Metabolism of Dursban in fish was studied in a tank ... After exposure to Dursban, the fish were sacrificed and the fish and some water examined by paper chromatography. In addition to oxygen analog (ii) of Dursban, the monoethyl analog (iii) of Dursban and its oxygen analog (iv), 3,5,6-trichloro-2-pyridyl phosphate (v), and 3,5,6-trichloro-2-pyridinol (vi) were also found. In the fish tissues themselves, compounds ii, iv, v, vi were found.
Two goats were fed [(14)C]ring labeled (positions 2 and 6) chlorpyrifos twice daily in capsules for 10 days at concentrations equivalent to 15-19 ppm in the feed. The majority (80%) of the radiolabel was recovered in urine, with smaller amounts in feces (3.6%), gut (0.9%), tissues (0.8%), and milk (0.1%). The major urinary metabolite (> 75% of the residual radiolabel) was the beta-glucuronide conjugate of TCP, with smaller amounts of unconjugated TCP. The major residue in fat was chlorpyrifos (0.12 ppm), while TCP was the major residue in liver and kidney. A similar pattern of elimination was seen in a study in which lactating goats were fed [(14)C]ring labeled chlorpyrifos twice daily by capsule; little radiolabel (0.05-0.14%), mainly associated with chlorpyrifos, was recovered in milk.
Chlorpyrifos (CPF) is a commonly used diethylphosphorothionate organophosphorus (OP) insecticide. Diethylphosphate (DEP), diethylthiophosphate (DETP) and 3,5,6-trichloro-2-pyridinol (TCPy) are products of metabolism and of environmental degradation of CPF and are routinely measured in urine as biomarkers of exposure. However, because these same chemicals can result from metabolism or by biodegradation, monitoring total urinary metabolite levels may be reflective of not only an individual's contact with the parent pesticide, but also exposure with the metabolites, which are present in the environment. The objective of the current study was to compare the pharmacokinetics of orally administered DEP, DETP and TCPy with their kinetics following oral dosing with the parent insecticide CPF in the rat. Groups of rats were orally administered CPF, DEP, TCPy or DETP at doses of 140 umol/kg body weight, and the time-courses of the metabolites were evaluated in blood and urine. Following oral administration, all three metabolites were well absorbed with peak blood concentrations being attained between 1 and 3 hr post-dosing. In the case of DEP and TCPy virtually all the administered dose was recovered in the urine by 72 hr post-dosing, suggesting negligible, if any, metabolism; whereas with DETP, approximately 50% of the orally administered dose was recovered in the urine. The CPF oral dose was likewise rapidly absorbed and metabolized to DEP, TCPy and DETP, with the distribution of metabolites in the urine followed the order: TCPy (22+/-3 umol)>DETP (14+/-2 umol)>DEP (1.4+/-0.7 umol). Based upon the total amount of TCPy detected in the urine a minimum of 63% of the oral CPF dose was absorbed. These studies support the hypotheses that DEP, DETP and TCPy present in the environment can be readily absorbed and eliminated in the urine of rats and potentially humans.
Non-invasive biomonitoring approaches are being developed using reliable portable analytical systems to quantify dosimetry utilizing readily obtainable body fluids, such as saliva. In the current study, rats were given single oral gavage doses (1, 10, or 50 mg/kg) of the insecticide chlorpyrifos (CPF). Saliva and blood were then collected from groups of animals (4/time-point) at 3, 6, and 12 hr post-dosing, and were analyzed for the CPF metabolite trichloropyridinol (TCP). Trichloropyridinol was detected in both blood and saliva at all doses and the TCP concentration in blood exceeded saliva, although the kinetics in blood and saliva were comparable. A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model for CPF incorporated a compartment model to describe the time-course of TCP in blood and saliva. The model adequately simulated the experimental results over the dose ranges evaluated. A rapid and sensitive sequential injection (SI) electrochemical immunoassay was developed to monitor TCP, and the reported detection limit for TCP was 6 ng/L (in water). ...
来源:Hazardous Substances Data Bank (HSDB)
代谢
氯吡硫磷已知的人类代谢物包括磷酸二乙硫酯、3,5,6-三氯-2-吡啶醇和氯吡硫磷氧化物。
Chlorpyrifos has known human metabolites that include Diethyl phosphorothioate, 3,5,6-Trichloro-2-pyridinol, and Chlorpyrifos-oxon.
