Residue levels in milk reached a plateau during days 3-4 of the dosing phase, at about 0.2 mg/kg eq. Similar (14)C levels were found in liver, kidney, milk, and muscle; while lower levels were reported in fat tissues. This study demonstrated that X11719474 is not metabolized in goats: no metabolites were identified, and the radioactivity found in all tissues was from X11719474.
When laying hens were orally dosed with labelled sulfoxaflor metabolite X11719474 at 11.8 ppm in the feed, approximately 0.5% of the applied dose was recovered in the combined eggs, fat, and tissues. Similar (14)C levels were noted in liver, muscle, and egg; lower levels were found in fat tissues. Approximately 92% of the dose was recovered from the excreta, and 0.3% in the cage rinse. Residue levels in eggs reached a plateau by day 4 of the dosing phase, with no compounds other than X11719474 being identified. This study demonstrated that X11719474 is not metabolized in hens: no metabolites were identified and the radioactivity found in all tissues was from X11719474. /Sulfoxaflor metabolite/
来源:Hazardous Substances Data Bank (HSDB)
代谢
所有检测的代谢物毒性都低于母化合物，除了X11519540，它的急性毒性和短期毒性高于母化合物。
All metabolites /tested/ were less toxic than the parent compound, except for X11519540, which had higher acute and higher short-term toxicity than the parent.
X11721061, a plant and animal (rat) metabolite of sulfoxaflor, was of low acute oral toxicity in rats (LD50 > 2000 mg/kg bw) and showed no genotoxic potential in vitro in mammalian or microbial test systems. In a 28-day oral toxicity study in rats, the NOAEL was 3000 ppm (equal to 236 mg/kg bw per day), based on reduced feed consumption at 8000 ppm (equal to 622 mg/kg bw per day). /Sulfoxaflor metabolite/
Investigators made isolated phrenic nerve-hemidiaphragm preparations from newborn rats. System included a muscle strain gauge transducer, a stimulating electrode fixed to the phrenic nerve, and tissue preparation anchored in a vessel which allowed changing of test solutions on demand. It was postulated that sulfoxaflor would be an agonist toward the embryonic nicotinic acetylcholine receptor (nAChR). Initial tests confirmed muscle contraction and reduced twitch response to phrenic nerve stimulation at 100 uM ACh, with return to normal upon solution wash. Ten uM tubocurarine rapidly reduced muscle tension and twitch response. Sulfoxaflor caused muscle contraction similar to ACh: at 100 uM sulfoxaflor there was no evident change on nerve-stimulated muscle twitch, whereas at 1 mM sulfoxaflor the twitch response was reduced to about 34% of normal. Ten uM tubocurarine administered simultaneously with 1 mM sulfoxaflor blocked muscle contraction by about 50%. Pre-incubation with 10 uM tubocurarine essentially eliminated the muscle contraction by 1 mM sulfoxaflor. Prolonged exposure to 1 mM sulfoxaflor (7 min) led to sustained muscle contraction and reduction in twitch response, which was reversible on washing. Tests support the hypothesis that neonatal death could have arisen from diaphragm failure by impairing respiration.
