Absorption, Distribution and Excretion
Absorption, biotransformation, and excretion of (14)C-ametryne was rapid after oral dose to rat. In 24 hr, 52% of (14)C from ring labelled ametryne was excreted in urine and 18% in feces, and within 72 hr elimination was almost complete when further 6% had been excreted in urine, 14% in feces, and <2% remained in carcass. After 6 hr, levels of (14)C-ametryne were maximal in organs of absorption, biotransformation, and excretion by the stomach, liver, and kidneys, and also in spleen and lung, but these levels decreased with time although blood levels remained constant for 72 hr.
The excretion of ametryn utilizing uniformly labeled compound with (14)C-ametryn in the ring or in the ethyl or isopropyl side chains. Forty eight hours after oral dosing of six male and six female Sprague Dawley rats, 57.6% of the ring labeled activity had been excreted in the urine and 32.1% in the feces (total 89.7% of dose). When the fed compound was labeled in the side chains, however, much of the (14)C was excreted in expired air as carbon dioxide. When the fed compound was labeled in the isopropyl side chain, rats excreted 41.9% of the label in expired air, 20% in the urine, 2% in the feces, and 7% remained in the carcass (total 70.9%) at 48 hours. When the ethyl side chain contained the label, 18.1% of the label was excreted as carbon dioxide, 45% in the urine, 5% in the feces and 9% remained in the carcass (total 77.1% of dose). After 72 hours, total recovery was approximately 88% for both of the side chain labeled compounds.
Ring labeled ametryn /was administered/ orally to male and female Sprague Dawley rats and measured distribution of label in tissues at 6, 48 and 72 hours after dosing. Tissue distribution at 6 hours was greatest in kidney, followed by liver, spleen, blood, lung, fat, carcass, brain, and muscle. Blood levels remained relatively constant for 72 hours after dosing, while all other tissue levels dropped rapidly to <0.1% of dose per gram of tissue.
... Most of the radioactive dose was excreted rapidly by lactating goats in urine (70%) and feces (20%) or predominantly in excreta (90%) by hens.
They are efficiently absorbed from intestine, and presumably there is some absorption across the skin and lung. /Urea-, uracil- and triazine-based herbicides/

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Metabolism / Metabolites
V79 Chinese hamster cell lines were genetically engineered for the stable expression of human NADPH-cytochrome P450 oxidoreductase (CYPOR) alone or for the combined expression of NADPH-cytochrome P450 oxidoreductase and human cytochrome P450 1A2 (CYP1A2). As determined by immunoblotting, the expression level of cytochrome P450 1A2 in the latter cell line was found to be the same as in a previously constructed V79 cell line expressing cytochrome P450 1A2 only. The heterologous expression of NADPH-cytochrome P450 oxidoreductase in V79 cells resulted in increased sensitivity to quinone-type cytotoxins, eg. duroquinone and menadione, that exert their toxicity primarily through the production of reactive oxygen species during redox cycling. The metabolic properties of the cell line expressing both NADPH-cytochrome P450 oxidoreductase and cytochrome P450 1A2 were characterized regarding dealkylation and deethylation of 7-alkoxyresorufins and sulfoxidation of the triazine derivatives ametryne and terbutryne, in comparison with the cell line expressing only cytochrome P450 1A2. Increased NADPH-cytochrome P450 oxidoreductase activity impaired the cytochrome P450 1A2-dependent fluorometric resorufin assay, presumably by conversion of the 8-alkoxyresorufins and resorufin to their one-electron-reduced semiquinoneimine forms. The cytochrome P450 1A2-dependent metabolism of the triazine derivatives ametryne and terbutryne was moderately enhanced by increased NADPH-cytochrome P450 oxidoreductase activity. Interestingly, with NADPH-cytochrome P450 oxidoreductase overexpression sulfoxidation was increased 2-3-fold, compared with N-deethylation, with a 1.3-1.9-fold increase. Thus, the level of NADPH-cytochrome P450 oxidoreductase not only had an influence on cytochrome P450 1A2 activity rates but also affected the relative proportions of metabolites in cytochrome P450 1A2-specific metabolite profiles.
Usually metabolized by tolerant plants, & to lesser extent by sensitive plants to nontoxic substances such as hydroxyl or dealkylated derivatives. It appears likely that hydroxy-atrazine is the first metabolite, & that degradation within plants is the major protective mechanism.
(14)C-labeled ametryn was administered orally to groups of six male and six female Sprague Dawley rats. When the label was in the isopropyl side chain, 41.9% of the label appeared as CO2. When the label was in the ethyl side chain, 18.1% of the label appeared as CO2. This indicated that the side chains were extensively metabolized. When the ring was uniformly labeled with carbon-14 and the compound fed orally to rats, 58% was excreted in the urine but it was not determined whether excretion of the original compound or metabolites had occurred.
... The participation of P450 and flavin-containing monooxygenase in the sulfoxidation of four sulfur containing pesticides, ametryne; terbutryne, prometryne and methiocarb was investigated using human liver microsomes. All four reactions were demonstrated to be catalyzed predominantly by cytochrome P450.
For more Metabolism/Metabolites (Complete) data for Ametryne (8 total), please visit the HSDB record page.
Ametryn has known human metabolites that include Desethylametryne and Deisopropylametryne.

