Absorption, Distribution and Excretion
Following oral administration of (14)C-atrazine to rats, its absorption, biotransformation, and excretion were rapid. Within 24 hours, 52% of the (14)C in the ring-labeled atrazine was excreted in the urine and 18% in the feces; within 72 hours, elimination was almost complete when 6% was excreted in the urine, 14% in the feces, and less than 2% remained in the carcass. After 6 hours, the concentrations of (14)C-atrazine in the organs of absorption, biotransformation, and excretion (stomach, liver, kidney), as well as in the spleen and lungs, reached peak levels, but these concentrations decreased over time, while the blood concentration remained stable within 72 hours. The excretion of atrazine was studied using compounds labeled with (14)C-atrazine on the ring or on either the ethyl or isopropyl side chain. Forty-eight hours after oral administration to six male and six female Sprague Dawley rats, 57.6% of the ring-labeled activity was excreted in urine and 32.1% in feces (89.7% of the total dose). However, when the fed compound was labeled on its side chain, most (14)C was excreted as carbon dioxide in exhaled breath. When the isopropyl side chain of the fed compound was labeled, 48 hours later, 41.9% of the label was excreted in exhaled breath, 20% in urine, 2% in feces, and 7% remained in the carcass (total 70.9%). When the ethyl side chain was labeled, 18.1% of the label was excreted as carbon dioxide, 45% in urine, 5% in feces, and 9% remained in the carcass (total 77.1%). After 72 hours, the total recovery rate for both side-chain labeled compounds was approximately 88%.
Ringed atrazine was orally administered to male and female Sprague Dawley rats, and the distribution of the marker in tissues was measured at 6, 48, and 72 hours post-administration. At 6 hours post-administration, the radioactive material was most significantly distributed in the kidneys, followed by the liver, spleen, blood, lungs, fat, carcass, brain, and muscle. At 72 hours post-administration, the concentration of radioactive material in the blood remained relatively stable, while the concentration in all other tissues rapidly decreased to <0.1% of the tissue dose per gram.
…Most of the radioactive material was rapidly excreted through the urine (70%) and feces (20%) of lactating goats, while in hens it was primarily excreted through feces (90%).
The radioactive material is effectively absorbed by the intestines and is presumably also absorbed through the skin and lungs. /Urea, uracil, and triazine herbicides/

---

Metabolism/Metabolites
The V79 Chinese hamster cell line has been genetically engineered to stably express human NADPH-cytochrome P450 oxidoreductase (CYPOR), or simultaneously express NADPH-cytochrome P450 oxidoreductase and human cytochrome P450 1A2 (CYP1A2). Immunoblot analysis showed that the expression level of cytochrome P450 1A2 in the latter cell line was the same as that in the previously constructed V79 cell line expressing only cytochrome P450 1A2. Heterologous expression of NADPH-cytochrome P450 oxidoreductase in V79 cells leads to increased sensitivity to quinone cytotoxins (e.g., ...). Duroquinone and menadione exert their toxicity primarily through the generation of reactive oxygen species during redox cycles. This study characterized the metabolic properties of cell lines simultaneously expressing NADPH-cytochrome P450 oxidoreductase and cytochrome P450 1A2, focusing on the dealkylation and deethylation of 7-alkoxyhalothrin, and the sulfoxide reaction of triazine derivatives amitriptyline and tert-butylene, and compared them with cell lines expressing only cytochrome P450 1A2. The results showed that enhanced NADPH-cytochrome P450 oxidoreductase activity impaired cytochrome P450 1A2-dependent fluorescent halothrin assays, possibly due to the conversion of 8-alkoxyhalothrin and halothrin to their single-electron reduced semiquinone imine forms. The metabolism of cytochrome P450 1A2-dependent triazine derivatives amitriptyline and tert-butylene was moderately enhanced by increased NADPH-cytochrome P450 oxidoreductase activity. Interestingly, compared with N-deethylation, overexpression of NADPH-cytochrome P450 oxidoreductase increased sulfoxide activity by 2-3 times, while N-deethylation only increased it by 1.3-1.9 times. Therefore, the level of NADPH-cytochrome P450 oxidoreductase not only affects the activity of cytochrome P450 1A2, but also the relative proportions of various metabolites in the cytochrome P450 1A2-specific metabolite profile. Generally, tolerant plants can metabolize these substances, while plants sensitive to non-toxic substances such as hydroxyl or dealkylated derivatives metabolize them to a lower degree. Hydroxyatrazine is likely the first metabolite, and degradation within the plant is the main protective mechanism. (14) C-labeled atrazine was orally administered to six male and six female Sprague Dawley rats. When the label was located on the isopropyl side chain, 41.9% of the label appeared as CO2. When the label was located on the ethyl side chain, 18.1% of the label appeared as CO2. This indicates that the side chain is extensively metabolized. When the compound was uniformly labeled with carbon-14 on the ring and administered orally to rats, 58% of the compound was excreted in the urine, but it has not been determined whether the excreted compound was the original compound or a metabolite. The roles of P450 and flavin-containing monooxygenases in the sulfonation reactions of four sulfur-containing pesticides (atrazine, terbufos, promethazine, and methomyl) were investigated using human liver microsomes. All four reactions were confirmed to be primarily catalyzed by cytochrome P450. For more complete data on the metabolism/metabolites of atrazine (a total of 8 metabolites), please visit the HSDB record page. Known human metabolites of atrazine include deethylatrazine and deisopropylatrazine.

