Within 48 hours of administration of carbonyl-(14)C labelled aldicarb rats eliminated over 60% of the (14)C as carbon dioxide, less than 30% was found in the urine. In other (14)C-studies rats excreted more than 80% of the degradation products in urine and less than 10% in faeces (an excretion pattern favoured by enterohepatic cycling of glucuronides which may also serve to extend the systemic activity of the toxic metabolites). The major urinary metabolites were aldicarb sulfoxide (40% of the dose), its oxime and nitrile forms (over 30%); the sulfone and related oxime and nitrile; and, the aldehyde and acid analogues. Aldicarb is not commonly found in the excreta. Bound residues of ingested plant tissues are not absorbed and therefore are found in the faeces. In single dose and short-term diet studies, lactating cows eliminated aldicarb metabolites as rapidly as rats and in the same array of metabolites. Approximately 1% of the dose was excreted in the milk, sulfone and sulfoxide were the major metabolites at 15 and 4% of the total milk residue content respectively.
... Aldicarb is metabolized by both oxidative pathways and hydrolytic processes. Oxidation results in cmpd which are also active cholinesterase inhibitors, while hydrolysis produces cmpd of little or no insecticidal activity or toxicity to other organisms.
The major route of elimination of Temik-(35)S /aldicarb/ ... admin to lactating cow was by way of urine. Extracted and tentatively identified in milk were 11 compounds, incl temik sulfoxide and sulfone, oxime sulfoxide and sulfone, nitrile sulfoxide & sulfone, temik oxime, and 4 unidentified compounds. Metabolites identified in urine were qualitatively identical but differed quantitatively. Only 5 metabolites were identified in feces: temik oxime, oxime sulfoxide, temik sulfoxide, temik sulfone and nitrile sulfone.
In rats, sulfoxide accounted for 40% of dose /of aldicarb/ and sulfone for 1%; both ... are more potent anticholinesterases than aldicarb. Metabolite in cow's milk and urine was hydroxymethyl analogue of sulfone; two other bovine metabolites were 2-methyl-2-(methylsulfinyl)propanol and 2-methyl-2-(methylsulfonyl)propanol.
IDENTIFICATION: Aldicarb is a carbamate ester pesticide. It is a white crystalline solid, moderately soluble in water, and susceptible to oxidation and hydrolytic reactions. HUMAN EXPOSURE: Exposure of the general population to aldicarb and its toxic metabolites (the sulfoxide and sulfone) occurs mainly through food. The ingestion of contaminated food has led to poisoning incidents from aldicarb and its toxic metabolites (the sulfoxide and sulfone). Due to the high acute toxicity of aldicarb, both inhalation and skin contact under occupational exposure conditions may be dangerous for workers if preventive measures are inadequate. There have been a few incidents of accidental exposure of workers due to improper use or lack of protective measures. Aldicarb is efficiently absorbed from the gastrointestinal tract and, to a lesser extent, through the skin. It could be readily absorbed by the respiratory tract if dust were present. It is metabolically transformed to the sulfoxide and the sulfone (both of which are toxic), and is detoxified by hydrolysis to oximes and nitriles. The excretion of aldicarb and its metabolites is rapid and primarily via the urine. A minor part is also subject to biliary elimination and, consequently, to enterohepatic recycling. Aldicarb does not accumulate in the body as a result of long-term exposure. The inhibition of cholinesterase activity in vitro by aldicarb is spontaneously reversible, the half-life being 30-40 min. The inhibition of acetylcholinesterase at the nervous synapse and myoneural junction is the only recognized effect of aldicarb in humans and is similar to the action of organophosphates. The carbamyolated enzyme is unstable, and spontaneous reactivation is relatively rapid compared with that of a phosphorylated enzyme. Non-fatal poisoning in man is rapidly reversible. Recovery is aided by the administration of atropine. ANIMAL STUDIES: Aldicarb is a potent inhibitor of cholinesterases and has a high acute toxicity. Recovery from its cholinergic effects is spontaneous and complete within 6 hr, unless death results. There is no substantial evidence to indicate that aldicarb is teratogenic, mutagenic, carcinogenic, or immunotoxic. Birds and small mammals have been killed as a result of ingesting aldicarb granules not fully incorporated into the soil as recommended. In laboratory tests, aldicarb is acutely toxic to aquatic organisms.
Evaluation: No data were available from studies in humans. There is inadequate evidence for the carcinogenicity of aldicarb in experimental animals. Overall evaluation: Aldicarb is not classifiable as to its carcinogenicity to humans (Group 3).
