Metalaxyl

279.33

279.33

260-979-7

DTXSID6024175

Fine, white powder|... Colorless crystals ... .

2924299034

55.8

1.65

1.20 g/cm³ @ Temp: 20 °C

71-72 °C

295.9 °C @ Press: 760 Torr

100 °C

1.528

H2O: 0.84 g/100 mL

APPROX 4°C

7.5 x 10 -4 Pa (25 °C)

1.2

Oral-Rat LD50: 566 mg/kg

Combustion produces toxic nitrogen oxide gas

Much less than 0

159.96 Ų [M+H]+ [CCS Type: TW]|160.4 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated]|160.08 Ų [M+H]+

MP = 63.5-72.3 °C /Technical/

UN16483/PG2

2

22-43-52/53-36-20/21/22-11

13-24-37-46-61-36-26-16

AY6910000

Xn,F

The warehouse is ventilated, low temperature and dry; stored and transported separately from food materials

Stable at normal temperatures and pressures.

P273-P280

H302-H317-H412

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

USEPA/Office of Pesticide Programs; Reregistration Eligibility Decision Document - Metalaxyl. EPA 738-R-94-017, September 1994. The RED summarizes the risk assessment conclusions and outlines any risk reduction measures necessary for the pesticide to continue to be registered in the U.S.[Available from, as of May 2, 2003: http://www.epa.gov/pesticides/reregistration/status.htm]

|Warning|H302: Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P272, P273, P280, P301+P312, P302+P352, P321, P330, P333+P313, P363, and P501|H302 (99.69%): Harmful if swallowed [Warning Acute toxicity, oral]|Aggregated GHS information provided by 326 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

SEDIMENT: The mean concentration of metalaxyl in sediments from the Sarno river in Italy was 1,560 ng/g dry wt(1).

moderately

Because metalaxyl is used on tobacco, a 90 day smoke inhalation study was conducted. Male & female Fischer 344 rats were exposed to smoke form cigarettes containing 0, 130, 3,900, or 13,000 ppm of metalaxyl for 4 hr/day, 5 days/wk. The max air concn of metalaxyl was 5 ug/L. The concns in test cigarettes were 100-1,000 times avg residue levels & 30-100 times greater than the expected max residue levels. Although the study was limited in its ability to simulate human exposure, the results were adequate to demonstrate toxicological effects from exposures are unlikely beyond that from exposures associated with heavy smoking. The profile of residues in inhalable smoke indicated 30% was metalaxyl, 4% was 2,6-dimethylaniline, & 65% was unidentified material.

LD50 Rat oral 669 mg/kg|LD50 Mouse oral 788 mg/kg|LD50 Hamster oral 7120 mg/kg|LD50 Rabbit dermal >6000 mg/kg

Metalaxyl's production may result in its release to the environment through various waste streams; its use as a fungicide(1) results in its direct release to the environment(SRC). In 1982, the annual use of metalaxyl in the US was 370,000 lbs AI/year(2).

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values ranging from 30 to 284(2) indicate that metalaxyl is expected to have very high to moderate mobility in soil(SRC). Volatilization of metalaxyl from moist soil surfaces is not expected to be an important fate process(3) given an estimated Henry's Law constant of 3.0X10-9 atm-cu m/mole(SRC), derived from its vapor pressure, 5.62X10-6 mm Hg(4), and water solubility, 8,400 mg/l(4). Metalaxyl is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(4). Metalaxyl undergoes fairly rapid degradation (half-life of approx 40 days) in soils incubated aerobically(5). Experiments with 14C-metalaxyl demonstrated that it was readily metabolized in soil with a history of fungicide treatment (half-life of 14 days) but not in a control soil(6). In a tobacco soil, rapid degradation of metalaxyl occurred with a half-life of 6 days(7). The main breakdown product of metalaxyl in soil was the acid metabolite(7).|AQUATIC FATE: Based on a classification scheme(1), Koc values ranging from 30 to 284(2), indicates that metalaxyl is not 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 3.0X10-9 atm-cu m/mole(SRC), derived from its vapor pressure, 5.62X10-6 mm Hg(4), and water solubility, 8,400 mg/l(4). According to a classification scheme(5), an estimated BCF of 4(SRC), from its log Kow(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Photolysis of metalaxyl in aqueous solution using UV light with wavelengths greater than 290 nm resulted in 10% substrate transformation in 3 hours(8). Long time (65 hr) irradiation under artificial sunlight in the presence of humic acids resulted in 65% degradation of the chemical(8). Photolysis leads not only to rearrangement of the N-acyl group to the aromatic ring but also to demethoxylation, N-deacylation, and elimination of the methoxycarbonyl group from the molecule(8). Based on biodegradation studies in soil, metalaxyl is expected to biodegrade in aqueous systems(SRC). Metalaxyl undergoes fairly rapid degradation (half-life of approx 40 days) in soils incubated aerobically(9). Experiments with 14C-metalaxyl demonstrated that its was readily metabolized in soil with a history of fungicide treatment (half-life of 14 days) but not in a control soil(10).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), metalaxyl, which has a vapor pressure of 5.62X10-6 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere(SRC). Vapor-phase metalaxyl is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 14 hours(SRC), calculated from its rate constant of 27X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase metalaxyl may be removed from the air by wet and dry deposition(SRC). Metalaxyl undergoes photolysis in water(4) and, by analogy, may undergo direct photolysis in the atmosphere(SRC).

