Fenpyroximate

421.49

421.49

DTXSID2032550

White crystalline powder

29331990

74.94000

6.44

light beige crystalline

1.245

102 °C

546.2±60.0 °C(Predicted)

100 °C

1.561

3.46e-08 M

0-6°C

5.63e-08 mmHg

Henry's Law constant = 1.5X10-10 atm-cu m/mole at 25 °C (calc)

Hydroxyl radical reaction rate constant = 4.82X10-11 cu cm/molec-sec at 25 °C (est)

III

6.1

UN30779/PG3

20-50/53

22-60-61

Xn,N

This product is stable for at least 12 months under normal storage conditions 25 deg +/- 2 °C. /FujiMite 5EC Miticide/Insecticide/

P273

H332-H400

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. 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 soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.|Wastes resulting from the use of this product may be disposed of on site or at an approved waste disposal facility. /FujiMite 5EC Miticide/Insecticide/|Container Disposal: Nonrefillable container. Do not reuse or refill this container. Triple rinse (or equivalent) promptly after emptying. Triple rinse as follows: Empty the remaining contents into application equipment or a mix tank and drain for 10 seconds after the flow begins to drip. Fill the container 1/4 full with water and recap. Shake for 10 seconds. Pour rinsate into application equipment or a mix tank or store rinsate for later use or disposal. Drain for 10 seconds after the flow begins to drip. Repeat this procedure two more times. Then, offer for recycling if available, or reconditioning, or puncture and dispose of in a sanitary landfill, or by incineration, or, if allowed by State or local authorities, by burning. If burned, stay out of smoke. /FujiMite 5EC Miticide/Insecticide/|SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.

|Warning|H332 (100%): Harmful if inhaled [Warning Acute toxicity, inhalation]|P261, P271, P273, P304+P312, P304+P340, P312, P391, and P501|Aggregated GHS information provided by 39 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Personal Protective Equipment (PPE). Applicators and other handlers must wear: Long-sleeved shirt and long pants; Chemical-resistant gloves (such as barrier laminate or viton); Protective eyewear (such as safety glasses, goggles, or face shield); Shoes plus socks; For overhead exposure, wear chemical-resistant headgear. /FujiMite 5EC Miticide/Insecticide/|Restricted entry interval (REI) of 12 hours. PPE required for early entry to treated areas that is permitted under the Worker Protection Standard and that involves contact with anything that has been treated, such as plants, soil, or water, is: coveralls worn over short-sleeved shirt and short pants; socks; chemical-resistant footwear; protective eyewear (such as safety glasses, goggles, or face shield); chemical-resistant gloves (such as barrier laminate or viton). /FujiMite 5EC Miticide/Insecticide/|Local exhaust ventilation may be necessary under certain confined conditions. If practical use ventilation at the sources of air contamination. /FujiMite 5EC Miticide/Insecticide/|Avoid breathing mist. Use approved respiratory protection equipment (combination or gas/vapor respirator) when handling large quantities without proper ventilation or handling large spills. /FujiMite 5EC Miticide/Insecticide/

Extinguishing media: water spray, foam, dry chemical, and carbon dioxide. /FujiMite 5EC Miticide/Insecticide/|Firefighters and others that may be exposed should wear fully protective clothing and self-contained breathing apparatus. Due to the danger of acute toxicity to aquatic organisms, avoid permitting extinguishing media, such as water, foam, and dry chemicals, flow into ponds, rivers, and lakes. /FujiMite 5EC Miticide/Insecticide/|Hazardous Combustion Products: Carbon dioxide, carbon monoxide, and nitrogen oxides. /FujiMite 5EC Miticide/Insecticide/