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
癌症分类：人类非致癌性证据E组
Cancer Classification: Group E Evidence of Non-carcinogenicity for Humans
CLASSIFICATION: D; not classifiable as to human carcinogenicity. BASIS FOR CLASSIFICATION: Aldicarb was not found to induce statistically significant increases in tumor incidence in mice or rats in feeding studies or mice in a skin painting study. In the feeding studies there were, however, significant trends in pituitary tumors in female rats and fibrosarcomas in the male mouse. This evidence, together with the fact that less than maximum tolerated doses were used, indictes that the available assays are inadequate to assess the carcinogenic potential of aldicarb. HUMAN CARCINOGENICITY DATA: None. ANIMAL CARCINOGENICITY DATA: Inadequate. /Based on former classification system/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
国际癌症研究机构致癌物：阿德卡宾
IARC Carcinogenic Agent:Aldicarb
来源:International Agency for Research on Cancer (IARC)
Male rats (Carworth Farms-Elias Stock) were treated orally or ip with labeled Temik in ethanol or Temik sulfoxide in water. Excretion of s-methyl-(14)C & tert-butyl-(14)C temik was completed, essentially, in 4 days. N-methyl-(14)C was excreted in urine & feces up to 11 days.
Aldicarb is readily absorbed from GI tract of treated animals. Excretion of radiolabeled cmpd admin to rats is primarily in urine, as approx 80% appears within 24 hr, with additional 1% in feces. Only traces of unchanged parent cmpd were found in excreta. When aldicarb is labeled on n-methyl carbon or carbonyl carbon large portion of radioactivity is found in expired air as (14)CO2. Very little aldicarb residues are found in tissues or carcasses of treated animals.
To measure the excretion of aldicarb admin repeatedly, dogs were maintained on diets determining an intake of 0.75 mg/dog/day for 20 days before & 10 days after being given a single (14)C-labeled dose. Of the radioactivity recovered in the urine, 90% was found within 24 hr after admin of the radiolabeled aldicarb.
Aldicarb is readily absorbed through the gut in rats and cows and through the skin in rats and rabbits. It is rapidly metabolized and excreted within 24 hours of exposure, almost all of the toxic and nontoxic metabolites being excreted in urine.
The synthesis of 1-chloroalkyl carbonates and their reaction with various type of amines are described. This reaction is useful for the synthesis of carbamate pesticides and for the protection of various amino groups, including amino acids.
Genetic toxicity of <i>N</i>-methylcarbamate insecticides and their <i>N</i>-nitroso derivatives
作者：T. C. Wang、C. M. Chiou、Y. L. Chang
DOI：10.1093/mutage/13.4.405
日期：——
N-Methylcarbamate esters are an important group of insecticides. They have lower acute toxicity to vertebrates than organophosphates, although their genotoxicity has not been adequately studied. Here we investigate the cytotoxicity and genotoxicity of N-methylcarbamateinsecticides and their N-nitroso derivatives in Chinese hamster V79 cells, using the hprt locus as a marker, and also assess inhibition
A Fluorescence Detection Scheme for Capillary Electrophoresis of <i>N</i>-Methylcarbamates with On-Column Thermal Decomposition and Derivatization
作者：Yuan Sheng Wu、Hian Kee Lee、Sam F. Y. Li
DOI：10.1021/ac990928d
日期：2000.4.1
conditions, fluorescence detection of 10 NMC compounds was achieved, with column efficiencies typically higher than 50,000 and detection limits better than 0.5 ppm. The present work represents an unprecedented effort in capillaryelectrophoresis (CE), in which an intact capillary was consecutively utilized as chambers for separation, decomposition, derivatization, and detection, without involving any
Determination of the rate of aldicarb sulphoxidation in rat liver, kidney and lung microsomes
作者：M. PELEKIS、K. KRISHNAN
DOI：10.1080/004982597239877
日期：1997.1
sulphoxidation of aldicarb (2-methyl-2-(methylthio) propanal O-[(methylamino) carbonyl oxime], Temik) in rat hepatic, renal and pulmonary microsomes was determined by quantitating the levels of aldicarb sulphoxide and aldicarb sulphone produced during incubations. Under in vitro experimental conditions used in the present study, aldicarb sulphoxide was the only metabolite produced, and further metabolism of aldicarb
1.通过定量涕灭威亚砜和涕灭威的含量，确定涕灭威（2-甲基-2-（甲硫基）丙醛O-[（甲基氨基）羰基肟]，Temik）在大鼠肝，肾和肺微粒体中的硫氧化速度。孵育过程中产生的砜。在本研究中使用的体外实验条件下，涕灭威亚砜是唯一产生的代谢产物，而涕灭威亚砜进一步代谢为涕灭威砜的作用可忽略不计。2.基于产物形成的测量，在肝脏，肾脏和肺微粒体中，涕灭威硫氧化的平均最大速度（mumol / min / mg蛋白质）分别为5.41、39.51和2.45。米氏常数（microM）的相应值分别为184、1050和188。3。
The delayed genotoxic effect of N-nitroso N-propoxur insecticide in mammalian cells
作者：Chih-Min Lin、L.Y. Wei、Tsing-Cheng Wang
DOI：10.1016/j.fct.2006.11.015
日期：2007.6
N-nitroso derivative of an extensively used insecticide, propoxur, consistently induced dose-responsive chromosome aberrations and sister-chromatid exchanges (SCEs) in Chinese hamster ovary (CHO-W8) cells. Further investigations indicated that post-treatment incubation with a regular 1.5-cell-cycle period did not offer an unbiased estimation of the genotoxicity of N-nitroso carbamate insecticides. The scale