The rate constant for the vapor-phase reaction of metalaxyl with photochemically-produced hydroxyl radicals has been estimated as 27X10-12 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 14 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Metalaxyl is resistant to chemical hydrolysis under environmental conditions(2). Under basic conditions, metalaxyl hydrolyzes according to first-order kinetics to metalaxyl acid(2). Half-life of metalaxyl at pH 10 and 25 °C is about 16 days(2). Photolysis of metalaxyl in aqueous solution at 290 nm resulted in 10% substrate transformation in 3 hours(3). Long time (65 hr) irradiation under artificial sunlight in the presence of humic acids resulted in 65% degradation of the chemical(3). Photolysis leads not only to rearrangement of the N-acyl group to the aromatic ring but also to demethoxylation, N-deacylation, and elimination of the methoxycarbonyl group from the molecule(3).

An estimated BCF of 4 was calculated for metalaxyl(SRC), using log Kow of 1.65(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).

37.15 L/kg|Koc values for metalaxyl range from 30 to 284(1,2). According to a classification scheme(3), this range of Koc values suggests that metalaxyl is expected to have very high to moderate mobility in soil(SRC).

The Henry's Law constant for metalaxyl is estimated as 3.0X10-9 atm-cu m/mole(SRC) derived from its vapor pressure, 5.62X10-6 mm Hg(1), and water solubility, 8,400 mg/l(1). This Henry's Law constant indicates that metalaxyl is expected to be essentially nonvolatile from moist soil and water surfaces(2). Metalaxyl is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

GROUNDWATER: The maximum concentration of metalaxyl in groundwater from the Netherlands was 2.2 ug/l (number of positive samples > 4)(1).|SURFACE WATER: The highest concentration of metalaxyl in surface waters of south Florida was 0.65 ug/l (number of detections = 3) from November 1991 to June 1995(1).|RAIN: The median concentration of metalaxyl in rainwater was 14 ng/l (max, 17 ng/l) in Gruze, Switzerland between February and October 1996(1). In Axios River basin, Greece, the mean concentration of metalaxyl was 0.14 ug/l in rainwater for 0.5% of the rain events(2). 40 rainwater samples were collected in Hanover, Germany and near Peine (lower Saxony, Germany) in 1992(3); the mean concentration of metalaxyl in these samples was 0.01 ug/l (range, 0.006-0.48 ug/l)(3); the concentration showed a seasonal dependance reflecting the application periods of metalaxyl(3).

The concn of metalaxyl in two samples of wine from Italy were 0.27 and 2.2 mg/kg(1). The mean concn of metalaxyl in endive, lettuce, apples, and strawberries were 0.008 ppm (max, 0.14 ppm; number of positive samples, 1.3%), 0.009 ppm (max, 0.38 ppm; number of positive samples, 0.9%), 0.002 ppm (max, 0.08 ppm; number of positive samples, 0.9%), and 0.009 ppm (max, 0.04 ppm; number of positive samples, 1.4%), respectively(2). The mean concn of metalaxyl in cucumber and tomato from Egyptian markets in 1995 was 0.24 mg/kg (frequency, 1 of 47 samples) and 0.15 mg/kg (frequency, 1 of 62 samples), respectively(3). The mean concn of metalaxyl in cucumber and grapes from Egyptian markets in 1996 was 0.18 mg/kg (frequency, 2 of 94 samples) and 0.20 mg/kg (frequency, 1 of 47 samples), respectively(4). Metalaxyl was found in 4 of 6,391 samples of domestic agricultural commodities sampled between Oct 1, 1981 and Sept 20, 1986 in US at concns of 0.1, 0.5, 1.0, and 2.0 ppm, respectively(5). The mean concn of metalaxyl in grapes from Ontario, Canada between 1991-1995 was 0.23 ug/g (0.9% of sample positive)(6).

