Plasma & tissue enzymes are responsible for hydrolysis /of organophosphorus compounds/ to the corresponding phosphoric & phosphonic acids. However, oxidative enzymes are also involved in the metabolism of some organophosphorus compounds. /Anticholinesterase agents/
The organophosphorus anticholinesterase agents are hydrolyzed in the body by a group of enzymes known as A-esterases or paroxonase. The enzymes are found in plasma and in the hepatic endoplasmic reticulum & can hydrolyze a large number of organophosphorus compounds ... by splitting the anhydride, P-F, P-CN, or ester bond. /Anticholinesterase agents/
These chemicals are detoxified by cytochrome p450 mediated monooxygenases in the liver, but some metabolites are more toxic than parent cmpd. ... Metabolites usually are detected from 12 to 48 hr postexposure. /Organophosphate cmpd/
The detoxification of bromophos takes place at both the methyl and the phenyl phosphate bonds. Following dermal application to cows, bromophos could be detected in the blood at a concentration of about 0.01 ppm, but bromoxon was not detectable. The main metabolite in this species was desmethylbromophos, which was detected in concentrations of 0.4 to 0.7 ppm in both milk and blood. Following ingestion, guinea pigs excrete a substantial proportion of insecticidal material in their feces, either as the parent compound or as some unidentified, insecticidal metabolite.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
副作用
职业性肝毒素 - 第二性肝毒素:在职业环境中的毒性效应潜力是基于人类摄入或动物实验的中毒病例。
Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
A number of phosphorothionate (P = S) insecticides, including bromophos and fenitrothion, prevent trialkyl phosphorothiolate (P = O) induced lung toxicity and the resulting increase in lung weight normally observed at 3 days in the rat. Oxidative metabolism of phosphorothionates known to occur at the P = S moiety, with suicidal loss of p450, may then prevent oxidative activation of an S-methyl on the phosphorothiolates, the most likely site for production of a reactive intermediate capable of damaging the lung. Lung 7- ethoxycoumarin O-deethylase in rat is sensitive to concentrations of the phosphorothionates bromophos and fenitrothion at 5-25 times less than those causing loss of liver 7-ethoxycoumarin O-deethylase activity and at doses 125-600 times less than their LD50s.
Airway protection. Insure that a clear airway exists. Intubate the patients and aspirate the secretions with a large-bore suction device if necessary. Administer oxygen by mechanically assisted pulmonary ventilation if respiration is depressed. Improve tissue oxygenation as much as possible before administering atropine, so as to minimize the risk of ventricular fibrillation. In severe poisonings, it may be necessary to support pulmonary ventilation mechanically for several days. /Organophosphate pesticides/
Atropine sulfate. Administer atropine sulfate intravenously, or intramuscularly if intravenous injection is not possible. Remember that atropine can be administered through an endotracheal tube if initial IV access if difficult to obtain. Depending on the severity of poisoning, doses of atropine ranging from very low to as high as 300 mg/day may be required, or even continuous infusion. The objective of atropine antidotal therapy is to antagonize the effects of excessive concentrations of acetylcholine at end-organs having muscarinic receptors. Atropine does not reactivate the cholinesterase enzyme or accelerate disposition of organophosphate. Recrudescence of poisoning may occur if tissue concentrations of organophosphate remain high when the effect of atropine wears off. Atropine is effective against muscarinic manifestations, but it is ineffective against nicotinic actions, specifically muscle weakness and twitching, and respiratory depression. Despite the limitations, atropine is often a life-saving agent in organophosphate poisonings. Favorable response to a test dose of atropine (1 mg in adults, 0.01 mg/kg in children under 12 years) can help differentiate poisoning by anticholinesterase agents from other conditions. However, lack of response, with no evidence of atropinization (atropine refractoriness) is typical of more severe poisonings. The adjunctive use of nebulized atropine has been reported to improve respiratory distress, decrease bronchial secretions, and increase oxygenation. /Organophosphate pesticides/
... The organophosphorus insecticides are, in contrast to the chlorinated insecticides, rapidly metabolized & excreted and are not appreciably stored in body tissues. /Organophosphorus insecticides/
1.周国泰,化学危险品安全技术全书,化学工业出版社,1997 2.国家环保局有毒化学品管理办公室、北京化工研究院合编,化学品毒性法规环境数据手册,中国环境科学出版社.1992 3.Canadian Centre for Occupational Health and Safety,CHEMINFO Database.1998 4.Canadian Centre for Occupational Health and Safety, RTECS Database, 1989
[EN] ISOXAZOLINE DERIVATIVES AS INSECTICIDES<br/>[FR] DÉRIVÉS D'ISOXAZOLINE EN TANT QU'INSECTICIDES
申请人:SYNGENTA PARTICIPATIONS AG
公开号:WO2011101402A1
公开(公告)日:2011-08-25
The present invention relates to compounds formula (I), wherein P is P1, P2, heterocyclyl or heterocyclyl substituted by one to five Z; and wherein A1, A2, A3, A4, G1, R1, R2, R3, R4, R5, R6, R17, R18, R19 and R20 are as defined in claim 1; or a salt or N-oxide thereof. Furthermore, the present invention relates to processes and intermediates for preparing compounds of formula (I), to insecticidal, acaricidal, nematicidal and molluscicidal compositions comprising the compounds of formula (I) and to methods of using the compounds of formula (I) to control insect, acarine, nematode and mollusc pests.
The present invention relates to compounds formula (I), wherein P is P1, P2, heterocyclyl or heterocyclyl substituted by one to five Z; and wherein A
1
, A
2
, A
3
, A
4
, G
1
, R
1
, R
2
, R
3
, R
4
, R
5
, R
6
, R
17
, R
18
, R
19
and R
20
are as defined in claim
1
; or a salt or N-oxide thereof. Furthermore, the present invention relates to processes and intermediates for preparing compounds of formula (I), to insecticidal, acaricidal, nematicidal and molluscicidal compositions comprising the compounds of formula (I) and to methods of using the compounds of formula (I) to control insect, acarine, nematode and mollusc pests.