The first step in the metabolism of carbamates is hydrolysis to carbamic acid, which decomposes to carbon dioxide (CO2) and the corresponding amine. The mechanism of hydrolysis is different for N -methyl and N -dimethyl derivatives. The N -methyl carbamates pass through an isocyanate intermediate, whereas in the hydrolysis of N - dimethylcarbamates, an addition product with a hydroxyl ion is formed yielding the alcohol and N -dimethyl substituted acid. The rate of hydrolysis by esterases is faster in mammals than in plants and insects. Apart from hydrolysis, oxidation also takes place including: hydroxylation of the aromatic ring, O -dealkylation, N -methyl hydroxylation, N -dealkylation, oxidation of aliphatic side chains, and sulfoxidation to the corresponding sulfone. Oxidation is associated with the mixed-function oxidase (MFO) enzymes. Conjugation leads to the formation of O - and N -glucuronides, sulfates, and mercapturic acid derivatives in mammals. Glycosides and phosphates are conjugation products more common in plants. /Carbamate Pesticides/
The fate of Croneton, 2-ethylthiomethylphenyl N-methylcarbamate, was determined in rats following single oral or dietary exposure to the 14C-carbonyl- and 14C-ring-labeled insecticide. Greater than 95% of the (14C)Croneton equivalents was excreted in the urine or as a combination of 14CO2 (47%) and urinary products (41%) 72 hr after a single oral dose. The feces contained 27% of the dose. A similar excretion pattern was observed during a 7-day feeding period. The principal urinary metabolites were Croneton sulfoxide (23-28% of the dose), phenol sulfoxide (20-23%), phenol sulfone (9-25%), and Croneton sulfone (3-11%) after a single oral dose and similar in the long term study. The carbamates were excreted primarily as free metabolites while the phenolic constituents were eliminated as acid labile conjugates.
The comparative ester hydrolysis and selective toxicity of carbamate insecticides were studied in 4 mammalian species. Hydrolysis rates of carbaryl and ethiofencarb (Croneton) were examined in the rat, mouse, guinea pig and gerbil. Respiratory 14CO2 resulting from the hydrolysis of orally administered (carbonyl-14C)carbamates (0.2 mg/kg) was taken as measure of in vivo hydrolytic capabilities. Ester hydrolysis was greater for ethiofencarb in all species tested, although the relative order of hydrolysis among species was the same with both compounds. After 24 hr, gerbils had hydrolyzed 91% of the ethiofencarb an 65% of the carbaryl. Guinea pigs hydrolyzed somewhat less of the compounds, 65 and 85%, but more than rats and mice, 40 and 25%.
About 75% of the radiocarbon in the eggs /from White Leghorn hens given one to 14 oral doses of croneton/ occurred as free phenol sulfoxide and sulfone, 10% occurred as free croneton sulfoxide and croneton sulfone, 5% occurred as water-soluble metabolites, and 5% occurred as unextracted residues. The remaining 5% was accounted for by unknown metabolites in the organo-extractable fraction.
Ethiofencarb is a cholinesterase or acetylcholinesterase (AChE) inhibitor. Carbamates form unstable complexes with chlolinesterases by carbamoylation of the active sites of the enzymes. This inhibition is reversible. A cholinesterase inhibitor suppresses the action of acetylcholine esterase. Because of its essential function, chemicals that interfere with the action of acetylcholine esterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses. Headache, salivation, nausea, vomiting, abdominal pain and diarrhea are often prominent at higher levels of exposure. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop.
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌物分类
对人类不具有致癌性(未被国际癌症研究机构IARC列名)。
No indication of carcinogenicity to humans (not listed by IARC).
Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Chronically high (>10 years) exposure leads to neuropsychological consequences including disturbances in perception and visuo-motor processing (A15321).