When cleaning equipment, wear a chemical-resistant apron. /FujiMite 5EC Miticide/Insecticide/|Do not contaminate water when cleaning equipment or disposing of equipment washwaters. /FujiMite 5EC Miticide/Insecticide/|Liquid spills on the floor or other impervious surfaces should be contained or diked and then absorbed with sawdust, sand, bentonite, or other absorbent clay. Collect contaminated absorbent, and place it in a metal drum. Thoroughly scrub the floor or other impervious surface with a strong industrial-type detergent and rinse with water. /FujiMite 5EC Miticide/Insecticide/|Liquid spills that soak into the ground should be dug up and placed in metal drums. When a large spill or leakage is found, wear protective clothing and self-contained breathing apparatus to avoid contact. /FujiMite 5EC Miticide/Insecticide/|Avoid permitting contaminated absorbents or water flow into ponds, rivers, and lakes, due to the danger of acute toxicity to aquatic organisms. /FujiMite 5EC Miticide/Insecticide/

Use this product only in accordance with its labeling and with the Worker Protection Standard, 40 CFR part 170. /FujiMite 5EC Miticide/Insecticide/|Do not apply this product in a way that will contact workers or other persons, either directly or through drift. Only protected handlers may be in the area during application. /FujiMite 5EC Miticide/Insecticide/|This pesticide is very highly toxic to fish and aquatic invertebrates. For terrestrial uses, do not apply directly to water, or to areas where surface water is present or to intertidal areas below the mean high water mark. Drift and runoff may be hazardous to aquatic organisms in water adjacent to treated areas. /FujiMite 5EC Miticide/Insecticide/|Users should: Wash thoroughly with soap and water after handling and before eating, drinking, chewing gum, or using tobacco. Remove and wash contaminated clothing before reuse. /FujiMite 5EC Miticide/Insecticide/|For more Preventive Measures (Complete) data for Fenpyroximate (9 total), please visit the HSDB record page.

LC50 Rat inhalation (female) 0.33 mg/L/4 hr /nose-only exposure/|LC50 Rat inhalation (male) 0.21 mg/L/4 hr /nose-only exposure/|LC50 Rat inhalation (female) 0.36 mg/L/4 hr /whole-body exposure/|LC50 Rat inhalation (male) 0.33 mg/L/4 hr /whole-body exposure/|For more Non-Human Toxicity Values (Complete) data for Fenpyroximate (9 total), please visit the HSDB record page.

/AQUATIC SPECIES/...The in vitro and in vivo acute toxicity of fenpyroximate was examined using the marine flounder Paralichthys olivaceus and its gill cell line (FG). The 48hr-IC(50) (95% confidence limits) values of fenpyroximate in the FG cells were 890 (790-990)nM, 950 (881-1019)nM and 1250 (1159-1341)nM, and 96hr-IC(50) (95% confidence limits) were 480 (388-572)nM, 490 (454-526)nM and 510 (469-551)nM, for methyl thiazolyl tetrazolium (MTT) assay, neutral red (NR) uptake and cell protein assay, respectively. The 48hr- and 96hr-LC(50) (95% confidence limits) values of fenpyroximate in living flounders were 28.84 (14.28-58.26)nM and 11.74 (6.06-22.8)nM, respectively. This indicated that fenpyroximate was highly toxic to both flounders and FG cells. Moreover, comparisons of the ratios of average 48hr-IC(50) to 48hr-LC(50) and average 96hr-IC(50) to 96hr-LC(50) showed that the length of exposure time did not significantly affect the correlation between the FG cells and living flounders in the acute toxicity estimation of fenpyroximate provided the selected exposure time is the same. Thus, we suggest that FG cells could be a good bioassay system in rapid estimation of the corresponding LC(50) values of pollutants to living fish, instead of whole living fish. Histopathological examinations showed that liver and gill were the major target organs of fenpyroximate, especially the damage of gill tissues may account much for the high lethality of exposed flounders. Consistent with the histopathological observations, analysis of the activities of two key detoxification metabolism-related enzymes, glutathione S-transferase (GST) and cytochrome P4501A1 (CYP1A1)-dependent ethoxyresorufin-O-deethylase (EROD), in the liver and gill tissues of exposed flounders indicated that liver has much higher detoxification capacity than gills, and this contributes to the higher tolerance of liver to the toxicity of fenpyroximate in the exposed flounders. Fenpyroximate can initially induce a quick and significant increase of the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in all the exposed FG cells, and liver and gill tissues of exposed flounders. Upon continuation of the exposure the enzyme activities were inhibited, implying the occurrence of oxidative stress in the exposed fish cells and the possible interruption of the mitochondrial respiratory chain which involves redox reactions by fenpyroximate.|/AQUATIC SPECIES/ The knowledge in oxidative stress in fish has a great importance for environmental and aquatic toxicology. Because oxidative stress is evoked by many chemicals including some pesticides, pro-oxidant factors' action in fish organism can be used to assess specific area pollution or world sea pollution. ...Oxidative damage from fenpyroximate actuation is related to the disruption of mitochondrial redox respiratory chain.