Toxicity Summary
IDENTIFICATION AND USE: Ametryne is a white powder. It is used as pre-emergence and post-emergence herbicide for field corn, popcorn, sugarcane, and pineapple. HUMAN EXPOSURE AND TOXICITY: Relatively few incidents of illness have been reported due to ametryne. Four exposures to ametryne products were reported to Poison Control Centers from 1993 through 2001. Two of the four cases, all adults, involved minor symptoms. One of the cases was seen in a health care facility and was not hospitalized and another case reported diarrhea and drowsiness/lethargy. There were no other reports of incidences in the other poisoning databases. ANIMAL STUDIES: No deaths were recorded or untoward effects noted among a group of rats exposed to ametryne aerosol at >27 mg/L during 4 hr exposure period. Undiluted ametryne was mildly irritating to eye of rabbit. Slight irritant to skin of rabbits. Ataxia, dyspnea, muscular weakness, salivation, and loss of reflexes occurred in poisoned rats. Body weight gain effects in rats fed 500 ppm or greater for 2 years were the only signs produced, and no effects were seen at 50 ppm. Rats and mice survived 2-year feeding of as much as 2000 ppm. In dogs, body weight effects were seen at 2000 ppm or greater in a 1-year feeding study, but no effects occurred at 200 ppm. Ametryne produced no reproductive impairment when fed to two generations of rats at concentrations of 20, 200, or 2000 ppm. Both parental and progeny weights were reduced at the two higher feeding levels. No teratogenic effects were seen in rats treated with up to 250 mg/kg. In another rat study, deformities of the skeleton were increased in pups derived from ametryne-treated rats (30.6 mg/kg orally, days 5 through 15 of gestation). Postimplantation deaths increased, and fetal weights decreased. Ametryne was inactive genetically both in Salmonella and in Saccharomyces cerevisiae. No clastogenic effects were seen when ametryne was tested in Chinese hamster ovary cell cultures, and it was negative in the DNA-repair test in cultured hepatocytes. Ametryne suppressed humoral immune response if administered orally at near lethal doses in mice during an ongoing immune response. It was also observed to have a suppressive effect on humoral immune competence if orally administered in a sufficiently large quantity at the time or prior to immunization. ECOTOXICITY STUDIES: Ametryne is slightly toxic to mammals on an acute oral exposure basis, following chronic exposure, reduced growth was observed. Ametryne is slightly to moderately toxic to freshwater fish and invertebrates, and moderately toxic to estuarine/marine fish and invertebrates on an acute exposure basis. Following chronic exposure, freshwater fish exhibited reduced, while freshwater invertebrates exhibited reduced reproduction. Consistent with its chemical use as an herbicide, ametryne is toxic to terrestrial plants.

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

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Non-Human Toxicity Values
LC50 Rat (albino) inhalation >27 mg/L/4 hr
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 Non-Human Toxicity Values (Complete) data for Ametryne (15 total), please visit the HSDB record page.

Crystals. Melting point 190-192 °F (88-89 °C). Used as a herbicide.
Ametryn is a methylthio-1,3,5-triazine that is 2-(methylsulfanyl)-1,3,5-triazine substituted by an ethylamino and an isopropylamino group at positions 4 and 6 respectively. It has a role as a herbicide and an environmental contaminant. It is a diamino-1,3,5-triazine and a methylthio-1,3,5-triazine.
Ametryn, a member of the Triazine chemical family, is a herbicide which inhibits photosynthesis and other enzymatic processes. It is used to control broadleaf weeds and annual grasses in pineapple, sugarcane and bananas. It is used on corn and potato crops for general weed control. It is also used as a vine desiccant on dry beans and potatoes. The EPA classifies it as Toxicity Class III, slightly toxic. Symptoms of acute exposure to high doses include nausea, vomiting, diarrhea, muscle weakness, and salivation.

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Mechanism of Action
Mode of Herbicidal Action: Like other triazines, ametryn inhibits photosynthesis and other enzymatic processes. It is a selective systemic herbicide, absorbed by the leaves and roots, with translocation acropetally in the xylem, and accumulation in the apical meristems.
... Their chief mode of action appears to involve carbohydrate metabolism. The chlorinated s-triazines inhibit starch accumulation by blocking the production of sugars. Similar behavior has been shown for the methoxy & methylthio-s-triazines. It has been reported that the s-triazines affect the tricarboxylic acid cycle with activation of phospho-phenyl pyruvate-carboxylase causing the disappearance of sucrose & glyceric acid with the formation of aspartic & malic acids. /s-Triazines/
Since chlorosis is the first sign of the effect of triazines on plants, interference with carbon dioxide assimilation and sugar formation can be expected. Studies showing that hill reaction is inhibited confirmed this. /Triazines/
Inhibition of photosynthesis by disruption of light reactions and blockade of electron transport is the mechanism of action of the 1,3,5-triazine herbicides. /1,3,5-Triazines, from 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.

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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.

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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.

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