5-one (IVa). By the similar route 4-amino-1, 2-dithiolane (Ib), 4-methylamino-1, 2-dithiolane (Ic) and two S-acyl derivatives (VIa, b) of dihydronereistoxin were synthesized and their insecticidal activities were tested.     

Effect of Four Organophosphorus Insecticides on Microbial Activities in Soil

Laboratory tests were conducted with four organophosphorus insecticides, Bay 37289 (O-ethyl O-2,4,5-trichlorophenyl ethylphosphonothioate), diazinon [O,O-diethyl O-(2-isopropyl-4-methyl-6-pyrimidinyl) phosphorothioate], Dursban (O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate), and Zinophos (O,O-diethyl O-2-pyrazinyl phosphorothioate), applied to a sandy loam at rates of 10 and 100 mug/g to determine whether these materials caused any serious effects on microbial activities related to soil fertility. All insecticides showed an effect on fungi and bacteria for the first and second week of incubation, but, subsequently, the populations returned to levels similar to those obtained in the controls. All insecticide applications increased ammonium production, but, in some instances, there appeared to be a slight depression of nitrification. Sulfur oxidation was equal to or better than that obtained with untreated soil in most cases. There was no significant effect on phosphorus mineralization. Oxygen consumption indicated that microbial respiration increased in proportion to the concentration of insecticides, suggesting the possibilities of microbial degradation of the insecticides or their degradation products and of uncoupling oxidative phosphorylation.     

Studies on Organic Insecticides

Insecticidally active sulfur derivatives (VI) of dihydronereistoxin (VIa) were synthesized in one step sequence starting from 2-dimethylamino-l,3-dichloropropane (III) or 1-dimethyl-amino-2,3-dichloropropane (IV) by utilizing intramolecular S_N 2 reaction.     

Studies on Nicotinoids as Insecticides

Synthesis of two nicotine isomers, 5′-methylnornicotine and 6-methylnornicotine is described. The latter shows slightly insecticidal action. Myosmine type bases are easily reduced to nornicotine type with sodium borohydride.     

Inhibition of Phenylamide Hydrolysis by Bacillus sphaericus with Methylcarbamate and Organophosphorus Insecticides

The degradation of the phenylamide herbicides monolinuron, linuron, and solan by cultures of Bacillus sphaericus ATCC 12123 was inhibited by the methylcarbamate insecticides metmercapturon, aldicarb, propoxur, and carbaryl and by the organophosphorus insecticides fenthion and parathion. The extent of inhibition was largest with metmercapturon and smallest with parathion inhibition of hydrolysis of the two phenylurea herbicides was greater than of the acylanilide compound. Tests with crude enzyme preparations of aryl acylamidase derived from B. sphaericus showed that the inhibition of the hydrolysis of linuron with methylcarbamates is a competitive one. The insecticides tested did induce the enzyme, nor could they serve as its substrate.     

Hydrolysis of Selected Organophosphorus Insecticides by Two Bacteria Isolated from Flooded Soil

Flavobacterium sp. ATCC 27551 hydrolysed both diethyl (parathion and diazinon) and dimethyl (methyl parathion and fenitrothion) phosphorothioates while Pseudomonas sp. ATCC 29353 hydrolysed only diethyl (parathion and diazinon) phosphorothioates. Glucose inhibited the hydrolysis of parathion by Pseudomonas sp., but not by Flavobacterium sp. Evidently, the Flavobacterium hydrolase differs from that of Pseudomonas sp. The Pseudomonas sp. converted 4-nitrophenol to 4-aminophenol in the presence of glucose and to nitrite in its absence; 4-nitrophenol was not metabolized by the Flavobacterium sp.     

环境中拟除虫菊酯类农药微生物降解技术研究进展

近年来,随着拟除虫菊酯类农药的大量及不合理使用,环境及食品中的农药残留对人类健康造成的负面影响日益显著。微生物降解农药作为去除农药污染安全高效的方法已成为当前研究热点之一。综述了国内外拟除虫菊酯类农药微生物降解菌的种类、降解机制、降解酶及降解菌应用的最新研究进展,并对亟须解决的重要问题进行了展望。     

Studies on the Mode of Action of Organophosphorus Compounds

It was presumed in the previous paper that sumithion was easily absorbed from the gastrointestestinal tract, similarly to methylparathion, following the oral administration to mammals. Inhibition of blood and brain cholinesterase of Guinea pigs and white rats in vivo after oral treatment with sumithion and methylparathion was determined. Inhibition of the enzymes was found to proceed rather rapidly and in most cases it reached maximum within one hour. Sumithion hindered the brain cholinesterase activity far less effectively than methylparathion. Intravenous administration of these phosphorothioates and their oxygen analogs clarified that the latters were more inhibitory on the cholinesterases and that of the two oxygen analogs, sumioxon was less effective. The poor susceptibility of the brain enzyme to sumithion was also observed in this case. This paper deals with the experimental results and their possible implications in the toxicity of the organophosphorus compounds toward mammals.     