Fenpyroximate's production may result in its release to the environment through various waste streams; its use as an acaricide(1) will result in its direct release to the environment(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1.2X10+4(SRC), determined from a log Kow of 5.01(2) and a regression-derived equation(3), indicates that fenpyroximate is expected to be immobile in soil(SRC). Volatilization of fenpyroximate from moist soil surfaces is expected to be an important fate process(SRC) given an calculated Henry's Law constant of 1.3X10-6 atm-cu m/mole(2). However, adsorption to soil is expected to attenuate volatilization(SRC). Fenpyroximate is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 5.58X10-8 mm Hg at 25 °C(2). When incubated in soil under aerobic conditions, fenpyroximate exhibited moderate to high persistence(4) indicating that biodegradation is not an important environmental fate process in soil(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1.2X10+4(SRC), determined from a log Kow of 50.1(2) and a regression-derived equation(3), indicates that fenpyroximate is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(4) based upon a calculated Henry's Law constant of 1.3X10-6 atm-cu m/mole(2). Using this Henry's Law constant and an estimation method(4), volatilization half-lives for a model river and model lake are 35 days and 260 days, respectively(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column. The estimated volatilization half-life from a model pond is 44 years if adsorption is considered(5). According to a classification scheme(6), an estimated BCF of 940(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is high, provided the compound is not metabolized by the organism(SRC). When incubated using dark natural sediment/water systems, fenpyroximate was lost from a sediment/water system but it was mostly due to adsorption to sediment(7) indicating that biodegradation is not an important environmental fate process in water(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), fenpyroximate, which has a vapor pressure of 5.58X10-8 mm Hg at 25 °C(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase fenpyroximate may be removed from the air by wet or dry deposition(SRC). Fenpyroximate contains chromophores that absorb at wavelengths >290 nm(3), and therefore may be susceptible to direct photolysis by sunlight(SRC).

Fenpyroximate is stable in acid and alkali(1). The compound was stable under sterile hydrolysis at pH 5, 7, and 9, maintained at 25 °C(2). A base-catalyzed second-order hydrolysis rate constant of 1.6X10-2 L/mole-sec(SRC) was estimated using a structure estimation method(2); this corresponds to half-lives of 13 and 1.3 years at pH values of 7 and 8, respectively(3). Fenpyroximate contains chromophores that absorb at wavelengths >290 nm(4), and therefore may be susceptible to direct photolysis by sunlight(SRC). Aqueous photolysis under sterile conditions at pH 7 and equated to June sunlight at 55 deg N resulted in a first-order half-life of 1 hour; the Z-isomer was formed after 4 hours(2).

An estimated BCF of 940 was calculated in fish for fenpyroximate(SRC), using log Kow of 5.01(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is high(SRC), provided the compound is not metabolized by the organism(SRC).

The Koc of fenpyroximate is estimated as 1.2X10+4(SRC), using a log Kow of 5.01(1) and a regression-derived equation(2). Calculated Koc values of 4X10+4 to 7.6X10+4 have also been reported, with no evidence to support correlation with pH(3). According to a classification scheme(4), these estimated Koc values suggest that fenpyroximate is expected to be immobile in soil.

