Absorption, Distribution and Excretion
Disposal studies in calves confirmed extremely low tissue retention at daily intakes of 2.6–23 mg/kg. At the highest daily intake level studied (1600 ppm [mg/kg]), the recorded tissue concentrations (ppm (mg/kg)) were: kidney, 15–18; blood, 1.4–2; liver, 1.1–1.6; muscle and fat, 0.3–0.5. Clearance was rapid after cessation of intake. The in vivo metabolism of Picolinic acid (4-amino-3,5,6-trichloroPicolinic acid), the active ingredient of the TORDON brand herbicide, was determined in six healthy male volunteers following single oral doses of 5.0 and 0.5 mg/kg, and transdermal administration of 2.0 mg/kg. Picolinic acid was administered orally as a sodium salt of grape juice. Transdermal administration involved applying the ethanol-soluble free acid to the back of the volunteers. Data show that pyrcloram is rapidly absorbed from the gastrointestinal tract (half-life of 20 minutes) and rapidly excreted unchanged in the urine. More than 90% of the oral dose is excreted unchanged in the urine within 72 hours; the majority of the dose (>75%) is excreted within 6 hours, with the remaining portion having an average half-life of 27 hours. In contrast, pyrcloram is slowly absorbed through the skin (half-life of 12 hours), and based on the amount of pyrcloram excreted in the urine, only a small amount (0.2%) of the pyrcloram applied to the skin is absorbed. These data suggest that due to the rapid excretion of pyrcloram, its accumulation in the human body is unlikely under repeated or prolonged exposure. Furthermore, the skin absorption rate of pyrcloram is very low, making it unlikely that acute toxic doses will be absorbed through this route. Pyrcloram is rapidly absorbed from the gastrointestinal tract and excreted almost unchanged in the urine and feces within 48 hours (male Fischer 344 rats). Following intravenous administration of 10 mg/kg (14)C-pyrrolam, the isotope was biphasically cleared and excreted in the urine. … Rats in homeostasis studies showed that 98.4% of the dose was recovered. Urinary recovery was 80% to 84%, fecal recovery was approximately 15%, and bile recovery was less than 0.5%, with almost no radioactive material recovered as captured (14)CO2 or other volatile compounds. Studies of (14)C-Picolinic acid showed that 90% of the compound in dog feed was excreted in the urine within 48 hours, with a small amount appearing in the feces. For more complete data on the absorption, distribution, and excretion of Picolinic acids (6 in total), please visit the HSDB record page. Metabolites/Metabolites The major metabolite is 2-ethyl-1,6-hexanoic acid (after administration of isooctyl 14C-Picolinic acid). This study confirmed that ethylhexyl pyrrolidone is rapidly hydrolyzed to pyrrolidone (free acid) and 2-ethylhexanol…
No measurable residues were detected in milk samples from cows fed 10–100 ppm pyrrolidone. Low concentrations (0.05–0.29 ppm) of residues were found in milk samples from cows fed 150–1000 ppm pyrrolidone; these residues decreased rapidly and were undetectable 58 hours after drug withdrawal.

---

Biological Half-Life
Following intravenous injection of 10 mg/kg (14)C-pyrrolidone into rats, the isotope was eliminated biphasically and excreted in the urine. The half-lives for rapid and slow clearance in plasma were 6.3 minutes and 128 minutes, respectively. After oral administration of the same dose, the half-lives were 29 minutes and 3.8 hours, respectively, which were similar. After oral administration of a high dose (1400 mg/kg), plasma drug concentrations remained stable for 3 hours before slowly decreasing.

