rac-(R*)-2-[N-(2,6-ジメチルフェニル)-N-(メトキシアセチル)アミノ]プロピオン酸メチル

Pesticide -> EPA IRIS

Agrochemicals -> Pesticide active substances

Active substance -> EU Pesticides database: Approved

Pesticides -> Fungicides

Fungicides

Pesticide and(or) Waste-water effluent contaminant

log Kow = 1.65

1.75

1.20 @ 20 °C

1.65

Fine, white powder

... Colorless crystals ... .

In ethanol 400, acetone 450, toluene 340, n-hexane 11, n-octanol 68 (all g/l at 25 °C)

In water, 8,400 mg/l @ 22 °C

295.9 °C @ 760 mm Hg

564.6 °F

71-72 °C

71 - 72 °C

159.8-161.6 °F

0.0000022 [mmHg]

Vapor pressure: 293 uPa at 20 °C

5.62X10-6 mm Hg @ 25 °C

5.62x10-6 mmHg

Warning

H302: Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P270, P272, P273, P280, P301+P317, P302+P352, P321, P330, P333+P317, P362+P364, and P501 (click each P-code to see the statement)

Warning

H302 (99.5%): Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P270, P272, P273, P280, P301+P317, P302+P352, P321, P330, P333+P317, P362+P364, and P501 (click each P-code to see the statement)

Commission Regulation (EU) No 1141/2010

Metalaxyl is listed in the dataset of EPA Human Health Benchmarks for Pesticides under the Safe Drinking Water Act (40 eCFR 141)

2010/28/EU, Reg. (EU) 2015/1885, Reg. (EU) 2017/2069, Reg. (EU) 2023/918, Reg. (EU) 2026/1826, Reg. (EU) No 540/2011

Metalaxyl: Does not have an individual approval but may be used under an appropriate group standard

An eye irritant; Causes liver injury in high-dose feeding studies; Not likely to be a human carcinogen; [EPA REDs] Injection into chick eggs causes malformations and embryo lethality; [REPROTOX] May cause irritation; May cause skin sensitization; [MSDSonline]

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]

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their future use. Under this pesticide reregistration program, EPA examines health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether they are eligible for reregistration. In addition, all pesticides must meet the new safety standard of the Food Quality Protection Act of 1996. Metalaxyl is found on List A, which contains most food use pesticides and consists of the 194 chemical cases (or 350 individual active ingredients) for which EPA issued registration standards prior to FIFRA '88. Case No: 0081; Pesticide type: fungicide; Registration Standard Date: 09/01/88; Case Status: RED Approved 09/94; OPP has made a decision that some/all uses of the pesticide are eligible for reregistration, as reflected in a Reregistration Eligibility Decision (RED) document.; Active ingredient (AI): Metalaxyl; Data Call-in (DCI) Date(s): 06/28/91, 01/24/95; AI Status: RED Completed - OPP has completed a Reregistration Eligibility Decision (RED) document for the case/AI.

