Absorption, Distribution and Excretion
S-metolachlor is extensively absorbed and metabolized following oral administration. Elimination is via the urine and feces. Tissue residues were highest in whole blood. /s-metolachlor/
Selective herbicide, absorbed predominantly by the hypocotyls and shoots.
Rats were administered a single oral dose (28.6 or 52.4 mg/kg) of metolachlor (purity not specified, but (14)C labeled and unlabeled metolachlor were synthesized for these experiments). The chemical was readily absorbed, since 70 to 90% of the metolachlor was excreted as metabolites within 48 hr.
Data from rats given radioactive metolachlor (approximately 3.2 to 3.5 mg/kg) orally demonstrated that the chemical is rapidly metabolized. Residues in meat tissue and blood were very low and only blood contained residue levels in excess of 0.1 ppm.
For more Absorption, Distribution and Excretion (Complete) data for METOLACHLOR (6 total), please visit the HSDB record page.

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Metabolism / Metabolites
METABOLISM IN PLANTS AFTER PREEMERGENCE APPLICATION OF METOLACHLOR APPEARS TO PROCEED BY NATURAL PRODUCT CONJUGATION OF THE ACETYL-CHLORO GROUP WITH THIS BOND LINKAGE PREDOMINANT OVER OXO. FURTHER REACTION OCCURS AT THE ETHER GROUP WITH HYDROLYSIS FOLLOWED BY SUGAR CONJUGATION. FINAL METABOLITES ARE RESULTS OF DISCONJUGATION, AND ARE POLAR, AQUEOUS SOLUBLE, NONVOLATILE AS WELL AS SENSITIVE TO DEGRADATION. HYDROLYSIS PROCEDURES CONVERT THE OXO-METABOLITES TO THE DEACETYLATED DERIVATIVE AND THE THIO-METABOLITES TO A MORPHOLINE DERIVATIVE.
STUDIES WITH THE ANTOR ANALOG METOLACHLOR (DUAL) WERE ALSO CONDUCTED WITH THE FUNGUS CHAETOMIUM GLOBOSUM. COMPOUNDS PRODUCED BY THIS ORGANISM WHEN INCUBATED WITH METOLACHLOR ARE: 2-CHLORO-N-(2-ETHYL-6- METHYLPHENYL)-N-(2-HYDROXY-1-METHYLETHYL)ACETAMIDE; 2-CHLORO-N-(2-ETHYL- 6-METHYLPHENYL)ACETAMIDE; N-(2-METHOXY-1-METHYLETHYL)-2-METHYL-6-VINYLANILINE; N-(2-METHOXY-1-METHYLETHYL)-2,3-DIHYDRO-7-METHYLINDOLE; 8-ETHYL-3-HYDROXY- N-(2-METHOXY-1-METHYLETHYL)-2-OXO-1,2,3,4-TETRAHYDROQUINOLINE; 8-ETHYL-3- HYDROXY-N-ISOPROPYL-2-OXO-1,2,3,4-TETRAHYDROQUINOLINE; 2-HYDROXY-N-(2- METHOXY-1-METHYLETHYL)-N-(2-METHYL-6-VINYLPHENYL)ACETAMIDE; N-(2-METHOXY- 1-METHYLETHYL)-8-METHYL-2-OXO-1,2,3,4-TETRAHYDROQUINOLINE.
IN FUNGI, ALPHA-CHLORINE ATOMS OF THESE PESTICIDES /INCLUDING METOLACHLOR/ ARE NOT DISPLACED BY SULFHYDRYL GROUPS BUT BY HYDROXYL GROUPS ALTHOUGH THE CHLORINE ATOM OF PROPACHLOR IS DISPLACED BY A SULFHYDRYL GROUP IN THE FIRST DEGRADATION STEP IN PLANTS. DEALKYLATION, DEACYLATION, AND RING FORMATION TO FORM INDOLINES AND QUINOLINES OCCUR IN FUNGI.
Studies conducted to identify urinary and fecal metabolites in the rat indicated that metolachlor is metabolized via dechlorination, o-methylation, N-dealkylation and side-chain oxidation. Urinary metabolites included 2-ethyl-6-methylhydroxyacetanilide and N-(2-ethyl-6-methyl- phenyl)-N-(hydroxyacetyl)-DL-alanine). Fecal metabolites included 2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-hydroxy-l-methylethyl) and N-(2-ethyl-6-methylphenyl)-N-(hydroxyacetyl)-DL-alamine).
For more Metabolism/Metabolites (Complete) data for METOLACHLOR (10 total), please visit the HSDB record page.
Metolachlor is metabolized via dechlorination, o-methylation, N-dealkylation and side-chain oxidation. Glutathione transferases mediathe the conjugation of metolachlor with with glutathione. Urinary metabolites included 2-ethyl-6-methylhydroxyacetanilide and N-(2-ethyl-6-methyl- phenyl)-N-(hydroxyacetyl)-DL-alanine). Fecal metabolites included 2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-hydroxy-l-methylethyl) and N-(2-ethyl-6-methylphenyl)-N-(hydroxyacetyl)-DL-alamine). Metolachlor is also excreted in urine. (A571, A270)

