NIOSH REL: TWA 1 mg/m3, IDLH 100 mg/m3; OSHA PEL: TWA 1
ppm; ACGIH TLV: TWA 0.1 ppm.
物理描述：
Dichlorvos appears as a colorless to amber liquid with an aromatic odor. When heated to high temperatures may emit toxic chloride fumes and phosgene gas. Toxic by inhalation, skin absorption or ingestion. Used as a pesticide. May be found in the form of a dry mixture where the liquid is absorbed onto a dry carrier.
颜色/状态：
Colorless liquid
气味：
Aromatic odor
蒸汽密度：
Relative vapor density (air = 1): 7.6
蒸汽压力：
1.58X10-2 mm Hg at 25 °C
稳定性/保质期：
Stable under recommended storage conditions.
分解：
Hazardous decomposition products formed under fire conditions - Carbon oxides, oxides of phosphorus, hydrogen chloride gas.
腐蚀性：
Corrosive to iron & mild steel
折光率：
Index of refraction = 1.451 at 25 °C/D
碰撞截面：
138.7 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]
Dichlorvos binds to acetylcholinesterase forming dimethoxy-phosphorylated acetycholinesterase and dichloroacetaldehyde. Alternatively, it is metabolized (primarily in the liver but also in the blood, adrenal, kidney, lung, and spleen) via 2 pathways. The major pathway is catalyzed by A-esterases and produces dimethyl phosphate and dichloroacetaldehyde. Dichloroacetaldehyde is converted to dichloroethanol which is then excreted as the glucuronide. Alternatively, dichloroacetaldehyde is dehalogenated and the carbon atoms are incorporated into normal tissue constituents via intermediary metabolism. The second minor pathway is catalyzed by glutahione-S-transferase and produced desmethyl dichlorvos and S-methyl glutathione. Subsequent degradation of desmethyl dichlorvos to dichloroacetaldehyde and monomethyl phosphate is catalyzed by A-esterases. S-methyl glutathione is broken down to methylmercapturic acid and excreted in urine. CO2 is also the major metabolite following inhalation exposures. The major urinary metabolite following either oral or inhalation exposures is dichloroethanol glucuronide.
Dichlorvos is rapidly metabolized in human blood by A-esterases ... Dichlorvos A-esterase appears to be normally distributed. Half-lives for degradation of dichlorvos in whole blood after inhalation were 8.1 min for men and 11.2 min for women.
来源:Hazardous Substances Data Bank (HSDB)
代谢
敌敌畏（DDVP）是一种甲基化剂。给予小鼠1.9 x 10-6摩尔/公斤的DDVP后，发现鸟嘌呤N-7的烷基化程度为每克DNA 8 x 10-13摩尔甲基。清除速率（估计）为29小时。
Dichlorvos (DDVP) is a methylating agent. DNA from mice given 1.9 x 10-6 mol/kg of DDVP, degree of alkylation of guanine-n-7 accounting to 8 x 10-13 mol methyl per gram of DNA was found. Rate of clearance was (estimated) to be 29 hr .
Dichlorvos, one of the active metabolites of trichlorofon ... is hydrolyzed to give dimethyl phosphate and dichloroacetaldehyde. The latter is subsequently reduced to beta,beta-dichloroethyl alcohol, characteristically converted by rats when administered intraperitoneally. After hydrolysis to a two-carbon fragment, dichloroacetaldhyde is able to enter a pathway of intermediary metabolism, and carbon dioxide is the major radioactive metabolic.
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: Dichlorvos is a colorless to amber liquid. It is a contact and stomach insecticide with fumigant and penetrant action, which is used as household and public health fumigant. Dichlorvos as a "No Pest Strip" is used as an ectoparasiticide for small mammals. It is also used as a premise spray to keep fly populations controlled. HUMAN STUDIES: Potential symptoms of overexposure are miosis, aching eyes, rhinorrhea, headache, chest tightening, wheezing, laryngeal spasms and salivation, cyanosis, anorexia, nausea, vomiting and diarrhea, sweating, muscle fasciculation, paralysis, giddiness and ataxia, convulsions, low blood pressure, cardiac irregularities, and irritation of eyes and skin. Red blood cell (RBC) acetylcholinesterase activity was reduced in some residents exposed to an estimated level of 0.2 mg/cu m dichlorvos for about 15.8 hr, and some residents complained of headache. Suicide attempts with dichlorvos have been described. Several cases of delayed extrapyramidal disorder described after acute dichlorvos poisonings. Dichlorvos did not cause sister chromatid exchange in vitro in human cells. ANIMAL STUDIES: In a guinea pig maximization test, induction with dichlorvos by intradermal injection and topical application and subsequent challenge with topical dichlorvos solutions showed sensitization. When rats were given single oral doses of 0.5, 35, or 70 mg/kg dichlorvos by gavage, the 35- and 70-mg/kg groups exhibited cholinergic signs within 15 min after dosing. Several animals in the 70-mg/kg group died. A saturated atmosphere of dichlorvos (230-341 mg/cu m) caused deaths in rats after 7 to 62 hr. RBC cholinesterase was inhibited in monkeys exposed to 12.9 mg/cu m. Cholinergic signs occurred within 7-15 min in dogs given a single oral dose of 11 or 22 mg/kg dichlorvos. Three of 12 dogs given 22 mg/kg died within 10-155 min of treatment. Three cynomolgus monkeys were given daily dermal doses of dichlorvos in xylene on a shaved area between the shoulder blades. A monkey receiving 100 mg/kg/day died after 4 days. A monkey given 50 mg/kg/day died after 8 doses over 10 days and a monkey given 75 mg/kg/day died after 10 doses over 12 days. Clinical signs in their order of appearance were nervousness, gritting of teeth, incoordination, muscle fasciculations, excessive salivation, labored breathing, miosis, and flaccidity. 