Absorption, Distribution and Excretion
AFTER ORAL ADMIN OF 180 MG/KG OR 45 MG/KG IV TO RATS, RELATIVELY HIGH CONCN OF NTA WERE FOUND IN LUNGS, INTESTINE, & MUSCLE. PATTERN OF DISTRIBUTION DEPENDED ON ROUTE OF ADMIN. APPROX 99% OF SINGLE ORAL DOSE ELIM IN 24 HR; 96% OF THIS WAS ELIM IN URINE.
NTA-(14)C ADMIN ORALLY TO RATS. 95% WAS EXCRETED IN URINE. LESS THAN 1% ... AS CO2. ABSORPTION OF NTA FROM GI TRACT VARIED: DOG GREATER THAN RAT GREATER THAN RABBIT & MONKEY ... DEPOSITED IN SKELETON. CONCN ... INCR WITH NUMBER OF ADMIN DOSES. MOST ACTIVE AREAS FOR ACCUMULATION ... @ SITES OF VERY ACTIVE BONE FORMATION. ALTHOUGH CONCN /NTA/ DECR RAPIDLY WITH CESSATION OF INTAKE, A SMALL AMT WAS RETAINED IN BONE AFTER EACH DOSE ... .
DOGS ADMIN 10, 20, & 50 MG NITRILOTRIACETIC ACID/KG EXCRETED MATERIAL IDENTIFIED AS CHONDROITIN A SULFATE &/OR CHONDROITIN C SULFATE.
The kidney attains concentrations of NTA greater than that in the plasma in rats with steady state plasma NTA levels. The relatively high kidney concentrations of NTA can be attributed to high concentrations of NTA in small volumes of urine. NTA is not metabolized in mammals and is excreted rapidly by filtration in the kidney ... .
A capsule containing 10 mg [1 14C]NTA in gelatin was given orally in fruit juice to each of eight male volunteers who had received no drugs for two weeks before entering the study. Twelve % of the admin radioactivity was excreted in the urine & 77% in the feces as unchanged NTA within 120 h of admin. A peak in the blood concn (6.5 ng/g serum) occurred 12 h after dosing ... .

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Metabolism / Metabolites
WASHED CELL SUSPENSION OF PSEUDOMONAS SP, ISOLATED FROM SEWAGE EFFLUENT, DEGRADED ALL NTA-NITROGEN TO AMMONIUM PRIOR TO TOTAL CONVERSION OF NTA TO CO2 AND WATER. SMALL AMOUNT OF NITRITE WERE ALSO FORMED. STUDY TENDED TO SUPPORT CONTENTION THAT NTA DEGRADATION PROCEEDED THROUGH AMINODIACETIC ACID AND GLYCINE ... .
In mammalian systems, NTA is not metabolized and is excreted rapidly by filtration in the kidney.

Interactions
MICE EXPOSED SC TO CADMIUM CHLORIDE WITH NTA SHOWED HISTOLOGICAL EVIDENCE OF LIVER NECROSIS AFTER 24 HR.
THE ADMIN OF A SINGLE IV DOSE OF LEAD ALONE (50 MG/KG) OR WITH EQUIMOLAR AMOUNTS OF CHELATING AGENTS TO PREGNANT RATS RESULTED IN APPROX A 400% INCREASE IN FETAL LEAD CONTENT WITH LEAD PENICILLAMINE (PBPEN) & LEAD NITRILOTRIACETIC ACID (PBNTA) & A 50% INCREASE WITH LEAD-EDTA BY 4 HR AFTER ADMIN AS COMPARED TO LEAD ALONE.
FOLLOWING INTUBATION OF (14)C-LABELED NTA (68.2 MG/KG) INTO LEAD & NON-LEAD-TREATED RATS, THE LEVELS OF NTA IN ALL TISSUES WERE LOWEST IN LEAD-TREATED RATS. APPARENTLY, LEAD FACILITATED THE ELIMINATION OF NTA.
The effect of single dose of NTA on the removal of radio-manganese in various organs and in plasma has been studied in rats which received single i.v. injection of 54Mn(II). The lowered value of radio-manganese in NTA treated rats as compared to control animal indicates that NTA binds rapidly and forms stable and diffusible complex resulting in the fast excretion of the injected 54Mn(II).
The possible interactions of pairs of carcinogens which act on different organ systems were studied in rats, and recurring design problems of such studies were identified and new statistical methodology tested. Fischer-344 rats were exposed through diet to the six possible pairs of four chemicals. Tested chemicals and their target organs were as follows: N-methyl-N'-nitro-N-nitrosoguanidine, stomach; N-butyl-n-(4-hydroxybutyl) nitrosamine, bladder; dipentylnitrosamine, liver; and nitrilotriacetic acid, kidney, ureter, and bladder. A 4x4 factorial design was used to study each chemical pair. Doses were 0, 20, 40, or 80 ppm N-methyl-N'-nitro-N-nitrosoguanidine, 0, 30, 60, or 120 ppm N-butyl-n-(4-hydroxybutyl) nitrosamine, 0, 50, 150, or 450 ppm dipentylnitrosamine, and 0, 200, 2000, or 20000 ppm nitrilotriacetic acid. The test period was 104 weeks. An independent interaction model was used to compute an index of additivity, which indicated interactions and their types. The endpoints considered were incidence of malignant tumor, time to death from any cause, and time to death with malignant tumor. It was determined that there was no interaction of dipentylnitrosamine with any of the other three carcinogens. Nitrilotriacetic acid in combination with N-methyl-N'-nitro-N-nitrosoguanidine or N-butyl-n-(4-hydroxybutyl) nitrosamine produced antagonism for the target sites of the latter two chemicals, while N-methyl-N'-nitro-N-nitrosoguanidine and N-butyl-n-(4-hydroxybutyl) nitrosamine did not interact with each other. No synergism was noted for any combination or target site. /It was/ concluded that antagonism can occur when these compounds are given in combination to rats, and although combined exposures can be highly carcinogenic, they do not produce more tumors than implied by independent action models.