The Henry's Law constant for fenpyroximate is calculated as 1.3X10-6 atm-cu m/mole(1). This Henry's Law constant indicates that fenpyroximate is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 35 days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 260 days(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column. The estimated volatilization half-life from a model pond is 44 years if adsorption is considered(3). Fenpyroximate's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). Fenpyroximate is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 5.58X10-8 mm Hg(1).

Occupational exposure to fenpyroximate may occur through inhalation and dermal contact with this compound at workplaces where fenpyroximate is produced or used. (SRC)

Fenpyroximate was relatively well absorbed by rats after oral administration. Absorbed fenpyroximate was excreted predominantly via the biliary route, with lesser amounts in urine. The residual levels in organs and tissues after 168 hr were low. There was no evidence of bioaccumulation.|Groups of four male Sprague-Dawley CD rats received single dermal applications of 14C-pyrazole-fenpyroximate suspended in water at doses of 0.1, 1.0, or 5.2 mg in 1 mL on a 10 sq cm area of skin for 0.5, 1, 2, 4, 10, or 24 hr and were sacrificed at the end of the exposure period, The concentration of radiolabel in blood was very low after all applications. Excretion in urine was slight but increased with duration of exposure; after 24 hr of exposure, 0.7-0.9% of the applied dose had been excreted. Radiolabel was found in feces after 10 and 24 hr of treatment, and fecal excretion was 1.4% at a dose of 1 mg, 0.5% at 10 mg, and 0.2% at 52 mg. These results suggest that fenpyroximate is barely absorbed from the skin and is excreted via the biliary-faecal and urinary routes.|Groups of six male and six female Sprague-Dawley rats with bile duct cannulae were given a single oral dose of 2 mg/kg of (14)C-pyrazole- or (14)C-benzyl-fenpyroximate. Within 48 hr after treatment with pyrazole-labelled fenpyroximate, 47% (females) to 55% (males) of the radiolabel had been excreted in the bile, 5%, (males) to 10% (females) in urine, and 17% (females) to 28% (males) in feces. Total excretion 48 hr after treatment was about 88% for males and 73% for females. The Tmax, Cmax, and half-lives of the radiolabel in the blood of cannulated rats were similar to those of rats with no cannulae. Within 48 hr after oral administration of benzyl-labelled fenpyroximate, 47% (females) to 51% (males) of the radiolabel had been excreted in the bile, 6% (males) to 8% (females) in urine, and 28% (females) to 40% (males) in feces.|Groups of six male and six female Sprague-Dawley (Crl;CD)rats were given single doses by gavage of 2 or 400 mg/kg bw of (3-(14)C)-pyrazole-(radiochemical purity, 96.4-99.9%) or (U-(14)C)-benzyl-fenpyroximate (radiochemical purity, 99.2-99.5%) suspended in 1% aqueous Tween 80. Blood was collected from the tail vein of five rats per group at various times up to 168 hrs after dosing. In rats given 2 mg/kg bw, the concentration of radiolabel in blood peaked within 1 hr after dosing and reached a plateau, which was sustained for about 18 hrs... In the group given 400 mg/kg bw, absorption was delayed, and radiolabel was not detectable in blood within the first 12 hrs after dosing. A nearly maximal level was achieved 12-24 hrs after dosing; the plateau was sustained for 80-100 hrs ...|For more Absorption, Distribution and Excretion (Complete) data for Fenpyroximate (7 total), please visit the HSDB record page.

