Absorption, Distribution and Excretion
Following oral administration, S-metolachlor is extensively absorbed and metabolized. It is primarily excreted via urine and feces. The highest tissue residues are found in whole blood. /s-metolachlor/ A selective herbicide, primarily absorbed by the hypocotyl and stem. Single oral administration of metolachlor to rats (28.6 or 52.4 mg/kg) (purity not specified, but both S-14C-labeled and unlabeled metolachlor were synthesized in this study). The chemical is readily absorbed, as 70% to 90% of metolachlor is excreted as metabolites within 48 hours. Data from oral administration of radioactive metolachlor to rats (approximately 3.2 to 3.5 mg/kg) indicate rapid metabolism of the chemical. Residues in meat tissue and blood are extremely low, with only blood residues exceeding 0.1 ppm. For more complete data on the absorption, distribution, and excretion of metolachlor (6 types), please visit the HSDB record page. Metabolites/Metabolic Substances Following pre-seeding application of metolachlor, plant metabolism appears to occur via the binding of naturally occurring acetyl chloride groups, a binding mode more prevalent than oxygen binding. The ether group undergoes further reactions, first hydrolysis, then sugar binding. The final metabolite is a product of the debinding reaction, polar, water-soluble, non-volatile, and readily degradable. The hydrolysis process converts oxytocin metabolites into deacetylated derivatives and thiotocin metabolites into morpholine derivatives. The anto analogue methoxychlor (bis) was also studied using the fungus Chaetomium globosum. The compounds produced when this organism is incubated with isopropyl methyl chloride include: 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, the α-chlorine atom of these insecticides (including methyl chloride) is not replaced by a thiol group, but rather by a hydroxyl group, although the chlorine atom of methyl chloride is replaced by a thiol group in the first step of degradation in plants. Fungi can generate indoline and quinoline compounds through dealkylation, deacylation, and cyclization reactions. Studies of rat urine and fecal metabolites show that the metabolic pathway of metolachlor includes dechlorination, ortho-methylation, N-dealkylation, and side-chain oxidation. Urinary metabolites include 2-ethyl-6-methylhydroxyacetanilide and N-(2-ethyl-6-methylphenyl)-N-(hydroxyacetyl)-DL-alanine. Fecal metabolites include 2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-hydroxy-1-methylethyl) and N-(2-ethyl-6-methylphenyl)-N-(hydroxyacetyl)-DL-alanine. For more complete data on the metabolites/metabolites of metolachlor (10 in total), please visit the HSDB record page. Metolachlor is metabolized via dechlorination, O-methylation, N-dealkylation, and side-chain oxidation. Glutathione transferase mediates the binding of metolachlor to glutathione. Urinary metabolites include 2-ethyl-6-methylhydroxyacetanilide and N-(2-ethyl-6-methylphenyl)-N-(hydroxyacetyl)-DL-alanine. Fecal metabolites include 2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-hydroxy-1-methylethyl) and N-(2-ethyl-6-methylphenyl)-N-(hydroxyacetyl)-DL-alanine. Metolachlor is also excreted in urine. (A571, A270)

Toxicity Summary
Metolachlor exerts its effects by inhibiting photosynthetic elongation enzymes and geraniol-geraniol pyrophosphate (GGPP) cyclase, both of which are part of the gibberellin pathway. It can also bind to nAChR in the nervous system and cause endocrine disorders in humans by binding to and inhibiting estrogen receptors. (T10, L913, A590)

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Toxicity Data
LD50: 1200-2780 mg/kg (oral, oral) (L914)
LD50: > 2000 mg/kg (skin, rat) (L914)
LC50: > 4.3 mg/L/4hr (L914)

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Interactions
The reproductive toxicity of a mixture of five pesticides (metolachlor, atrazine, cypermethrin, metolachlor, and cypermethrin) and one fertilizer (ammonium nitrate) was evaluated in Swiss mice using a continuous breeding protocol. These chemicals and their relative concentrations in the mixture were selected based on groundwater survey data from Iowa. The mice's drinking water was supplemented with mixtures at concentrations of 0X, 1X, 10X, and 100X, where 1X is the median concentration of each component determined by the survey. F0 generation mice remained fertile during the 18-week exposure period. The mixture did not adversely affect the reproductive capacity, body weight, food and water consumption, organ weight, or sperm parameters of F0 generation mice. No treatment-related clinical symptoms were observed. The mixture had no effect on the growth, development, and maturity of F1 generation mice before weaning. No treatment-related clinical symptoms were observed, nor were adverse effects of the mixture on the reproductive capacity, food and water consumption, body weight of male or female mice, organ weight of specific males and females, sperm parameters, vaginal cytology, or histology of specific organs observed in F1 generation mice. In summary, exposure doses of the mixture in drinking water up to 100 times the median concentrations of each component in contaminated groundwater did not cause significant systemic or reproductive toxicity in the F0 or F1 generations of Swiss mice. Male Fischer 344 rats and female B6C3F1 mice were exposed to drinking water containing a mixture of pesticides and ammonium nitrate (California Chemicals Mixture), respectively, simulating contaminated groundwater in California. The exposure periods were 71 and 91 days, respectively. Additionally, female B6C3F1 mice were exposed to a mixture of another pesticide and ammonium nitrate (Iowa Chemicals) via drinking water for 91 days. Spleens were harvested from the animals, and spleen cells were cultured for analysis of sister chromatid exchange, chromosomal aberrations, and micronuclei in cytochalasin B-induced binucleated cells. Increased sister chromatid exchange was observed in rat spleen cells treated with 1x, 10x, and 100x concentrations of the California Chemicals, and in mice treated with 100x concentrations of the California Chemicals. No other consistent cytogenetic effects were observed with the California Chemicals, and no statistically significant cytogenetic damage was observed in mice exposed to the Iowa Chemicals. This paper discusses evidence from the literature to infer which chemicals in the California Chemicals might contribute to the observed sister chromatid exchange response.

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Non-human toxicity values
Rat inhalation LC50 >2.02 mg/L/4 hours air
Rabbit skin LD50 >2000 mg/kg body weight
Rat skin LD50 3170 mg/kg body weight
Rat inhalation LC50 >4.33 mg/L/4 hours
For more complete (12) non-human toxicity values for methoxychloride, please visit the HSDB records 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 brown to dark brown oily liquid with a slightly sweet taste. It is slightly soluble in water, but denser than water, and therefore sinks. It is soluble in most organic solvents. Metolachlor is a selective herbicide. 2-Chloro-N-(2-ethyl-6-methylphenyl)-N-(1-methoxypropyl-2-yl)acetamide is an organochlorine compound formed by replacing the nitrogen atom of 2-chloroacetamide with a (2-ethyl-6-methylphenyl)-N-(1-methoxypropyl-2-yl) group. It is an aromatic amide, ether, benzene compound, and organochlorine compound. Metolachlor is a selective herbicide widely used in the cultivation of corn, soybeans, and other crops. High concentrations of this herbicide and its degradation products have been detected in both surface water and groundwater. (A252) Metolachlor is an organic compound widely used as a herbicide. It is a derivative of aniline and belongs to the chloroacetanilide class of herbicides. It is very effective against grass weeds, 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.)