Nitenpyram

270.72

270.72

601-735-5

3A837VZ81Y

DTXSID8041080|DTXSID3058292

Pale yellow crystals

29333990

74

1.90

light-yellow crystal

1.254±0.06 g/cm3(Predicted)

83-84°

417.2±45.0 °C(Predicted)

>70 °C

1.568

In water, 3.45X10+4 mg/L at 25 °C (est)

0-6°C

8.20e-12 mmHg

LD50 in male, female rats, male, female mice (mg/kg): 1680, 1575, 867, 1281 orally; in male, female rats (mg/kg): >2000, >2000 dermally; LC50 (48 hr) in carp, water fleas (ppm): >1000, >10000 (Kashiwada)

Henry's Law constant = 7.88X10-11 atm-cu m/mole at 25 °C (est)

pKa1 = 3.1; pKa2 = 11.5

160.32 Ų [M+H]+ [CCS Type: TW]

NONH for all modes of transport

2

22-36/37/38

26-36

KH8589450

Xn

Stable under recommended storage conditions.

P261-P305 + P351 + P338

H302-H315-H319-H335

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.|Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material; Contaminated packaging: Dispose of as unused product.

Incompatible materials: Strong oxidizing agents.

Oral dosage form new animal drugs. Nitenpyram. ... Conditions of use-(1) Dogs - ... For the treatment of flea infestations on dogs and puppies 4 weeks of age and older and 2 lbs of body weight or greater. ... (2) Cats - ... For the treatment of flea infestations on cats and kittens 4 weeks of age and older and 2 lbs of body weight or greater.|The Generic Animal Drug and Patent Restoration Act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Nitenpyram is included on this list.

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P301+P312, P330, and P501|Aggregated GHS information provided by 157 companies from 2 notifications to the ECHA C&L Inventory.|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 39 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302: Harmful if swallowed [Warning Acute toxicity, oral]

Eye/face protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).|Skin protection: Handle with gloves.|Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.|Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator. For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.|Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Do not let product enter drains.|Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection.|Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.|Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.|For more Preventive Measures (Complete) data for Nitenpyram (6 total), please visit the HSDB record page.

Rabbit: Non-irritating to skin, slightly irritating to eyes.

RURAL/REMOTE: Nitenpyram was not detected (detection limit 2.0 pg/cu m) in the particulate phase atmospheric samples collected Jun-Sep 2013 from Osoyoos and Oliver, BC, Canada, in the Okanagan Valley, a southern agricultural region(1).

Nitenpyram was not detected (detection limit 0.5 ng/g) in seven pollen samples collected in Massachusetts in 2012 or six pollen samples collected in New Zealand in 2011(1). In a storage stability test of mixed pesticides, nitenpyram degradation was 28, 75 and 76% over simulated 6, 12 and 24 month storage, respectively(2).

IDENTIFICATION AND USE: Nitenpyram is neonicotinoid insecticide that controls aphids, leafhoppers, thrips, whiteflies on rice and glasshouse crops. It is also used to control fleas in dogs and cats. HUMAN STUDIES: There are no data available. ANIMAL STUDIES: The following adverse events are listed in decreasing order of reporting frequency. Cats: hyperactivity, panting, lethargy, itching, vocalization, vomiting, fever, decreased appetite, nervousness, diarrhea, difficulty breathing, salivation, incoordination, seizures, pupil dilation, increased heart rate, and trembling. Dogs: lethargy/depression, vomiting, itching, decreased appetite, diarrhea, hyperactivity, incoordination, trembling, seizures, panting, allergic reactions including hives, vocalization, salivation, fever, and nervousness. The frequency of serious signs, including neurologic signs and death, was greater in animals under 2 pounds of body weight, less than 8 weeks of age, and/or reported to be in poor body condition. In some instances, birth defects and fetal/neonatal loss were reported after treatment of pregnant and/or lactating animals. ECOTOXICITY STUDIES: The toxic effect of nitenpyram on the brain of juvenile Chinese rare minnows (Gobiocypris rarus) was investigated by determining the oxidative stress, and acetylcholinesterase (AChE) activity. The superoxide dismutase (SOD) activities did not significantly change after long-term exposure to nitenpyram. A noticeable increase of catalase (CAT) activities was observed on the brain tissues under nitenpyram treatments. The malondialdehyde (MDA) content increased markedly under 0.1 mg/L nitenpyram treatments. The AChE activities decreasing under 2.0 mg/L nitenpyram. Changes in the antioxidant enzyme activities in zebrafish are reported for nitenpyram. Nitenpyram was highly toxic to earthworm (Eisenia fetida), and can significantly inhibit fecundity and cellulase activity of E. fetida, and it was also damaging to the epidermal and midgut cells of earthworms.

