Absorption, Distribution and Excretion
A single lactating goat received (propyl-1-(14)C)-clethodim at 1.16 mg/kg bw per day in alfalfa diet, in three equal daily doses of 14.2 mg for three days and then a single dose of 14.2 mg on the fourth day, for a total of 10 doses. One female goat served as control. The treated goat was sacrificed 4 hrs after the final dose. Clethodim was rapidly absorbed: the peak blood radiocarbon concentration (0.273 ppm) was achieved within the first hour after the initial dose. The mean amount of radiolabel recovered in the urine represented 56% of the administered dose and that in the feces, 34%. The total amount of radiolabel found in the milk, blood and tissues represented less than 1% of the amount administered. ... The tissues contained 0.37% and the blood, 0.22% of the dose. The highest residual tissue concentrations were detected in the liver and kidney.
Groups of 8-10 white Leghorn laying hens were given (cyclohexene-4,6-(14)C)-clethodim at 0, 2.1 or 51.3 mg/kg bw per day for five consecutive days and were sacrificed about 4 hrs after the final treatment. Radioanalysis showed that 78% of the low dose and 85% of the high dose of administered radioactivity was excreted in the feces; 1.9% of the low dose and 4.2% of the high dose were found in the tissues. The radiolabel was distributed in the tissues in the following order of decreasing concentration: gastrointestinal tract > kidney > liver. In eggs, 0.1% of the low dose and 0.3% of the high dose were found; the levels were highest in egg whites, intermediate in shells and lowest in yolks.
Male and female Crl:CD(SD)BR rats were given single oral doses of [propyl-1-(14)C]-clethodim at 4.4 or 468 mg/kg bw or unlabelled test material at 4.5 mg/kg bw per day for 14 consecutive days before treatment with a single radiolabeled dose of 4.8 mg/kg bw. Elimination was rapid: 94-98% of the administered dose was excreted within 48 hrs after treatment. The principal route of excretion was the urine (87-93%), and a smaller percentage (9-17%) of the radioactivity was eliminated in the feces. The mean amount of radioactivity excreted in expired air as carbon dioxide represented 0.5-1% of the administered dose. Although the elimination patterns were similar in all groups, the rate of elimination was somewhat faster in animals that were administered the single low dose of 4.4 mg/kg bw (98% eliminated within 40 hrs) than in those given the single high dose of 468 mg/kg bw (98% within 50 hrs). No differences in elimination rate were seen for animals of either sex administered repeated low doses of clethodim. Seven days after treatment, the total amount of radiolabel recovered from organs and tissues was less than 1% of the administered dose. The highest residual tissue concentrations were found in the adrenals, kidney and liver. There were no significant dose-related or sex-specific differences in tissue distribution, when expressed as a proportion of the dose administered, and there was no evidence of bioaccumulation.