90-day studies of dichlorvos in rats have shown that dietary levels up to 70 mg/kg/day do not result in overt cholinergic toxicity, although exposures inhibit RBC cholinesterase. Rabbits are more sensitive than rats or mice to dichlorvos vapor. Carcinogenicity was not reported in male or female mice given 58 or 95 mg/kg/day or 56 or 102 mg/kg/day, respectively, in their drinking water for 2 yr. No adverse effect occurred on fetuses when pregnant rabbits were administered doses of 0.1 to 7.0 mg/kg/day dichlorvos by gavage on gestation days 7 through 19 or when rabbits were exposed for 23 hr/day to 0.25 to 6.25 mg/ cu m dichlorvos vapor on gestation days 1 through 28. When dichlorvos (15 mg/kg/day) was administered to guinea pigs between day 42 and 46 of gestation, offspring exhibited severe reductions in brain weight. In a 3-generation reproduction study in weanling rats no effects on fertility, number and size of litters, body weight, or viability of the pups were found. Dichlorvos was a mutagen in the screening test for mutagenicity using a REC-assay procedure, with H17 REC(+) and M45 REC(-) strains of Bacillus subtilis and reversion assays on auxotrophic strains of Escherichia coli (WP2) and Salmonella typhimurium (Ames series). Dichlorvos increased the frequency of chromosomal damage and micronucleus formation in Chinese hamster ovary cells; induced sister chromatid exchange, chromosomal aberrations, and transformation in cultured rat tracheal epithelial cells; induced DNA single-strand breaks in isolated rat hepatocytes; and caused increases in cell transformation of hamster embryo cells. It was negative in the sex-linked lethal mutation test in Drosophila. ECOTOXICITY STUDIES: In mallards and pheasants the symptoms of acute oral toxicity included: goose-stepping ataxia, use of wings to aid in balance, tremors, convulsions. Various internal hemorrhages were found at autopsy in sacrificed survivors of both species. Exposure of white-footed mice to pelleted dichlorvos caused 3%, 20%, and 53% mortality in mice exposed to 1, 3, and 6 g dichlorvos per cage. Iberian toothcarp was able to tolerate high concentrations of dichlorvos, and resist high levels of brain and muscle ChE inhibition without mortality. Dichlorvos is not toxic to mussels or periwinkles at 1.0 ppm, for 1 hr exposure, but is toxic to larval lobsters, adult lobsters, zooplankton and phytoplankton. It was also toxic to bees.
Dichlorvos 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：有致癌性的提示性证据，但不足以评估对人类致癌的可能性
Cancer Classification: Suggestive Evidence of Carcinogenicity, but Not Sufficient to Assess Human Carcinogenic Potential
Evaluation: There is inadequate evidence in humans for the carcinogenicity of dichlorvos. There is sufficient evidence in experimental animals for the carcinogenicity of dichlorvos. Overall evaluation: Dichlorvos is possibly carcinogenic to humans (2B).
At least 85% of an oral dose of dichlorvos is absorbed. Dichlorvos is well absorbed following inhalation exposure based on the occurrence of toxic symptoms associated with inhalation exposures and the detection of specific dichlorvos metabolites (dichloroethanol and dimethyl phosphate) in urine of individuals exposed to dichlorvos.
An elimination half-life of 13.5 min was estimated based on dichlorvos concentration in rat kidney after 2 or 4 hr exposure to 5 mg/cu m. In mice and rats given single oral doses of dichlorvos, 59-65% was eliminated in urine, 3-7% was eliminated in feces, 14-18% was eliminated as CO2 by 4 days after dosing, and the vast majority was eliminated by 24 hr. Retained dichlorvos following either oral or inhalation exposure is high because it is incorporated into intermediary metabolism.
The vinyl moiety of the dichlorvos molecule undergoes two routes of biotransformation: conversion to dichloroethanol and subsequent formation of dichloroethanol glucuronide; or dehalogenation and incorporation of the carbon atoms into various metabolic pathways in the body. These pathways result in the production of hippuric acid, urea, carbon dioxide, and other endogenous compounds that result in a prolonged half-life of radioactivity in the tissues following the administration of [vinyl-C14] dichlorvos. Both radiolabelled dichloroethanol glucuronide and urea have been identified in the urine of men treated with [vinyl-C14] dichlorvos indicating that both pathways occur in humans.
Dichlorvos was undetectable (<0.1 mg/liter) in the blood of two men immediately after exposure, one to air concentrations of 0.25 mg dichlorvos/cu m for 10 hours and one to 0.7 mg dichlorvos/cu m for 20 hours.
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] 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.
