Absorption, Distribution and Excretion
The primary route of excretion for low-dose (0.5 mg/kg) radiolabeled simazine was urine, while for high-dose (200 mg/kg) it was feces. Significant radioactive residues remained in rat tissues for extended periods. Results showed that 94% to 99% of the radioactive material was cleared within 48 to 72 hours, with a half-life of 9 to 15 hours. The clearance half-life of the remaining radioactive material was 21 to 32 hours. The heart, lungs, spleen, kidneys, and liver appeared to be the main sites of radioactive retention. However, erythrocytes showed higher enrichment of radioactive material than other tissues, likely due to the high affinity of the triazine ring for cysteine residues in hemoglobin, a phenomenon seemingly unique to rodents. In a skin absorption study, male Charles River Sprague-Dawley rats were administered 0.1 mg/cm² and 0.5 mg/cm² of 14C-simazine (using two vials: radiochemical purity: 98% for the low-dose group and 96% for the high-dose group; specific activity: 28.0 μCi/mg and 2.4 μCi/mg, respectively). Four animals were treated in each dose group, and the treated skin area and surrounding area were then covered with a protective device. The animals were then placed in metabolic cages until the end of the exposure. Animals were sacrificed at 2, 4, 10, or 24 hours post-exposure. After sacrifice, the exposed area was washed with liquid dopamine and water, and the treated skin area and surrounding skin (skin covered by the protective device) were collected. Radioactive analysis was performed on the soap wash, skin samples, urine, feces, blood, cadavers, cage washing solution, and other relevant samples. Skin absorption was less than 1% at all doses and time points. However, 11-20% of simazine residues remained on the skin in the low-dose group and 31-41% in the high-dose group, suggesting potential absorption. Simazine is primarily absorbed through plant roots, with minimal penetration through leaves. Its adhesion is low, and it is easily washed away from leaves by rainwater. After root absorption, simazine is transported upwards in the xylem and accumulates in the apical meristem and leaves. Simazine is readily absorbed and distributed in spruce seedlings. Simazine degrades into hydroxy analog metabolites in roots and stems, but is not detected in needles.
For more complete data on absorption, distribution, and excretion of simazine (8 species), please visit the HSDB records page.

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Metabolism/Metabolites
Simazine is metabolized and excreted within 72 hours of administration to rats. The majority of excreted simazine residues were detected in urine (49%) and feces (41%), with a small amount excreted as carbon dioxide via respiration. Simazine is metabolized in rats via the removal of the alkyl side chain and triazine ring, which is then bound to glutathione S-transferase. The monodealkylated compound 2-chloro-4-ethylamino-6-amino-triazine and the didealkylated compound diaminochlorotriazine (DACT) are the main degradation products of simazine in rats, respectively. Additionally, conjugated thiouric acid esters of hydroxysimazine were also detected. The metabolic pathway in plants is similar to that in rats. Plant metabolism occurs through several competing pathways. One major pathway involves the cleavage of the N-ethyl group, leaving a naked amino group attached to the ring. First, one ethyl group is lost, then both ethyl groups are lost, ultimately generating diaminochlorotriazine (DACT). DACT can then proceed, with the chlorine atom being replaced by proline, which is linked to the triazine ring via the proline nitrogen atom. In another major metabolic pathway, the chlorine atom on simazine is replaced by a hydroxyl group to generate hydroxysimazine, which can then generate diaminohydroxytriazine, a hydroxy analog of DACT, by losing an ethyl group. Diaminohydroxytriazine can then have one or two amino groups replaced by hydroxyl groups, ultimately producing cyanuric acid. Alternatively, the chlorine in simazine can be replaced by glutathione and eventually cleaved through various intermediate conjugates to produce aminosimazine, which may then lose one or two ethyl groups. The metabolic pathway in livestock is similar to that in plants and rats, with one exception: animals do not directly metabolize simazine to hydroxysimazine, but they may ingest hydroxysimazine through feed. Several studies have investigated the metabolism of simazine in livestock and poultry. In animals, simazine residues typically tend to lose one or two ethyl groups to form chlorinated metabolites, or the chlorine group is replaced by a hydroxyl group, followed by the loss of one or two ethyl groups. Feeding hydroxysimazine results in the hydroxy metabolite losing one or two ethyl groups, thus forming a glutathione conjugate. Hydroxysimazine can also form glutathione conjugates. Ruminants. A goat fed [14C]simazine for 10 consecutive days at a dose equivalent to 5 ppm (12 times the maximum theoretical dietary load (MTDB)) plateaued at 0.10 ppm in milk on day 5. TRR in tissue samples collected 48 hours after the last administration ranged from 0.02 ppm in fat to 0.93 ppm in liver. After the milk residues plateaued at 2% of the administered dose, the major metabolite in milk (23.5% of the TRR) was identified as diaminochlorotriazine, along with trace amounts of simazine (0.25% of the TRR) and desethylsimazine (1.3% of the TRR). Metabolites in the aqueous phase and casein hydrolysate were identified as amino acid and peptide conjugates of simazine. In another study, a goat fed [14C]simazine for 7 consecutive days at a dose equivalent to 50 ppm (119 times) of the dietary intake. During the 7-day dosing period, the TRR concentration in breast milk ranged from 0.71 to 1.07 ppm. In tissues collected within 24 hours of the last dose, the TRR concentrations were 0.06–0.10 ppm in fat, 0.69–0.71 ppm in muscle, 3.03 ppm in kidney, 2.59 ppm in brain tissue, 0.78 ppm in heart, and 3.24 ppm in liver. The table below lists the TRR components identified in breast milk and tissues. Simazine accounted for 3.8–10.8% of the TRR in tissues but was not detected in breast milk. DACT was the major metabolite in breast milk (30.3% of total reference intake), 4.2–5.2% of total reference intake in liver and kidney, and 13.8% in muscle. Deethylsimazine was detected in liver and kidney (10.7–16.9% of total reference intake) but was not detected in muscle or breast milk. Glutathione conjugates of deethylsimazine were also preliminarily identified in the kidneys (18.7% of total reference intake) and breast milk (14.9% of total reference intake). Deethylhydroxysimazine accounted for 32.9% of the radionuclide clearance (TRR) in the liver, but this is likely a product of proteolysis. For more complete metabolite/metabolite data on simazine (13 metabolites in total), please visit the HSDB record page. Known human metabolites of simazine include N-deethylsimazine. Biological half-life results showed that in rats, 94% to 99% of the radioactive material was eliminated within 48 to 72 hours, with a half-life of 9 to 15 hours. The elimination half-life of the remaining radioactive material was 21 to 32 hours.

