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Radiotracer Approaches to Carbamate Insecticide Toxicology; Emploi des radio indicateurs pour l'etude de la toxicologie des insecticides a base de carbamates; Primenenie radioaktivnykh indikatorov dlya izucheniya toksikologii karbamatnykh insektitsidov; Estudio con radioindicadores de la toxico logia de los insecticidas a base de carbamatos

Conference:

Abstract

Methylcarbamates constitute one of the major groups of insecticides. Many unresolved problems in their toxicology may be readily approached with radiotracer studies. Dimethylcarbamates have been prepared with carbonyl-C{sup 14}-labelling and methylcarbamates withmethyl-, carbonyl-and ring-labelling utilizing carbon-{sup 14}. The pharmacological action of these.compounds presumably results from acetylcholinesterase inhibition and may involve carbamylation. Reaction of carbonyl- or methyl-labelled carbamates with purified cholinesterase or other esterases would allow a critical examination of this carbamylation reaction and the ease of spontaneous and induced reactivation or decarbamylation. The physiological significance of cholinesterase inhibition might be examined by administering acetate-C{sup 14} and analysis for radiolabelled acetylcholine accumulation in nervous tissue, or by utilizing acetyl-C{sup 14}-choline as the substrate for in vitro determination of the degree of cholinesterase inhibition in tissues of poisoned animals with minimal dilution of the inhibitors and enzymes during analysis. Some progress has been made with radiolabelled materials in investigating the metabolism of carbamate insecticides. Sevin (1-naphthyl methylcarbamate) has been most extensively studied along with its potential hydrolysis products. The assumption that the metabolism of Sevin involves an initial hydrolysis and then further decomposition of the fragments was not supported by carbon-14 studies. The major detoxification mechanism in mammals, and probably also in  More>>
Authors:
Casida, J. E. [1] 
  1. University of Wisconsin, Madison, WI (United States)
Publication Date:
Sep 15, 1963
Product Type:
Conference
Resource Relation:
Conference: Symposium on the Use and Application of Radioisotopes and Radiation in the Control of Plant and Animal Insect Pests, Athens (Greece), 22-26 Apr 1963; Other Information: 1 fig., 74 refs.; Related Information: In: Radiation and Radioisotopes Applied to Insects of Agricultural Importance. Proceedings of the Symposium on the Use and Application of Radioisotopes and Radiation in the Control of Plant and Animal Insect Pests| 526 p.
Subject:
60 APPLIED LIFE SCIENCES; CARBAMATES; CARBON 14; CHOLINESTERASE; COCKROACHES; DETOXIFICATION; HYDROLYSIS; INSECTICIDES; LABELLING; MAMMALS; METABOLISM; METABOLITES; MILK; NADH2; OXIDATION; RESIDUES; TOXICITY; TRACER TECHNIQUES
OSTI ID:
22100727
Research Organizations:
International Atomic Energy Agency, Vienna (Austria); Food and Agriculture Organization of the United Nations, Rome (Italy)
Country of Origin:
IAEA
Language:
English
Other Identifying Numbers:
Other: ISSN 0074-1884; TRN: XA13R0287058775
Submitting Site:
INIS
Size:
page(s) 223-239
Announcement Date:
Jun 06, 2013

Conference:

Citation Formats

Casida, J. E. Radiotracer Approaches to Carbamate Insecticide Toxicology; Emploi des radio indicateurs pour l'etude de la toxicologie des insecticides a base de carbamates; Primenenie radioaktivnykh indikatorov dlya izucheniya toksikologii karbamatnykh insektitsidov; Estudio con radioindicadores de la toxico logia de los insecticidas a base de carbamatos. IAEA: N. p., 1963. Web.
Casida, J. E. Radiotracer Approaches to Carbamate Insecticide Toxicology; Emploi des radio indicateurs pour l'etude de la toxicologie des insecticides a base de carbamates; Primenenie radioaktivnykh indikatorov dlya izucheniya toksikologii karbamatnykh insektitsidov; Estudio con radioindicadores de la toxico logia de los insecticidas a base de carbamatos. IAEA.
Casida, J. E. 1963. "Radiotracer Approaches to Carbamate Insecticide Toxicology; Emploi des radio indicateurs pour l'etude de la toxicologie des insecticides a base de carbamates; Primenenie radioaktivnykh indikatorov dlya izucheniya toksikologii karbamatnykh insektitsidov; Estudio con radioindicadores de la toxico logia de los insecticidas a base de carbamatos." IAEA.