Fenpyroximate was extensively metabolized in rats; 23 metabolites were identified. No parent compound was found in the urine; metabolites found in the excreta represented 0-11% of the administered dose. Multiple pathways have been proposed for the metabolism of fenpyroximate, including oxidation, hydroxylation, demethylation, hydrolysis, and isomerization.|Fenpyroximate is metabolized extensively by hydrolytic cleavage of the oxime ether bond, hydrolysis of the tert-butyl ester, oxidation of the tert-butyl, hydroxylation of the phenoxy ring and 3-methyl, isomerization, N-demethylation, and conjugation, producing a large number of metabolites. The major metabolites identified are (E)-4-[(1,3-dimethyl-5-phenoxypyrazol-4-yl) methyleneaminooxymethyl] benzoic acid, (Z)-4-[(1,3-dimethyl-phenoxypyrazol-4yl) methyleneaminooxymethyl] benzoic acid, (E)-4-{[1,3-dimethyl-5-(4-hydroxyphenoxy) pyrazol-4-yl]methyleneaminooxymethyl} benzoic acid, 1,3-dimethyl-5-phenoxypyrazole-4-carboxylic acid, 4-hydroxymethyl benzoic acid, terephthalic acid, 4-cyano-1-methyl-5-phenoxypyrazole-3-carboxylic acid, (E)-2-{4-[(1,3-dimethyl-5-phenoxypyrazol-4-yl) methyleneaminooxymethyl] benzoyloxy}-2-methylpropanoic acid, (E)-2-{4-[1,3-dimethyl-5-(4-hydroxyphenoxy) pyrazol-4-yl] methyleneaminooxymethyl} benzoyloxy]-2-methylpropionic acid, and (E)-2-[{4-[3-hydroxymethyl-1-methyl-5-phenoxypyrazol-4-yl] methyleneaminooxymethyl} benzoyloxy]-2-methylpropionic acid.|Groups of six male and six female Sprague-Dawley rats with bile-duct cannulae were given a single oral dose of 2 mg/kg (14)C-pyrazole-labeled fenpyroximate. No parent fenpyroximate was found in bile, but metabolites (E)-4-[(1,3-dimethyl-5-phenoxypyrazol-4-yl)-methyleneaminooxy-methyl] benzoic acid, (Z)-4-[(1.3-dimethyl-5-phenoxy-pyrazol-4-yl)-methyleneaminooxy-methyl] benzoic acid, (E)-4-{[1,3-dimethyl-5-(4-hydroxyphenoxy) pyrazol-4-yl] methyleneaminooxymethyl} benzoic acid, (E)-2-{4-[(1,3-dimethyl-5-phenoxypyrazol- 4-yl) methyleneaminooxymethyl] benzoyloxy}-2-methylpropanoic acid, 1,3-dimethyl-5-(4-hydroxyphenoxy)pyrazole-4-carbaldehyde, 1,3-dimethyl-5-phenoxypyrazole-4-carboxylic acid, 3-methyl-5-phenoxypyrazole-4-carbaldehyde, 1,3-dimethyl-5-(4-hydroxyphenoxy)-pyrazole-4-carbonitrile, (E)-1,3-dimethyl-5-phenoxypyrazole-4-carbaldehydeoxime, 3-methyl-5-(4-hydroxyphenoxy)-pyrazole-4-carbaldehyde, and (E)-2-[4-[(1,3-dimethyl-5-phenoxy-pyrazol-4-yl)methyleneamniooxy-methyl]benzoyloxy]-2-methyl-propanoic acid, and conjugates of (E)-4-[(1,3-dimethyl-5-phenoxypyrazol-4-yl)-methyleneaminooxy-methyl] benzoic acid, (Z)-4-[(1.3-dimethyl-5-phenoxy-pyrazol-4-yl)-methyleneaminooxy-methyl] benzoic acid, (E)-4-{[1,3-dimethyl-5-(4-hydroxyphenoxy) pyrazol-4-yl] methyleneaminooxymethyl} benzoic acid, and 1,3-dimethyl-5-phenoxypyrazole-4-carboxylic acid were found. Total radiolabel represented less than 2% of the dose. The metabolic pathway proposed for fenpyroximate in rats is cleavage of the ester bond, hydroxylation at the phenoxypyrazole group, oxidation at the tert-butyl group, and conjugation with sulfate and glucuronide.|Groups of four male Sprague-Dawley (SLC) rats were treated with a single oral dose of 1.5 mg/kg bw (14)C-pyrazole- or (14)C-benzoyl- labeled fenpyroximate (radioactive purity, > 99%), and urinary and fecal samples were collected for 0-72 hrs. Six urinary and 17 fecal metabolites were identified by thin-layer co-chromatography with authentic samples. ... The major urinary metabolites were 1,3-dimethyl-5-phenoxypyrazole-4-carboxylic acid (7.3% of the dose), 4-cyano-1-methyl-5-phenoxy-pyrazole-3-carboxylic acid (2.5%), and terephthalic acid (3.8%). The major fecal metabolites were (E)-4-[(1,3-dimethyl-5-phenoxypyrazol-4-yl)-methyleneaminooxy-methyl] benzoic acid (4.1-11.0% of the dose), (E)-4-{[1,3-dimethyl-5-(4-hydroxyphenoxy) pyrazol-4-yl] methyleneaminooxymethyl} benzoic acid (2.9-4.2%), and (E)-2-[4-[(1,3-dimethyl-5-phenoxy-pyrazol-4-yl)methyleneamniooxy-methyl]benzoyloxy]-2-methyl-propanoic acid (3.5-4.3%); 4-hydroxymethyl benzoic acid (7.5%) was found as a precursor of terephthalic acid and (E)-2-[4-[1,3-dimethyl-5-(4-hydroxyphenoxy) pyrazol-4-yl] methyleneaminooxymethyl} benzoyloxy]-2-methylpropionic acid (2.0-9.7%) and (E)-2-[{4-[3-hydroxymethyl-1-methyl-5-phenoxypyrazol-4-yl] methyleneaminooxymethyl} benzoyloxy]-2-methylpropionic acid (3.3-4.5%) as hydroxylated bodies of (E)-2-[4-[(1,3-dimethyl-5-phenoxy-pyrazol-4-yl)methyleneamniooxy-methyl]benzoyloxy]-2-methyl-propanoic acid. The concentrations of the urinary metabolites 1,3-dimethyl-5-(4-hydroxyphenoxy)-pyrazole-4-carbonitrile and 3-methyl-5-(4-hydroxyphenoxy)-pyrazole-4-carbaldehyde and the fecal metabolites tert-butyl(E)-4-[(1,3-dimethyl-5-(4-hydroxyphenoxy)pyrazol-4-yl)methyleneaminooxymethyl] benzoate, (E)-2-[4-[(1,3-dimethyl-5-phenoxy-pyrazol-4-yl)methyleneamniooxy-methyl]benzoyloxy]-2-methyl-propanoic acid, (E)-2-[4-[1,3-dimethyl-5-(4-hydroxyphenoxy) pyrazol-4-yl] methyleneaminooxymethyl} benzoyloxy]-2-methylpropionic acid, and (E)-2-[{4-[3-hydroxymethyl-1-methyl-5-phenoxypyrazol-4-yl] methyleneaminooxymethyl} benzoyloxy]-2-methylpropionic acid were increased by enzymatic hydrolysis of the excreta with beta-glucuronidase or sulfatase.|In the present study, least 3 rats/sex/dose/time interval combination were treated with a single oral dose of (Pyrazole-(14)C) Fenpyroximate (NNI-850, purity: 99.6%), prior to collection of urine, feces, organic volatiles, and carbon dioxide. The preliminary study found no detectable carbon dioxide, and organic volatiles were either non-detectable or below quantifiable levels. ... Single oral doses were low (2 mg/kg) or high (400 mg/kg). Sacrifice time intervals after radiolabeled Fenpyroximate treatment were 12, 24, and 168 hr for low dose groups, and 12, 24, 96, 120, and 168 hr for high dose groups. Repeat dose groups received 2 mg/kg/day unlabeled Fenpyroximate for 14 days, followed by a single treatment with labeled Fenpyroximate at 2 mg/kg. This group was maintained for 168 hr before sacrifice. All 168-hr groups consisted of 5/sex, and these were used for excretion samples at intervals throughout that period. Metabolite identification was performed by comparisons of 2-dimensional TLC mobilities of excreta extracts with mobilities of a series of proposed metabolites in two sets of solvent systems (i.e. standard chromatograms by visualization under UV light were compared to autoradiograms of fecal or urinary extracts). ... A single 2 mg/kg dose found about 8% of fecal metabolites as parent compound, about 13% presumed to be the ester hydrolysis product, with other characterized metabolites accounting for about 5% or less of fecal radioactivity. Uncharacterized metabolites which remained at the origin of the 0-24 hr TLC plates of 2 mg/kg groups constituted 47-50% of fecal label, compared to 2-4% in 400 mg/kg groups, suggesting that most of the dose was absorbed and metabolized following low dose administration. ... The major identified urinary metabolite was evidently 1,3-dimethyl-5-phenoxypyrazol- 4-carboxylic acid. This compound, designated M-8, was substantially conjugated as a glucuronide. ...

