Using (32)P-labeled Bidrin and rats, 83% of the recovered activity after injection was in the form of dimethylphosphate after 20 hr. ...Extensive oxidation occurred with the formation of hydroxymethyl Bidrin and N-methyl bidrin (azodrin). Subsequent hydrolysis gave rise to dimethyl phosphate, Bidrin acid, desmethyl Bidrin acid, monomethylphosphate, and... inorganic phosphate. ... Significant amounts of N-hydroxymethylamide analog of Azodrin appeared following administration to rats of either Bidrin or azodrin while the N-methyl-N-hydroxymethylamide cmpd was present only following Bidrin treatment... .
...In rats /Bidrin/ undergoes n-demethylation, O-demethylation and hydrolysis of the amide and alkyl phosphate linkages. ...It forms relatively stable N-hydroxymethyl derivatives which are intermediates in its progressive metabolic demethylation. (32)P-Bidrin administered sc to rats is rapidly metabolized and in 24 hr total of 81% of activity is excreted in urine as hydroxymethyl Bidrin (about 11% of dose), N-desmethyl Bidrin (4%), hydrolytic products (28%) and unchanged Bidrin (1%). The N-demethylation pathway of metabolism is one of intoxication, for N-desmethyl bidrin (SD 9129), is a highly toxic compound... .
In mammals, including rats, mice, dogs, rabbits and goat, metabolites consisted mainly of hydrolysis products, but substantial amounts of Azodrin and smaller amount of hydroxymethyl Bidrin, hydroxymethyl Azodrin and desmethyl Azodrin also were found. Further, trace amounts of N-methylacetoacetamide and 3-hydroxy-N,N-dimethylbutyramide were indicated in the urine of Bidrin treated rats.
...In cotton plants ...Bidrin is converted into at least three compounds in which phosphate ester linkage is intact. Two of the 3 metabolites proved to be hydroxymethyl Bidrin and ...Azodrin. Third metabolite... was... more polar... than either Bidrin or hydroxymethyl Bidrin but... less polar than hydrolysis product... . Hydrolysis products found in cotton plant were O-desmethyl Bidrin, O-desmethyl Bidrin acid, dimethyl phosphoric, monomethyl phosphoric and phosphoric acid. ...No O-desmethyl Azodrin was detected.
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.
Dicrotophos 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
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
A4；不可归类为人类致癌物。
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. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.
Dermal Absorption Factor: 15 %. A well-conducted, acceptable guideline study was conducted with monocrotophos that indicated a dermal absorption of 15 %. /According to EPA/ It is reasonable to conclude that because structure activity relationship is so similar between dicrotophos and monocrotophos that dermal absorption is also similar.
When administered orally to rats, 63-71% of (32)P was excreted in 48 hr. ...Most of the radioactivity was excreted in urine within 6 hr. An additional 5-6% appeared in feces within 48 hr... Residual (32)P in tissues did not vary with sex.
Goats treated orally with bidrin or azodrin excreted in urine a high proportion of administered (32)P or N-methyl-(14)C labels. Trace amount of bidrin, azodrin, the N-hydroxymethylamide analog of azodrin and the unsubstituted amide were present in the urine. Labeled compound appeared in goat milk after treatment with either (32)P- or (14)C-labeled bidrin or azodrin. No N,N-dimethylacetoacetamide, N-methyl-acetoacetamide, or 3-hydroxy-N,N-dimethylbutyramide was present in milk and nature of (14)C materials remained unknown.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
敌敌畏...可以渗透皮肤；然而，其效果似乎不是累积的。
Dicrotophos... can penetrate skin; however, the effect does not appear to be cumulative.
来源:Hazardous Substances Data Bank (HSDB)
文献信息
[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.