Toxicity Summary
Identification and Uses: Atrazine is a white powder. It is used as a pre- and post-emergence herbicide for corn, popcorn, sugarcane, and pineapple in the field. Human Exposure and Toxicity: Reports of illness caused by atrazine are relatively few. Between 1993 and 2001, poison control centers received four reports of atrazine product exposure. Of these four cases, two (both adults) had mild symptoms. One patient was treated at a medical facility and did not require hospitalization; the other reported diarrhea and lethargy/sluggishness. No other cases were reported in other poisoning databases. Animal Studies: A group of rats exposed to atrazine aerosol at concentrations >27 mg/L for 4 hours did not experience any deaths or adverse reactions. Undiluted atrazine is slightly irritating to the eyes and skin of rabbits. Poisoned rats exhibited symptoms such as ataxia, dyspnea, muscle weakness, salivation, and loss of reflexes. Rats fed atrazine at concentrations of 500 ppm or higher for two consecutive years showed only weight gain, while no symptoms were observed at a concentration of 50 ppm. Rats and mice survived after two consecutive years of feeding at concentrations up to 2000 ppm. In a one-year feeding study, dogs showed weight gain at concentrations of 2000 ppm or higher, while no symptoms were observed at a concentration of 200 ppm. No reproductive disorders were observed in two generations of rats fed at concentrations of 20, 200, or 2000 ppm. At the two higher concentration levels, both parental and offspring weight decreased. No teratogenic effects were observed in rats receiving atrazine doses up to 250 mg/kg. In another rat study, rats treated with amitriptyline (orally 30.6 mg/kg on days 5 to 15 of gestation) had an increased rate of skeletal malformations in their offspring. Post-implantation mortality was increased, and fetal weight decreased. Amitriptyline has no genetic activity in Salmonella and Saccharomyces cerevisiae. No chromosome breakage was observed in amitriptyline tests on Chinese hamster ovary cell cultures, and the results were negative in DNA repair assays of cultured hepatocytes. During the immune response in mice, oral administration of near-lethal doses of amitriptyline suppresses humoral immune responses. Furthermore, oral administration of sufficient doses of amitriptyline at or before immunization also suppresses humoral immune function. Ecotoxicity studies: Amitriptyline is mildly toxic to mammals under acute oral exposure; growth retardation was observed after chronic exposure. Atrazine is mildly to moderately toxic to freshwater fish and invertebrates, and moderately toxic to estuarine/marine fish and invertebrates (acute exposure). Long-term exposure leads to decreased fertility in both freshwater fish and freshwater invertebrates. Atrazine is toxic to terrestrial plants as a herbicide.