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Metabolism / Metabolites
... A lactating goat received (propyl-1-(14)C)-clethodim / at 1.16 mg/kg bw per day in alfalfa diet, in three equal daily doses of 14.2 mg for three days and then a single dose of 14.2 mg on the fourth day, for a total of 10 doses. One female goat served as control. The treated goat was sacrificed 4 hrs after the final dose. / ... hind- and forequarter muscle, peritoneal and subcutaneous fat, liver, kidneys, heart and blood were collected to allow characterization of metabolites. The major urinary metabolite was clethodim sulfoxide, which accounted for 67% of the urinary radiocarbon. Other urinary radiolabelled components were identified as clethodim (3-27%) and demethyl sulfoxide (12-18%), S-methyl (7-13%), imine sulfoxide (1.5-2.8%), sulfone (1.5-2.2%) and 5-hydroxy sulfoxide (0-3%). In the milk, about half of the radiocarbon could be extracted into organic solvents and occurred in clethodim, clethodim sulfoxide and clethodim demethyl sulfoxide; the other half of the radiocarbon was water soluble and was shown to be (14)C-lactose. In blood and tissues, the maximal extractable radiocarbon residues accounted for 77-95% of the radiolabel and were identified as clethodim and the sulfoxide, demethyl sulfoxide, imine sulfoxide, sulfone and 5-hydroxy sulfone. The proposed metabolic pathway in goats was essentially the same as that proposed for rats.
Two groups of eight white Leghorn laying hens were given daily doses of (cyclohexene-4,6-(14)C)-clethodim at 2.1 or 51.3 mg/kg bw per day by capsule for five consecutive days. The hens were sacrificed about 4 hrs after the final dose, and tissues were collected for analysis. Two major metabolites, clethodim sulfone and clethodim sulfoxide, were identified in tissues and eggs. Clethodim sulfone accounted for up to 57% of tissue levels of radiolabel, whereas clethodim sulfoxide accounted for 10-31%. Clethodim sulfoxide was the principal metabolite in egg white (26-82%) and yolk (25-37%); parent clethodim was detected in significantly smaller amounts in both tissues and eggs. The proposed metabolic pathway in chickens was different from and considered to be simpler than that observed in rats and goats, since none of the imine, 5-hydroxy or S-methyl analogues was detected in chickens.
... A group of male rats /Crl:CD(SD)BR/ were given a single oral dose of 450 mg/kg bw radiolabeled compound to ensure a sufficiently large quantity of labeled metabolites. Urine and feces were collected and analyzed for the parent compound and its metabolites. The metabolic profiles of males and females in all dose groups were remarkably similar. Nine urinary metabolites were identified and characterized. The major metabolite was clethodim sulfoxide (representing 65-75% of the administered dose), and smaller amounts were found of the imine sulfoxide (6-13%), the sulfone (1-3%), the 5-hydroxy sulfoxide/sulfone (0.5-1.5%) and the oxazole sulfone (0-5%). The primary fecal metabolites, which accounted for more than 1% of the radiolabel, were identified as clethodim sulfoxide and the imine sulfoxide. Minor (present as < 1% of the dose) urinary and fecal metabolites were the oxazole sulfoxide, the demethyl sulfoxide and the aromatic sulfone. Other minor fecal metabolites were clethodim sulfone, the trione sulfoxide and c-olefins. Parent clethodim accounted for about 1% of the administered dose.
The proposed metabolic pathways for clethodim in rats ... is postulated that once clethodim has been absorbed it can be: oxidized to clethodim sulfoxide (dominant process); converted to the S-methyl via a sulfonium cation intermediate; cleaved at the oxime N-O bond to generate imine or hydroxylated at the 5 position.

Non-Human Toxicity Values
LC50 Rat inhalation 3.9 mg/L/4 hr
LD50 Rabbit dermal >5000 mg/kg
LD50 Mouse oral (female) 2430 mg/kg
LD50 Mouse oral (male) 2570 mg/kg
For more Non-Human Toxicity Values (Complete) data for Clethodim (6 total), please visit the HSDB record page.

Clethodim is an oxime O-ether resulting from the formal conversion ot the acyclic keto group of 5-[2-(ethylsulfanyl)propyl]-3-hydroxy-2-propionylcyclohex-2-en-1-one to the corresponding oxime with subsequent O-alkylation of the oxime by an (E)-3-chloroallyl group. It is used as a selective postemergence herbicide for the control of annual and perennial grasses in numerous crops, including alfalfa, celery, clover, conifers, cotton, cranberries, garlic, onions, ornamentals, peanuts, soybeans, strawberries, sugarbeet, sunflowers, and vegetables; the (-)-enantiomer has been reported to be more active than the (+)-enantiomer. It has a role as a herbicide and an EC 6.4.1.2 (acetyl-CoA carboxylase) inhibitor. It is an organic sulfide, a cyclic ketone, an organochlorine compound, an oxime O-ether, a beta-diketone and an enol.

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Mechanism of Action
... Fatty acid synthesis inhibitor.

C17H26CLNO3S

359.9

359.132

99129-21-2

135491728

Clear amber liquid

1.2±0.1 g/cm3

467.3±55.0 °C at 760 mmHg

236.4±31.5 °C

0.0±1.2 mmHg at 25°C

1.531

4.05

1

5

9

23

488

0

CC/C(=N\OC/C=C/Cl)/C1=C(CC(CC(C)SCC)CC1=O)O

SILSDTWXNBZOGF-KUZBFYBWSA-N

InChI=1S/C17H26ClNO3S/c1-4-14(19-22-8-6-7-18)17-15(20)10-13(11-16(17)21)9-12(3)23-5-2/h6-7,12-13,20H,4-5,8-11H2,1-3H3/b7-6+,19-14+

2-[(E)-N-[(E)-3-chloroprop-2-enoxy]-C-ethylcarbonimidoyl]-5-(2-ethylsulfanylpropyl)-3-hydroxycyclohex-2-en-1-one

Prism; Centurion; Clethodim

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.)