IDENTIFICATION AND USE: Chlorpyrifos (CPF) is a colorless to white crystalline solid with a mild mercaptan odor. CPF is an organophosphate insecticide, acaricide, and miticide used to control foliage and soil-borne insect pests on a variety of food and feed crops. It is 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: CPF can cause cholinesterase inhibition in humans leading to an overstimulated nervous system causing nausea, dizziness, confusion, and respiratory paralysis and death at very high exposures. Significant changes in plasma cholinesterase inhibition were seen in repeated doses of 0.1 mg/kg of CPF but not in single doses. Organophosphate poisoning may mimic acute complications in pregnancy, such as eclampsia and seizures. Poisoning during pregnancy may result in serious adverse effects for both mother and the fetus or neonate. Prompt diagnosis and treatment including general supportive measures and use of specific pharmacological agents such as atropine and oximes are necessary to avoid adverse outcomes. ANIMAL STUDIES: CPF affects cardiac cholinesterase (ChE) activity and muscarinic receptor binding in neonatal and adult rats. Dose- and time-related changes in body weight and cholinergic signs of toxicity (involuntary movements) were noted in both age groups. With 1x LD(10), relatively similar maximal reductions in ChE activity and muscarinic receptor binding were noted, but receptor binding reductions appeared earlier in adults and were more prolonged in neonates. Studies were performed in dogs to find out whether exposure limits that protect brain acetylcholinesterase (AChE) will protect peripheral tissue AChE after exposure to CPF. The results show that red blood cells AChE is more sensitive than brain or peripheral tissue AChE to inhibition by CPF, and that protection of brain AChE would protect peripheral tissue AChE. Fetal or neonatal exposure to CPF or related organophosphate pesticides leads to abnormalities of brain cell development, synaptic function, and behavior. Studies in rats indicate profound effects on serotonin (5HT) systems that originate during CPF exposure and that are still present at 2 months posttreatment in the young adult. Findings at 5 months of age replicate those seen in young adulthood and strongly suggest that the effects of neonatal CPF exposure on 5HT systems are permanent. Developmental exposure to CPF alters cell signaling both in the brain and in peripheral tissues, affecting the responses to a variety of neurotransmitters and hormones. When tested in adulthood, CPF-exposed male animals displayed elevations in plasma cholesterol and triglycerides, without underlying alterations in nonesterified free fatty acids and glycerol. Similarly, in the postprandial state, male rats showed hyperinsulinemia in the face of normal circulating glucose levels but demonstrated appropriate reduction of circulating insulin concentrations after fasting. Apparently subtoxic neonatal chlorpyrifos exposure, devoid of effects on viability or growth, produce a metabolic pattern for plasma lipids and insulin that resembles the major adult risk factors for atherosclerosis and type 2 diabetes mellitus. CPF was evaluated for clastogenic potential using rat lymphocytes treated for 4 hours with concentrations of up to 5000 mg/mL with and without metabolic activation. No increase in chromosomal aberrations was detected. ECOTOXICITY STUDIES: Intoxication in the bobwhite was characterized by reduced food consumption and diarrhea in 48 hr, followed by lethargy, wing droop, muscular incoordination, tremors and tetany immediately preceding death. There was a significant correlation between ChE activity and total food consumption. A major spillage of the insecticide Dursban (500 L) occurred along the River Roding, Essex, UK on 2 Apr 1985. Within 30 to 40 hr, Dursban had entered tidal reaches of the river, 26 km downstream from the spillage point. 90% of the previous biomass of fish (4740 kg) and all aquatic arthropods were killed over a 23 km stretch of the River Roding. Mollusks and annelids, which are relatively tolerant of chlorpyrifos, survived.
Chlorpyrifos 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：E组 人类非致癌性证据
Cancer Classification: Group E Evidence of Non-carcinogenicity for Humans
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
A4；不能归类为人类致癌物。
A4; Not classifiable as a human carcinogen.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
喷洒和应用非砷杀虫剂涉及到的暴露可能对人类具有致癌性（2A组）。
Spraying and application of nonarsenical insecticides entail exposures that are probably carcinogenic to humans (Group 2A). (L135)
... Five volunteers ingested 1 mg (2852 nmol) of chlorpyrifos. Blood samples were taken over 24 hours and total void volumes of urine were collected over 100 hours. Four weeks later 28.59 mg (81567 nmol) of chlorpyrifos was administered dermally to each volunteer for 8 hours. Unabsorbed chlorpyrifos was washed from the skin and retained for subsequent measurement. The same blood and urine sampling regime was followed as for the oral administration. Plasma and erythrocyte cholinesterase concentrations were determined for each blood sample. The concentration of two urinary metabolites of chlorpyrifos, diethylphosphate and diethyl-thiophosphate was determined for each urine sample. ... Most of the oral dose (mean (range) 93% (55-115%)) and 1% of the applied dermal dose was recovered as urinary metabolites. About half (53%) of the dermal dose was recovered from the skin surface. The absorption rate through the skin, as measured by urinary metabolites was 456 ng/sq cm/hr. ...
Male volunteers received chlorpyrifos as an oral dose of 0.5 mg/kg bw and 1 month later a dermal dose of 5 mg/kg bw. The time to the maximal concentration of TCP in blood was 0.5 hr after oral dosing and 22 hr after dermal treatment. The elimination half-time, irrespective of the route of administration, was 27 hr. The percentage of the administered dose recovered from the urine was 70% after oral dosing and 1.3% after dermal administration.
In persons poisoned with chlorpyrifos formulations, chlorpyrifos was detected in serum samples only and at lower concentration than the diethylphosphorus metabolites, which were excreted mainly in urine.
By 72 hr after a single oral dose of 19 mg/kg bw [(14)C]ring-labelled chlorpyrifos was given by intubation to male Sprague-Dawley rats, 83-87% had been eliminated, mainly in the urine (68-70%), feces (14-15%), and expired air (0.15-0.39%). The residues found at this time represented about 1.7% of the total dose, and the concentration, while highest in fat, was < 1 ppm in any tissue.
[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.