@misc{etde_22100727,
title = {Radiotracer Approaches to Carbamate Insecticide Toxicology; Emploi des radio indicateurs pour l'etude de la toxicologie des insecticides a base de carbamates; Primenenie radioaktivnykh indikatorov dlya izucheniya toksikologii karbamatnykh insektitsidov; Estudio con radioindicadores de la toxico logia de los insecticidas a base de carbamatos}
author = {Casida, J. E.}
abstractNote = {Methylcarbamates constitute one of the major groups of insecticides. Many unresolved problems in their toxicology may be readily approached with radiotracer studies. Dimethylcarbamates have been prepared with carbonyl-C{sup 14}-labelling and methylcarbamates withmethyl-, carbonyl-and ring-labelling utilizing carbon-{sup 14}. The pharmacological action of these.compounds presumably results from acetylcholinesterase inhibition and may involve carbamylation. Reaction of carbonyl- or methyl-labelled carbamates with purified cholinesterase or other esterases would allow a critical examination of this carbamylation reaction and the ease of spontaneous and induced reactivation or decarbamylation. The physiological significance of cholinesterase inhibition might be examined by administering acetate-C{sup 14} and analysis for radiolabelled acetylcholine accumulation in nervous tissue, or by utilizing acetyl-C{sup 14}-choline as the substrate for in vitro determination of the degree of cholinesterase inhibition in tissues of poisoned animals with minimal dilution of the inhibitors and enzymes during analysis. Some progress has been made with radiolabelled materials in investigating the metabolism of carbamate insecticides. Sevin (1-naphthyl methylcarbamate) has been most extensively studied along with its potential hydrolysis products. The assumption that the metabolism of Sevin involves an initial hydrolysis and then further decomposition of the fragments was not supported by carbon-14 studies. The major detoxification mechanism in mammals, and probably also in insects, results from initial oxidative attack on the carbamate by the microsomes in the presence of reduced nicotinamide-adenine dinucleotide phosphate. Sevin is rapidly metabolized in mammals, but the fate of certain of the fragments has not been resolved. Some of the metabolites appear in the milk of lactating animals. One step in the metabolism appears to be formation of the N-methylol derivative. Preliminary studies on the metabolism of radiolabelled Dimetilan (2-diraethylcarbamyl- 3-methylpyrazolyl-(5)-dimethylcarbamate) and a related compound in cockroaches also indicate that oxidative attack forms N-methyl N-methylol derivatives. Much remains to be done on the relationship of these detoxification reactions to the resistance mechanism, the action of synergists, the selective toxicity in this group of insecticides, and the nature and significance of residues. Metabolism of Sevin following injection into plants is probably also oxidative rather than hydrolytic, but the nature of the products and the enzymatic mechanism have not yet been established. (author) [French] Les methylcarbamates constituent l'un des principaux groupes d'insecticides. Les radioindicateurs permettent d'etudier facilement de nombreux problemes que pose leur toxicologie. On a prepare des dimethylcarbamates en marquant le groupe carbonyle par {sup 14}C, et des methylcaibamates en marquant par {sup 14}C les groupes methyle et carbonyle et le noyau. L'action pharmacologique de ces composes resulte vraisemblablement de l'inhibition de l'acetylcholinesterase et peut impliquer une carbamylation. La reaction, avec de la cholinesterase ou d'autres esterases purifiees, des carbamates dont on a marque les groupe carbonyle et methyle permettrait de faire une etude critique de cette carbamylation et de la facilite avec laquelle se produit la reactivation ou decarbamylation, spontanee ou induite, L'importance physiologique de l'inhibition de la cholinesterase peut etre etudiee en administrant de l'acetate marque par {sup 14}C et en analysant