Toxicity Summary
Metolachlor acts by inhibition of elongases and of the geranylgeranyl pyrophosphate (GGPP) cyclases, which are part of the gibberellin pathway. It also binds to nAChRs in nervous systems and causes endocrine disruption in humans by binding to and inhibiting the estrogen receptor. (T10, L913, A590)

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Toxicity Data
LD50: 1200-2780 mg/kg (Oral, Oral) (L914)
LD50: > 2000 mg/kg (Dermal, Rat) (L914)
LC50: > 4.3 mg/L/4hr (L914)

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Interactions
The reproductive toxicity of a mixture of 5 pesticides (alachlor, atrazine, cyanazin, metolachlor, and metribuzin) and one fertilizer (ammonium nitrate) was evaluated in Swiss mice using the continuous breeding protocol. These chemicals and their relative concn in the stock mixture were selected on the basis of groundwater survey data from Iowa. Mice received the mixture in the drinking water at 0X, 1X, 10X and 100X, where 1X was the median concn of each component as determined by the surveys. F0 mice were fertile throughout 18 weeks exposure. mixture did not adversely affect reproductive competence, F0 body weight, food or water consumption, organ weights, or sperm parameters at necropsy. No treatment related clinical signs were noted. F1 preweaning growth and maturation were unaffected by mixture. No treatment related clinical signs or adverse effect of mixture on F1 reproductive competence, food and water consumption, male or female body weight, or selected male and female organ weights, sperm parameters, vaginal cytology, or histology of selected organs was observed. In summary, exposure to mixture in the drinking water at dose levels as high as 100X the median concn of the components in contaminated groundwater did not cause clearcut generalized or reproductive toxicity in either the F0 or F1 generation of Swiss mice.
Male Fischer 344 rats and female B6C3F1 mice were each exposed through their drinking water to a mixture of pesticides and ammonium nitrate that simulated contaminated groundwater in California (California Chemical Mixture). Exposures were for 71 or 91 days, respectively. In addition, B6C3F1 female mice were exposed for 91 days to another pesticide and ammonium nitrate mixture (Iowa Chemical Mixture) through their drinking water. The spleen were removed from the animals, and the splenocytes were cultured for analyses of sister chromatid exchange, chromosome aberrations, and micronuclei in cytochalasin B induced binucleate cells. A concn related increase in sister chromatid exchanges was found in the splenocytes of the rat at the 1X, 10X and 100X levels of the California Chemical Mixture and at the 100X concn of the California Chemical Mixture in the mouse. There were no other consistent cytogenetic effects observed with the California Chemical Mixture, and no statistically significant cytogenetic damage was observed in mice exposed to the Iowa Chemical Mixture. Evidence from the literature is discussed in order to infer which chemical or chemicals in the California Chemical Mixture might be responsible for the observed sister chromatid exchange response.

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Non-Human Toxicity Values
LC50 Rat inhalation >2.02 mg/L/4 hr air
LD50 Rabbit dermal >2000 mg/kg bw
LD50 Rat dermal 3170 mg/kg bw
LC50 Rat inhalation >4.33 mg/L/4 hr
For more Non-Human Toxicity Values (Complete) data for METOLACHLOR (12 total), please visit the HSDB record page.

[1]. Metolachlor Stereoisomers: Enantioseparation, Identification and Chiral Stability. J Chromatogr A. 2016 Sep 9;1463:42-8.

[2]. Biodegradation of the Acetanilide Herbicides Alachlor, Metolachlor, and Propachlor. Crit Rev Microbiol. 1998;24(1):1-22.

Metolachlor is a tan to brown oily liquid with a slightly sweet odor. Slightly soluble in water and denser than water. Hence sinks in water. Soluble in most organic solvents. Used as a selective herbicide.
2-chloro-N-(2-ethyl-6-methylphenyl)-N-(1-methoxypropan-2-yl)acetamide is an organochlorine compound that is 2-chloroacetamide substituted by a (2-ethyl-6-methylphenyl)-N-(1-methoxypropan-2-yl) group at the nitrogen atom. It is an aromatic amide, an ether, a member of benzenes and an organochlorine compound.
Widely used selective herbicides worldwide in corn, soybean and other crop cultures. Elevated concentrations of these herbicides and their degradation products have been detected in surface and groundwater. (A252) Metolachlor is an organic compound that is widely used as a herbicide. It is a derivative of aniline and is a member of the chloroacetanilide herbicides. It is highly effective toward grasses but its application is also controversial (L913).

C15H22NO2CL

283.79368

283.133

51218-45-2

(S)-Metolachor;87392-12-9;Metolachlor-d6;1219803-97-0

4169

Colorless to light yellow liquid

1.1±0.1 g/cm3

406.8±45.0 °C at 760 mmHg

-62.1 °C

199.8±28.7 °C

0.0±0.9 mmHg at 25°C

1.533

3

0

2

6

19

285

0

CCC1=CC=CC(=C1N(C(C)COC)C(=O)CCl)C

WVQBLGZPHOPPFO-UHFFFAOYSA-N

InChI=1S/C15H22ClNO2/c1-5-13-8-6-7-11(2)15(13)17(14(18)9-16)12(3)10-19-4/h6-8,12H,5,9-10H2,1-4H3

2-chloro-N-(2-ethyl-6-methylphenyl)-N-(1-methoxypropan-2-yl)acetamide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)