LD50 Rat (male) oral 1680 mg/kg|LD50 Rat (female) oral 1575 mg/kg|LD50 Rat (male) dermal >2000 mg/kg|LD50 Rat (female) dermal >2000 mg/kg|For more Non-Human Toxicity Values (Complete) data for Nitenpyram (6 total), please visit the HSDB record page.

/AQUATIC SPECIES/ Adverse impacts of immunity in terrestrial non-target organisms exposed to neonicotinoid insecticides have been reported, but the causal link between insecticide exposure and possible immune alterations in fish remains limited. In the present study, the potential genotoxicity and immunotoxicity of three neonicotinoids (imidacloprid, nitenpyram, and dinotefuran) were assessed in Chinese rare minnows by using a 60-day chronic toxicity test. The hematological and biochemical parameters of juvenile Chinese rare minnows and changes in the transcription of six inflammation-related genes were determined after exposure to neonicotinoids at 0.1, 0.5, or 2.0 mg/L. A clear difference in the frequency of erythrocytes with micronuclei (MN) was observed after treatment with 2.0 mg/L imidacloprid (p<0.05). Additionally, exposure to 0.5 or 2.0 mg/L imidacloprid significantly increased the binucleated (BN) erythrocytes and those with notched nuclei (NT) (p<0.05). A serum protein electrophoresis (SPE) assay showed significant alterations in the serum protein in all treatments (p<0.05), and further analysis indicated decreases in immunoglobulin (Ig) in treatments with 0.5 or 2.0 mg/L imidacloprid or dinotefuran or with 0.1 mg/L nitenpyram (p<0.05). Moreover, a biochemical assay confirmed that immunoglobulin M (IgM) levels were indeed significantly decreased upon treatment with imidacloprid or dinotefuran at 0.5 or 2.0 mg/L (p<0.05). In addition, the transcriptional levels of the inflammatory cytokines IL-6, INF-alpha, TNF-alpha, and IL-1beta were markedly down-regulated after all imidacloprid treatments (p<0.05), whereas the expression levels of only TNF-alpha and IL-1beta were significantly down-regulated following the 0.5 and 2.0 mg/L dinotefuran treatments (p<0.05). Taken together, results clearly demonstrate that imidacloprid, rather than nitenpyram and dinotefuran, can induce genotoxicity. The responsiveness of these immune indicators provides new insight into and evidence of the adverse effects of neonicotinoids on aquatic non-target organisms.|/AQUATIC SPECIES/ Imidacloprid and nitenpyram are widely used neonicotinoid pesticides worldwide and were observed to adversely affect non-target aquatic organisms. In this study, the toxic effect of imidacloprid and nitenpyram on the brain of juvenile Chinese rare minnows (Gobiocypris rarus) was investigated by determining the oxidative stress, 8-hydroxy-2-deoxyguanosine (8-OHdG) content and acetylcholinesterase (AChE) activity. The superoxide dismutase (SOD) activities did not significantly change after long-term exposure to imidacloprid and nitenpyram. A noticeable increase of catalase (CAT) activities was observed on the brain tissues under 0.1 mg/L imidacloprid and under all nitenpyram treatments (p<0.05). The malondialdehyde (MDA) content increased markedly under 2.0 mg/L imidacloprid and 0.1 mg/L nitenpyram treatments (p<0.05). The glutathione (GSH) content in the brain significantly increased under 0.5 and 2.0 mg/L imidacloprid (p<0.05). A significant decrease was observed in the mRNA levels of Cu/Zn-SOD under 2.0 mg/L imidacloprid and those of CAT under 0.1 and 0.5 mg/L nitenpyram (p<0.05). The mRNA levels of gpx1 clearly decreased under 2.0 mg/L imidacloprid and under 0.1 mg/L nitenpyram (p<0.05). The treatments of 0.1 and 0.5 mg/L nitenpyram decreased CAT expression levels markedly (p<0.05). 2.0 mg/L imidacloprid raised the 8-OHdG content. The AChE activities increased markedly under 0.5 and 2.0 mg/L imidacloprid while clearly decreasing under 2.0 mg/L nitenpyram (p<0.05). Therefore, results indicate that imidacloprid and nitenpyram might cause adverse effects on juvenile Chinese rare minnow's brain. Notably, imidacloprid had greater impacts on juvenile rare minnows compared to nitenpyram.