---

Toxicity Data
LC50 (Rat)> 5,030 mg/m3/

---

Non-human Toxicity Values
LC50 Rat (Albino) Inhalation> 27 mg/L/4 hours
LD50 Rat Oral> 3,170 mg/kg.
LD50 Rat Oral 1100 mg/kg /Technical/
LD50 Rat (Male) Oral 1356 (1164-1581) mg/kg
For more complete non-human toxicity data (out of 15) for atrazine, please visit the HSDB records page.

Crystals. Melting point 88-89 °C (190-192 °F). Used as a herbicide. Atrazine is a methylthio-1,3,5-triazine compound, consisting of 2-(methylthio)-1,3,5-triazine with ethylamino and isopropylamino groups substituted at positions 4 and 6, respectively. It is both a herbicide and an environmental pollutant. It is a diamino-1,3,5-triazine and methylthio-1,3,5-triazine compound. Atrazine belongs to the triazine class of compounds and is a herbicide that inhibits photosynthesis and other enzymatic processes. It is used to control broadleaf weeds and annual grasses in pineapple, sugarcane, and banana fields. It is also used for weed control in corn and potato crops. Additionally, it can be used as a desiccant for dried beans and potatoes. The U.S. Environmental Protection Agency classifies it as Toxicity Group III, meaning mild toxicity. Symptoms of acute high-dose exposure include nausea, vomiting, diarrhea, muscle weakness, and salivation.

---

Mechanism of Action
Herbic Mechanism of Action: Like other triazine herbicides, atrazine inhibits photosynthesis and other enzymatic processes. It is a selective systemic herbicide that is absorbed by leaves and roots, transported upwards in the xylem, and accumulates in the apical meristem.
...Their primary mode of action appears to be related to carbohydrate metabolism. Chlorothiazine herbicides inhibit starch accumulation by blocking sugar production. Methoxy and methylthiotriazine herbicides also exhibit similar effects. S-triazine herbicides have been reported to affect the tricarboxylic acid cycle by activating phosphophenylpyruvate carboxylase, leading to the consumption of sucrose and glyceric acid, and the production of aspartic acid and malic acid. /S-Triazines/
Since yellowing is the primary symptom of triazine herbicides' effects on plants, it is expected that they will interfere with carbon dioxide assimilation and sugar production. Studies showing inhibition of the Hill reaction confirm this. /Triazines/
The mechanism of action of 1,3,5-triazine herbicides is to inhibit photosynthesis by interfering with the light reaction and blocking electron transport. /1,3,5-Triazines, from the table/

C9H17N5S

227.33

227.12

834-12-8

Ametryn-13C,d3

13263

White powder
Colorless crystals

1.2±0.1 g/cm3

396.4±25.0 °C at 760 mmHg

84-85°C

193.5±23.2 °C

0.0±0.9 mmHg at 25°C

1.556

3.09

2

6

5

15

178

0

N1C(NCC)=NC(NC(C)C)=NC=1SC

RQVYBGPQFYCBGX-UHFFFAOYSA-N

InChI=1S/C9H17N5S/c1-5-10-7-12-8(11-6(2)3)14-9(13-7)15-4/h6H,5H2,1-4H3,(H2,10,11,12,13,14)

4-N-ethyl-6-methylsulfanyl-2-N-propan-2-yl-1,3,5-triazine-2,4-diamine

Ametryn GesapaxDoruplant GardopaxCemerin Crisatrine Topazol

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 : ~125 mg/mL (~549.86 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (9.15 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 20.8 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.

---

Solubility in Formulation 2: ≥ 2.08 mg/mL (9.15 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 20.8 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.

---

View More

Solubility in Formulation 3: ≥ 2.08 mg/mL (9.15 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

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