Absorption, Distribution and Excretion
At the low dose (0.5 mg/kg) of radiolabeled simazine, the principal route of excretion was via the urine, however, at the higher dose (200 mg/kg) the principal route of excretion was via the feces. Significant radioactive residues remained in the tissues of the rat for extended periods of time. Results indicate that 94 to 99% of the elimination of radioactive material occurred within 48 to 72 hours with a half-life of 9 to 15 hours. Elimination of the remaining radioactivity exhibited 21- to 32-hour half-life values. Heart, lung, spleen, kidney, and liver appear to be principal sites of retention of radioactivity. However, erythrocytes concentrated radioactivity to higher levels than did other tissues, perhaps due to high affinity of the triazine ring for cysteine residues of hemoglobin, a phenomenon apparently unique to rodent species.
In a dermal absorption study, male Charles River Sprague-Dawley rats received either 0.1, 0.5 mg/sq cm of 14C-simazine ( two vials used: radiochemical purity: 98% for the low dose and 96%, for the high dose, specific activity: 28.0 uCi/mg and 2.4 uCi/mg). Four animals per dose were treated and then the treated area of skin and the surrounding area were covered with a protective device. Animals were then placed in metabolism cages for the duration of the exposure period. Either 2, 4, 10 or 24 hrs following exposure animals were sacrificed. Following sacrifice the exposure sites were washed with liquid Dove and water and both the treated area of skin and skin surrounding the treated area (the skin covered by the protective device) were collected. The soap and water rinses, the skin samples, urine, feces, blood, carcass, cage wash, and other relevant samples were all analyzed for radioactivity. Dermal absorption was less than 1% at both doses and all time points. However, 11-20% of the low dose and 31-41% of the high dose remained on the skin and is thus potentially absorbable.
/Simazine is/ absorbed mostly through plant roots with little or no foliar penetration. It has low adhering ability and is readily washed from foliage by rain. Following root absorption it is translocated acropetally in the xylem, accumulating in apical meristems and leaves of plants.
Simazine was readily absorbed and distributed in spruce seedlings. Degradation of simazine took place in roots and stem to the hydroxy analog... metabolites, but no simazine, were observed in needles.
For more Absorption, Distribution and Excretion (Complete) data for SIMAZINE (8 total), please visit the HSDB record page.

