Famoxadone

374.39

374.39

200-835-2

DTXSID8034588

Pale cream powder

67.9

4.65 at pH 7

1.31 g/cu cm at 22 deg C

141 °C

491.3±55.0 °C(Predicted)

2 °C

1.659

In water, 0.052 mg/L (unbuffered water pH 7.8-8.9 at 20 deg C)

0-6°C

6.4 x 10 -7 Pa (20 °C)

LD50 in rats (mg/kg): >5000 orally; >2000 dermally (Joshi, Sternberg)

Not explosive by impact, nor thermally sensitive. /Tanos 50 DF/ /from table/

Henry's Law constant = 4.6X10-8 atm-cu m/mol at 20 °C /Estimated/

pKa = 10 /Estimated/

log Kow = 4.59 at pH 3; 4.80 at pH 5; 5.55 at pH 9|Hydroxyl radical reaction rate constant = 5.7X10-11 cu cm/molecule-sec at 25 °C /Estimated/

UN16483/PG2

2

48/22-50/53-36-20/21/22-11

46-60-61-36-26-16-36/37

Xn,N,F

Storage stability: No significant change in the level of active substance, nor in the container, was observed after two years' storage in the commercial container, under ambient warehouse conditions. /Tanos 50 DF/ /from table/

P210-P280-P305 + P351 + P338

H225-H302-H312-H319-H332

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure 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, aquatic, and plant life; and conformance with environmental and public health regulations.

Not an oxidizer or reducer. /Tanos 50 DF/ /from table/

California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summaries. Available from: http://www.cdpr.ca.gov/docs/toxsums/toxsumlist.htm on Famoxadone (131807-57-3) as of October 4, 2004|Health Canada, Pest Management Regulatory Agency; Regulatory Note- Famoxadone/Tanos 50DF REG2003-10 (Septemder 24, 2003). Available from: http://www.pmra-arla.gc.ca/english/pdf/reg/reg2003-10-e.pdf as of October 20, 2004.

|Warning|H373 **: Causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]|P260, P273, P314, P391, and P501|H373 (100%): Causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]|Aggregated GHS information provided by 226 companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H373: Causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]

Not explosive by impact, nor thermally sensitive. /Tanos 50 DF/ /from table/

LD50 Rat oral >5000 mg/kg|LD50 Rat dermal >2000 mg/kg

/OTHER TERRESTRIAL SPECIES/ Several studies were conducted to determine the effect of famoxadone on beneficial insects. ...An application of 0.7 kg DPX-KP481/ha (25% famoxadone and 25% cymoxanil) is not potentially harmful to green lacewings. No harmful effects were observed in ground beetles or staphylinid beetles when treated with an application of 0.7 kg DPX-KP481/ha. Using the same application rate of DPX-KP481, there was a 28-69% reduction in reproductive success, relative to the controls, in hoverflies. Therefore, a treatment of 0.7 kg DPX-KP481/ha is considered potentially harmful to hoverflies. The end-use products DPX-KX007 SC and DPX-KX007 WG were found to be slightly harmful to harmful to predatory mite /in/ studies.

Famoxadone's production may result in its release to the environment through various waste streams; it's use as a fungicide(1) will result in its direct release to the environment(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values ranging from 3,300 to 4,030(2) indicate that famoxadone is expected to be slightly mobile to immobile in soil(SRC). Famoxadone was not detected above the detection limit (0.007 ppm) below a soil depth of 15 cm in any of these studies(2). Volatilization of famoxadone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.6X10-8 atm-cu m/mole(SRC) based on its vapor pressure, 4.80X10-9 mm Hg(3), and water solubility, 5.20X10-2 mg/L(3). Famoxadone is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(3). Biodegradation and hydrolysis of famoxadone are expected to be competing processes in both aerobic and anaerobic soil(4). The half-life of famoxadone in soil has been reported to be 6 days under aerobic conditions and 28 days under anaerobic conditions(4). Reported field dissipation half-lives collected from several studies range from 6.5 to 32.9 days(2). The reported half-life of famoxadone measured during an aerobic aqueous sediment metabolism study was less than 1 day(4). The half-life for famoxadone in irradiated soil has been reported to be 3.3 to 4.9 days, which, after correction for dark controls, is said to be equivalent to 9.5 to 16.2 days of natural sunlight(2).|AQUATIC FATE: Based on a classification scheme(1), Koc values ranging from 3,300 to 4,030 (2) indicate that famoxadone 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 4.6X10-8 atm-cu m/mole(SRC)calculated from a vapor pressure of 4.80X10-9 mm Hg(4) and a water solubility of 5.20X10-2 mg/L(4). According to a classification scheme(5), BCF values ranging from 971 to 3,608(2) suggest the potential for bioconcentration in aquatic organisms is very high(SRC). Famoxadone is expected to undergo hydrolysis based on reported half-lives of 31-41 days in a pH 5 buffer solution, 2-2.7 days in a pH 7 buffer solution, and 1.55-1.8 days in a pH 9 buffer solution(2,6,7). The reported half-life of famoxadone measured during an aerobic aqueous sediment metabolism study was less than 1 day indicating that this substance may biodegrade in aquatic systems(6). The half-life for famoxadone in an irradiated solution at pH 5 has been reported to be 1.1 to 1.9 days, which, after correction for dark controls, is said to be equivalent to half-lives of 2.6-4.6 days in natural sunlight(2). The half-life for the dark control was 41 days.|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), famoxadone, which has a vapor pressure of 4.80X10-9 mm Hg at 20 °C(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase famoxadone may be removed from the air by wet and dry deposition(SRC).