Tolerances are established for the combined residues of the fungicide metalaxyl (N-(2,6-dimethylphenyl)-N-(methoxyacetyl)alanine methylester) and its metabolites containing the 2,6-dimethylaniline moiety, and N-(2-hydroxymethyl-6-methylphenyl)-N-(methoxyacetyl)-alanine methyl ester, each expressed as metalaxyl equivalents, in or on the following food commodities: alfalfa, forge; alfalfa, hay; almond; almond, hulls; apple; apple, wet pomace; apricot, dried; asparagus; avocado; beet; beet, sugar; beet, sugar, molasses; beet, sugar, roots; beet, sugar, tops; beet, tops; blueberry; broccoli; Brussels sprouts; cabbage; cattle, fat; cattle, kidney; cattle, liver; cattle, meat; cattle, meat byproducts, except kidney and liver; cauliflower; citrus, oil; citrus, pulp; clover, forage; clover, hay; cottonseed; cranberry; egg; fruit, citrus; fruit, stone, group; ginseng; goat, fat; goat, kidney; goat, liver; goat, meat; goat, meat byproducts, except kidney and liver; grain, ceral (except wheat, barley, and oats); grain, crop; grape; grass, forage; grass, hay; hog, fat; hog, kidney; hog, liver; hog, meat; hog, meat byproducts, except kidney and liver; hop, dried cone; hop, green; horse, fat; horse, kidney; horse, liver; horse, meat; horse, meat byproducts, except kidney and liver; leafy vegetables (except brassica) group (except spinach); leaves of root and tuber vegetables (human food or animal feed) group; legume vegetable group (dry or succulent); lettuce, head; milk; mustard greens; onion, dry bulb; onion, green; peanut, hay; peanut, meal; peanut, nut; peanut, shells; peanut, vines; pineapple; pineapple, fodder; pineapple, forage; plum, prune, dried; potato waste, dried, processed; potato, processed (including potato, chips); poultry, fat; poultry, kidney; poultry, liver; poultry, meat; poultry, meat byproducts, except kidney and liver; potato; raisins; raspberry; sheep, fat; sheep, kidney; sheep, liver; sheep, meat; sheep, meat byproducts, except kidney and liver; soybean, grain; soybean, hulls; soybean, meal; spinach; strawberry; sunflowers; sunflower, forage; tomato, processed; vegetables, brassica, leafy, group (except broccoli, cabbage, cauliflower, Brussels sprouts, and mustard greens); vegetable, cucurbit, group; vegetable, fruiting (except cucurbits) group; vegetable, legume, cannery waste; vegetable, legume, foliage; vegetable, root and tuber group; walnut.

Tolerances with regional registration (refer to section 180.1(n)) are established for the combined residues of the fungicide metalaxyl (N-(2,6-dimethylphenyl)-N-(methoxyacetyl)alanine methyl ester) and its metabolites containing the 2,6-dimethylaniline moiety, and N-(2-hydroxymethyl-6-methyl)-N-(methoxyacetyl)-alanine methylester, each expressed as metalaxyl, in or on the following raw agricultural commodity: papaya.

Tolerances are established for indirect or inadvertent residues of metalaxyl in or on the food commodities when present therein as a result of the applicatiion of metalaxyl to growing crops listed in paragraph (a) of this section and other non-food crops to read as follows: barley, grain; barley, fodder; barley, milling fractions; barley, straw; grain, cereal group (except wheat, barley and oats), fodder; grain, cereal group (except wheat, barley and oats), forage; grain, cereal group (except wheat, barley and oats), straw; oat, fodder; oat, forage; oat, grain; oat milling fractions; oat, straw; wheat, fodder; wheat, forage; wheat, grain; wheat, milling fractions; wheat, straw.

Acute Tox. 4 (99.5%)

Acute toxicity - category 4

Acute Tox. 4 *

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.

