Absorption, Distribution and Excretion
Approximately 90% of the oral dose in rats is absorbed. The primary route of excretion of dicloimidazole is urinary excretion, consistently accounting for 60-78% of the administered dose within 48-168 hours after a single oral dose. Fecal excretion accounts for approximately 8-20% of the single oral dose. Approximately 70-77% of urinary excretion (equivalent to 52-54% of the administered dose) occurs within 24 hours. No sex-specific differences in urinary excretion rate or volume were observed. No significant accumulation in vivo was observed. Metabolism/Metabolites Dicloimidazole is metabolized via two pathways: 1. Dechlorination, leading to various chlorinated water-soluble metabolites; 2. Formation of various chlorinated metabolites.

Toxicity Summary
Identification and Uses: Diclofenac is used to improve the tolerance of corn to chloroacetanilide and thiocarbamate herbicides. It is also effective for phytoremediation of water bodies contaminated with metals (or other toxic compounds). Human Studies: Diclofenac alone does not cause any damage to human erythrocytes or any changes in oxidative stress parameters. When used in combination with other herbicides, diclofenac does not reduce erythrocyte hemolysis compared to herbicide use alone. Diclofenac reduces herbicide-induced lipid peroxidation, indicating its antioxidant protective effect. Animal Studies: Diclofenac is mildly irritating to rabbit skin and severely irritating to rabbit eyes. Diclofenac is a mild skin sensitizer. In a subchronic inhalation toxicity study, rats were exposed systemically for 6 hours daily, 5 days a week for 14 weeks, and weight loss and liver weight increase were observed at the highest tested dose. A 90-day toxicity study in dogs reported reduced weight gain, altered hematologic and clinical chemistry parameters, liver toxicity, and voluntary muscle pathology. In a 90-day rat toxicity study, toxicity manifested as slight decreases in weight gain and food utilization, and increased liver weight in female rats. No treatment-related increase in tumor incidence was observed in either mice or rats. In a mouse carcinogenicity study, changes in the kidneys and reproductive organs were observed, while rats exhibited weight loss and liver toxicity. In a two-generation rat reproductive study, no treatment-related changes in reproductive parameters were observed. Parental animals showed slight increases in liver weight, slight decreases in weight gain, and slight decreases in food consumption. Offspring animals showed increased liver weight. The mutagenicity of diclofenac was assessed through a series of in vivo and in vitro tests. Except for one in vitro test (mouse lymphoma test), all tests showed negative results. However, the in vivo mouse micronucleus test was negative.

---

Interactions
Diclofenac is a safener for thiocarbamate herbicides. It was mixed with several photosystem II inhibitor herbicides or the herbicide etorpheniramine and applied after morning glory emergence. Diclofenac alone had no significant effect on plants, but showed synergistic effects with herbicides in the mixed treatment. Diclofenac significantly reduced the ascorbic acid content in morning glory cotyledons. Ascorbic acid is known to protect plant tissues from photo-oxidative damage. Herbicides that synergize with diclofenac are thought to exert their phytotoxic effects by generating excessive singlet oxygen. Studies have shown that diclofenac treatment reduces the ascorbic acid content in ivy cotyledons, leading to impaired singlet oxygen scavenging systems and exacerbating damage to plants under the action of singlet oxygen-generating herbicides. This study investigated the effects of the cyclohexanedione herbicide clethodim and the safener diclofenac, alone or in combination, on total lipid synthesis, protein synthesis, and acetyl-CoA carboxylase (ACCase, EC 6.4.1.12) activity in sorghum [Sorghum bicolor (L.) Moench, var. G623]. The tested concentrations of clethodim and diclofenac were 0, 5, 50, and 100 μM, respectively. Cetoxidine alone at concentrations of 50 and 100 μM inhibited the incorporation of (14)C-acetate into the total lipids of sorghum leaf protoplasts by more than 50% after 4 hours of incubation. Dichloramine only partially antagonized the inhibitory effect of cetocilidine on acetate incorporation into the total lipids of sorghum protoplasts at a concentration of 100 μM. Cetoxidine alone inhibited the incorporation of [(14)C]leucine into sorghum leaf protoplasts at a concentration of 100 μM. Dichloramine did not inhibit this process at any concentration. The combined effect of cetocilidine and dichloramine on this process was mainly additive, indicating that there was no interaction between the two chemicals. Cetoxidine alone at concentrations of 5 μM and 50 μM inhibited the activity of acetyl-CoA carboxylase (ACCase) extracted from sorghum seedling leaf tissue by 58% and 90%, respectively. Even at high concentrations of 50 μM, the addition of the safener diclofenac to the test medium did not inhibit ACCase activity in sorghum leaves. The combined effect of cetocilizumab and diclofenac on sorghum ACCase activity was similar to that observed with cetocilizumab alone. These results suggest that the protective effect of diclofenac against clethodim damage in sorghum cannot be explained by the antagonistic effects of the two chemicals on the target metabolic process (liposynthesis) or the target enzyme (acetyl-CoA carboxylase).