|/AQUATIC SPECIES/ Nitenpyram is one of the most commonly used neonicotinoid pesticide worldwide and was found to be toxic to non-target aquatic organisms. Therefore, the purpose of this study was to investigate the oxidative stress, changes in the detoxifying system and DNA damage in zebrafish induced by nitenpyram. In the present study, zebrafish (Danio rerio) were exposed to four concentrations (0.6, 1.2, 2.5, and 5.0 mg/L) for 28 days and then sampled in triplicate on days 7, 14, 21 and 28. Superoxide dismutase (SOD) and catalase (CAT) activities were dramatically inhibited at most exposure times compared with the control group, except SOD at low concentration (0.6 mg/L) of nitenpyram and CAT on day 21. This difference is due to the excess reactive oxygen species (ROS) produced and increased malondialdehyde (MDA) content in zebrafish livers. The activity of glutathione S-transferase (GST) increased in the treatment groups at a higher concentration compared with the control group. ...Nitenpyram exposure could affect the antioxidant enzymes and DNA damage in the exposed zebrafish livers. Additionally, the changes in the antioxidant enzyme activities could be an adaptive response protecting against the toxicity induced by nitenpyram.|/OTHER TERRESTRIAL SPECIES/ Avoidance behavior of earthworms (Eisenia fetida) against six neonicotinoids (NEOs) (acetamiprid, dinotefuram, clothianidin, thiacloprid, nitenpyram, imidacloprid) was studied following the protocol of ISO. The results showed obvious avoidance behavior of E. fetida against the tested insecticides, and the medium effective concentration for avoidance behavior (EC50) of the six pesticides was 0.14, 0.55, 0.91, 7.87, 1.32 and 0.77 mg/kg, respectively. Compared to the acute toxicity, avoidance behavior was more sensitive as an indicator of soil contamination with NEOs. Chronic toxicity of above six NEOs to E. fetida was also evaluated; cocoon production, hatchability, cocoon weight and adult weight were all affected in the test. Cocoon production and hatchability were more sensitive than cocoon weight and adult weight. The reproduction of earthworms were significantly reduced with a 56 day half-maximal effective hatchability concentration (EC50) of 0.37, 0.74, 1.30, 3.57, 1.20 and 0.70 mg/kg (acetamiprid, dinotefuram, clothianidin, thiacloprid, nitenpyram, imidacloprid), respectively. Most of the tested NEOs were highly toxic to E. fetida. Avoidance behavior and reproduction damage of E. fetida was observed at very low concentrations. The existing levels of pollution with NEOs in soil frequently exceed the lowest observed adverse effect concentrations, which are likely to have negative biological and ecological impacts on earthworms.|/OTHER TERRESTRIAL SPECIES/ Earthworms (Eisenia fetida) are one of the most abundant terrestrial species, and play an important role in maintaining the ecological function of soil. Neonicotinoids are some of the most widely used insecticides applied to crops. Studies on the effect of neonicotinoids on E. fetida are limited. In the present work, we evaluated the effects of five neonicotinoid insecticides on reproduction, cellulase activity and the tissues of E. fetida. The results showed that, the LC50 of imidacloprid, acetamiprid, nitenpyram, clothianidin and thiacloprid was 3.05, 2.69, 4.34, 0.93 and 2.68 mg/kg, respectively. They also could seriously affect the reproduction of E. fetida, reducing the fecundity by 84.0%, 39.5%, 54.3%, 45.7% and 39.5% at the sub-lethal concentrations of 2.0, 1.5, 0.80, 2.0 and 1.5 mg/kg, respectively. The cellulase activity of E. fetida was most sensitive to clothianidin. Significant disruption of the epidermal and midgut tissue was observed after 14 day exposure. In summary, ...imidacloprid, acetamiprid, nitenpyram, clothianidin and thiacloprid have high toxicity to earthworm, and can significantly inhibited fecundity and cellulase activity of E. fetida, and they also damage the epidermal and midgut cells of earthworm.

