Absorption, Distribution and Excretion
Dermal Absorption /in rats/ ... at 10 hrs = 13 %. Cyromazine /was/ apparently rapidly absorbed into the skin in an inverse dose related manner. The absorption into the skin is followed by a slower release into the body. The main route of excretion is apparently by the urine. There is no evidence that the compound is sequestered in the skin. Mean absorption based on blood, urinary/ fecal excretion, and carcass, ranged from 0.6 to 7% for animals sacrificed at the end of the exposure periods. For animals exposed for 10 and 24 hours and followed for 48 hours post-exposure, mean absorption ranged from 8 to 14.5%. Total radioactivity absorbed generally decreased as dose increased indicating saturation of absorption with increasing dose. Amounts remaining in/on the skin at termination ranged from 4.5% (10 mg dose/2 hr exposure) to 24% ( 0.1 mg dose/24 hr exposure). The majority of the absorbed radioactivity was found in the urine and carcass. Most of the unabsorbed radioactivity was found in the skin washes from each dose/ duration. /In another portion of the same study in rats/ absorption at 10 hrs = 10%. Mean total recoveries of applied radioactivity from all dose groups ranged from 85 to 101%. Mean absorption based on blood, urinary/ fecal excretion, and carcass, ranged from 2% to 11%. Total radioactivity absorbed generally increased with increasing exposure time but decreased with increasing dose indicating saturation of penetration with increasing dose. The majority of the absorbed radioactivity was found in the urine and carcass. Most of the unabsorbed radioactivity was found in the skin washes from each dose/duration (35-90%). However, based on measurements of skin absorption, a significant amount of radioactive dose was also found in the skin itself (9-40%). Mean absorption with inclusion of radioactivity in dissolved skin ranged from 10 to 45%. The ratio of the amount of radioactive dose in the skin wash to the radioactivity in the skin itself decreased with time indicating penetration into the subsurface of the skin with time after treatment.
Cyromazine was well absorbed after oral administration /to rats/. Excretion was rapid at the dose (3 mg/kg), but an apparent delay in excretion occurred at the high dose (300 mg/kg). Fecal elimination was equivalent among dose groups except the high dose males, where a greater percentage was eliminated by this route. The origin of fecal radioactivity was via biliary elimination. Residual radioactivity in tissues was minimal in all dose groups. Urinary and fecal metabolites of 14C-cyromazine were isolated and identified by TLC, HPLC, and GC/MS. The major compounds were the N-dealkylated product melamine, hydroxycyromazine, and unmetabolized cyromazine identified
A single dose of 0.5 mg/kg bw of 14C-cyromazine (uniformly triazine ring labeled) was given orally to two male and one female Charles River white rats (not further identified). By 72 hours after dosing, 95% of the administered dose had been excreted in urine, essentially all within the first 24 hours. About 3% was excreted in feces, again predominantly in the first 24 hours. Negligible amounts were excreted as volatiles or CO2 in another two males and one female given the same dose. Tissue residues were below the level of detection except in liver; however, liver levels were too low to permit accurate quantitation (about 0.007 ppm).
Two chickens (strain not indicated) were given daily oral doses of 14C-cyromazine (uniformly triazine ring labeled) of 0.75 mg/hen/day by capsule for seven days. By 24 hours after the last dose 99.1% of the administered radioactivity had been recovered in the excreta with essentially none in volatiles and CO2. Both egg whites and egg yolks contained about 0.12-0.15 ppm consistently. Tissue levels were: byproducts (i.e. head and feet) 0.047 ppm test material equivalents; reproductive tract 0.047 ppm; liver 0.032 ppm; all other tissues 0.008-0.019 ppm.
For more Absorption, Distribution and Excretion (Complete) data for CYROMAZINE (10 total), please visit the HSDB record page.

---

Metabolism / Metabolites
Cyromazine was well absorbed after oral administration /to rats/. ... Urinary and fecal metabolites of 14C-cyromazine were isolated and identified by TLC, HPLC, and GC/MS. The major compounds were the N-dealkylated product melamine, hydroxycyromazine, and unmetabolized cyromazine identified.
Urine from a female rat given a single oral dose of 14C-cyromazine (uniformly triazine ring labeled) of 0.5 mg/kg bw was analyzed using TLC and a cation exchange column chromatography system. With both systems the majority of the urinary radioactivity was determined to be in the form of unchanged parent compound. Unchanged parent compound in urine accounted for about 80% of the administered dose. Three metabolites were detected with each system and were presumed to be the same compounds. These metabolites accounted for 2.2-3.2%, 3.0-5.5%, and 4.6-5.3% of the administered dose, respectively, but no identification was made. Fecal material from a male rat given the same dose as the above female was found to contain little unchanged parent compound: <0.1% of the administered dose. The same three metabolites as observed in urine were found and represented 0.1, 0.1 and 4.1% of the administered dose, respectively.
One male and one female albino Sprague-Dawley rats were given diet containing 3000 ppm of 14C-cyromazine for 10 days. In the male the liver was found to contain 31.3 ppm cyromazine and 0.96 ppm melamine and the kidney 62.4 ppm cyromazine and 1.3 ppm melamine. In the female liver residues were 13.2 ppm and 0.51 ppm and kidney residues 22.2 and 0.68 ppm of cyromazine and melamine, respectively. This study indicated that there was some conversion of cyromazine to melamine in vivo.
Urine from male and female monkeys (Macaca fasicicula) given single oral doses of 14C-cyromazine (uniformly triazine ring labeled) of 0.05 or 0.5 mg/kg bw by capsule was found to have the majority of the radioactivity present in the form of unchanged parent compound. Regardless of dose 93.6-96.1% of the urinary radioactivity was present as unchanged cyromazine. Additionally, 2.9-6.4% of the radioactivity as identified as melamine ... In a second study with the same strain of monkey given the same dose levels, urine collected during the first 24 hours after dosing had 95-100% of the recovered radioactivity in the form of unchanged cyromazine. In one male dosed at 0.05 mg/kg bw, no melamine was detected in the urine. In one female at 0.05 mg/kg bw and one monkey of each sex given 0.5 mg/kg bw 3.0-3.9% of the urinary radioactivity was in the form of melamine.
For more Metabolism/Metabolites (Complete) data for CYROMAZINE (9 total), please visit the HSDB record page.

