Absorption, Distribution and Excretion
Approximately 90% of the orally administered dose was absorbed in rats. Urinary excretion was the major route of elimination of orally administered dichlormid, consistently accounting for 60-78% of the administered dose over 48-168 hours following a single oral dose. Fecal excretion accounted for approximately 8-20% of a single oral dose. Approximately 70-77% of urinary excretion (representing 52-54% of the administered dose) occurred within 24 hours. No gender-related difference in rate or amount of urinary excretion was observed. No significant accumulation in the body was observed.

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Metabolism / Metabolites
Dichlormid was metabolized via two pathways: 1. Initial dechlorination followed by formation of various chlorinated, water-soluble metabolites, and 2. Formation of various chlorinated metabolites.

Toxicity Summary
IDENTIFICATION AND USE: Dichlormid is used to increase tolerance of corn to chloroacetanilide and thiocarbamate herbicides. It can also be effective in phytoremediation of water polluted with metals (or other toxic compounds). HUMAN STUDIES: Dichlormid alone did not produce any damage to human erythrocytes and did not elicit any changes in oxidative stress parameters. Combination of dichlormid with another herbicide did not attenuate hemolysis of erythrocytes compared to the herbicide alone. Dichlormid reduced lipid peroxidation induced by herbicides, which suggest the role of safeners as antioxidants. ANIMAL STUDIES: Dichlormid is mildly irritating to the skin of rabbits and severely irritating to the eyes of rabbits. Dichlormid is a mild dermal sensitizer. In a subchronic inhalation toxicity study in rats via whole body exposure for 6 hours a day, 5 days/week for 14 weeks, decreased body weights and increased liver weights were observed at the highest dose tested. 90-day toxicity studies in dogs reported decreased body weight gains, hematological and clinical chemistry alternations, liver toxicity and voluntary muscle pathological changes. In a 90-day rat toxicity study, toxicity was manifested as minor decreases in body weight gains and food efficiency in females and increased liver weight. No increased incidences of treatment related tumors were observed in mice and rats. In the carcinogenicity study in mice, kidney changes and changes in reproductive organs were observed, while rats exhibited decreased body weights and liver toxicity. In a 2-generation reproduction study in rats, no treatment related effects on reproductive parameters were observed. Minimal increased liver weight, minimal decreased weight gain and minimal decrease in food consumption was observed in parental animals. Increased liver weights were observed in the offspring. Mutagenic potential for dichlormid was evaluated in a battery of in vivo and in vitro assays. A negative response was observed in these assays except in one in vitro assay (mouse lymphoma assay). However, the in vivo mouse micronucleus assay was negative.

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Interactions
Dichlormid, a safener for thiolcarbamate herbicides, was tank-mixed with several herbicidal inhibitors of photosystem II, or with the herbicide acifluorfen, and applied postemergence to Ipomoea hederacea plants. Dichlormid had no visible effects on the plants when applied alone, but interacted synergistically with the herbicides in the combination treatments. Dichlormid strongly decreased the ascorbic acid levels in the Ipomoea hederacea cotyledons. Ascorbate is known to protect plant tissue from photooxidative damage. The herbicides which interacted synergistically with dichlormid are believed to generate their phytotoxic action via the production of excess singlet oxygen. It is suggested that the decreased ascorbate levels in the lpomoea hederacea cotyledons after dichlormid treatment result in an impaired singlet oxygen scavenging system and consequently lead to increased plant damage in the presence of singlet oxygen generating herbicides.
The effects of individual or combined treatment of the cyclohexanedione herbicide sethoxydim and the safener dichlormid on total lipid synthesis, protein synthesis and acetyl-CoA carboxylase (ACCase, EC 6.4.1.12) activity of grain sorghum [Sorghum bicolor (L.) Moench, var. G623] were investigated. Sethoxydim and dichlormid were tested at concentrations of 0, 5, 50, and 100 uM each. Sethoxydim applied alone at 50 and 100 uM, inhibited the incorporation of (14)C-acetate into total lipids of sorghum leaf protoplasts by more than 50%, following a 4 hr incubation. Dichlormid antagonized partially the inhibitory effects of sethoxydim on the incorporation of acetate into total lipids of sorghum protoplasts only when it was used at 100 uM. Sethoxydim applied alone inhibited the incorporation of [(14)C]leucine into sorghum leaf protoplasts only at 100 uM. Dichlormid was not inhibitory of this process at any concentration. The combined effects of sethoxydim and dichlormid on this process were mainly additive indicating no interactions of the two chemicals. Sethoxydim applied alone at 5 and 50 uM inhibited the activity of ACCase extracted from leaf tissues of grain sorghum seedlings by 58 and 90%, respectively. Addition of the safener dichlormid to the assay medium did not inhibit ACCase activity of sorghum leaves even at the high concentration of 50 uM. The combined effects of sethoxydim and dichlormid on the activity of sorghum ACCase were similar to those observed when sethoxydim was used alone. These results indicate that the protection conferred by dichlormid on grain sorghum against sethoxydim injury can not be explained on the basis of an antagonistic interaction of the two chemicals on target metabolic processes (lipid synthesis) or target enzymes (ACCase).

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Non-Human Toxicity Values
LD50 Rat (male) oral >2816 mg/kg
LD50 Rat (female) oral 2146 mg/kg
LD50 Rabbit dermal >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 carboxamide.

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Mechanism of Action
The thiocarbamates, such as pebulate (S-propyl butyl (ethyl) thiocarbamate) are a well-established class of herbicides. They inhibit fatty acid elongation, which is necessary for the biosynthesis of constituents of surface waxes and suberin and this has been proposed to be important for their toxicity. In this study lipid metabolism was investigated in herbicide-treated barley (Hordeum vulgare) and a pernicious weed, wild oats (Avena ludoviciana), to test the hypothesis that inhibitory effects on fatty acid elongation could be counteracted by the safer, dichlormid. Pebulate and its sulfoxide derivative (thought to be the active metabolite in vivo) were tested against lipid metabolism in barley or wild oat shoots. In both plants there was a significant inhibition of very long chain fatty acid (VLCFA) synthesis at herbicide concentrations > or =25 uM. The extent to which safener dichlormid could prevent the inhibition of VLCFA synthesis was different in the two species. Previous treatment of barley with dichlormid (N,N-diallyl-2,2-dichloroacetamide) enabled fatty acid elongation in the presence of pebulate or pebulate sulphoxide, but had no effect on wild oats. The effects on fatty acid elongation mimicked the differential safening action of dichlormid observed on shoot elongation and growth in the two species. These data provide further evidence that inhibition of VLCFA formation is important for the mechanism of action of thiocarbamates.
The changes in fatty acid composition of maize leaf lipids caused by EPTC were generally similar to known effects of this herbicide in other plants: decreasing of linolenic acid content and increasing of its precursors, palmitic, stearic, oleic and linoleic acids. However, novel effects were detected in roots where the proportion of minor fatty acid palmitoleic acid was increased from 2.1 to 7.6 and 16.6% by EPTC and EPTC + dichlormid treatments, respectively. Simultaneously, the phospholipid content of root lipids was increased by both EPTC as well as EPTC + dichlormid treatments.

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.

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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.

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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.

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