IDENTIFICATION AND USE: Sulfoxaflor is a white powder with a sharp odor that is registered for pesticide use in the USA but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. Sulfoxaflor is the first member of a new class of insecticides, the sulfoximines, and is a highly efficacious activator of the nicotinic acetylcholine receptor (nAChR) in insects. HUMAN EXPOSURE AND TOXICITY: Sulfoxaflor was shown to have no agonism on human fetal or adult muscle nAChRs. The data support the conclusion that the developmental effects of sulfoxaflor in rats are mediated via sustained agonism on the fetal muscle nAChR during late fetal development and are considered not relevant to humans. ANIMAL STUDIES: Toxicity and mechanistic studies in rats, rabbits, dogs and mice indicate that sulfoxaflor is an activator of the mammalian nAChR as well, but to a much lesser degree and in a species-specific manner. The nervous system and liver are the target organ systems of sulfoxaflor and its major metabolites resulted in hepatotoxicity; including liver weight and enzyme changes, hypertrophy, proliferation, and hepatocellular adenocarcinomas in subchronic and chronic studies in rodents. Developmental toxicity, manifested as skeletal abnormalities and neonatal deaths, was observed in rats only. The skeletal abnormalities, including forelimb flexure, bent clavicles, and hindlimb rotation, likely resulted from skeletal muscle contraction due to activation of the skeletal muscle nAChR in utero. Contraction of the diaphragm, also related to skeletal muscle nAChR activation, prevented normal breathing in neonates and resulted in increased mortality in the reproduction studies. Oral studies of mid- and high-dose sulfoxaflor resulted in decreased food consumption and subsequent decreased body weight as well as changes in the male reproductive system. Effects in the male reproductive organs were observed in the carcinogenicity study in rats that included increased testicular and epididymal weights, atrophy of seminiferous tubules, and decreased secretory material in the coagulating glands, prostate, and seminal vesicles. Additionally, there was an increased incidence of interstitial cell (Leydig cell) tumors, considered secondary to loss of normal testicular function. At the highest dose tested, muscle tremors and twitches, convulsions, hindlimb splaying, increased lacrimation and salivation, decreased pupil size and response to touch, gait abnormalities and decreased rectal temperature were observed. Decreased motor activity was also observed in the mid- and high-dose groups. Sulfoxaflor was negative for chromosomal aberrations with and without metabolic activation, and tested negative in Salmonella typhimurium strains TA 1535, TA 100, TA 1537, TA 98, and E. coli: WP2 uvrA in a standard reverse mutation assay.
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Sulfur and related compounds/
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Administer activated charcoal ... . Cover skin burns with dry sterile dressings after decontamination ... . /Sulfur and related compounds/
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag-valve-mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasms ... . Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Sulfur and related compounds/
Four beagle dogs/sex/group were dosed by gavage at 0, 1, 3, or 6 mg/kg/day for 1 year with Sulfoxaflor, purity 96.6%... Periodic blood and urine collection was done to estimate tissue clearance and excretion patterns of parent sulfoxaflor. NOEL = 3 mg/kg/day, based on food consumption decrements in the first 2-3 weeks on study in both sexes, on increased soft or watery feces in males, and on a modest increase in tan vomitus in both sexes. Plasma concentration of parent sulfoxaflor over time peaked at about 2 hours, with about 40% of peak residues at 24 hours, with no obvious effect of sex on plasma levels. An estimated terminal plasma half-life of sulfoxaflor was about 20 hours for either sex. Typically about 60% to 80% of administered dose was recovered as parent sulfoxaflor in 24-hr urine collections.
When rats were orally dosed with labelled sulfoxaflor, approximately 93% of the dose was eliminated in the urine and faeces as parent sulfoxaflor. The main metabolite in urine was a glucuronide conjugate of sulfoxaflor metabolite X11721061, accounting for approximately 2-4% of the dose. Several other unidentified minor components, each less than 1% of the administered dose, were present in the urine and fecal samples...
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
当哺乳期的山羊口服标记磺酰氟后，在大约4%的剂量出现在乳汁中，3%出现在组织中。
/MILK/ When lactating goats were orally dosed with labelled sulfoxaflor at 12.2 ppm in the diet, approximately 4% of the dose appeared in the milk and 3% in the tissues.
