...Rats were given 30 mg/kg isoxathion and subjected to whole body autoradiography 1 and 24 hours after dosing. ...At least 11 radioactive metabolites were detected. Four of these were identified: 3-hydroxy-5-phenylisoxazole, hippuric-acid, 3-(beta-D-glucopyranuronosyloxy)-5-phenylisoxazole, and 5-phenyl-3-isoxazolyl-sulfate.
Metabolism occurs principally by oxidation, hydrolysis by esterases, and by transfer of portions of the molecule to glutathione. Oxidation of organophosphorus insecticides may result in more or less toxic products. In general, phosphorothioates are not directly toxic but require oxidative metabolism to the proximal toxin. The glutathione transferase reactions produce products, that are, in most cases, of low toxicity. Hydrolytic and transferase reactions affect both the thioates and their oxons. /Organophosphorus Pesticides/
Because different classes of enzymes may be inhibited, the effects of organophosphorus pesticide poisoning may be complex and potentially at least could involve interactions with drugs as well as with other pesticides or chemicals. Potentiation may also involve solvents or other components of formulated pesticides. Certain drugs such a phenothiazines, antihistamines, CNS depressants, barbiturates, xanthines (theophylline), aminoglycosides and parasympathomimetic agents are to be avoided because of increased toxicity. /Organophosphorus pesticides/
Airway protection. Ensure 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...high... . 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 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. ...Do not administer atropine or pralidoxime prophylactically to workers exposed to organophosphate pesticides. Prophylactic dosage with either atropine or pralidoxime may mask early signs and symptoms of organophosphate poisoning and thus allow the worker to continue exposure and possibly progress to more severe poisoning. Atropine itself may enhance the health hazards of the agricultural work setting: impaired heat loss due to reduced sweating and impaired ability to operate mechanical equipment due to blurred vision. This can be caused by mydriasis, one of the effects of atropine. /Organophosphate pesticides/
Male Wistar-rats were dosed orally with 20 mg/kg carbon-14 labeled isoxathion. Urine, feces, and expired air were collected for up to 24 hours after dosing and assayed for carbon-14. Selected animals were killed between 30 min and 24 hr after dosing and the tissue distribution of carbon-14 activity was determined. Urine and feces samples were analyzed for metabolites. Rats were given 30 mg/kg isoxathion and subjected to whole body autoradiography 1 and 24 hours after dosing. Radiolabel was rapidly excreted mainly in the urine, 82.5% being eliminated in the first 24 hr. Cumulative excretion of carbon-14 amounted to 85% in the urine and 14% in the feces. Only negligible amounts of radiolabel were excreted in expired gases. Tissue carbon-14 activity was maximal 30 min after dosing, the largest amounts occurring in the liver, kidney, and blood. Only negligible amounts of tissue radioactivity were found after 24 hr. Autoradiography showed that initially the highest radioactivity occurred in the gastrointestinal contents. Large amounts were observed in the liver and kidney. After 24 hours, significant radioactivity occurred only in the intestinal contents.
[EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
申请人：GILEAD APOLLO LLC
公开号：WO2017075056A1
公开（公告）日：2017-05-04
The present invention provides compounds I and II useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.
[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.