Famoxadone is expected to undergo hydrolysis based on reported half-lives of 31-41 days at pH 5, 2-2.7 days at pH 7, and 1.55-1.8 days at pH 9 in aqueous buffer solutions(1,2,3). The half-life for famoxadone in an irradiated solution at pH 5 has been reported to be 1.1 to 1.9 days, which, after correction for dark controls, is said to be equivalent to 2.6-4.6 days of natural sunlight(3). The half-life for the dark control was 41 days. The half-life for famoxadone in irradiated soil has been reported to be 3.3 to 4.9 days, which, after correction for dark controls, is said to be equivalent to 9.5 to 16.2 days of natural sunlight(3).

BCF values of 971 to 1,286 were measured for famoxadone in edible bluegill sunfish tissue(1). BCF values were 3,327 to 3,608 for the nonedible tissue and 2,434 to 3,425 for the whole fish tissues(1). According to a classification scheme(2), these BCF values suggest the potential for bioconcentration in aquatic organisms is very high(SRC), provided the compound is not altered physically or chemically once released into the environment.

Measured Koc values of famoxadonehave been reported to be 3,890 for sand soil(2.29% organic carbon), 3,300 for sandy loam soil(1.34% organic carbon), and 4,030 for sandy clay loam soil(0.58% organic carbon)(1). According to a classification scheme(2), these Koc values suggest that famoxadone is expected to be slightly mobile to immobile in soil.

The Henry's Law constant for famoxadone is estimated as 4.6X10-8 atm-cu m/mole(SRC) derived from its vapor pressure, 4.80X10-9 mm Hg(1), and water solubility, 5.20X10-2 mg/L(1). This Henry's Law constant indicates that famoxadone is expected to be essentially nonvolatile from moist soil and water surfaces(2). Famoxadone is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