Rats were administered sulfoxaflor, purity 95.6%... containing suitable specific activity of C14 ring-labeled sulfoxaflor, purity 97.6%, with over 2% XR-208 ketone byproduct. Groups were (1) a single low (5 mg/kg) gavage dose, (2) a single high (100 mg/kg) gavage dose, (3) daily low doses of 5 mg/kg unlabeled sulfoxaflor, followed on day 15 with 5 mg/kg labeled sulfoxaflor, or (4) a single iv dose of 5 mg/kg. Sacrifice was at 168 hr. Generally label was measured in blood, excreta, and tissues to assess kinetics. Metabolic residues were determined in urine and feces. Tissue residues were very low or below detection levels. About 65-70% of administered dose was excreted in urine within 12 hr of dosing, with continuing rapid clearing. Feces comprised 4-5% of administered dose within 24 hr. Carbon trap results were normally below detection. There was no apparent effect of 14-day pre-treatment with low doses. In all of these cases, about 92% of administered dose was excreted in urine and 5-7% in feces, with no apparent sex difference and no difference due to dose level. Intravenous dosing yielded 97-101% of estimated administered dose in urine, and 6-9% in feces. As with the gavage treatments, residues in blood or internal organs were minimal after 7 days. Tmax estimates in plasma for single gavage treatments were typically 1-2 hr. Plasma elimination first phase t1/2 regardless of dose or route ranged from 4-6 hr, with second elimination phases of about 40 hr duration. Patterns were comparable based on RBC's except that second phase t1/2 ranged from about 50 to 75 hours. Two large adjacent peaks, identified as the two diastereomers of parent sulfoxaflor, comprised the bulk of radioactivity in excreta. The first of these peaks eluting in urine ("Peak F") comprised about 53% of administered dose, compared to about 37% for the second peak ("Peak G"). This ratio often exceeded 2:1 for the smaller amounts of radioactivity in feces. These results suggest that the labeled test article was not a racemic mixture, and further that metabolism of one isomer might be favored over the other. Other than one glucuronide (designated X11721061), no other metabolite exceeded 1% of administered dose. The glucuronide evidently involved cleavage between the sulfur and the methylene carbon of sulfoxaflor prior to conjugation at the cleavage site. None of the lesser peaks was characterized. This conjugate was only quantifiable in urine...
The present invention relates to processes for preparing certain 2-pyridones and 2-pyridinols, to novel compounds of these two types and to their use as biologically active compounds, in particular for controlling harmful microorganisms in crop protection, in the medicinal field and in the protection of materials.
[EN] BICYCLIC PYRAZOLE PESTICIDES<br/>[FR] PYRAZOLES BICYCLIQUES UTILISÉS COMME PESTICIDES
申请人：DU PONT
公开号：WO2016164200A1
公开（公告）日：2016-10-13
Disclosed are compounds of Formula 1, including all geometric and stereoisomers, N-oxides, and salts thereof, (1) wherein Q is (Q-1) or (Q-2); and A, R1, m, X1, X1a, X1b, X2, R2, R5, q and t are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound or a composition of the invention.
Provided are 2-pyridone derivatives which have excellent herbicidal activity and exhibit high safety to useful crops and so on; salts thereof; and herbicides containing same. In more detail, 2-pyridone derivatives represented by general formula [I] or agrochemically acceptable salts thereof, and herbicides containing these compounds are provided. In general formula [I], X
1
is an oxygen atom or a sulfur atom; X
2
, X
3
, and X
4
are to each CH or N(O)
m
; m is an integer of 0 or 1; R
1
is a hydrogen atom, a C
1-12
alkyl group, or the like; R
2
is a halogen atom, a cyano group, or the like; n is an integer of 0 to 4; R
3
is a hydroxyl group, a halogen atom, or the like; A
1
is C(R
11
R
12
); A
2
is C(R
13
R
14
) or C═O; A
3
is C(R
15
R
16
); and R
11
, R
12
, R
13
, R
14
, R
15
, and R
16
are each independently a hydrogen atom or a C
1-6
alkyl group.
[EN] META-DIAMIDE INSECTICIDES<br/>[FR] INSECTICIDES À BASE DE MÉTA-DIAMIDE
申请人：FMC CORP
公开号：WO2021055905A1
公开（公告）日：2021-03-25
Disclosed are compounds of Formula 1, including all geometric and stereoisomers, N-oxides, and salts thereof, wherein Q, Y, R1a, R1b, Z, W, R2, R3, R4, m, R5a and R5b are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound or a composition of the invention.
The present invention relates to compounds which are of use in the field of agriculture as insecticides and acaricides. The compounds contain butenolide rings, oxazoline and isoxazoline rings, pyridine rings or pyranone rings. The invention also relates to compositions comprising said compounds and methods of using said compounds.