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

Chemicals that kill or inhibit the growth of fungi in agricultural applications, on wood, plastics, or other materials, in swimming pools, etc. (See all compounds classified as Fungicides, Industrial.)

In a single dose study, male & female rats were administed 0.5 or 25 mg/kg of metalaxyl by gavage. Over 60% of the low or high dose was excreted within 24 hr in urine or feces. Negligible amounts were eliminated in expired air. Low tissue residues 6 days after treatment indicated no appreciable bioaccumulation. Female rats eliminated the majority of the dose (55-65%) in urine, & males eliminated most (60-70%) in feces. Although metabolites were not identified, the chromatographic pattern was similar for both sexes & doses.

A recent comprehensive study evaluated metalaxyl pharmacokinetics with male & female Sprague-Dawley rats following a single iv dose (1 mg/kg), single oral low dose (1 mg/kg), single oral high dose (200 mg/kg), or repeated oral low doses (1 mg/kg/day for 14 days). The absorption distribution, & elimination patterns were consistent with previous findings. No major dose or sex differences were observed except that urine was th predominant elimination route for females whereas feces was the major route for males. Metalaxyl was readily absorbed (similar iv & oral elimination profiles), extensively metabolized (<1% parent compound in excreta), & rapidly eliminated (70-80% in 24 hr). Ten metabolites were identified. The majority of urinary metabolites were conjugated (glucuronide or sulfate) whereas fecal metabolites were mostly unconjugated. The major metabolite in urine & feces was N-(2,6-dimethylphenyl)-N-(hydroxyacetyl) alanine. Three major & one minor metabolic pathways were proposed. One pathway involved hydrolysis of the ether, followed by oxidation of the resulting alcohol, ester hydrolysis, or N-dealkylation of the ester chain. A second pathway involved oxidation of an aromatic methyl to the benzylic acid or ester hydrolysis. The third major pathway was ester hydrolysis, sometimes followed by benzylic acid formation. The minor pathway involved hydroxylation at the meta position of the phenyl ring. Two major metabolited in urine were not identified. ...|Metalaxyl has known human metabolites that include 2-[(2,6-Dimethyl-3-hydroxyphenyl)(methoxyacetyl)amino]propionic acid methyl ester, Metalaxyl acid, Methyl N-(2-(hydroxymethyl)-6-methylphenyl)-N-(methoxyacetyl)-DL-alanine, and demethylmetalaxyl.

Intraperitoneal injection of metalaxyl (250 mg/kg) produced a decrease in heart rate lasting for more than 60 min in anesthetized rats. Pretreatment of rats with phentolamine (a nonselective alpha-adrenoreceptor antagonist, ip at 20 mg/kg) and prazosin (an alpha 1-adrenoreceptor antagonist, ip at 5 mg/kg) significantly reduced the bradycardia induced by metalaxyl. Yohimbine (an alpha 2-adrenoreceptor antagonist, ip at 10 mg/kg) did not change the effect of metalaxyl on heart rate. The results suggest that alpha 2-adrenoreceptors mediate the bradycardic effect of metalaxyl.|The ability of metalaxyl ... to affect specific biomarkers related to non-genotoxic cocarcinogenesis was investigated. Several CYP-dependent reactions /were/ ... studied in liver, kidney and lung microsomes derived from male and female Swiss Albino CD1 mice treated i.p. with single (200 or 400 mg/kg b.w.) or repeated (200 mg/kg b.w., 3 days) administrations of fungicide. No significant changes in absolute or relative liver, kidney and lung weights were observed after metalaxyl treatment. Although a single dose did not significantly affect the ... monooxygenases, ... selective CYP3A induction was recorded in different tissues after repeated treatment. An approximately 3-fold increase in CYP3A isozymes ... was observed in the liver (both sexes)... and an approximately 5-fold increase (averaged between male and female) in this oxidase activity was present in the kidney. No significant change of the selected biomarkers was observed in the lung. A weak, but significant reduction of CYP2B1... in liver (male) was also recorded. Liver and kidney CYP3A overexpression was corroborated by means of Western immunoblotting analysis... Northern blotting analysis with CYP3A cDNA biotinylated probe showed that, in the liver, the expression of this isozyme is regulated at the mRNA level. On the whole, these data seem to indicate the cotoxic and cocarcinogenic potential of this fungicide.|... the action of ... /metalaxyl/ on nucleic acid and protein synthesis in liquid cultures of Phytophthora nicotianae /was investigated/. The uptake of 32P, 3H-uridine, 3H-thymidine and 14C-leucine as precursors of nuclei acid and protein synthesis by the mycelium was not inhibited by metalaxyl. RNA synthesis as indicated by 3H-uridine incorporation was strongly inhibited (about 80%) by 0.5 ug/ml of metalaxyl. The inhibition was visible already a few minutes after addition of the toxicant. Since the inhibition of incorporation of 3H-thymidine into DNA and of 14C-leucine into protein became significant 2-3 hours later, ... metalaxyl primarily interferes with RNA synthesis. Synthesis of ribosomal RNA is more affected (more than 90%) than that of tRNA (about 55%) and poly(A)-containing RNA. ...it is also evident that mRNA synthesis is less strongly inhibited, at least during the early period of metalaxyl action. The molecular mechanism of metalaxyl inhibition of the transcription process remains open. The fungicide did not inhibit the activity of a partially purified RNA polymerase isolated from the fungus. On the other hand, the RNA synthesis (14C-UTP-incorporation) by a cell homogenate and by isolated nuclear fractions was inhibited significantly. Possibilities of the molecular action of metalaxyl are discussed. The RNA synthesis of some plant systems (cell cultures of Lycopersicon peruvianum, isolated nuclei from the same cell cultures, purified RNA polymerase from Spinacia oleracea chloroplasts) was not inhibited by metalaxyl, not even at high concentrations.