Interactions
A single oral dose of 720 mg/kg in sheep…no obvious toxicity was observed. …Pyrrolidone and (2,4-dichlorophenoxy)acetic acid (2,4-D) appear to have a synergistic toxic effect in sheep. A dose of 36 mg/kg of pyrrolidone combined with a dose of 134 mg/kg of 2,4-D caused death in livestock. Treatment of male rat microsomes with pyrrolidone (100 mg/kg/day) for 7 days resulted in a 48% reduction in 16α-hydroxylase activity after incubation with (4-14C)androstenedione. These data are consistent with the assertion that pyrrolidone reduces the titer of hepatic male-specific cytochrome P-450h. First, SDS-PAGE showed a significant increase in the intensity of a 54,000 polypeptide band in liver microsomes after pyrrolidone pretreatment. The polypeptide co-migrated with protein bands whose intensity was correspondingly enhanced after pretreatment with known cytochrome P-450d inducers (3-methylcholanthrene and safrole). Secondly, compared to the control group, the binding of metheprone to microsomes in the pyrrolim-treated group was not increased, indicating that phenobarbital-induced cytochrome P-450 form was not increased. Thirdly, liver microsomes in the pyrrolim-treated group activated 2-amino-3-methylimidazo[4,5-f]quinoline (a catalytic product mediated by cytochrome P-450d), resulting in a 5-fold increase in the number of induced Salmonella typhimurium TA98 reversion mutant colonies compared to the control group. Fourthly, compared to 3-methylcholanthrene-treated rat liver microsomes, the binding of n-octylamine to liver microsomes showed an increased proportion of high-spin cytochrome P-450. Cytochrome P-450d is a high-spin heme protein.

---

Non-human toxicity values
Oral LD50 of rats (male, Sprague-Dawley strain): 950 mg/kg (95% CI: 812-1120 mg/kg)
Oral LD50 of rats (female, Sprague-Dawley strain): 686 mg/kg (95% CI: 599-786 mg/kg)
Oral LD50 of rabbits: 2000 mg/kg
Oral LD50 of guinea pigs: 1922 mg/kg
For more complete non-human toxicity data for PICLORAM (11 items in total), please visit the HSDB record page.

Arabidopsis PIC30 Encodes a Major Facilitator Superfamily Transporter Responsible for the Uptake of Picolinate Herbicides. Plant J. 2020 Apr;102(1):18-33.

Atrazine appears as small, pale yellow crystals or a white powder with a chlorine odor. (NTP, 1992)
Atrazine is a pyridine monocarboxylic acid, specifically pyridine-2-carboxylic acid, with chlorine atoms substituted at positions 3, 5, and 6, and an amino group substituted at position 4. It is a systemic herbicide used to control deep-rooted herbaceous and woody plants in right-of-way areas, woodlands, pastures, grasslands, and crops such as wheat. It is both a herbicide and a synthetic auxin. It is an aminopyridine, pyridine monocarboxylic acid, chloropyridine, and organochlorine pesticide. Its function is similar to that of Picolinic acid.
Atrazine is a persistent systemic herbicide used to control woody plants and broadleaf weeds in non-cultivated land and utility areas. It is also effective against many broadleaf weeds, but most grasses are resistant to it. It is a chlorinated derivative of Picolinic acid and belongs to the pyridine class of herbicides. It can be systematically absorbed and translocated by plant roots and leaves.
A Picolinic acid derivative used as a herbicide.

C6H3CL3N2O2

241.45

239.926

1918-02-1

15965

White to off-white solid powder

1.8±0.1 g/cm3

420.5±45.0 °C at 760 mmHg

200 °C (dec.)(lit.)

208.1±28.7 °C

0.0±1.0 mmHg at 25°C

1.677

2.94

2

4

1

13

216

0

NQQVFXUMIDALNH-UHFFFAOYSA-N

InChI=1S/C6H3Cl3N2O2/c7-1-3(10)2(8)5(9)11-4(1)6(12)13/h(H2,10,11)(H,12,13)

4-amino-3,5,6-trichloropyridine-2-carboxylic acid

Grazon Tordon Picloram

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 : ~100 mg/mL (~414.15 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.

---

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).

View More

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)

---

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).

View More

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

---

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.

---

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