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

Following oral application to rats, elimination is rapid. Unmetabolized famoxadone was the major component in the feces; mono- (at 4'-phenoxyphenyl) and di- (also at 4-phenylamino) hydroxylated famoxadone were the primary fecal metabolites. In urine, products arising from cleavage of the heterocyclic ring were found. In goats and hens, there was little residue in the tissues; the majority of the administered famoxadone (about 60%) was unmetabolized and recovered in the feces. Metabolism was complex, involving hydroxylation, cleavage of the oxazolidinedione-aminophenyl linkage, cleavage of the phenoxyphenyl ether linkage and opening of the oxazolidinedione ring.|Ten groups of 4 or 5 Crl:CD/BR (Sprague-Dawley) albino rats per sex received a single oral gavage dose of [14C-PA]DPX-JE874 at 5 or 100 mg/kg. One group (G) of 5 per sex had been exposed (oral gavage) to non-radiolabelled DPX-JE874 for fourteen consecutive days prior to the radiolabelled dose. Two other groups (B (4/sex) and E (5/sex)) received a single dose (oral gavage) of [14C-POP]DPX-JE874 at 100 mg/kg. Groups A, B, and C: the absorption half-lives of [14C-PA]DPX-JE874 in whole blood and plasma increased from 0.8 - 1.2 hours to 3.5 - 7.1 hours as the dose increased from 5 to 100 mg/kg. Absorption half-lives of [14C-POP]DPX-JE874 at 100 mg/kg were 0.4 to 1.4 hours. Elimination half-lives were 2 to 3 fold slower in whole blood compared to plasma with [14C-PA]DPX-JE874 (indication of binding to red blood cells). No indication of binding with [14C-POP]DPX-JE874. Groups D, E, F, G: No accumulation of [14C-PA]DPX-JE874 residues in organs and tissues was observed at 5 and 100 mg/kg 120 hours post-treatment. [14C-POP]DPX-JE874 treated animals (Group E, 100 mg/kg) showed highest radioactivity in fat (< 2 ppm). Gonads, uterus, adrenals, and bone marrow also contained slightly increased levels of 14C-residues (< 2 ppm) (possibly associated with body fat adhering to the tissues). > 75% of administered radiolabel was excreted in feces and less than 10% in urine during 24 hours post-dosing. There was no significant difference in the elimination profile between single (D, E, and F) and multiple (G) dosings, between sexes, nor between [14CPA]DPX-JE874 and [14C-POP]DPX-JE874. ... Groups H and I: Liver and fat were the two primary tissues for distribution of [14C-PA]DPX-JE874 residues at 5 hours (5 mg/kg) and 14 hours (100 mg/kg) post-dosing. At 36 hours (5 mg/kg) and 48 hours (100 mg/kg), liver was the only tissue containing slightly elevated residues.|Seven rats per sex received a single oral gavage dose of [14C-PA]DPX-JE874 or [14C-POP]DPX-JE874 at 5 mg/kg. The animals had biliary and duodenal cannulae surgically implanted 3 days prior to treatment. Bile was collected continuously and sampled 1, 3, 6, 10, 16, 24, 36, and 48 hours post-dosing. Urine and feces were collected 12, 24, and 48 hours after dosing. After the final urine and feces collection, cage washes were collected and analyzed. Blood was collected from all animals at termination (48 hours post-treatment). Carcasses were homogenized and analyzed for radioactivity. 30% to 39% of administered radiolabel was excreted in bile 1 to 10 hours post-dosing. Higher amounts of [14C-POP]DPX-JE874 (39%) than of [14C-PA]DPX-JE874 (31%) were excreted in males. The average urinary excretion of radiolabel was from 2% to 6% of administered dose. 56% to 65% of administered dose was excreted in feces. 0.22% and 0.31% of administered dose was found in blood of [14C-PA]DPX-JE874 treated males and females respectively at termination. 0.03% was found in blood of both males and females treated with [14C-POP]DPX-JE874. The average amount of radiolabel in carcasses ranged from 0.4% to 3.0%.|Six male beagle dogs received a single oral gavage dose of [14C-PA]DPX-JE874 at 15 mg/kg. 3 animals (Group A) were used for pharmacokinetic sampling (sacrificed at 96 hours post-dose), 3 others (Group B) were used for tissue distribution evaluation at the peak plasma concentrations (sacrificed 2 hours post-dose) observed in Group A. The final one was used as vehicle control (Group C) (sacrificed at 96 hours). The mean recovery of radioactivity from Group A dogs during 96 hours post-dosing was 7.67% in urine, 70.3% in feces, and 0.74% in cage wash and cage wipes. Peak mean excretion of radioactivity occurred during 24 to 48 hrs post-dosing in urine and during 12-24 hours in feces. ... Group mean radioactivity concentration in plasma peaked 2 hours post-dosing at 1.53 ppm and at 4 hours in RBCs (0.626 ppm). At 96 hours, values were 0.597 ppm (plasma) and 0.648 ppm (RBCs). The highest mean concentrations of radioactivity were detected in liver (1.34 ppm) and mesenteric fat (0.945 ppm) at the 96-hour sacrifice. Mean levels in aqueous humor, eye, and eye remainder were 0.091 ppm, 0.135 ppm, and 0.173 ppm, respectively. In Group B animals (2-hour sacrifice), the highest mean concentrations of radioactivity were found in liver (4.45 ppm), mesenteric fat (2.80 ppm), plasma (0.999 ppm), and RBCs (0.413 ppm). Residues in the aqueous humor, eye, and eye remainder were 0.061 ppm, 0.106 ppm, and 0.131 ppm, respectively.|For more Absorption, Distribution and Excretion (Complete) data for FAMOXADONE (6 total), please visit the HSDB record page.

Hydroxylation of the two phenyl rings at the para position is the major routes of metabolism.|... Groups of 4 or 5 Crl:CD/BR (Sprague-Dawley) albino rats per sex received a single oral gavage dose of [14C-PA]DPX-JE874 at 5 or 100 mg/kg ... /or/ a single dose (oral gavage) of [14C-POP]DPX-JE874 at 100 mg/kg. ... Three radioactive components were observed in feces of both [14C-PA] and [14C-POP] treated animals. Unmetabolized 14C-DPX-JE874 was the major component. The other two were monohydroxylated (IN-KZ007) and di para hydroxylated (IN-KZ534) DPX-JE874. One major radioactive component (a sulfate conjugate) was observed in urine of [14C-POP] treated animals. The primary metabolite in urine from [14C-PA] treated animals coincided with 4-acetoxyaniline (HPLC).

Famoxadone is an extremely potent inhibitor of mitochondrial electron transport acting at complex III in mitochondria from fungi, plants and mammals ... The site of inhibition is cytochrome b within the Qo domain which prevents transfer of electrons from cytochrome b to cytochrome c1.

/SRP:/ Basic treatment: Establish a patent airway. 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 normal saline 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 ... . /Poison 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 respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

5-methyl-5-(4-phenoxyphenyl)-3-(phenylamino)-2,4-oxazolidinedione

Famoxadone is used in the U.S. in combination with cymoxanil in the formulated product Tanos DF (water dispersible granules with 25% Famoxadone/25% cymoxanil)... .|Tradenames: Famoxate; 'Equation. Mixtures: Charisma (+flusilazole); Clip (+mancozeb); Equation Contact (+mancozeb); Equation Pro (+cymoxanil); Horizon (+cymoxanil); Tanos (+cymoxanil).|Nominal purity of active substance: 97.8%|Tanos 50DF is a dry flowable fungicide, containing 25% famoxadone and 25% cymoxanil... .

Agrochemicals -> Fungicides|Fungicides|Environmental transformation -> Pesticides (parent, predecessor)

Famoxadone has known environmental transformation products that include IN-JS940, IN-KZ007, IN-MN467, and IN-MN468.