Groups of six male and six female Sprague-Dawley (Crl;CD)rats were given single doses by gavage of 2 or 400 mg/kg bw of (3-(14)C)-pyrazole-(radiochemical purity, 96.4-99.9%) or (U-(14)C)-benzyl-fenpyroximate (radiochemical purity, 99.2-99.5%) suspended in 1% aqueous Tween 80. Blood was collected from the tail vein of five rats per group at various times up to 168 hrs after dosing. In rats given 2 mg/kg bw ... slow elimination phase with a half-life of 6-9 hrs. In the group given 400 mg/kg bw ... elimination phase with a half-life of 35-49 hrs.|Two studies used five rats/sex/group, dosed with 2 or 400 mg/kg (Pyrazole-(14)C) Fenpyroximate (NNI-850) or (Benzyl- (14)C) Fenpyroximate (NNI-850) by gavage in 1% aqueous Tween 80. Tail vein blood was collected at intervals for 7 days. Pyrazole-(14)C Study: Half-lives in blood were 8.9 hr for both M and F at 2 mg/kg. ... In contrast, 400 mg/kg led to half-lives in blood of 49 and 45 hr for M and F. ... Benzyl-(14)C Study: Half-lifes in blood were 6.1 hr and 7.9 hr for M and F, respectively, at 2 mg/kg. ... In contrast, 400 mg/kg led to half-lives in blood of 47 and 35 hr for M and F.

