The mean arthritis scores and radiographic scores were considerably lowered by etanercept (10 mg/kg; subcutaneous injection; every 3 days for 3 weeks) [4].

Animal/Disease Models: Sixweeks old male Lewis rat (adjuvant-induced arthritis (AIA) model) [4]
Doses: 10 mg/kg
Route of Administration: Sc; every 3 days for 3 weeks
Experimental Results: Average arthritis score Significant decrease; radiographic score diminished Dramatically at the end of the treatment period.

Metabolism / Metabolites
Within tissues in organisms, V3+ and V4+ predominate because of largely reducing conditions; in plasma, however, which is high in oxygen, V5+ is formed.
Within tissues in organisms, V3+ and V4+ predominate because of largely reducing conditions; in plasma, however, which is high in oxygen, V5+ is formed.
/In/ calves given 10-20 mg/kg of ammonium metavanadate by mouth daily ...levels of vanadium in the liver ranged from 0.3 to 5.1 ppm of wet tissue, in the kidney from 6.0 to 40.

Toxicity Summary
IDENTIFICATION AND USE: Ammonium vanadate is an orange powder. It is used as a spray color revealing device in analytical toxicology of drugs. HUMAN EXPOSURE AND TOXICITY: There are no data available. ANIMAL STUDIES: Ammonium vanadate (10 or 20 mg/L) in drinking water had no influence on tumor development of large-bowel neoplasms in mice treated with 1,2-dimethylhydrazine (DMH) given by subcutaneous injection for 20 weeks. Although thymidine incorporation was increased, ammonium vanadate did not have any effect on the incidence or type of tumor induced by DMH. Rats fed 15 mg vanadium/kg as ammonium vanadate for 2 months showed increased ventricular pressure and pulmonary hypertension, but no changes in systemic circulation. When ammonium vanadate was administered orally to rats and mice in doses of 0.005-1 mg vanadium/kg for 21 days (higher levels) to 6 months (lower levels), a dose of 0.05 mg vanadium/kg was found to be the threshold for functional disturbances in the conditioned reflex activity in both rats and mice. ECOTOXICITY STUDIES: A concentration of 0.02 mg/L ammonium vanadate interfered with the cell division of the fresh-water algae Chlorella pyrenoidosa, whereas 0.25 mg/L was lethal.
IDENTIFICATION AND USE: Ammonium metavanadate is a white or slightly yellow, crystalline powder. It is used in dyeing and printing on woolens; staining wood black; manufacture of vanadium black and "indelible ink"; producing vanadium luster on pottery; as photographic developer; in hematoxylin staining in microscopy; as a reagent in analytical chemistry. Because of its ready conversion to vanadium pentoxide at elevated temperatures, it is used as a substitute. HUMAN EXPOSURE AND TOXICITY: One worker was exposed to large amounts of dry ammonium vanadate dust over a 6-hr period while shovelling powder into a bin. Within 2 hr of commencing work, retro-orbital headache, tears, dry mouth, and green discoloration of the tongue were reported. There was a marked green discoloration of the skin of the fingers, scrotum, and upper legs. His nose was reported to be stuffy, and he was lethargic. The next day, his testicles were swollen and tender, and, on the third day after exposure, he developed wheezing, dyspnea, and a cough productive of green sputum. He had several small hemoptyses over the following 2 weeks. Wheezing and dyspnea persisted for about 1 month; chest symptoms were at their worst 3 weeks after the incident. On examination 6 weeks after the last exposure, he was asymptomatic, with the exception of a partially blocked left nostril and the reddened appearance of nasal mucosa. Chest examination revealed no abnormality. Pulmonary function assessment showed normal lung volume, forced expiratory flow rate, and gas transfer. He had a mild eosinophilia of the peripheral blood. In human fibroblast cultures VO3- can induce DNA synthesis and cell growth. Ammonium metavanadate was not found to increase the frequency of structural chromosome aberrations in human leukocytes, whereas a significant increase in numerical aberrations, micronuclei, and satellite associations was found. Fluorescence in situ hybridization (FISH) applied to the human lymphocyte micronucleus assay, by means of an alphoid centromere-specific DNA probe, confirmed the aneuploidogenic potentiality of vanadium. ANIMAL STUDIES: Acute tubular necrosis, pulmonary hemorrhage, and necrosis of lymphoid tissue were demonstrated in mice receiving 20 mg vanadium/kg of ammonium metavanadate solutions. In a 3-month study, rats received ammonium metavanadate at a concentration of 200 mg/L (in terms of vanadium) in their drinking water. Animals exhibited retardation of body weight gain and anemia. Gross pathology examination revealed parenchymatous dystrophy of the liver and kidneys with the formation of cylinders in the tubules in some animals. Neurophysiological effects have been reported following acute exposure (oral and sc injection) of dogs and rabbits to vanadium oxides and salts including ammonium metavanadate. These include disturbances of the central nervous system (impaired conditioned reflexes and neuromuscular excitability). The teratogenicity of ammonium vanadate was studied in hamsters. Twenty pregnant hamsters per dose group received 0, 0.47, 1.88, and 3.75 mg/kg of ammonium vanadate by ip injection on gestation days 5 through 10. Pregnant females were killed on day 15. There was a statistically significant increase in skeletal abnormalities and a decrease in the male:female ratio. Ammonium metavanadate increased the convertant and revertant frequencies in the D7 strain of Saccharomyces cerevisiae; the highest activity was observed without metabolic activation. The micronucleus test was found to be positive for ammonium metavanadate in bone marrow of mice following intragastric treatment. In contrast, no difference was found between controls and treated animals in the structural chromosome aberration test performed 24 and 36 hr after treatment. In studies with ammonium metavanadate at concentrations of 5-40 uM, weak mutagenesis was demonstrated at the hprt gene of Chinese hamster V79 cells, and at the gpt locus of hprt-/gpt+ transgenic cell line G12. Female mice given ammonium metavanadate ip at doses of 2.5, 5, or 10 mg/kg, every 3 days for 3, 6, or 9 weeks, showed a dose-related increase in resistance to E. coli endotoxin lethality up to 6 weeks and a dose-related decrease in resistance to Listeria lethality. Enlargement of the liver and spleen with enhanced formation of splenic megakaryocytes and red blood cell precursors was also observed.

