Fenitrothion is a brownish-yellow oil. Used as a selective acaricide and a contact and stomach insecticide against chewing and sucking insects on rice, orchard fruits, vegetables, cereals, cotton and forest. Also used against flies, mosquitoes, and cockroaches. (EPA, 1998)
Fenitrothion is metabolized unremarkably in the goat. The metabolites result from one or more of the following pathways: reduction of the nitro-group to an amine followed by conjugation with sulfate or acetate; formation of oxon; O-demethylation.
来源:Hazardous Substances Data Bank (HSDB)
代谢
在大鼠和豚鼠接触硫磷后，发现了去甲基类似物、二甲基硫代磷酰氧、二甲磷酸以及4种未识别的化合物。
After exposure of rats and guinea pigs to sumithion, desmethyl analog, dimethyl phosphorothioate, dimethyl phosphate, and 4 unidentified compounds were found.
In comparative study of biotransformations in mice of sumithion ... and methyl parathion ... similar urinary metabolites resulted. They included methyl phosphorothioates, ... dimethyl phosphates ... and methyl phosphates ... and together with dimethyl phosphorothionate, dimethylphosphate, methyl phosphate and phosphate.
After the beetle Tribolium castaneum was topically treated with fenitrothion, main hydrolytic metabolite was o-demethyl analog. Dimethyl thiophosphate and dimethyl phosphate were also found. Fenitroxon and ... phenol were observed. Application of formic, acetic or n-propionic acid to tribolium castaneum inhibited formation of oxon and desmethyl analogs.
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: Fenitrothion is a yellow-brown liquid. It is used as an insecticide (acaricide). HUMAN EXPOSURE AND TOXICITY: The signs and symptoms of poisoning in humans were those of parasympathetic stimulations. It has been suggested that the slow release of the insecticide from adipose tissue can give rise to a protracted clinical course or late symptoms of intoxication. In some cases, contact dermatitis has been attributed to exposure to this insecticide. There is no evidence of delayed neurotoxicity or of an association with Reye's syndrome. Moderate poisoning of 25 workers was reported, where a formulation containing 50% fenitrothion was applied by aircraft during a strong wind. Onset of poisoning developed 2.5-6 hr after inhalation and the symptoms were typical. Whole blood ChE activity was decreased by 48%. Recovery required 3 days of treatment with atropine. In another study, Cholinesterase activity was significantly reduced at the end of the working week in 3 out of 28 fenitrothion workers in Haiti. ANIMAL STUDIES: In experimental animals, fenitrothion causes cholinesterase activity depression in plasma, red blood cells, and brain and liver tissues. It is metabolized to fenitrooxon, which is more acutely toxic. Its toxicity may be potentiated by some other organophosphate compounds. Fenitrothion is only minimally irritating to the eyes and is nonirritating to the skin. A single oral dose of 250 mg fenitrothion/kg resulted in a slight decrease in a number of biochemical indices of liver function in rats, including mitochondrial ATPase activity, cytochrome P450 content, aniline hydroxylase activity, and aminopyrine N-demethylase activity. A dose of 25 mg/kg also had a slight effect on P450 content and xenobiotic metabolism, while 5 mg/kg did not have any significant effects. The magnitude of the effects was greater in females than in males. Mice that received fenitrothion at dietary level of 1000 ppm (about 12.8 mg/kg/day) developed symptoms within a week and at the end of a 20 day feeding period had cholinesterase activity in brain, red cells, and plasma reduced to 45, 26, and 5% of normal, respectively; body weight and liver weight were not affected. Prenatal administration in rats at 5, 10 and 15 mg/kg from days 7 to 15 of gestation, resulted in dose related decrease in open field activity and motor coordination in the offspring treated with the two higher doses. Long lasting alterations in the acquisition and extinction of a conditioned escape response, as well as increased social interactions were observed in the adult offspring. No embryotoxic or teratogenic effects were observed in