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Metabolism / Metabolites
Simazine is metabolized and excreted in the rat within 72 hours of dosing. Most of the excreted simazine residues were detected in the urine (49%) and feces (41%) with minor amounts respired as CO2. Simazine is metabolized in the rat through the removal of alkyl side chains and conjugation of the triazine ring with glutathione-S-transferase. The mono- and di-dealkylated compounds, 2-chloro-4-ethylamino- 6-amino-s-triazine and diaminochlorotriazine (DACT), respectively, are the major rat degradates. Conjugated mercapturates of hydroxy simazine were also detected.
The metabolic pathway in plants is similar to that in rats. Plant metabolism occurs via several competing routes. In one major route the N-ethyl groups are cleaved leaving the bare amine attached to the ring. First one ethyl group is lost, then both are lost, ultimately leaving diaminochlorotriazine (DACT). DACT can subsequently proceed to replacement of the chlorine with a proline group, which is attached to the triazine via the proline nitrogen. In a second major route of metabolism, the chloro group on simazine is replaced by a hydroxy group to hydroxysimazine, which can proceed by loss of the ethyl groups to diaminohydroxytriazine, the hydroxy equivalent of DACT. The diaminohydroxytriazine can then under go replacement of one or both amines by hydroxy groups ultimately leading to cyanuric acid. Alternatively, the chlorine in simazine can be replaced by glutathione and through a variety of intermediate conjugates can be eventually lysed to NH2-simazine, and then presumably loss of one or both ethyl groups.
The metabolic pathway in livestock is also similar to that in plants and rats with one exception; animals do not metabolize simazine directly to hydroxy-simazine, but animals may receive hydroxy simazine through feeds. Several studies have been performed on the metabolism of simazine in livestock and poultry. In animals, in general, simazine residues tend to lose one or both ethyl groups to form the chloro-metabolites or to replace the chloro- group with a hydroxygroup and then to lose one of both ethyl groups. Feeding with hydroxy-simazine leads to formation, through loss of one or both ethyl groups of hydroxy-metabolites only. A glutathione conjugate is also formed from the hydroxy-simazine.
Ruminants. In a goat dosed for 10 days with [14C]simazine at a dose equivalent of 5 ppm [12x the maximum theoretical dietary burden (MTDB)], total radioactive residue (TRR) in milk plateaued by Day 5 at 0.10 ppm. TRR in tissue samples collected 48 hours after the final dose ranged from 0.02 ppm in fat to 0.93 ppm in liver. After residues plateaued in milk (at 2% of the administered dose), the major metabolite in milk (23.5% TRR) was identified as diaminochlorotriazine, along with minor amounts (0.25% TRR) of simazine and of desethylsimazine (1.3% TRR). Metabolites in the aqueous fraction and the hydrolysate of the casein fraction were characterized as amino acid and peptide conjugates of simazine. In another study, a goat was dosed for 7 days with [14C]simazine at a dose equivalent to 50 ppm in the diet (119x). TRR in milk ranged from 0.71-1.07 ppm during the 7-day dosing period. TRR in tissues collected within 24 hours of the final dose were 0.06-0.10 ppm in fat, 0.69-0.71 ppm in muscle, 3.03 ppm in kidneys, 2.59 ppm in brain, 0.78 ppm in heart, and 3.24 ppm in liver. Components of the TRR identified in milk and tissues are listed in the table below. Simazine accounted for 3.8-10.8% of the TRR in tissues, but was not detected in milk. DACT was the major metabolite in milk (30.3% TRR) and accounted for 4.2-5.2% TRR in liver and kidney, and 13.8% TRR in muscle. Desethylsimazine was detected in liver and kidney at 10.7-16.9% TRR, but was not detected in muscle and milk. A glutathione conjugate of desethylsimazine was also tentatively identified in kidney (18.7% TRR) and milk (14.9% TRR). Desethylhydroxy-simazine constituted up to 32.9% of the TRR in liver, but may have been an artifact of proteolysis.
For more Metabolism/Metabolites (Complete) data for SIMAZINE (13 total), please visit the HSDB record page.
Simazine has known human metabolites that include N-Desethylsimazine.

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Biological Half-Life
Results indicate that /in rats/ 94 to 99% of the elimination of radioactive material occurred within 48 to 72 hours with a half-life of 9 to 15 hours. Elimination of the remaining radioactivity exhibited 21- to 32-hour half-life values.

Simazine can cause developmental toxicity and female reproductive toxicity according to The Environmental Protection Agency (EPA).
Simazine is a white to off-white crystalline powder. (NTP, 1992)
Simazine is a diamino-1,3,5-triazine that is N,N'-diethyl-1,3,5-triazine-2,4-diamine substituted by a chloro group at position 6. It has a role as a herbicide, a xenobiotic and an environmental contaminant. It is a chloro-1,3,5-triazine and a diamino-1,3,5-triazine.
Simazine is a herbicide of the triazine class. The compound is used to control broad-leaved weeds and annual grasses.
A triazine herbicide.