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Etanercept is minimally excreted into breastmilk and poorly absorbed by the infant, which would be expected because of its high molecular weight of approximately 150,000 Da. Waiting for at least 2 weeks postpartum to resume therapy may minimize transfer to the infant. Long-term follow-up data on infants breastfed during maternal etanercept use are not available. The risk of adverse effects in older infants is not known, but thought to be unlikely. Most experts and professional guidelines feel that the drug is a low risk to the nursing infant and can be given during breastfeeding.
◉ Effects in Breastfed Infants
A woman with rheumatoid arthritis began etanercept 25 mg subcutaneously twice a week at 3 months postpartum and later switched to a dose of 50 mg subcutaneously once a week. Her infant was breastfed (extent not stated) until 6 months of age. The infant was reportedly healthy at 3 years of age.
A case-control study of women with chronic arthritic conditions found 5 women who received etanercept during pregnancy and lactation (extent not stated). No differences were observed in the 5 infants' growth parameters, developmental milestones, vaccinations and diseases in the first year of life compared to those not exposed to the drugs with lactation.
Six infants were breastfed (2 fully, 4 partially) by mothers with rheumatoid arthritis or ankylosing spondylitis who were receiving etanercept during pregnancy and up to the time they were enrolled in the study. One mother reported a nonserious rash and high-pitched crying in her infant, both of which resolved without intervention. All infants had growth measures within normal range at their 6-month well-child visit.
A national prospective registry of patients with rheumatic diseases who were treated with biological DMARDs was conducted in Spain. Three infants whose mothers were taking etanercept were breastfed (extent not stated) with no mild or severe adverse events reported in the infants.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Toxicity Data
LC50 (rat) = 7.8 mg/m3/4h
LC50 (rat) = 340 mg/m3/4h