According to the U.S. Environmental Protection Agency (EPA), simazine can cause developmental toxicity and female reproductive toxicity. Simazine is a white to off-white crystalline powder. (NTP, 1992) Simazine is a diamino-1,3,5-triazine, namely N,N'-diethyl-1,3,5-triazine-2,4-diamine, with chlorine substituted at the 6-position. It is a herbicide, exogenous substance, and environmental pollutant. It is both chloro-1,3,5-triazine and diamino-1,3,5-triazine. Simazine belongs to the triazine class of herbicides. This compound is used to control broadleaf weeds and annual grass weeds. A triazine herbicide.
Mechanism of Action
The potential mechanisms underlying neuroendocrine and related changes induced by atrazine and similar triazine compounds involve dysregulation of the hypothalamic-pituitary-gonadal axis (HPG axis)... Specifically, various triazine compounds can alter the levels of hypothalamic gonadotropin-releasing hormone (GnRH) and catecholamines (dopamine and norepinephrine). In humans and rodents, hypothalamic GnRH controls the secretion of pituitary hormones, namely luteinizing hormone (LH) and prolactin (PRL). Changes in GnRH and catecholamine levels, in turn, lead to alterations in pituitary LH and PRL secretion. The hypothalamic-pituitary axis is involved in the development of the reproductive system and maintains its function in adulthood. Furthermore, reproductive hormones regulate the function of many other metabolic processes, such as bone formation, the immune system, the central nervous system (CNS), and the cardiovascular system.
Multiple species exhibit neuroendocrine effects following subchronic or chronic exposure to simazine, resulting in reproductive and developmental consequences considered relevant to humans. These effects are biomarkers of neuroendocrine toxicity mechanisms also present in several other structurally related chlorotriazine compounds, including atrazine, promethazine, and three chlorodegradants—desopropyl atrazine (DIA), deethyl atrazine (DEA), and iminochlorotriazine (DACT)—the former and the latter being produced by the degradation of simazine. These six compounds disrupt the hypothalamic-pituitary-gonadal axis (HPG axis) (part of the central nervous system), leading to cascade changes in hormone levels and developmental delays. These neuroendocrine effects are considered the primary toxicological effects of simazine. All subchronic and chronic exposure scenarios require monitoring, including dietary, residential, and occupational risks from food and drinking water. The two chlorodegradants of simazine, DIA and DACT, are considered to have the same toxicity as the parent compound due to their shared neuroendocrine toxicity mechanism. Another degradation product, hydroxysimazine, has been discovered. Based on toxicological data of hydroxyatrazine, a metabolite similar to atrazine, its toxicological characteristics are expected to differ from simazine. Simazine has been grouped with several structurally related chlorotriazine compounds (such as atrazine, promethazine, and three chlorotriazine degradation products shared by atrazine, simazine, and promethazine) because they all share a common toxic mechanism that interferes with the hypothalamic-pituitary-gonadal axis (HPG axis). Due to their shared toxic mechanism, exposure to simazine, similar to atrazine, is also expected to lead to reproductive and developmental effects and consequences that are considered relevant to humans. ...This mechanism involves central nervous system (CNS) toxicity, specifically alterations in neurotransmitters and neuropeptides at the hypothalamic level, leading to a cascade of hormonal changes, such as inhibition of the pre-ovulatory surge in luteinizing hormone, resulting in prolonged estrus in adult female rats (as confirmed by both atrazine and simazine), and developmental delays, specifically delayed vaginal opening and prepuce separation in developing rats (studied in atrazine but not in simazine). ...This CNS toxicity mechanism also leads to mammary tumors in female Sprague-Dawley rats exposed to simazine and atrazine; however, the cascade of events leading to tumor formation in this particular rat strain is not considered likely to occur in humans. Therefore, atrazine is classified as "probably not carcinogenic." In humans, multiple studies have shown that the ability of triazine compounds to interfere with photosynthesis is the reason for their biological activity. Simazine consumes carbohydrates by inhibiting sugar formation. Triazine compounds inhibit the Hill reaction, the process by which chloroplasts in some plants produce oxygen in the presence of light and iron salts. For more complete data on the mechanisms of action of simazine (7 types), 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.)