THE MAJOR URINARY METABOLITES /FOLLOWING ORAL DOSE OF (14)CARBON-PARAOXON TO MALE ALBINO RATS/ ... WERE DIETHYL PHOSPHATE (ABOUT 60%) AND DE-ETHYL-PARAOXON (6-7%).
... THE DEALKYLATION OF PARAOXON TO DE-ETHYL-PARAOXON OBSERVED IN THE METABOLISM OF BOTH PARAOXON AND PARATHION IN VIVO HAS BEEN SHOWN TO BE CATALYZED BY CYTOCHROME P450 DEPENDENT MONO-OXYGENATION.
Paraoxon 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.
CLASSIFICATION: D; not classifiable as to human carcinogenicity. BASIS FOR CLASSIFICATION: No human data and no animal data available. HUMAN CARCINOGENICITY DATA: None. ANIMAL CARCINOGENICITY DATA: None.
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.
Symptoms of low dose exposure include excessive salivation and eye-watering. Acute dose symptoms include 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. Hypertension, hypoglycemia, anxiety, headache, tremor and ataxia may also result.
... SLICES OF RABBIT SKIN HYDROLYZE PARAOXON AT A CONCN OF 7.7X10-3 MOL TO THE EXTENT OF 20% IN 1 HR PER G OF TISSUE. SINCE ABSORPTION OF PARAOXON ... IS SLOW.
On the basis of radioautographic studies in man and animals, it appears that skin absorption is transepidermal. The rate of dermal absorption /of paraoxon/ in the rabbit is 0.059 ug/min/cu m. The animals exhibit about a tenfold individual variation in permeability of the skin.
Effect of pregnancy & lactation on distribution of parathion & paraoxon in mice was examined. Pregnant mice treated with 5 mg/kg of parathion demonstrated higher concn of both parathion & paraoxon in blood & brain than controls which correlated with the enhanced cholinesterase inhibition in pregnant animals.
[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.
The present invention provides triazole compounds useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.
[EN] ISOXAZOLINE DERIVATIVES AS INSECTICIDES<br/>[FR] DÉRIVÉS D'ISOXAZOLINE EN TANT QU'INSECTICIDES
申请人：SYNGENTA PARTICIPATIONS AG
公开号：WO2011101402A1
公开（公告）日：2011-08-25
The present invention relates to compounds formula (I), wherein P is P1, P2, heterocyclyl or heterocyclyl substituted by one to five Z; and wherein A1, A2, A3, A4, G1, R1, R2, R3, R4, R5, R6, R17, R18, R19 and R20 are as defined in claim 1; or a salt or N-oxide thereof. Furthermore, the present invention relates to processes and intermediates for preparing compounds of formula (I), to insecticidal, acaricidal, nematicidal and molluscicidal compositions comprising the compounds of formula (I) and to methods of using the compounds of formula (I) to control insect, acarine, nematode and mollusc pests.
The present invention relates to compounds formula (I), wherein P is P1, P2, heterocyclyl or heterocyclyl substituted by one to five Z; and wherein A
1
, A
2
, A
3
, A
4
, G
1
, R
1
, R
2
, R
3
, R
4
, R
5
, R
6
, R
17
, R
18
, R
19
and R
20
are as defined in claim
1
; or a salt or N-oxide thereof. Furthermore, the present invention relates to processes and intermediates for preparing compounds of formula (I), to insecticidal, acaricidal, nematicidal and molluscicidal compositions comprising the compounds of formula (I) and to methods of using the compounds of formula (I) to control insect, acarine, nematode and mollusc pests.