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Interactions
Today, vanadium compounds are frequently included in nutritional supplements and are also being developed for therapeutic use in diabetes mellitus. Previously, tissue uptake of vanadium from bis(maltolato)oxovanadium(IV) (BMOV) was shown to be increased compared to its uptake from vanadyl sulfate (VS). Our primary objective was to test the hypothesis that complexation increases vanadium uptake and that this effect is independent of oxidation state. A secondary objective was to compare the effects of vanadium complexation and oxidation state on tissue iron, copper, and zinc. Wistar rats were fed either ammonium metavanadate (AMV), VS, or BMOV (1.2 mM each in the drinking water). Tissue uptake of V following 12 wk of BMOV or AMV was higher than that from VS (p<0.05). BMOV led to decreased tissue Zn and increased bone Fe content. The same three compounds were compared in a cellular model of absorption (Caco-2 cells). Vanadium uptake from VS was higher than that from BMOV or AMV at 10 min, but from BMOV (250 uM only, 60 min), uptake was far greater than from AMV or VS. These results show that neither complexation nor oxidation state alone are adequate predictors of relative absorption, tissue accumulation, or trace element interactions.
Previous studies from our laboratory have demonstrated the potential anticarcinogenicity of vanadium, a dietary micronutrient in rat liver, colon, and mammary carcinogenesis models in vivo. In this paper, we have investigated further the antihepatocarcinogenic role of this essential trace element by studying several biomarkers of chemical carcinogenesis with special reference to cell proliferation and oxidative DNA damage. Hepatocarcinogenesis was induced in male Sprague-Dawley rats by chronic feeding of 2-acetylaminofluorene (2-AAF) at a dose of 0.05% in basal diet daily for 5 days a week. Vanadium in the form of ammonium metavanadate (0.5 ppm equivalent to 4.27 umol/L) was supplemented ad lib to the rats. Continuous vanadium administration reduced relative liver weight, nodular incidence (79.99%), total number, and multiplicity (p<0.001; 68.17%) along with improvement in hepatocellular architecture when compared to carcinogen control. Vanadium treatment further restored hepatic uridine diphosphate (UDP)-glucuronosyl transferase and UDP-glucose dehydrogenase activities, inhibited lipid peroxidation, and prevented the development of glycogen-storage preneoplastic foci (p<0.01; 63.29%) in an initiation-promotion model. Long-term vanadium treatment also reduced bromodeoxyuridine (BrdU)-labelling index (p<0.02) and inhibited cell proliferation during hepatocellular preneoplasia. Finally, short-term vanadium exposure abated the formations of 8-hydroxy-2'-deoxyguanosines (p<0.001; 56.27%), length:width of DNA mass (p<0.01), and the mean frequency of tailed DNA (p<0.001) in preneoplastic rat liver. The study indicates the potential role of vanadium in suppressing cell proliferation and in preventing early DNA damage in vivo. Vanadium is chemopreventive against the early stages of 2-AAF-induced hepatocarcinogenesis in rats.
Metallo-elements including Vanadium (V) have strong affinity for sulfhydryl (-SH) groups in biological molecules including Glutathione (GSH) in tissues. Because of this fact it was of interest to further investigate the interaction of Ammonium Vanadate [NH(4)VO(3)] with Glutathione as a biomarker of toxicity and the role of Glutathione in the detoxification and conjugation pr(o)Cesses in whole blood components including plasma and cytosolic fraction. Effects of different concentrations of Ammonium Vanadate [NH(4)VO(3)] on the level of reduced Glutathione in whole blood components (Plasma and Cytosolic fraction) were examined. GSH depletion in plasma and cytosolic fraction was Ammonium Vanadate's concentration-dependent. Depleted GSH level was more pronounced with more incubation time period. These findings show that changes in the GSH status produced by Ammonium Vanadate could be due to either by adduct formation of Vanadium and glutathione, i.e., (V-SG) or by increased production of oxidized Glutathione (2GSH +V(+5) /produces/ GSSG). This change in GSH metabolic status provides some information regarding the mechanism of toxicity by Ammonium Vanadate and the protective role of glutathione.
Expression pattern of heat shock proteins (Hsp) 72/73 and glucose regulated protein (Grp) 94 was studied in liver, kidney and testis of rats injected with sublethal doses of ammonium metavanadate (5 mg/kg/day). In addition, some batches of animals were given green tea decoction, known to be rich in anti-oxidative compounds, as sole beverage in order to evaluate its protective properties. In control animals, the stress proteins expression was found to be organ-dependent: anti-Grp94 antibody revealed two bands at 96 and 98 kDa in kidney and liver whereas the 98 kDa band only was found in testis; anti-Hsp72/73 antibody revealed that the constitutive Hsp73 was present in all organs whereas the inducible Hsp72 was only present in kidney and testis. In kidney of vanadium-treated rats, Hsp73 was over-expressed by about 50% whereas Hsp72 was down-regulated by 50-80%. No such effects were observed in liver and testis. In liver and kidney of vanadium-treated rats, Grp94 was over-expressed by 50% and 150%, respectively, whereas no change was found in testis. In rats given green tea as sole beverage, the 96 kDa protein expression level in liver was reduced both in controls and in vanadium-treated animals. However, green tea drinking failed to prevent the vanadium-induced Hsp72 under-expression in kidney of vanadium-treated rats.
For more Interactions (Complete) data for AMMONIUM METAVANADATE (10 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LC50 Rat inhalation 0.34 mg/L/4 hr
LD50 Rat oral 162 mg/kg bw
LD50 Rat oral 58.1 mg/kg
LD50 Rat dermal 2102 mg/kg
LD50 Rat ip 18 mg/kg
LD50 Rat sc 23 mg/kg
LC50 Rat inhalation 7.8 mg/cu m/4 hr

[1]. Etanercept: An overview. J Am Acad Dermatol. 2003;49(2 Suppl):S105-S111.

[2]. Goldenberg MM. Etanercept, a novel drug for the treatment of patients with severe, active rheumatoid arthritis. Clin Ther. 1999;21(1):75-2.

[3]. Etanercept in the treatment of rheumatoid arthritis. Ther Clin Risk Manag. 2007;3(1):99-105.

[4]. Etanercept improves endothelial function via pleiotropic effects in rat adjuvant-induced arthritis. Rheumatology (Oxford). 2016;55(7):1308-1317.

Ammonium metavanadate appears as a white crystalline powder. Slightly soluble in water and denser than water. Decomposes at 410 °F. May release toxic fumes. Moderately toxic. An irritant. Used as a dryer for paints and inks, and for dyes. Loses ammonia upon heating.
See also: Etanercept (annotation moved to).

H4NO3V

116.978161811829

185243-69-0

516859

Colorless to light yellow liquid

200 °C (with decomposition)

1

3

0

5

36.5

0

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.)