Nitenpyram's production may result in its release to the environment through various waste streams; its use as an insecticide(1) will result in its direct release to the environment(SRC). It has never been registered for use in the US(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1600(SRC), determined from a structure estimation method(2), indicates that nitenpyram is expected to have low mobility in soil(SRC). Volatilization of nitenpyram from moist soil surfaces is not expected(SRC) given an estimated Henry's Law constant of 7.9X10-11 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Nitenpyram is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 8.2X10-12 mm Hg at 20 °C(3). Nitenpyram's half-life in soil is 1-15 days depending on soil type(3), suggesting that biodegradation may be an important environmental fate process in soil(SRC). The half-life of nitenpyram was about 8 days in fields planted with treated seeds(4).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1600(SRC), determined from a structure estimation method(2), indicates that nitenpyram is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 7.9X10-11 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Nitenpyram is expected to undergo hydrolysis(4). The photolytic lifetime of nitenpyram in water was reported as 269 minutes(5). According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow of -0.66(7) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low. Biodegradation data in water were not available(SRC, 2019).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), nitenpyram, which has a vapor pressure of 8.2X10-12 mm Hg at 20 °C(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase nitenpyram may be removed from the air by wet or dry deposition(SRC). The photolytic lifetime of particulate nitenpyram is 36 minutes(3), suggesting that nitempyram may be susceptible to direct photolysis by sunlight(SRC).

Nitenpyram degradation in unpreserved finished drinking water was likely the result of oxidation, hydrolysis and reaction with chlorine, six products were identified(1). Based on studies done with mercury lamps at 254, 313 and 350 nm, the photolytic lifetime of solid nitenpyram at a solar zenith angle at 35 deg is calculated to be 36 minutes; in water the lifetime is 269 minutes(2).

An estimated BCF of 3 was calculated in fish for nitenpyram(SRC), using a log Kow of -0.66(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of nitenpyram can be estimated to be 1600(SRC). According to a classification scheme(2), this estimated Koc value suggests that nitenpyram is expected to have low mobility in soil(SRC).

The Henry's Law constant for nitenpyram is estimated as 7.9X10-11 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that nitenpyram is expected to be essentially nonvolatile from water and moist soil surfaces(2). Nitenpyram is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 8.2X10-12 mm Hg(3).

SURFACE WATER: Nitenpyram was not detected (detection limit 0.1-5 ng/L) in tap and river water samples collected from Quebec, Canada(1).

Nitenpyram was not detected (detection limit 0.1 ng/g) in 29 fruit and vegetable samples (apple, nectarine, orange, strawberry, watermelon, cantaloupe, honeydew, olive, spinach, tomato, pepper, potato, eggplant, cucumber, pumpkin, zucchini, summer squash) purchased from grocery stores in Boston, MA in 2012(1). Nitenpyram was detected at 0.2 ng/g in raw honey samples collected directly from one of three hives in the Boston, MA area in 2012; it was not detected in five other honey samples purchased around Boston or in two samples purchased in Israel in 2012(1). Nitenpyram was detected in 6.3% of fruits and vegetables collected in 2015 from the US Congressional Cafeteria; it was detected in strawberries and cucumbers at

Occupational exposure to nitenpyram may occur through inhalation and dermal contact with this compound at workplaces where nitenpyram is produced or used. Monitoring data indicate that the general population may be exposed to nitenpyram via ingestion of imported food containing residual pesticide. (SRC)

