Cattle tick Boophilus microplus was exposed to labeled coumaphos. ... UV and IR spectroscopy and chromatography were used to show the presence of unchanged coumaphos, oxygen analog, ethyl phosphate, ethyl phosphorothioate, orthophosphate, desethyl analogs, and an unknown metabolite.
(32)P ... coumaphos was applied dermally to a cow and a goat. Unextractable residues were significant in tissues of both animals. Most of the radioactivity appearing in the urine was as hydrolysis products. Some of oxygen deriv of coumaphos was found in initial (up to 6 hr) collections, but thereafter, hydrolysis products were predominant: 35% phosphoric acid, 17% diethyl phosphoric acid, 29% diethyl phosphorothioic acid and 18% as the the de-ethylated coumaphos and as oxygen analog, primarily.
In vitro studies with house fly and cattle grub ... homogenates have shown that coumaphos is activated to a cholinesterase inhibitor, presumably to oxygen analog but no degradation occurs. ... These findings are consistent with selective toxicity of coumaphos.
Metabolism of organophosphates occurs principally by oxidation, by hydrolysis via esterases and by reaction with glutathione. Demethylation and glucuronidation may also occur. Oxidation of organophosphorus pesticides may result in moderately 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. Paraoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of organophosphate exposure.
IDENTIFICATION AND USE: Coumaphos is an organophosphate insecticide used for control of a wide variety of insects on cattle and parasitic mites (Varroa jacobson) on bees. It is also used in veterinary medicine for the treatment of screwworms, maggots, and ear ticks on livestock. Registered for use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. HUMAN EXPOSURE AND TOXICITY: The signs and symptoms of a human exposure to coumaphos are similar to general exposure to organophosphates: potent cholinesterase enzyme inhibitors that act by interfering with the metabolism of acetylcholine, which results in accumulation of acetylcholine at neuroreceptor transmission sites. Exposure produces a broad spectrum of clinical effects indicative of massive overstimulation of the chlorinergic system, including muscarinic effects (parasympathetic), nicotinic effects (sympathetic and motor), and CNS effects. These effects present clinically as feeling of headache, weakness, dizziness, blurred vision, psychosis, respiratory difficulty, paralysis, convulsions, and coma. According to case reports, human exposure can occur due to accidental ingestion from contaminated food, intentional ingestion or inhalation. ANIMAL STUDIES: Dermal administration of single (50-500 mg/kg) or daily (100 mg/kg) doses of coumaphos resulted in delayed neurotoxicity in hens. Coumaphos caused loss of weight and produced ataxia, which progressed to paralysis and death. Some hens given a single oral 50 mg/kg dose or daily 5 mg/kg doses of coumaphos recovered from the initial cholinergic effect and developed clinical signs of delayed neurotoxicity. A bioassay of coumaphos for possible carcinogenicity was conducted by administering the test chemical in feed to rats and mice. In both rats and mice, no tumors occurred in the dosed groups of either sex at incidences that were significantly higher than those in corresponding control groups. Weekly spraying at concentration of 200-400 ppm or weekly dipping in solution containing 200 ppm for 2 year period had no adverse effect on cattle. ECOTOXICITY STUDIES: In water fowl exposed to coumaphos, signs appeared as soon as 40 min in mallard ducks and 90 min in pheasants and mortalities usually occurred between 2 and 3 hour after treatment. Recovery took up to 14 days.
Coumaphos is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. 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. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌性证据
癌症分类：不太可能对人类致癌
Cancer Classification: Not Likely to be Carcinogenic to Humans
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
A4；不可分类为人类致癌物。
A4; Not classifiable as a human carcinogen.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
对人类不具有致癌性（未列入国际癌症研究机构名录）。
No indication of carcinogenicity to humans (not listed by IARC).
... Rats treated orally eliminated 70% of the applied dose in 7 days compared to about 5% after dermal treatment. ... Tissues from animals treated with coumaphos have been shown to contain largely degradation products.
When Rhode island hens were fed mash containing labeled coumaphos, considerably more radioactive material appeared in yolk than ... white or shell of eggs. Peak of radioactivity in eggs appeared 11-15 days after beginning of treatment and was present ... 6-8 days after return to normal diets.
Albino Wistar rats were given (14)C-labeled chlorferron, a metabolite of the ectoparasiticide coumaphos, in a a single dose of 20 mg/kg. In another experiment, a group of male rats were given single equimolar doses of either (14)C-labeled chlorferron (0.5 mg/kg) or (14)C-labeled coumaphos (0.86 mg/kg). Following both dose levels of chlorferron, more than 90% of the total (14)C admin was excreted in urine and feces during the first 24 hr. Fecal route of excretion was minor. The total urinary and fecal recoveries of (14)C after a period of 7 days following the admin of coumaphos were significantly lower at 79.1% chlorferron than at 93.7% chlorferron. Results indicate that chlorferron is not the end product of coumaphos metabolism in rats, and rapidly degrades to another metabolite.
[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.