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Non-Human Toxicity Values
LD50 Mouse oral 3160 mg/kg
LD50 Rat oral 1470 mg/kg

[1]. A review of the environmental and mammalian toxicology of nitrilotriacetic acid. Crit Rev Toxicol. 1985;15(1):1-102.

Nitrilotriacetic Acid can cause cancer according to an independent committee of scientific and health experts.
Nitrilotriacetic acid is an odorless white solid. Sinks in and mixes with water. (USCG, 1999)
Nitrilotriacetic acid is a tricarboxylic acid and a NTA. It has a role as a nephrotoxic agent and a carcinogenic agent. It is a conjugate acid of a nitrilotriacetate(1-).
Nitrilotriacetic acid is a derivative of acetic acid, N(CH2COOH)3. It is a complexing (sequestering) agent that forms stable complexes with Zn2+. (From Miall's Dictionary of Chemistry, 5th ed.)
Nitrilotriacetic Acid is a white, crystalline solid compound. Nitrilotriacetic acid is mainly used as a chelating and eluting agent and is found in laundry detergents. Exposure to Nitrilotriacetic acid irritates the skin, eyes and respiratory tract and causes kidney and bladder damage. Nitrilotriacetic acid is reasonably anticipated to be a human carcinogen. (NCI05)
A derivative of acetic acid, N(CH2COOH)3. It is a complexing (sequestering) agent that forms stable complexes with Zn2+.
A derivative of acetic acid, N(CH2COOH)3. It is a complexing (sequestering) agent that forms stable complexes with Zn2+. (From Miall's Dictionary of Chemistry, 5th ed.)

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Mechanism of Action
A positive synergistic action was produced by nitrilotriacetic acid in combination with soluble chromium(VI) as potassium dichromate in the induction of gene mutations in Salmonella typhimurium and Drosophila melanogaster. The possibility that this action depended on an effect of nitrilotriacetic acid on chromium(VI) reduction by cellular proteins was demonstrated. Gene mutations were detected by the Ames plate incorporation test on strains (TA-100), (TA-92), (TA-104) and (TA-103) of Salmonella typhimurium. In both the Salmonella and Drosophila systems, the nitrilotriacetic acid synergistically increased the mutagenicity of subtoxic doses of chromium(VI) while at higher chromium(VI) dose levels a decline of mutation frequency was noted in the presence of nitrilotriacetic acid, probably as a result of toxicity. Both effects may be referred to enhanced availability of the final genotoxic agent in the presence of nitrilotriacetic acid. The interaction was particularly evident in strains (TA-100) and (TA-104) which carried mutations affecting cell wall permeability and DNA repair. In these strains, the uptake of chromium(VI) and nitrilotriacetic acid was increased and the resulting DNA damage repaired less efficiently or by error prone mechanisms. Nitrilotriacetic acid may facilitate chromate uptake by the anion carriers of the cell membrane. Other mechanisms linked to its chelating action may also be important as suggested by the significant synergistic effect on chromium(VI) mutagenicity produced by ethylenedinitrilotetraacetic acid at very low doses, which do not modify chromium(VI) reduction by Salmonella proteins in cell free conditions.

C6H9NO6

191.1388

191.042

139-13-9

Nitrilotriacetic acid trisodium salt;5064-31-3;Nitrilotriacetic acid-d9;807630-34-8;Nitrilotriacetic acid disodium salt;15467-20-6

8758

White to off-white solid powder

1.6±0.1 g/cm3

498.2±40.0 °C at 760 mmHg

245 °C (dec.)(lit.)

255.1±27.3 °C

0.0±2.7 mmHg at 25°C

1.558

-1.76

3

7

6

13

187

0

MGFYIUFZLHCRTH-UHFFFAOYSA-N

InChI=1S/C6H9NO6/c8-4(9)1-7(2-5(10)11)3-6(12)13/h1-3H2,(H,8,9)(H,10,11)(H,12,13)

2-[bis(carboxymethyl)amino]acetic acid

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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.)