Nitenpyram was not detected in urine samples collected in 1994 and 2000 from 20 women in Kyoto, Japan; in 2003, 2009 and 2011 the maximum concentration of nitenpyram in 20, 17 and 18 Japanese women was 0.15, 0.40 and 0.82 ug/g creatinine, respectively(1). Nitenpyram concentrations were 0.17-1.03 ug/L in 29% of urine samples collected from 52 (41 men, 11 women) adults from Aichi Prefecture, Japan(2). Nitenpyram was detected in 21% of urine samples collected from 223 three year old children (108 male, 115 female) from Japan(3).|Neonicotinoid insecticides that have been on the market since 1992 have been used globally including in Japan. Because they are sprayed over forests and agricultural areas, inadvertent toxicity in nontarget insects (especially honey bees) and humans is a matter of public concern. However, information on exposure levels and potential health impacts of neonicotinoids in children living around sprayed areas is scarce. Thus, we determined neonicotinoid exposure levels in children living in communities where thiacloprid was used to control pine wilt disease. A total of 46 children (23 males and 23 females) were recruited for the present study, and informed written consent was obtained from their guardians. Urine specimens were collected before, during, and after insecticide spraying events; and atmospheric particulate matter was also collected. Concentrations of thiacloprid and 6 other neonicotinoid compounds were determined in urine samples and in atmospheric particulate matter specimens using liquid chromatography-electrospray ionization-tandem mass spectrometry. In urine specimens, thiacloprid concentrations were <0.13 ug/L and were detectable in approximately 30% of all samples. Concentrations of the other neonicotinoids, N-dm-acetamiprid, thiamethoxam, dinotefuran, and clothianidin, were 18.7, 1.92, 72.3, and 6.02 ug/L, respectively. Estimated daily intakes of these neonicotinoids were then calculated from urinary levels; although the estimated daily intakes of the neonicotinoids were lower than current acceptable daily intake values, the children were found to be exposed to multiple neonicotinoids on a daily basis.

VET: Nitenpyram inhibits the nicotinic acetylcholine receptor. It is used to treat Ctenocephalides spp in dogs and cats ... . It is toxic to fleas for only 24-48 hr and is normally used in combination with an insect growth regulator to provide continuous flea control.|VET: Nitenpyram is indicated as a flea adulticide in dogs and cats that are, at a minimum, 2 pounds in weight and 4 weeks old. It does not repel fleas or ticks and does not reliably kill ticks, flea eggs, larvae or immature fleas. Nitenpyram may be effective for treating fly larvae (maggots) of various species. Fleas begin to fall from treated animals about 30 minutes after dosing and a single dose can protect animals for 1-2 days.

VET: The following adverse events are based on post-approval adverse drug experience reporting. Not all adverse reactions are reported to FDA CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using this data. The following adverse events are listed in decreasing order of reporting frequency. Cats: hyperactivity, panting, lethargy, itching, vocalization, vomiting, fever, decreased appetite, nervousness, diarrhea, difficulty breathing, salivation, incoordination, seizures, pupil dilation, increased heart rate, and trembling. Dogs: lethargy/depression, vomiting, itching, decreased appetite, diarrhea, hyperactivity, incoordination, trembling, seizures, panting, allergic reactions including hives, vocalization, salivation, fever, and nervousness. The frequency of serious signs, including neurologic signs and death, was greater in animals under 2 pounds of body weight, less than 8 weeks of age, and/or reported to be in poor body condition. In some instances, birth defects and fetal/neonatal loss were reported after treatment of pregnant and/or lactating animals.

Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. (See all compounds classified as Insecticides.)

Nitenpyram is rapidly and practically completely absorbed after oral administration. Peak levels occur approximately 80 minutes after dosing in dogs; approximately 40 minutes in cats. Elimination half-lives are: approximately 3 hours for dogs; 8 hours for cats. Nitenpyram is excreted primarily as conjugated metabolites in the urine and excretion is complete within 48 hours of dosing. In dogs, approximately 3% of a dose is excreted in feces; in cats approximately 5% is excreted in the feces.|Nitenpyram is administered PO in pill form to kill fleas in both dogs and cats. It is absorbed rapidly, with maximal blood concentrations reached within 1.2 hr and 0.6 hr in dogs and cats, respectively. ... The compound is rapidly eliminated, with >90% excreted in the urine within 24-48 hr, primarily as unchanged nitenpyram.

