Absorption, Distribution and Excretion
In a rat metabolism study, (14)C-terbuthylazine (3.6 mg) was administered orally to Wistar rats. Terbuthylazine was rapidly (50% excreted by 16-17 hrs) and completely metabolized and did not accumulate in tissues. Radioactivity was excreted equally in urine and feces in males, but in females about 66% of the radiolabel was excreted in the urine.
In mammals, following oral administration, 72-84% is eliminated in the urine and feces within 24 hr, and almost all within 48 hr.
Terbuthylazine (TBA) is an herbicide widely used in corn cultivation. Herein we evaluate the measurement of hair TBA as biomarkers of exposure. Five Sprague Dawley rats were gavaged with TBA for 3 days, and then the back hair was shaved and analyzed for TBA. In addition, head hair samples from 10 corn farmers, 9 rural residents, and 6 urban residents were collected at the end of the application season. Hair TBA was detected by liquid chromatography triple quadrupole mass spectrometry after solvent extraction. TBA was quantifiable in all rat samples with a mean concentration of 0.92 (+ or - 0.26)ng/mg, which corresponds to a 0.12% incorporation rate. TBA was quantifiable in all farmer samples (median: 0.67 ng/mg), in 75% of rural resident samples (0.01ng/mg) and in none of the urban resident samples (<0.01 ng/mg), with a statistical difference among groups (P<0.01). Our results suggest that TBA is incorporated in hair and prompt further investigation on the use of hair TBA as a potential biomarker of cumulative exposure.

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Metabolism / Metabolites
Metabolism of terbuthylazine in rats is similar to other chloro-s-triazine herbicides. The major routes of metabolism are hydrolysis of the chlorine moiety and mono- or didealkylation. Hydroxylation of one or both of the dealkylated amine groups may also occur.
Urine and feces contained up to 25 and 15 identified metabolites, respectively, most of which were polar. Degradation of the triazine ring did not occur. Ammeline and ammelide, 2 dechlorinated and dealkylated/hydroxylated metabolites common to all triazines, were identified in low amounts in the feces.
In mammals, following oral administration, ...a de-ethyl metabolite forms rapidly, followed by conjugates of products formed by oxidation of one methyl group of the tert-butyl moiety. All are rapidly excreted.
/Terbutylethylazine/ was rapidly metabolized to water soluble compounds in the leaves of corn, sorghum, and sugar cane and more slowly in susceptible barley, by displacement of the 2-chloro group with glutathione or gamma-glutamylcysteine.
The metabolism of atrazine (and three other triazine herbicides, terbuthylazine, ametryne, and tebutryne) has been investigated in vitro in liver microsomes from rats, pigs, and humans. The principal phase-1 reactions in all three species were N-monodealkylation, hydroxylation of the isopropyl or tert-butyl moiety and sulfoxidation of the substrate. Although all species produced the same type of metabolites, there were spiecies specific differences in the metabolite ratios. Subsequent studies have shown that cytochrome P450 1A2 is the major phase-1 enzyme involved in the metabolism of s-triazine in human liver micrsomes. /Triazine herbicides/
Terbuthylazine has known human metabolites that include 1-[[4-(tert-butylamino)-6-chloro-1,3,5-triazin-2-yl]amino]ethanol and 2-[[4-Chloro-6-(ethylamino)-1,3,5-triazin-2-yl]amino]-2-methylpropan-1-ol.

Toxicity Data
LC50 (rat) > 3,510 mg/m3/4h

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Non-Human Toxicity Values
LD50 Rat oral 1845 mg/kg
LD50 Rat dermal >2000 mg/kg
LD50 Rat percutaneous >2000 mg/kg
LC50 Rat inhalation >5.3 mg/L air/4 hr

[1]. Does the effect of herbicide pulse exposure on aquatic plants depend on Kow or mode of action? Aquat Toxicol. 2005 Feb 10;71(3):261-271.

Terbutylazine is a diamino-1,3,5-triazine that is N-tert-butyl-N'-methyl-1,3,5-triazine-2,4-diamine substituted by a chloro group at position 6. It has a role as a herbicide, an environmental contaminant and a xenobiotic. It is a diamino-1,3,5-triazine and a chloro-1,3,5-triazine. It is functionally related to a 6-chloro-1,3,5-triazine-2,4-diamine.

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Mechanism of Action
Photosynthetic electron transport inhibitor at the photosystem II receptor site. Maize tolerance of triazines is attributed to conjugation with glutathione. ...Herbicide, absorbed mainly by the roots.

C9H16N5CL

229.70984

229.109

5915-41-3

Terbuthylazine-d5;222986-60-9

22206

White to off-white solid powder

1.3±0.1 g/cm3

290.8±23.0 °C at 760 mmHg

177-179ºC

129.7±22.6 °C

0.0±0.6 mmHg at 25°C

1.580

1.26

2

5

4

15

193

0

FZXISNSWEXTPMF-UHFFFAOYSA-N

InChI=1S/C9H16ClN5/c1-5-11-7-12-6(10)13-8(14-7)15-9(2,3)4/h5H2,1-4H3,(H2,11,12,13,14,15)

2-N-tert-butyl-6-chloro-4-N-ethyl-1,3,5-triazine-2,4-diamine

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 : ~23 mg/mL (~100.13 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.)