mice or rats. Fenitrothion was found to be non-mutagenic in Salmonella typhimurium strains of TA98, TA1535 and TA1537 and in Escherichia coli WP2uvrA both with and without S9 mix, while weak mutagenicity was observed only in Salmonella typhimurium TA100 and enhanced by the addition of S9 mix. ECOTOXICITY STUDIES: The unexpectedly high sensitivity of Australian marsupials to fenitrothion was described. Signs of intoxication in mallards and pheasants from acute oral administration: regurgitation (in mallards), ataxia, high carriage, wing-drop, wing shivers, falling, salivation, tremors, loss of righting reflex, tetanic seizures, dyspnea, miosis, lacrimation, and wing-beat convulsions. Short term fenitrothion treatment in bluerock pigeons (Columba livia Gmelin) resulted in a reduction of total count of peripheral erythrocytes, hemoglobin content, hematocrit and total spleen cell count, but an increase in total peripheral leukocyte count, with marked heterophilia along with lymphopenia and monocytopenia. Also, there was consistent prolongation of both bleeding and clotting time in the experimental birds. Fenitrothion appears to have anti-androgenic effects on both the physiology and behavior of the male stickleback. Fenitrothion was highly toxic to crayfish, a nontarget organism that can be used for monitoring of environmental effects. Prawns exposed to fenitrothion showed alterations in enzymes involved in the production of energy (LDH and IDH) possibly in an attempt to cope with additional energetic demands. Pregnant female guppies were exposed to 10 mg fenitrothion/liter for 4 hr, 5, 10, or 15 days before the next parturition. Half of the females gave premature birth when exposed 5 or 10 days before parturition, and only 32 or 63%, respectively, of the eggs were delivered alive. The females exposed to the fenitrothion 15 days before parturition had normal births and only 9.4% of the offspring were stillborn. The body lengths of the young produced by the females after exposure were significantly shorter than those produced before exposure in all the studies.
Fenitrothion 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：人类非致癌性证据E组
Cancer Classification: Group E Evidence of Non-carcinogenicity for Humans
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.
We aimed to evaluate prognostic factors and toxicokinetics in acute fenitrothion self-poisoning. We reviewed 12 patients with fenitrothion self-poisoning admitted to the intensive care unit between 2003 and 2006. We compared the characteristics, initial vital signs, physiological scores, corrected QT interval on electrocardiogram and laboratory data (serum fenitrothion concentration and cholinesterase activity) of non-survivors and survivors. Furthermore, we evaluated the correlation between the prognostic factors and severity of poisoning (lengths of intensive care unit and hospital stays), and the toxicokinetics of the patients. In the 2 non-survivors, the estimated fenitrothion ingestion dose and the serum fenitrothion concentration at the emergency department and at 24 hr after ingestion were significantly higher than those in the 10 survivors. (p=0.008, 0.003, and 0.04, respectively). In the 10 survivors, the serum fenitrothion concentration at 24 hr after ingestion was significantly correlated with the lengths of intensive care unit and hospital stays (p=0.004 and 0.04, respectively); however, the initial vital signs, physiological scores, corrected QT interval on electrocardiogram at the emergency department, and serum cholinesterase activity did not show any correlation. In five patients successfully fitted to a two-compartment model, the distribution and elimination half-lives were 2.5 and 49.8 hr, respectively, which is compatible with the slow and prolonged clinical course of fenitrothion poisoning. Estimated fenitrothion ingestion dose and serum fenitrothion concentration at the emergency department and at 24 hr after ingestion may be useful prognostic factors in acute fenitrothion self-poisoning. Furthermore, we should take care for the patients whose serum fenitrothion concentration is high.