BACKGROUND: Nitenpyram is a member of the economically important neonicotinoid class of insecticides. The in vivo metabolism of nitenpyram is not well characterized, but cytochrome P450 activity is the major mechanism of resistance to neonicotinoids identified in insect pests, and P450s metabolize other neonicotinoids including imidacloprid. RESULTS: Here, we used the GAL4-UAS targeted expression system to direct RNA interference (RNAi) against the cytochrome P450 redox partners to interrupt P450 functions in specific tissues in Drosophila melanogaster. RNAi of the mitochondrial redox partner defective in the avoidance of repellents (dare) in the digestive tissues reduced nitenpyram mortality, suggesting an activation step in the metabolism of nitenpyram carried out by a mitochondrial P450. RNAi of the mitochondrial cytochrome P450 Cyp12a5, which is expressed in the digestive tissues, resulted in the same phenotype, and transgenic overexpression of Cyp12a5 increased nitenpyram sensitivity. CONCLUSION: These results suggest that in vivo metabolism of nitenpyram by the mitochondrial P450 CYP12A5 results in the formation of a product with higher toxicity than the parent compound.

Elimination half-lives /after oral dosing/ are: approximately 3 hours for dogs; 8 hours for cats.

Nitenpyram is in the class of neonicotinoid insecticides. It enters the systemic circulation of the adult flea after consuming blood from a treated animal. It binds to nicotinic acetylcholine receptors in the postsynaptic membranes and blocks acetylcholine-mediated neuronal transmission causing paralysis and death of the flea. Nitenpyram is 3500x more selective for insect alpha-4beta-2 nicotinic receptors than in vertebrate receptors. It does not inhibit acetylcholinesterase.

Provide supportive treatment, as there is no specific antidote for neonicotinoid poisoning. Patients with significant mental status changes should ideally be managed in the intensive care setting, at least initially. Use GI decontamination ... . Control extreme agitation with lorazepam or propofol. Consider cardiac monitoring, especially in patients with risk factors for coronary artery disease. In a severe poisoning, send patient to an intensive care setting for respiratory support. /Neonicotinoid insecticides/|/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 if 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. /Poisons A and B/|/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 needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock 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 ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/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 bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /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. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

(1E)-N-((6-chloro-3-pyridinyl)methyl)-N-ethyl-N'-methyl-2-nitro-1,1-ethenediamine

Nitenpyram Oral Tablets: 11.4 mg and 57 mg in boxes containing blister packs of 6 tablets; Capstar; (OTC); FDA-approved for use in dogs and cats. Also available in combination packs with Lufenuron [Program Flavor Tabs and Capstar Flea Management System for Dogs and Program Flavor Tabs (OTC); and Capstar Flea Management System for Cats (OTC)] and in combination with milbemycin and lufenuron [Sentinel Flavor Tabs and Capstar Flea Management System for Dogs (Rx)].|Premix Partners: Pymetrozine.