---

Non-human toxicity values
Oral LD50 in male rats >2816 mg/kg
Oral LD50 in female rats 2146 mg/kg
Dermal LD50 in rabbits >2000 mg/kg

[1]. Purification, Regulation and Cloning of a Glutathione Transferase (GST) From Maize Resembling the Auxin-Inducible type-III GSTs. Plant Mol Biol. 1998 Jan;36(1):75-87.

[2]. Co-induction of a glutathione-S-transferase, a Glutathione Transporter and an ABC Transporter in Maize by Xenobiotics. PLoS One. 2012;7(7):e40712.

Dichlormid is a tertiary amide compound.

---

Mechanism of Action
Thiocarbamate herbicides, such as piperazine (S-propyl butyl (ethyl) thiocarbamate), are a class of well-established herbicides. They inhibit fatty acid elongation, which is essential for the synthesis of surface waxes and suberin components, and is considered closely related to their toxicity. This study investigated lipid metabolism in herbicide-treated barley (Hordeum vulgare) and a harmful weed, wild oat (Avena ludoviciana), to verify whether the safer Dichlormid could counteract the inhibitory effect of herbicides on fatty acid elongation. This study tested the effects of piperazine and its sulfoxide derivatives (considered to be the in vivo active metabolites) on lipid metabolism in barley or wild oat seedlings. In both plants, at herbicide concentrations ≥25 μM, the synthesis of very long-chain fatty acids (VLCFAs) was significantly inhibited. The safener Dichlormid showed different degrees of inhibition on VLCFA synthesis in the two plants. Pretreatment of barley with dichloramine (N,N-diallyl-2,2-dichloroacetamide) followed by the addition of velvetleaf or velvetleaf sulfoxide resulted in fatty acid chain elongation, but had no effect on wild oats. This effect on fatty acid chain elongation is consistent with the different safety effects of dichloramine on stem elongation and growth in the two plants. These data further confirm that the inhibition of very long-chain fatty acid (VLCFA) formation is an important component of the mechanism of action of thiocarbamate herbicides. The changes in lipid fatty acid composition in maize leaves induced by EPTC were generally similar to the known effects of this herbicide in other plants: a decrease in linolenic acid content and an increase in its precursors palmitic acid, stearic acid, oleic acid, and linoleic acid. However, a new effect was detected in the roots, where EPTC and EPTC+dichlorimazole treatments increased the proportion of the minor fatty acid palmitoleic acid from 2.1% to 7.6% and 16.6%, respectively. Simultaneously, both EPTC and EPTC+dichlorimazole treatments increased the phospholipid content in root lipids.

C8H11CL2NO

208.09

207.021

37764-25-3

37829

Colorless to light yellow liquid

1.2±0.1 g/cm3

253.8±40.0 °C at 760 mmHg

5.0-6.5°C

107.3±27.3 °C

0.0±0.5 mmHg at 25°C

1.495

1.98

0

1

5

12

170

0

ClC([H])(C(N(C([H])([H])C([H])=C([H])[H])C([H])([H])C([H])=C([H])[H])=O)Cl

YRMLFORXOOIJDR-UHFFFAOYSA-N

InChI=1S/C8H11Cl2NO/c1-3-5-11(6-4-2)8(12)7(9)10/h3-4,7H,1-2,5-6H2

2,2-dichloro-N,N-bis(prop-2-enyl)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)

DMSO: 100 mg/mL (480.56 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (12.01 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (12.01 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (12.01 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

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