The high specificity of fenpyroximate as a miticide is not based primarily on differences in target site sensitivity since it inhibits the mitochondrial complex I from rat liver and from spider mites with less than a 10-fold difference in potency. The main mechanism of selectivity has been shown to depend on differential rates of metabolic detoxification, particularly through removal of the t-Bu group yielding the free carboxylic acid analog. This metabolite is inactive as a complex I inhibitor. This apparent hydrolysis is largely catalyzed by cytochrome PA50 through hydroxylation of the t-Bu group followed by intramolecular ester cleavage. Oxidative ester cleavage was rapid in the several mammals, fish, and insects tested but it did not occur in mites.|Parkinson's disease (PD) brains show evidence of mitochondrial respiratory Complex I deficiency, oxidative stress, and neuronal death. Complex I-inhibiting neurotoxins, such as the pesticide rotenone, cause neuronal death and parkinsonism in animal models. We have previously shown that DJ-1 over-expression in astrocytes augments their capacity to protect neurons against rotenone, that DJ-1 knock-down impairs astrocyte-mediated neuroprotection against rotenone, and that each process involves astrocyte-released factors. To further investigate the mechanism behind these findings, we developed a high-throughput, plate-based bioassay that can be used to assess how genetic manipulations in astrocytes affect their ability to protect co-cultured neurons. We used this bioassay to show that DJ-1 deficiency-induced impairments in astrocyte-mediated neuroprotection occur solely in the presence of pesticides that inhibit Complex I (rotenone, pyridaben, fenazaquin, and fenpyroximate); not with agents that inhibit Complexes II-V, that primarily induce oxidative stress, or that inhibit the proteasome. This is a potentially PD-relevant finding because pesticide exposure is epidemiologically-linked with an increased risk for PD. Further investigations into our model suggested that astrocytic GSH and heme oxygenase-1 antioxidant systems are not central to the neuroprotective mechanism.|... In this study, ...the in vitro toxicity and mechanism of action of several putative complex I inhibitors that are commonly used as pesticides/ tebunfenpyrad. A similar order of potency was observed for reduction of ATP levels and competition for (3)H-dihydrorotenone (DHR) binding to complex I, with the exception of pyridaben (PYR). Neuroblastoma cells stably expressing the /rotenone/ (ROT)-insensitive NADH dehydrogenase of Saccharomyces cerevisiae (NDI1) were resistant to these pesticides, demonstrating the requirement of complex I inhibition for toxicity. ... PYR was a more potent inhibitor of mitochondrial respiration and caused more oxidative damage than ROT. The oxidative damage could be attenuated by NDI1 or by the antioxidants alpha-tocopherol and coenzyme Q(10). PYR was also highly toxic to midbrain organotypic slices. These data demonstrate that, in addition to ROT, several commercially used pesticides directly inhibit complex I, cause oxidative damage, and suggest that further study is warranted into environmental agents that inhibit complex I for their potential role in Parkinson's Disease.