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Mechanism of Action
The underlying mechanism of the neuroendocrine and neuroendocrine-related changes associated with atrazine and similar triazines involves the disruption of the hypothalamic-pituitary-gonadal (HPG) axis .... Specifically, several triazines can alter hypothalamic gonadotrophin-releasing hormone (GnRH) and catecholamine (dopamine and norepinephrine) levels. In both humans and rats, hypothalamic GnRH controls pituitary hormone secretion, i.e., LH and PRL. The result of changes in GnRH and catecholamines in turn leads to alterations in pituitary LH and PRL secretion. The hypothalamic-pituitary axis is involved in the development of the reproductive system, and its maintenance and functioning in adulthood. Additionally, reproductive hormones modulate the function of numerous other metabolic processes (i.e., bone formation, and immune, central nervous system (CNS) and cardiovascular systems.
After subchronic and chronic exposure to simazine, a variety of species were shown to exhibit neuroendocrine effects resulting in both reproductive and developmental consequences that are considered relevant to humans. These effects are biomarkers of a neuroendocrine mechanism of toxicity that is shared by several other structurally-related chlorinated triazines including atrazine, propazine, and three chlorinated degradates -des-isopropyl atrazine or DIA, and des-ethyl atrazine or DEA, and iaminochlorotriazine or DACT - the first and last of which can result from the degradation of simazine. These six compounds disrupt the hypothalamic-pituitary-gonadal (HPG) axis, part of the central nervous system, causing cascading changes to hormone levels and developmental delays. These neuroendocrine effects are considered the primary toxicological effects of regulatory concern for all subchronic and chronic exposure scenarios including dietary risk from food and drinking water, residential risk, and occupational risk. Simazine's two chlorinated degradates, DIA and DACT, are considered to have toxicity equal to the parent compound in respect to their common neuroendocrine mechanism of toxicity. Another degradate, hydroxy-simazine, was identified, which is expected to have a different toxicological profile from simazine based on the toxicological data available for an analogous metabolite for atrazine, hydroxy-atrazine.
Simazine has been grouped with several structurally-related, chlorinated triazines (e.g., atrazine, propazine, and 3 chlorotriazine degradates common to atrazine, simazine and propazine) on the basis of a common mechanism of toxicity for disruption of the hypothalamic-pituitary-gonadal (HPG) axis. As a result of their common mechanism of toxicity, exposure to simazine, like exposure to atrazine, results in reproductive and developmental effects and consequences that are considered relevant to humans. ...This mechanism involves a central nervous system (CNS) toxicity, specifically, neurotransmitter and neuropeptide alterations at the level of the hypothalamus, which cause cascading changes to hormone levels, e.g., suppression of the luteinizing hormone surge prior to ovulation resulting in prolonged estrus in adult female rats (demonstrated with atrazine and simazine), and developmental delays, i.e., delayed vaginal opening and preputial separation in developing rats (studied in atrazine but not simazine). ...This CNS mechanism of toxicity also results in mammary tumors specific to female Sprague- Dawley rats exposed to simazine and atrazine; however, the particular cascade of events leading to tumor formation in this specific strain of rat is not considered to be operative in humans. Consequently, atrazine has been classified as "Not Likely to be Carcinogenic to Humans."
Various investigations indicate that the ability of triazines to interfere with photosynthesis is responsible for their biological activity. Simazine depletes carbohydrate by inhibiting the formation of sugars. The triazines inhibit the Hill reaction, ie, the formation of oxygen by chloroplasts of certain plants in the presence of light & ferric salts.
For more Mechanism of Action (Complete) data for SIMAZINE (7 total), please visit the HSDB record page.

C7H12CLN5

201.66

201.078

122-34-9

Simazine-d10;220621-39-6

5216

White solid
Colorless powder
Crystals from ethanol or methyl Cellosolve

1.4±0.1 g/cm3

268.9±23.0 °C at 760 mmHg

225°C

116.4±22.6 °C

0.0±0.6 mmHg at 25°C

1.617

1.19

2

5

4

13

131

0

CCN=C1NC(=NC(=NCC)N1)Cl

ODCWYMIRDDJXKW-UHFFFAOYSA-N

InChI=1S/C7H12ClN5/c1-3-9-6-11-5(8)12-7(13-6)10-4-2/h3-4H2,1-2H3,(H2,9,10,11,12,13)

s-Triazine, 2-chloro-4,6-bis(ethylamino)-

Simazine Aquazine Tafazine RadoconHerbex

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 : ~16.67 mg/mL (~82.66 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.)