An unblinded crossover study of fenitrothion 0.18 mg/kg/day [36 times the acceptable daily intake (ADI)] and 0.36 mg/kg/day (72 X ADI) administered as two daily divided doses for 4 days in 12 human volunteers was designed and undertaken after results from a pilot study. On days 1 and 4, blood and urine samples were collected for analysis of fenitrothion and its major metabolites, as well as plasma and red blood cell cholinesterase activities, and biochemistry and hematology examination. Pharmacokinetic parameters could only be determined at the higher dosage, as there were insufficient measurable fenitrothion blood levels at the lower dosage and the fenitrooxone metabolite could not be measured. There was a wide range of interindividual variability in blood levels, with peak levels achieved between 1 and 4 hr and a half-life for fenitrothion of 0.8-4.5 hr. Although based on the half-life, steady-state levels should have been achieved; the area under the curve (AUC)(0-12 hr) to AUC(0-(infinity) )ratio of 1:3 suggested accumulation of fenitrothion. There was no significant change in plasma or red blood cell cholinesterase activity with repeated dosing at either dosage level of fenitrothion, and there were no significant abnormalities detected on biochemical or hematologic monitoring.
The purpose of this study was to characterize tissue esterase activity and blood fenitrothion concentrations in the rat dam and fetus following in-utero exposure to the organophosphate insecticide fenitrothion. Time-mated, 8-week-old rats were gavaged on gestation day 19 with 0, 5, or 25 mg fenitrothion/kg. Fenitrothion was absorbed rapidly from the gastrointestinal tract, with peak maternal and fetal blood levels observed 0.5-1.0 hr after dosing. Fenitrothion concentrations in maternal and fetal blood were virtually identical and demonstrated a non-linear dose-response relationship. Acetylcholinesterase and carboxylesterase activities in maternal liver and blood and in fetal liver and brain decreased within 30-60 min of fenitrothion exposure. Esterase inhibition occurred at a fenitrothion dose (5 mg/kg) that has not been previously associated with reproductive toxicity, suggesting that esterase inhibition should be considered as the critical effect in risk assessments for this pesticide.
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
用于通过肟酸磷酸酯（对氧磷）和硫代磷酸酯（对硫磷，杀螟松）的酯的水解反应速率常数（pyridinealdoxime 2- PyOx -和4- PyOx - ）及其官能化的表面活性剂吡啶鎓4-（肟基）甲基）-1-烷基吡啶鎓溴化物 在阳离子表面活性剂溴化十六烷基三甲基铵（CTAB）和十六烷基溴化吡啶（CPB）的胶束介质中，已在pH 9.5和27°C下动力学测定了离子（烷基= C n H 2 n +1，n = 10、12、14、16） 。酸解离常数，p K a还通过分光光度法，动力学和电位法确定了肟的含量。已经探索了阳离子胶束的速率加速作用。吡啶鎓头基（CPB）的阳离子胶束显示出比铵头基团（CTAB）更大的催化作用。已经讨论了pH，肟酸浓度和表面活性剂的影响。
Unequivocal Identification of Compounds Formed in the Photodegradation of Fenitrothion in Water/Methanol and Proposal of Selected Transformation Pathways
摘要：
The photodegradation of fenitrothion was examined in a mixture of distilled water/methanol (5:1), The UV irradiation was carried out with a high-pressure Hg lamp during 7 h. For the identification of further breakdown products, fenitrooxon and carboxyfenitrothion were also irradiated under experimental conditions identical to those for fenitrothion. The identification of the breakdown products formed was carried out by gas chromatography-mass spectrometry (GC-MS) with electron impact (EI) and comparison with authentic standards synthesized in the laboratory. A total of 21 photoproducts of oxidation, isomerization, denitration, and solvolysis that may be of concern in environmental studies were unequivocally identified. Among them were formyldenitrofenitrothion, carbomethoxydenitro-fenitrooxon, and hydroxymethyldenitrofenitrooxon. A proposed mechanism of the process is presented. Selected pathways for the photodegradation of fenitrothion were examined: (i) degradation through hydrolysis, with eventual remethylation; (ii) P=S to P=O oxidation; (iii) denitration; and (iv) oxidation of the methyl substituent through hydroxymethyl and formyl to give the corresponding carboxy derivatives.
[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.