Tolerances are established for the combined residues of the fungicide metalaxyl (N-(2,6-dimethylphenyl)-N-(methoxyacetyl)alanine methylester) and its metabolites containing the 2,6-dimethylaniline moiety, and N-(2-hydroxymethyl-6-methylphenyl)-N-(methoxyacetyl)-alanine methyl ester, each expressed as metalaxyl equivalents, in or on the following food commodities: alfalfa, forge, 6.0 ppm; alfalfa, hay, 20.0 ppm; almond, 0.5 ppm; almond, hulls, 10.0 ppm; apple, 0.2 ppm; apple, wet pomace, 0.4 ppm; apricot, dried, 4.0 ppm; asparagus, 7.0 ppm; avocado, 4.0 ppm; beet, 0.1 ppm; beet, sugar, 0.1 ppm; beet, sugar, molasses, 1.0 ppm; beet, sugar, roots, 0.5 ppm; beet, sugar, tops, 10.0 ppm; beet, tops, 0.1 ppm; blueberry, 2.0 ppm; broccoli, 2.0 ppm; Brussels sprouts, 2.0 ppm; cabbage, 1.0 ppm; cattle, fat, 0.4 ppm; cattle, kidney, 0.4 ppm; cattle, liver, 0.4 ppm; cattle, meat, 0.05 ppm; cattle, meat byproducts, except kidney and liver, 0.05 ppm; cauliflower, 1.0 ppm; citrus, oil, 7.0 ppm; citrus, pulp, 7.0 ppm; clover, forage, 1.0 ppm; clover, hay, 2.5 ppm; cottonseed, 0.1 ppm; cranberry, 4.0 ppm; egg, 0.05 ppm; fruit, citrus, 1.0 ppm; fruit, stone, group, 1.0 pmm; ginseng, 3.0 ppm; goat, fat, 0.4 ppm; goat, kidney, 0.4 ppm; goat, liver, 0.4 ppm; goat, meat, 0.05 ppm; goat, meat byproducts, except kidney and liver, 0.05 ppm; grain, ceral (except wheat, barley, and oats), 0.1 ppm; grain, crop, 0.1 ppm; grape, 2.0 ppm; grass, forage, 10.0 ppm; grass, hay, 25.0 ppm; hog, fat, 0.4 ppm; hog, kidney, 0.4 ppm; hog, liver, 0.4 ppm; hog, meat, 0.05 ppm; hog, meat byproducts, except kidney and liver, 0.05 ppm; hop, dried cone, 20.0 ppm; hop, green, 2.0 ppm; horse, fat, 0.4 ppm; horse, kidney, 0.4 ppm; horse, liver, 0.4 ppm; horse, meat, 0.05 ppm; horse, meat byproducts, except kidney and liver, 0.05 ppm; leafy vegetables (except brassica) group (except spinach), 5.0 ppm; leaves of root and tuber vegetables (human food or animal feed) group, 15.0 ppm; legume vegetable group (dry or succulent), 0.2 ppm; lettuce, head, 5.0 ppm; milk, 0.02 ppm; mustard greens, 5.0 ppm; onion, dry bulb, 3.0 ppm; onion, green, 10.0 ppm; peanut, hay, 20.0 pmm; peanut, meal, 1.0 ppm; peanut, nut, 0.2 ppm; peanut, shells, 2.0 ppm; peanut, vines, 20.0 ppm; pineapple, 0.1 ppm; pineapple, fodder, 0.1 ppm; pineapple, forage, 0.1 ppm; plum, prune, dried, 4.0 ppm; potato waste, dried, processed, 4.0 ppm; potato, processed (including potato, chips), 4.0 ppm; poultry, fat, 0.4 ppm; poultry, kidney, 0.4 ppm; poultry, liver, 0.4 ppm; poultry, meat, 0.05 ppm; poultry, meat byproducts, except kidney and liver, 0.05 ppm; potato, 0.5 ppm; raisins, 6.0 ppm; raspberry, 0.5 ppm; sheep, fat, 0.4 ppm; sheep, kidney, 0.4 ppm; sheep, liver, 0.4 ppm; sheep, meat, 0.05 ppm; sheep, meat byproducts, except kidney and liver, 0.05 ppm; soybean, grain, 1.0 ppm; soybean, hulls, 2.0 ppm; soybean, meal, 2.0 ppm; spinach, 10.0 ppm; strawberry, 10.0 ppm; sunflowers, 0.1 ppm; sunflower, forage, 0.1 ppm; tomato, processed, 3.0 ppm; vegetables, brassica, leafy, group (except broccoli, cabbage, cauliflower, Brussels sprouts, and mustard greens), 0.1 ppm; vegetable, cucurbit, group, 1.0 ppm; vegetable, fruiting (except cucurbits) group, 1.0 ppm; vegetable, legume, cannery waste, 5.0 ppm; vegetable, legume, foliage, 8.0 ppm; vegetable, root and tuber group, 0.5 ppm; walnut, 0.5 ppm.

Tolerances with regional registration (refer to section 180.1(n)) are established for the combined residues of the fungicide metalaxyl (N-(2,6-dimethylphenyl)-N-(methoxyacetyl)alanine methyl ester) and its metabolites containing the 2,6-dimethylaniline moiety, and N-(2-hydroxymethyl-6-methyl)-N-(methoxyacetyl)-alanine methylester, each expressed as metalaxyl, in or on the following raw agricultural commodity: papaya, 0.1 ppm.