l'accumulation de l'acetylcholine marquee dans les tissus nerveux, ou bien en utilisant de l'acetyl-{sup 14}C-choline comme substrat pour determiner in vitro le degre d'inhibition de la cholinesterase dans les tissus d'animaux traites, avec une dilution minimum des inhibiteurs et des enzymes pendant l'analyse. Les produits marques ont permis certains progres dans l'etude du metabolisme des insecticides a base de carbamates. On a etudie de maniere tres approfondie le Sevin (1-naphtyl methylcarbamate), en meme temps que ses produits d'hydrolyse eventuels. L'hypothese selon laquelle le metabolisme du Sevin implique une hydrolyse initiale, puis une nouvelle decomposition des produits d'hydrolyse, n'a pas ete confirmee par les etudes faites avec le carbone-14. Chea les mammiferes et probablement aussi chez les insectes, la detoxification resulte principalement d'une oxydation initiale du carbamate par les microsomes en presence de phosphate de nicotinamide adenide dinucleotide reduit. La metabolisation du Sevin est rapide chez les mammiferes, mais on n'a pas encore pu determiner le sort de certains des fragments. Quelques metabolites apparaissent dans le lait des animaux en lactation. L'une des etapes du metabolisme semble etre la formation d'un derive de N-methylol. Des etudes preliminaires sur le metabolisme du Dimetilan radiomarque (dimethylcarbamate de 5-[3-methyl-2 dimethylcarbamyl]-pyrazoline) et d'un compose voisin chez les blattes a montre egalement que l'oxydation forme des derives de N-methyl- N-methylol. P reste encore beaucoup a faire pour determiner le rapport qui existe entre ces reactions de detoxification et la resistance, l'action des agents synergetiques et la toxicite selective dans ce groupe d'insecticides, ainsi que pour determiner la nature et l'importance des residus. Il est egalement probable que le metabolisme du Sevin, a la suite d'injection dans des plantes, suit une voie oxydante plutot qu'une voie hydrolytique, mais la nature des produits et le mecanisme enzymatique n'ont pas encore ete determines. (author) [Spanish] Los metilcarbamatos constituyen uno de los principales grupos de insecticidas. Muchos de los problemas que su toxicologie plantea se pueden estudiar facilmente mediante radioindicadores. Se han preparado dimetilcarbamatos marcados con {sup 14}C en el grupo carbonilo, y metilcarbamatos marcados con {sup 14}C en los grupos metilo, carbonilo y, en el caso de derivados ciclicos, en el anillo. La accion farmacologica de estos compuestos se debe probablemente a la inhibicion de la acetilcolinesterasa y es posible que implique una carbamilacion. La reaccion con colinesterasa purificada u otras esterasas de los carbamatos marcados en los grupos carbonilo o metilo permitiria un examen critico de esta reaccion de carbamilacion y de la tendencia a la reactivacion o descarbamilacion espontanea e inducida. La importancia fisiologica de la inhibicion de la colinesterasa se podria estudiar administrando acetato-{sup 14}C y analizando la acumulacion de acetilcolina marcada en el tejido nervioso, o bien utilizando acetil-{sup 14}C-colina como substrato para la determinacion in vitro del grado de inhibicion de la colinesterasa en tejidos de animales envenenados, con una dilucion minima de los inhibidores y las enzimas durante el analisis. El empleo de. sustancias marcadas ha permitido realizar algunos progresos en la investigacion del metabolismo de los insecticidas a base de carbamato. Se ha estudiado principalmente el Sevin (metilcatbamato de 1-naftilo) y sus posibles productos de hidrolisis. Los estudios con {sup 14}C no corroboraron la hipotesis de que el metabolismo del Sevin implica una hidrolisis inicial seguida de una mayor descomposicion de los fragmentos. La principal desintoxicacion en los mamiferos, y probablemente tambien en loe insectos, es el resultado de un ataque oxidante inicial del carbamato por los microsomas en presencia de fosfato de nicotinamida-adenina-dinucleotido reducido. Los mamiferos metabolizan rapidamente el Sevin, pero