/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 the 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 /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's 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 or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/SURVEILLANCE/ The results of medical surveillance of workers manufacturing a 5% formulation of fenpyroximate were reported. Ocular and dermal irritation were seen in July and November 1990 and March 1991. The concentrations of fenpyroximate in the air at eight to nine sites in the working place were 0.117 mg/cu m in January 1991, 0.012 mg/cu m in April 1991, 0.005 mg/cu m in November 1991, and 0.004 mg/cu m in January 1993; however, the actual exposure of the workers to fenpyroximate was not determined.|/GENOTOXICITY/ Fenpyroximate (NNI-850, purity: 97.3%) was tested for the formation of chromosomal aberrations with human lymphocytes in culture. Whole blood was obtained from a male volunteer, placed into culture with phytohemagglutinin for 48 hrs, then exposed to fenpyroximate at concentrations of 0 (acetone), 1.25, 5 or 20 ug/mL, for 2 hrs with and without activation with rat liver S-9. Following the two hrs, cells were washed, resuspended in complete medium, and the test solutions added at the original concentrations for an additional 22 hrs of exposure without S9 activation. Colcemid was added for the last 3 hrs of the incubation. There were triplicate cultures per group. Negative control was untreated, positive controls were chlorambucil for minus S9 and cyclophosphamide with activation. A single trial was conducted. Mitotic indices were determined by counting approximately 1000 lymphocytes per culture. For chromosomal aberrations, 100 cells per culture were scored. Results were reported as percent cells with aberrations including and excluding gaps. The mitotic indices for the treated groups were lower than the vehicle and negative controls. Excluding gaps, there was no indication of a treatment-induced increase in chromosomal aberrations under the study conditions.

fenperoximate

Suspension concentrate|Emulsifiable concentrate|Akari 5SC Miticide-Insecticide (Nichino America, Inc.) Fenpyroximate 5%|Fenpyroximate Technical (Nichino America, Inc.) Fenpyroximate 99.5%|Fujimite 5EC Miticide/Insecticide (Nichino America, Inc.) Fenpyroximate 5%

The WHO Recommended Classification of Pesticides by Hazard identifies fenpyroximate (technical grade) as Class II: moderately hazardous; Main Use: acaricide.

An acceptable enforcement method, gas chromatography with nitrogenphosphorus detector (GC/NPD) method DFG S19, is available for enforcement of tolerances for residues in or on plant commodities.|Product analysis by HPLC. Residues in soil by GLC, in water by HPLC/UV, in plants by LC/MS/MS.

Agrochemicals -> Acaricides