Tolerances are established for indirect or inadvertent residues of metalaxyl in or on the food commodities when present therein as a result of the applicatiion of metalaxyl to growing crops listed in paragraph (a) of this section and other non-food crops to read as follows: barley, grain, 0.2 ppm; barley, fodder, 2.0 ppm; barley, milling fractions, 1.0 ppm; barley, straw, 2.0 ppm; grain, cereal group (except wheat, barley and oats), fodder, 1.0 ppm; grain, cereal group (except wheat, barley and oats), forage, 1.0 ppm; grain, cereal group (except wheat, barley and oats), straw, 1.0 ppm; oat, fodder, 2.0 ppm; oat, forage, 2.0 ppm; oat, grain, 0.2 ppm; oat milling fractions, 1.0 ppm; oat, straw, 2.0 ppm; wheat, fodder, 2.0 ppm; wheat, forage, 2.0 ppm; wheat, grain, 0.2 ppm; wheat, milling fractions, 1.0 ppm; wheat, straw, 2.0 ppm.

Consider gastric lavage, as well was dilution with milk or water after ingestion. Administer charcoal as a slurry following ingestion; however, activated charcoal should not be given to patients ingesting strong acidic or basic caustic chemicals. In case of inhalation, move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with inhaled beta2 agonist and oral or parenteral corticosteroids. Irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. Following dermal exposure, remove contaminated clothing and wash exposed area thoroughly with soap and water. Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines. Administer symptomatic treatment as necessary. (T36)

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.

LC50 Rainbow trout 130-132 mg/L /Conditions of bioassay not specified/

LC50 Bluegill sunfish 139-150 mg/L /Conditions of bioassay not specified/

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 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).

Metalaxyl is mildly irritating to the skin and eyes. Exposure to metalaxyl often results in such nonspecific symptoms as headache, dizziness, weakness, and nausea. Metaxyl poisoning can produce an allergic hypersensitivity dermatitis or asthma with bronchospasm and wheezing with chronic exposure. (T36)

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their future use. Under this pesticide reregistration program, EPA examines health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether they are eligible for reregistration. In addition, all pesticides must meet the new safety standard of the Food Quality Protection Act of 1996. Metalaxyl is found on List A, which contains most food use pesticides and consists of the 194 chemical cases (or 350 individual active ingredients) for which EPA issued registration standards prior to FIFRA '88. Case No: 0081; Pesticide type: fungicide; Registration Standard Date: 09/01/88; Case Status: RED Approved 09/94; OPP has made a decision that some/all uses of the pesticide are eligible for reregistration, as reflected in a Reregistration Eligibility Decision (RED) document.; Active ingredient (AI): Metalaxyl; Data Call-in (DCI) Date(s): 06/28/91, 01/24/95; AI Status: RED Completed - OPP has completed a Reregistration Eligibility Decision (RED) document for the case/AI.

Tolerances are established for the combined residues of the fungicide metalaxyl (N-(2,6-dimethylphenyl)-N-(methoxyacetyl)alanine methylester) and its metabolites containing the 2,6-dimethylaniline moiety, and N-(2-hydroxymethyl-6-methylphenyl)-N-(methoxyacetyl)-alanine methyl ester, each expressed as metalaxyl equivalents, in or on the following food commodities: alfalfa, forge; alfalfa, hay; almond; almond, hulls; apple; apple, wet pomace; apricot, dried; asparagus; avocado; beet; beet, sugar; beet, sugar, molasses; beet, sugar, roots; beet, sugar, tops; beet, tops; blueberry; broccoli; Brussels sprouts; cabbage; cattle, fat; cattle, kidney; cattle, liver; cattle, meat; cattle, meat byproducts, except kidney and liver; cauliflower; citrus, oil; citrus, pulp; clover, forage; clover, hay; cottonseed; cranberry; egg; fruit, citrus; fruit, stone, group; ginseng; goat, fat; goat, kidney; goat, liver; goat, meat; goat, meat byproducts, except kidney and liver; grain, ceral (except wheat, barley, and oats); grain, crop; grape; grass, forage; grass, hay; hog, fat; hog, kidney; hog, liver; hog, meat; hog, meat byproducts, except kidney and liver; hop, dried cone; hop, green; horse, fat; horse, kidney; horse, liver; horse, meat; horse, meat byproducts, except kidney and liver; leafy vegetables (except brassica) group (except spinach); leaves of root and tuber vegetables (human food or animal feed) group; legume vegetable group (dry or succulent); lettuce, head; milk; mustard greens; onion, dry bulb; onion, green; peanut, hay; peanut, meal; peanut, nut; peanut, shells; peanut, vines; pineapple; pineapple, fodder; pineapple, forage; plum, prune, dried; potato waste, dried, processed; potato, processed (including potato, chips); poultry, fat; poultry, kidney; poultry, liver; poultry, meat; poultry, meat byproducts, except kidney and liver; potato; raisins; raspberry; sheep, fat; sheep, kidney; sheep, liver; sheep, meat; sheep, meat byproducts, except kidney and liver; soybean, grain; soybean, hulls; soybean, meal; spinach; strawberry; sunflowers; sunflower, forage; tomato, processed; vegetables, brassica, leafy, group (except broccoli, cabbage, cauliflower, Brussels sprouts, and mustard greens); vegetable, cucurbit, group; vegetable, fruiting (except cucurbits) group; vegetable, legume, cannery waste; vegetable, legume, foliage; vegetable, root and tuber group; walnut.