Toxicity Data
LC50 (rat) > 3,600 mg/m3/4H

---

Non-Human Toxicity Values
LD50 Mouse (M, F) oral 2029 mg/kg
LD50 Rabbit (M,F) oral 1467 mg/kg
LD50 Rat oral 3387 mg/kg /Technical cyromazine/
LC50 Rat inhalation >2.720 mg/L air/4 hr
LD50 Rat percutaneous >3100 mg/kg

[1]. Survival advantage of cyromazine-resistant sheep blowfly larvae on dicyclanil- and cyromazine-treated Merinos. Aust Vet J. 2014 Nov;92(11):421-6.

[2]. Cyromazine Effects the Reproduction of Drosophila by Decreasing the Number of Germ Cells in the Female Adult Ovary. Insects. 2022 Apr 27;13(5):414.

[3]. Cyromazine and Chlorpyrifos Induced Renal Toxicity in Rats: The Ameliorated Effects of Green Tea Extract. Journal of Environmental and Analytical Toxicology. 2012 June 9; 2(5): 1000146.

[4]. Cyromazine affects the ovarian germ cells of Drosophila via the ecdysone signaling pathway. Front Physiol. 2022 Sep 29;13:992306.

[5]. The ameliorating effects of green tea extract against cyromazine and chlorpyrifos induced liver toxicity in male rats. Asian Journal of Pharmaceutical and Clinical Research. 2013 January; 6(1):47-55.

Cyromazine is a triamino-1,3,5-triazine. It has a role as a triazine insecticide and a mouse metabolite.
Ectoparasiticide. Insect growth regulator. Specific activity against dipterous larvae. Cyromazine is a fda approved for use in livestock. Cyromazine belongs to the family of Aminotriazines. These are organic compounds containing an amino group attached to a triazine ring.
See also: Vetrazine (annotation moved to).

---

Mechanism of Action
Insect growth regulator with contact action, which interferes with moulting and pupation. When used on plants, action is systemic.
Cyromazine is an effective insecticide used to control dipteran insects. Its precise mode of action is yet to be determined, although it has been suggested that it interferes with the hormone system, sclerotization of the cuticle, or nucleic acid metabolism. To understand the way in which cyromazine acts, /the authors/ positionally cloned a cyromazine resistance gene from Drosophila melanogaster. Six cyromazine resistance alleles had previously been generated by ethyl methanasulfonate treatment. Two of these failed to complement each other and here /the authors/ identify them as having independent non-sense mutations in CG32743, which is an ortholog of Smg1 of worms and mammals and encodes a phosphatidylinositol kinase-like kinase (PIKK). RNAi experiments confirm that cyromazine resistance can be achieved by knocking down CG32743. These are the first cyromazine resistant mutations identified at the nucleotide level. In mammals Smg1 phosphorylates P53 in response to DNA damage. This finding supports the hypothesis that cyromazine interferes with nucleic acid metabolism.

---

Therapeutic Uses
MEDICATION (VET): ectoparasiticide
MEDICATION (VET): Cyromazine, a triazine derivative, is effective against blowfly larvae on sheep and lambs and also against other Diptera such as houseflies and mosquitos. At recommended dose rates, cyromazine shows only limited activity against established strikes and must therefore be used preventively. Blowflies usually lay eggs on damp fleece of treated sheep. Although larvae are able to hatch, the young larvae immediately come into contact with cyromazine, which prevents the molt to second instars. The efficacy of a pour-on preparation of cyromazine does not depend on factors such as weather, fleece length, and whether the fleece is wet or dry. Control can be maintained for up to 13 wk after a single pour-on application, or longer if cyromazine is applied by dip or shower.

C6H10N6

166.19

166.096

66215-27-8

Cyromazine-d4;1219804-19-9;Cyromazine-13C3;1808990-94-4

47866

White to off-white solid powder

1.6±0.1 g/cm3

480.6±28.0 °C at 760 mmHg

223-227 °C(lit.)

244.5±24.0 °C

0.0±1.2 mmHg at 25°C

1.851

-0.04

3

6

2

12

148

0

LVQDKIWDGQRHTE-UHFFFAOYSA-N

InChI=1S/C6H10N6/c7-4-10-5(8)12-6(11-4)9-3-1-2-3/h3H,1-2H2,(H5,7,8,9,10,11,12)

2-N-cyclopropyl-1,3,5-triazine-2,4,6-triamine

HSDB-6602; HSDB 6602; Cyromazine

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 : ≥ 1.8 mg/mL (~10.83 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.

---

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).

View More

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)

---

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).

View More

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

---

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.

---

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