no se ha averiguado todavia la evolucion ulterior de algunos de sus fragmentos. Algunos metabolitos aparecen en la leche de animales lactantes. Al parecer, una de las etapas metabolicas es la formacion de un derivado N-metilol. Estudios preliminares, efectuados en la cucaracha, del metabolismo del Dimetilan radiomarcado (dimetilcarbamato de 5-[3-metil-2-dimetilcarbamil]- pirazolina) y un compuesto comparable indican tambien que el ataque oxidante forma derivados N-metilo y N-metilol. Faltan todavia muchos datos sobre la relacion entre esas reacciones de desintaxicacion y el mecanismo de resistencia, la accion de las sustancias sinergicas, la toxicidad selectiva de este grupo de insecticidas, y la naturaleza y el significado de los residuos. Es probable tambien que el metabolismo del Sevin inyectado en las plantas sea oxidativo mas que hidrolitico, pero no se ha establecido todavia la naturaleza de los productos y el mecanismo enzimatico. (author) [Russian] Metilkarbamaty yavlyayutsya odnoj iz glavnykh grupp insektitsidov. Mnogie nerazreshennye problemy toksikologii ehtikh veshchestv mogut byt' legko izucheny pri pomoshchi radioaktivnykh indikatorov. Byli izgotovleny N, N-dimetidkarbamaty, karbonilovaya gruppa kotorykh metilas' C{sup 14}, a takzhe N-metilkar- bamaty, metilovaya, karbonilovaya gruppa i kbl'tsa kotorykh byli mecheny C{sup 14}. Farmakologicheskoe dejstvie ehtikh slozhnykh soedinenij, veroyatno, svyazano s tormozheniem atsetilkholinesteraehy i mozhet vklyuchat' karbamilatsiyu. Mechenie karbonilovoj ili metilovoj gruppy karbamatov daet vozmozhnost' v ikh reaktsiyakh s ochishchennoj kholinesterazoj ili s drugimi ehsterazami kriticheski izuchit' reaktsiyu karbamida tsii, a takzhe legkost' samoproizvol'noj ili vyzvannoj reaktivatsii ili dekarbamilatsii. Fiziologicheskoe znachenie tormozheniya kholinesterazy mozhet byt' izucheno pri pomoshchi vvedeniya mechennogo C{sup 14} atsetata i analiza mechenogo atsetilkholina, nakopivshegosya v nervnykh tkanyakh, ili zhe putem ispol'zovaniya atsetil-C{sup 14}-kholina v kachestve substrata dlya opredeleniya In vitro stepeni tormozheniya kholiya- esterazy v tkanyakh otravlennykh zhivotnykh pri minimal'nom rastvorenii vo vremya analiza ingibitorov i fermentov.Nekotorye'uspekhi byli dostignuty pri pomoshchi mechennykh radioizotopami veshchestv v issledovanii metabolizma karbamatnykh insektitsidov. Sevin (1-naphtyl N-methylcarbamate) byl naibolee tshchatel'no izuchen parallel'no s vozmozhnymi produktami ego gidroliza. Issledovaniya s pomoshch'yu ugleroda-14 ne podtverdili gipotezy o tom, chto pri metabolizme sevina proiskhodit pervonachal'nyj gidroliz, a zatem dal'nejshee razlozhenie produktov gidroliza. Osnovnoj mekhanizm obezvrezhivaniya insektitsida v organizme mlekopitayushchikh i, veroyatno, nasekomykh zaklyuchaetsya v pervonachal'nom okislyayushchem vozdejstvii mikrosom na kehrbamaty v prisutstvii vosstanovlennogo nikotinamid-adenindi-nukleotid fosfata. Sevin bystro podvergaetsya raspadu u mlekopitayushchikh, no sud'ba nekotorykh produktov raspada eshche ne vyyasnena. Nekotorye iz produktov metabolizma mogut byt' obnaruzheny v moloke zhivotnykh. Odnoj iz stupenej metabolizma, po-vidimomu, yavlyaetsya obrazovanie proizvodnogo N-metilola. Predvaritel'nye issledovaniya metabolizma mechennogo radioaktivnymi veshchestvami dime-tilana (2-dimetilkarbamid-3-metilpirazolil-(5)-dimetilkarbamat) i metabolizma podobnogo soedineniya u tarakanov ukazyvaet takzhe na to, chto pri okislenii obrazuyutsya proizvodnye N-metila i N-metilola. Mnogoe ostaetsya sdelat' dlya vyyasneniya svyazi ehtikh reaktsij obezvrezhivaniya s mekhanizmom soprotivlyaemosti, dejstviem sinergistov, selektivnoj toksichnost'yu ehtoj gruppy insektitsidov, a takzhe s prirodoj i znacheniem ostatkov insektitsida. Metabolizm sevina, vvedennogo v rasteniya, nosit, veroyatno, takzhe skoree okislitel'nyj, a ne gidroliticheskij kharakter, ko kharakter produktov i fermentativnye mekhanizmy eshche ne ustanovleny. (author)}
place = {IAEA}
year = {1963}
month = {Sep}
}