Tolerances with regional registration (refer to section 180.1(n)) are established for the combined residues of the fungicide metalaxyl (N-(2,6-dimethylphenyl)-N-(methoxyacetyl)alanine methyl ester) and its metabolites containing the 2,6-dimethylaniline moiety, and N-(2-hydroxymethyl-6-methyl)-N-(methoxyacetyl)-alanine methylester, each expressed as metalaxyl, in or on the following raw agricultural commodity: papaya.

Tolerances are established for indirect or inadvertent residues of metalaxyl in or on the food commodities when present therein as a result of the applicatiion of metalaxyl to growing crops listed in paragraph (a) of this section and other non-food crops to read as follows: barley, grain; barley, fodder; barley, milling fractions; barley, straw; grain, cereal group (except wheat, barley and oats), fodder; grain, cereal group (except wheat, barley and oats), forage; grain, cereal group (except wheat, barley and oats), straw; oat, fodder; oat, forage; oat, grain; oat milling fractions; oat, straw; wheat, fodder; wheat, forage; wheat, grain; wheat, milling fractions; wheat, straw.

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.

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, demethylmetalaxyl, Metalaxyl acid, and Methyl N-(2-(hydroxymethyl)-6-methylphenyl)-N-(methoxyacetyl)-DL-alanine.

Three major and one minor metabolic pathways are proposed. One pathway involves hydrolysis of the ether, followed by oxidation of the resulting alcohol, ester hydrolysis, or N-dealkylation of the ester chain. A second pathway involves oxidation of an aromatic methyl to the benzylic acid or ester hydrolysis. The third major pathway is ester hydrolysis, sometimes followed by benzylic acid formation. The minor pathway involves hydroxylation at the meta position of the phenyl ring. The majority of urinary metabolites are conjugated (glucuronide or sulfate) whereas fecal metabolites are mostly unconjugated. The major metabolite in urine & feces is N-(2,6-dimethylphenyl)-N-(hydroxyacetyl) alanine. Metalaxyl is excreted in urine and the feces. (L918)

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.

Used as fungicide for food crops, shrubs, and turf; [Merck Index] Used as a food additive; [Hawley] Used as a fungicide, wood preservative, and bactericide; [REPROTOX] Used as a systemic fungicide on many crops (food, feed, tobacco, turf, and ornamental); [EPA REDs]

Applying Wood Preservatives [Category: Other]

For metalaxyl (USEPA/OPP Pesticide Code: 113501) ACTIVE products with label matches. /SRP: Registered for use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

Metalaxyl ... is used as a seed treatment, foliar spray, soil application, or postharvest fungicide.

Metalaxyl is a systemic fungicide used to control plant diseases caused by the Oomycetes or water-mold fungi. It is used on many food & feed crops, & on non-food, residential & greenhouse crops such as tobacco, ornamental plants, trees, shrubs & vines, & lawns & turf.

Widely used selective herbicide worldwide in corn, soybean and other crop cultures. Elevated concentrations of this herbicide and its degradation products have been detected in surface and groundwater. (A252)

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.

Metalaxyl is produced by reaction of 2,6-dimethylaniline with an excess of methyl 2-bromopropionate in the presence of sodium bicarbonate, followed by acetylation with methoxyacetyl chloride.

Prepn: A. Hubele, DE 2515091 corresp to US 4151299 (1975, 1979 to Ciba-Geigy).

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.