Studies on the Mode of Action of Organophosphorus Compounds

For the purpose of distinguihsing sumithion from methylparathion in the mammalian metabolism, phosphorus³² labeled compounds were administered to Guinea pig and white rat. Both compounds were found to be absorbed readily, and phosphorus containing metabolites excreted chiefly into urine. By chromatographic separation and identification of the metabolites, the decomposition of sumithion was observed to proceed presumably more easily than methylparathion. From these results lower toxicity of the former toward mammals than the latter was discussed. In addition, compounds remaining in rice plant and German cockroach were also analysed.     

Studies on Organophosphorus Pesticides Synthesis of Some Sulphanilamide Derivatives

Several N¹-aryl-N⁴(O, O-diethylthiophosphoryl) sulphanilamides and N¹-aiyl-N⁴-(N, N-diarylthiophosphoramidic) sulphanilamides have been prepared with a view to study their pesticidal properties. Six such compounds have been tested against two species of fungi.     

Studies on the Mode of Action of Organophosphorus Compounds

In order to further elucidate the mechanism of metabolic difference between sumithion and methylparathion, distribution of sumithion and methylparathion into several tissues, activation, that is, conversion into more toxic oxygen analogs, and degradation into non-toxic compounds were examined in vivo following the intravenous administration of the phosphorothioates to Guinea pigs and white rats. Sumioxon and methylparaoxon were detected in all tissues tested, among which lung and liver were richest in them. More sumioxon than methylparaoxon was found. Chese organophosphorus compounds were found to be decomposed to non-toxic desmethyl compounds and dimethyl phosphorothioic acid mainly in liver and kidney. From these results it seems improbable that the lower toxicity of sumithion than that of methylparathion results from the different in their rate of metabolism.     

Environmental Fate of Two Organophosphorus Insecticides in Soil Microcosms under Mediterranean Conditions and Their Effect on Soil Microbial Communities

Assessing dissipation is an integral part of determining pesticide risk. The adsorption and dissipation characteristics of two model insecticides, chlorpyrifos (CHP) and dimethoate (DMT), in a Mediterranean soil were investigated in order to evaluate soil microbial toxicity and to study their soil bioavailability for the purpose of managing pesticide residue with potential bioremediation of contaminated soil. The aim of this study was also to define novel methods for assessing the ecotoxicity of CHP and DMT on microorganisms in the soil. Koc values ranged between 33420–91601 cm³/g and 129–184 cm³/g for CHP and DMT, respectively, indicating that the former is characterized by a strong adsorption affinity, whereas, the latter has a weaker one. In the dissipation study, the half-life (T_1/2) of CHP in top soil was 11.55days; whereas, when dissipation was studied in the same soil sterilized, the half-life was 13.86 days, showing a relatively important abiotic degradation effect. For DMT, however, T_1/2 was 17.32 days and 13.86 days in sterilized soil and non-sterilized soil, respectively, illustrating partial biotic degradation. In terms of leaching behavior, the groundwater ubiquity scores calculated for CHP and DMT were 0.85 and 1.95, respectively, indicating that CHP is a non-leacher, while DMT can be considered a transition insecticide.     

Studies on the Mode of Action of Organophosphorus Fungicide,Kitazin

Studies were conducted on the influence of Kitazin analogues on the incorporation of ¹⁴C-glucosamine into the mycelial cell wall fraction of Pyricularia oryzae. Compounds of thiolates and phosphates, both having in vitro inhibitory activities toward the mycelial growth, inhibited the incorporation, whereas those of thionates and dithioates, either having no fungitoxicity, did not inhibit the incorporation. Mycelia of P. oryzae treated with Kitazin-P (S-benzyl O,O′-diisopropyl phosphrothioate; IBP) accumulated about twice as much an amino sugar derivative as untreated ones. Mycelia treated with thiono or dithio analogues, which have no fungitoxicity, showed no accumulation. The accumulated substance gave a identical spot with authentic UDP-N-acetyl glucosamine on paper chromatograms developed with four solvent systems.     

Toxicity of Binary Mixtures of Enantiomers in Chiral Organophosphorus Insecticides: The Significance of Joint Effects Between Enantiomers

The existence of enantiomer‐enriched mixtures of chiral pesticides in the environment is overwhelmingly positive. However, interactions between enantiomers have not been considered so far in risk assessments. Here, we chose three organophosphorus pesticides as representative chiral pesticides to investigate the possible interaction mode between each pair of enantiomers both in in vivo and in vitro. Data show that the enantiomers of methamidophos and profenofos have a simple additive effect, <zaq;1> whereas fensulfothion acts as an antagonist in AChE‐inhibition model. In contrast, enantiomers of methamidophos and fensulfothion had an additive effect in an acute toxicity test against Daphnia magna. A synergistic effect was observed in the joint toxicity of the profenofos enantiomers. The ability for enantiospecific biodegradation in the in vivo model contributed to the different interaction observed between the in vitro and in vivo models. Moreover, binding affinities were suspected as another reason for the different mode of action of mixture enantiomers. Our study recommends using a joint research model to treat chiral compounds in the real environment. Chirality 25:787–792, 2013. © 2013 Wiley Periodicals, Inc.