来源:Toxin and Toxin Target Database (T3DB)
毒理性
暴露途径
这种物质可以通过吸入、皮肤接触和摄入被身体吸收。
The substance can be absorbed into the body by inhalation, through the skin and by ingestion.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
When administered as a single oral dose to rats, 41% of the carbonyl-labelled compound was eliminated in the urine and 7% in the feces (within 72 hr), while 47% was eliminated as 14CO2. When similarly administered but in ring-labelled form, 96% was eliminated in the urine and 2% in the feces within 72 hr. The compound, therefore, undergoes hydrolysis, producing a phenol and a carbamic acid derivative which breaks down further to CO2.
Maintenance of rats on a diet containing 6.6 ppm of ethiofencarb gave ...total excretion (urine plus feces) decreasing to 1% of one day's intake by the third day after return of the animals to the normal diet. The major metabolites identified were the sulfoxide and sulfone of ethiofencarb and the sulfoxide and sulfone of the phenol; the latter two compounds were excreted mainly as conjugates, and the parent compound was detected in the urine only in trace amounts. Tissue residues detected after either a single oral dose of 0.5 mg/kg bw or administration of 6.6 ppm in the diet for one week were below 1 mg/kg, and these declined more rapidly after administration of the ring-labelled than the carbonyl-labelled compound. This suggests that the carbonyl-labelled residues were incorporated into normal tissues components, as would be expected.
Bile-duct-cannulated rats were orally administered 14C-ethiofencarb. Biliary radioactive carbon measurements made two days after administration revealed the following percentage of the dose 20.2%. /Most/ of the dose was eliminated in the urine, while the feces did not exceed an elimination rate of 3%. Enterohepatic circulation of metabolites is suggested by these findings.
A lactating Holstein cow and a male Yorkshire pig treated with a single oral dose (0.5 mg/kg) of ring (14C) croneton excreted 97.8% and 90.0% of the dose, respectively, in the urine after 24 hr. None of the swine tissues examined 24 hr after treatment contained detectable residues, and of the bovine tissues, only the kidney, liver, and skin contained detectable activity (0.016, 0.017, and 0.05 ppm 14C-croneton equivalents, respectively). Milk collected from the cow 6 hr after treatment contained 128 ppb 14C residues; 60% of this was as the free carbamate metabolites, croneton sulfoxide and sulfone. White Leghorn hens given ring 14C-croneton as a single oral dose (0.5 mg/kg) or in twice-daily doses (0.5 mg/kg) over 7 consecutive days showed patterns of metabolism and excretion similar to those observed in the pig and cow. Birds sacrificed 4 hr after the last dose contained from 0.019 ppm 14C-croneton equivalents in the fat to 0.324 ppm in the kidney. By 24 hr, only the liver and kidney (0.044 and 0.022 ppm, respectively) contained residues in excess of 0.01 ppm, and within 4 days the residues in these organs were 0.01 ppm or less. Residues in eggs laid by these hens were 0.03 to 0.04 ppm 14C-croneton equivalents 2 days after treatment; egg residues reached a maximum of 0.06 to 0.07 ppm 7 days after treatment and declined rapidly following the termination of treatment. About 75% of the radiocarbon in the eggs occurred as free phenol sulfoxide and sulfone, 10% occurred as free croneton sulfoxide and croneton sulfone, 5% occurred as water-soluble metabolites, and 5% occurred as unextracted residues. The remaining 5% was accounted for by unknown metabolites in the organo-extractable fraction.
[EN] BICYCLYL-SUBSTITUTED ISOTHIAZOLINE COMPOUNDS<br/>[FR] COMPOSÉS ISOTHIAZOLINE SUBSTITUÉS PAR UN BICYCLYLE
申请人:BASF SE
公开号:WO2014206910A1
公开(公告)日:2014-12-31
The present invention relates to bicyclyl-substituted isothiazoline compounds of formula (I) wherein the variables are as defined in the claims and description. The compounds are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.
The present invention relates to azoline compounds of formula (I) wherein A, B1, B2, B3, G1, G2, X1, R1, R3a, R3b, Rg1 and Rg2 are as defined in the claims and the description. The compounds are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.