A microextraction procedure based on vortex-assisted surfactant-enhanced-emulsification liquid-liquid microextraction with solidification of floating organic droplet (VSLLME-SFO) for preconcentration of neonicotinoid pesticides, including acetamiprid, clotianidin, nitenpyram, imidacloprid, and thiamethoxam, has been developed. In VSLLME-SFO process, the addition of surfactant (as an emulsifier), could be enhance the mass-transfer from the aqueous solution into the extraction solvent. The extraction solvent could be dispersed into the aqueous by vortex process. Other experimental parameters affected the extraction efficiency, including the kind and concentration of salt, concentration and volume of HCl, kind and concentration of surfactant and its volume, kind and volume of extraction solvent, vortex time and the centrifugation extraction time, were also optimized. The optimum extraction conditions of VSLLME-SFO were 10.00 mL of sample, 0.3% (w/v) Na2SO4, 50 uL of 0.050 mol/L SDS, 1.0 mol/L HCl (400 uL), 150 uL of octanol, vortex time 1 min and centrifugation time 10 min. The sediment phase was analyzed by subjecting it to HPLC using a mobile phase of 25% acetonitrile in water, at a flow rate of 1.0 mL/min, and photodiode array detection at 254 nm. Under the optimum extraction conditions, high enrichment factors (20-100 fold) and low limit of detection (0.1-0.5 ug/L) could be obtained. This method provided high sensitivity, low toxic organic solvents used, and simplicity of the extraction processes. The proposed method was successfully applied in the analysis of neonicotinoids in fruit juice and water samples.|A sensitive, selective, and validated HPLC-diode-array detection method was developed for the simultaneous determination of five neonicotinoid insecticides-acetamiprid, imidacloprid, nitenpyram, flonicamid, and thiacloprid-and their primary metabolite, 6-chloronicotinic acid, in cucumbers and soil based on the quick, easy, cheap, effective, rugged, and safe (QuEChERS) technique as a pretreatment procedure. In the QuEChERS procedure, cucumber samples were extracted with acetonitrile and cleaned using C18, whereas soil samples were extracted with an acetonitrile-dichloromethane mixture (1 + 2). The HPLC conditions were optimized by separating neonicotinoids using an acetonitrile-water mixture (25 + 75) and a Synergi Hydro RP C18 column. Matrix-matched calibration standards were prepared in cucumber and soil to eliminate any matrix interference. RSDs were

OBJECTIVES: Agricultural use of neonicotinoid (NEO) insecticides has been increasing in recent years, but their biological monitoring methods have been scarcely reported. In this study, we developed and validated a rapid and sensitive method for quantifying urinary NEO concentrations using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). METHODS: After phosphate-induced acidification of a urine sample, urinary NEOs were trapped by a solid-phase extraction column and eluted with methanol for acetamiprid, imidacloprid, thiacloprid, thiamethoxam, clothianidin and dinotefuran and with an acetonitrile and methanol solution (1:1, v/v) containing 5% NH3 for nitenpyram. A separation analysis was performed by LC-MS/MS within 10 minutes for the sample. This method was applied to first morning urine obtained from 52 Japanese (40.9 +/- 10.5 years old, mean +/- standard deviation) without occupational NEO exposure. RESULTS: The linear dynamic ranges and their limit of quantification (LOQ, signal to noise ratio=10) levels were 0.3-20 or 50 ug/L (r=0.998-0.999) and 0.05-0.36 ug/L, respectively. The absolute recovery was 64-95%, and the intra- and inter-day precisions were less than 16.4% (relative standard deviation, %RSD). This method was successfully applied for analysis of NEOs in human urine samples obtained from 52 adults. The frequencies of individuals who showed more than LOD levels was above 90% for imidacloprid, thiamethoxam, clothianidin and dinotefuran, more than 50% for acetamiprid and thiacloprid and 29% for nitenpyram. CONCLUSIONS: These results indicated that our new method could be applied to biological monitoring of NEO exposure even at environmental exposure levels in Japanese adults without occupational spraying histories.|A semiautomated method based on ultra-high performance liquid chromatography (UHPLC) coupled to Orbitrap high resolution mass spectrometry has been developed for the determination of neonicotinoids (imidacloprid, acetamiprid, clothianidin, dinotefuran, nitenpyram, thiacloprid and thiamethoxam) and the metabolite acetamiprid-n-desmethyl in urine samples. Two automated methods were tested (solid-phase extraction "SPE" and turbulent flow chromatography "TurboFlow"), obtaining the best results when TurboFlow was applied. The total analysis time for the developed method was 14min. The optimized method was validated, obtaining suitable results for all validation parameters. Recoveries ranged from 78% to 116% meanwhile repeatability and reproducibility were evaluated obtaining values lower than 10% and 20% respectively (except for dinotefuran and nitenpyram at 0.2 ug/L). The limit of quantification (LOQ) for all compounds was established at 0.2 ug/L. The proposed analytical methodology was applied to analyze the target compounds in thirty six urine samples from pregnant women living in agricultural areas of Almeria (Spain). Imidacloprid, acetamiprid and acetamiprid-n-desmethyl were detected in some of the samples at concentrations ranging from 0.23 to 1.57 ug/L. Furthermore, dinotefuran was identified in two samples at trace levels.

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