Absorption, Distribution and Excretion
...(Toluene-(14)C)chlorotoluene was administered to rats daily for 2 weeks... The radioactivity concentrations in the blood and various organs reached their peak on day 1 or 2... and did not increase for the remainder of the experiment. Radioactivity in all tissues decreased below detectable levels within 9 days after administration of the label.
After oral administration of phenylurea drugs labeled with ¹⁴C at different locations to rats, total radioactivity was observed to be rapidly and efficiently excreted in urine and feces. Within 72 hours of administration, 90% or more of the radioactive material was excreted in feces. (Toluene-¹⁴C)chlorotoluene. For most of the mentioned CMPD/(toluene-(14)C)chlorotoluene/, the majority of the drug on the label is excreted in urine, while fecal radioactivity typically does not exceed 20% of the administered dose.

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Metabolism/Metabolites
Known N-demethylation and/or N-demethoxylation reactions of phenylurea herbicides in biological environments—chlorotoluene—soil/microbial media: in silty clay soils; plants: in wheat; mammals: in rats/excerpted from tables/
...(14) Fate of C-tolyl-labeled herbicides/chlorotoluene/ in rats. ...The methyl ring substituents undergo stepwise oxidation, first generating the corresponding hydroxymethyl derivative, and then the carboxyl derivative. ...The N-demethylation/side-chain oxidation combined pathway in rats is SRP: 3-(3-chloro-4-hydroxymethylphenyl)-1,1-dimethylurea; 3-(3-chloro-4-carboxyphenyl)-1,1-dimethylurea; 3-(3-chloro-4-hydroxymethylphenyl)-1-methylurea; 3-(3-chloro-4-carboxyphenyl)-1-methylurea; 3-(3-chloro-4-hydroxymethylphenyl)urea and 3-(3-chloro-4-carboxyphenyl)urea. Chlorotoluene metabolism in wheat exhibits a largely similar degradation pattern. However, most of the hydroxymethyl metabolites (3-(3-chloro-4-hydroxymethylphenyl)-1,1-dimethylurea) are initially captured as water-soluble conjugates. Further oxidation to the corresponding carboxyl derivatives occurs only in later stages of plant growth. Furthermore, N-demethylation only proceeds to the N-monomethyl stage. The metabolism of chlorotoluene in various plants was investigated. Chlorotoluene can be degraded via N-demethylation and cyclomethylation. The latter is the main degradation pathway in wheat and barley. The presence of this detoxification mechanism in these cereal crops, since cyclomethylation products are non-phytotoxic, may explain their enhanced resistance to chlorotoluene. The main metabolites in susceptible cereal weeds such as wild oat (Avena fatua), myriophyllum (Alopecurus myosuroides), and perennial ryegrass (Lolium perenne), as well as resistant cotton, are N-demethylation products. In cereal weeds, this reaction only slightly exceeds the state of monodemethylation metabolites, some of which still possess considerable phytotoxicity. However, in cotton, demethylation is more efficient, producing a large number of non-phytotoxic didemethylation metabolites. For more complete metabolite/metabolite data on chlorotoluene (7 metabolites in total), please visit the HSDB record page.

Interactions
This study investigated the levels of cytochrome P450 and the activity of monooxygenases in microsomes prepared from wheat cell suspension cultures. Pretreatment of cells with 2,4-D, propargyl, methoxypropionic acid, chlorotoluene, and oxime ether safeners increased cytochrome content and enzyme activity (i.e., the enzyme systems responsible for chlorotoluene cyclic methyl hydroxylation and N-demethylation). Furthermore, this study determined the effects of various agrochemicals directly added to the microsomal formulation on chlorotoluene cyclic methyl hydroxylase and N-demethylase. Plant growth regulators, fungicides, and synergistic ethers all reduced the activity of these two enzymes, with tetracycline and propargyl showing particularly significant inhibitory effects. Naphthalene anhydride, oxime ether safeners, dichloroisocyanuric acid, and trichloroisocyanuric acid had weaker effects. This study also investigated the substrate specificity of chlorotoluene cyclic methyl hydroxylase and N-demethylase using herbicide structural analogs. Among the phenylurea herbicides tested, diuron exhibited the strongest inhibitory effect. Other wheat-metabolizable herbicides affected the activities of both enzymes to varying degrees. However, dichloropyridinic acid only enhanced the activity of chlorotoluene N-demethylase.

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Non-human toxicity values
Oral LD50 in rats >10000 mg/kg
Subcutaneous LD50 in rats >2000 mg/kg

Chlorotoluene belongs to the phenylurea class of compounds. Its structure is that of a urea compound, with one nitrogen atom replaced by two methyl groups and the other nitrogen atom replaced by 3-chloro-4-methylphenyl. It is a herbicide, non-toxic to bees, but moderately toxic to mammals, birds, earthworms, and most aquatic organisms. It is both an exogenous substance and an environmental pollutant, agricultural chemical, and herbicide. It belongs to the monochlorobenzene and phenylurea classes.

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Mechanism of Action
Inhibition of photosynthesis.

C10H13CLN2O

212.677

212.071

15545-48-9

Chlorotoluron-d6;1219803-48-1

27375

COLORLESS CRYSTALS
white powder

1.2±0.1 g/cm3

345.9±52.0 °C at 760 mmHg

147-148ºC

163.0±30.7 °C

0.0±0.8 mmHg at 25°C

1.541

2.62

1

1

1

14

208

0

CC1=C(Cl)C=C(NC(N(C)C)=O)C=C1

JXCGFZXSOMJFOA-UHFFFAOYSA-N

InChI=1S/C10H13ClN2O/c1-7-4-5-8(6-9(7)11)12-10(14)13(2)3/h4-6H,1-3H3,(H,12,14)

3-(3-chloro-4-methylphenyl)-1,1-dimethylurea

Chlorotoluron Dikurin Dicuran

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

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

DMSO : ~50 mg/mL (~235.09 mM)

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.)