Coccidia

To enhance the anti-coccidial effect of dinitolmide and reduce its residual, the dinitolmide/MMT compounds were synthesized by the method of solution intercalation via dinitolmide intercalated into Na + -montmorillonite (Na + -MMT). The structure of compounds was characterized by X-ray diffraction and Fourier transformed infrared. Its anti-coccidial effect was examined by Eimeria tenella infection experiment. One hundred fifty AA broiler chickens were divided into five groups. Chickens were orally inoculated with 5 × 10(4) E. tenella oocysts after dinitolmide was given. Their curative effects were observed. The results showed that intercalated dinitolmide expanded the basal spacing (d 001) of MMT from 12.6 to 15.2 Å. The IR bands of amide group in dinitolmide/MMT were detected at 1,533 cm(-1) which showed that dinitolmide was successfully intercalated into the interlayer spaces of MMT. The dinitolmide/MMT showed higher anti-coccidian oocyst activity compared with dinitolmide (p < 0.05). The dinitolmide/MMT compound can significantly increase body weight gains and reduce bloody diarrhea, lesion score, and oocyst excretion. The anti-coccidia index of dinitolmide/MMT group (165.21) is much higher than dinitolmide group (88.84). The dinitolmide/MMT hybrid systems can be more effective in control of coccidiosis in comparison to dinitolmide[1].

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Dinitolmide intercalated into montmorillonite (dinitolmide/MMT) showed significantly higher anticoccidial activity against E. tenella infection in chickens compared to dinitolmide alone. The hybrid compound improved body weight gain, reduced bloody diarrhea, lowered lesion scores, decreased oocyst excretion, and increased survival rate. The anticoccidial index (ACI) for the dinitolmide/MMT group was 165.21, significantly higher than that of the dinitolmide group (88.84).[1]

A total of 150 fourteen-day-old AA broiler chickens were randomly divided into five groups (30 birds each, with 3 subgroups of 10). Groups were treated as follows for seven consecutive days: Group A received 125 mg dinitolmide per kg feed; Group B received dinitolmide/MMT hybrid (equivalent to 125 mg dinitolmide per kg feed); Group C received a physical mixture of dinitolmide and MMT (each at 125 mg/kg feed); Group D was an uninfected, unsupplemented negative control; Group E was an infected, unsupplemented positive control. Chickens in groups A, B, C, and E were orally inoculated with 5×10⁴ sporulated E. tenella oocysts 24 hours after supplementation began. Body weight, feed intake, diarrhea scores, lesion scores, oocyst excretion, and survival rates were monitored.[1]

Non-human toxicity values:
Rats, oral LD50: 600 mg/kg
>Dogs, intravenous LD50: 75 mg/kg

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Ecotoxicity values:
Daphnia magna EC50 (poisoning, activity restriction): 155 mg/L/48 hours (95% confidence interval: 146-164 mg/L); static PMID: 938765
Daphnia magna LC50 (Daphnia magna): 165 mg/L/48 hours (95% confidence interval: 157-173 mg/L); static

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Adverse reactions:
Occupational hepatotoxicity - Grade II hepatotoxicity: Potential toxicity in the occupational environment is based on cases of human ingestion poisoning or animal studies.
Methemoglobinemia - Elevated levels of methemoglobin in the blood; this compound is classified as a minor toxicity.

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Non-human toxicity values
Oral LD50 in rats: 600 mg/kg
Intravenous LD50 in dogs: 75 mg/kg

[1]. Effect of dinitolmide intercalated into Montmorillonite on E. tenella infection in chickens. Parasitol Res. 2014 Mar;113(3):1233-8.

Yellowish crystalline solid. Melting point: 177 °C. Slightly soluble in water. Soluble in acetone, acetonitrile, and dimethylformamide. Used as an antiparasitic drug for poultry. Store in a cool, well-ventilated place, away from fire hazards and easily oxidized substances.
Dinitrotoluidine is a dinitrotoluene derivative.
Dinitrotoluidine is a feed additive used to prevent coccidiosis infection in poultry.
An anticoccidial drug for poultry.

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Veterinary terminology: Dinitrotoluidine exerts its strongest anticoccidial activity by inhibiting the asexual reproductive stage of the parasite. Unless used in combination with other products, its efficacy is limited to Eimeria tenell and Eimeria necatrix.

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FDA Food Additive Status
Zoalene - Feed, Regular, 2 ppm - Residue in raw chicken fat - 556.770; 3 ppm - Residue in raw chicken muscle - Same as above; 3 ppm - Residue in raw turkey muscle and liver - Same as above; 6 ppm - Residue in raw chicken liver and kidney - Same as above; For use in chicken and turkey feed - 558.60; 558.62; 558.78; 558.128; 558.248; 558.274; 558.450; 558.530; 558.680

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Source/Use
Used as an anticoccidial agent in veterinary medicine and as a food additive; [ACGIH] Anticoccidial agents are a class of chemical preparations, such as furacilin, nitroaniline, and nicarbazin, mixed into feed or drinking water to control coccidiosis in animals. [Dorland's Illustrated Medical Dictionary]
No matching label is found for 3,5-dinitro-o-toluamide (USEPA/OPP pesticide code: 037510). /Suggested retail price: Not currently registered for use in the United States, but approved pesticide uses may change periodically, so you must consult federal, state, and local authorities for currently approved uses. /

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Therapeutic use
(Veterinary): Anticoccidial agent
Veterinary use: /Dinitro-o-toluamide exerts maximum anticoccidial activity against the asexual stage by inhibiting parasite development. Its efficacy is limited to Eimeria tenell and E. necatrix unless used in combination with other products.

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Dinitropamide (Zoalene) is an anticoccidial agent used in poultry to control Eimeria tenell infection. It has poor water solubility and limited solubility in organic solvents, which affects its efficacy and leads to drug resistance. In this study, a dinitrodrug/MMT hybrid was developed by solution intercalation to enhance its delivery and anticoccal activity. Compared with micronized dinitrodrug, MMT, as a carrier, may have mucosal adhesion, sustained release and anticoagulant effects. [1]

C8H7N3O5

225.1583

225.038

148-01-6

3092

Crystals from dilute alcohol
Yellowish, crystalline solid
Yellowish solid or needles from aqueous ethanol

1.5±0.1 g/cm3

298.0±40.0 °C at 760 mmHg

183-185 °C(lit.)

134.0±27.3 °C

0.0±0.6 mmHg at 25°C

1.636

1.01

1

5

1

16

321

0

O=C(C1C([H])=C(C([H])=C(C=1C([H])([H])[H])[N+](=O)[O-])[N+](=O)[O-])N([H])[H]

ZEFNOZRLAWVAQF-UHFFFAOYSA-N

InChI=1S/C8H7N3O5/c1-4-6(8(9)12)2-5(10(13)14)3-7(4)11(15)16/h2-3H,1H3,(H2,9,12)

2-methyl-3,5-dinitrobenzamide

dinitolmide; 2-Methyl-3,5-dinitrobenzamide; 148-01-6; Zoalene; 3,5-Dinitro-o-toluamide; Zoamix; Coccidot; Coccidine A;

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 (~444.13 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (11.10 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 (11.10 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 (11.10 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.)