Impurities such as 2,6-dimethylaniline, N-methyl-2,6-dimethylaniline, N-(1-methoxycarbonyl-ethyl)-2,6-dimethylaniline, N-methyl-N-(1-methoxycarbonyl-ethyl)-2,6-dimethylaniline, N-methyl-N-(1-methoxyacetyl)-2,6-dimethylaniline, N-(1-methoxyacetyl)-2,6-dimethylaniline & N-ethyl-N-(methoxyacetyl)-2,6-dimethylaniline present in samples of technical metalaxyl were isolated by column chromatography and identified by nuclear magnetic resonance, mass spectroscopy & comparison with reference compounds.

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/|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/|Gastrointestinal decontamination. If a large amount of the fungicide has been ingested in the last few hours, and if copious vomiting has not already occurred, it may be reasonable to consider GI decontamination. Activated charcoal can be used along with the addition of the cathartic sorbitol to the charcoal slurry. If sorbitol is given separately, it should be diluted with an equal volume of water before administration. No more than one dose of sorbitol is recommended and it should be used with caution in children and the elderly... . If contact with the toxicant has been minimal (for example, oral contamination only, promptly flushed out of the mouth), administration of charcoal without a cathartic, followed by careful observation of the patient, probably represents optimal management. /Miscellaneous organic fungicides/|Skin decontamination. Dermal contamination should be washed off with soap and water. Flush contamination from the eyes with copious amounts of water. If irritation persists, specialized medical care should be obtained. /Miscellaneous organic fungicides/|Porphyria. Persons affected by porphyria should avoid sunlight, which exacerbates the dermal injury by porphyrins. /Miscellaneous organic fungicides/

Acylon

Emulsifiable concentrate, granule, flowable & wettable powder.|USEPA/OPP Pesticide Code: 113501; Trade Names: Ridomil; Ridomil MZ, component of (with 014504); CGA-48988; Subdue; Apron.|Trade names: ... Fubol, Acylon.

Pesticide or Metabolite (M) Common Name: Metalaxyl; Commodity: Cottonseed; Method Source: Ciba-Geigy; Method ID: AG-348; Method Date: 11/25/80; Instrument: GC/NPD. /From table/|Pesticide or Metabolite (M) Common Name: Metalaxyl; Commodity: Canola seed, dried basil, fresh mint, starfruit; Method Source: Novartis Crop Protection; Method ID: 456-98; Method Date: 3/1/99; Instrument: HPLC/MSD; Estimated LOQ (ppm): 0.01. /From table/|Pesticide or Metabolite (M) Common Name: Metalaxyl; Commodity: Liver, milk; Method Source: Ciba-Geigy; Method ID: AG-349; Method Date: 11/25/80; Instrument: GC/NPD. /From table/|Pesticide or Metabolite (M) Common Name: Metalaxyl; Commodity: Peanut hay, peanuts; Method Source: Ciba-Geigy; Method ID: AG-345; Method Date: 12/7/82; Instrument: GC/NPD. /From table/

Agrochemicals -> Fungicides|Fungicides

Metalaxyl has known environmental transformation products that include (R)-2-((2,6-Dimethyl-phenyl)-(2-methoxy-acetyl)-amino)-propionic acid, 2-(((R)-1-Carboxy-ethyl)-(2-methoxy-acetyl)-amino)-3-methyl-benzoic acid, N-(2,6-Dimethyl-phenyl)-2-methoxy-acetamide, and N-(2,6-dimethylphenyl)-N-(methoxyacetyl)alanine.