Absorption, Distribution and Excretion
Approximately 20% to 30% of dietary zinc is absorbed, primarily in the duodenum and ileum. The amount absorbed depends on the bioavailability of zinc in the food. Red meat and oysters have the highest zinc bioavailability. Phytates may inhibit zinc absorption through chelation and the formation of insoluble complexes at alkaline pH. After absorption, zinc binds to metallothioneins in the intestine. Endogenous zinc can be reabsorbed in the ileum and colon, forming the enteropancreatic circulation. Zinc is primarily excreted in feces (approximately 90%); a small amount is excreted in urine and sweat. After absorption, zinc binds to metallothioneins in the intestine. Zinc is widely distributed throughout the body. It is mainly stored in red blood cells, white blood cells, muscles, bones, skin, kidneys, liver, pancreas, retina, and prostate. This study compared the pharmacokinetics of zinc sulfate and a novel zinc pantothenate in rabbits. Both salts were administered to rabbits at a dose of 3.3 μCi zinc-65/kg body weight. The pharmacokinetics of both compounds conformed to a two-compartment open model. Both zinc pantothenate and zinc sulfate exhibit similar urinary excretion and distribution in skin and hair, but zinc pantothenate is less retained in the liver than zinc sulfate (ZnSO4). Absorption rate: 20%–30%. Protein binding rate: 99%. Excretion route: via the small intestine. In women at different stages of pregnancy, daily oral administration of 200 mg zinc sulfate increased serum zinc levels from 109.7 mg/dL to 205.4 mg/dL. In the control group, serum zinc levels decreased from 113.0 mg/dL in early pregnancy to 83.8 mg/dL in late pregnancy. …It has been reported that when 10 healthy young men received a single dose of 45 mg zinc sulfate (Zn2+, in gelatin capsule form), the absorption half-life was 0.4 hours. Serum concentrations were frequently measured during the total 8-hour study period. The mean maximum concentration of Zn2+ in serum was found to be 8.2 μmol/L after 2.3 hours (tmax). Evidence suggests intestinal recirculation, with the first rebound effect occurring 1.4 hours after the absorption phase, prior to reaching tmax, at an average reabsorption rate of 70% of the administered dose. Subsequent rebound effects (up to 5) occur at regular 1.2-hour intervals, with the amount of reabsorption gradually decreasing. For more complete data on the absorption, distribution, and excretion of zinc sulfate (14 items in total), please visit the HSDB record page.

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Metabolism / Metabolites
Zinc can enter the body through the lungs, skin, and gastrointestinal tract. Intestinal zinc absorption is regulated by the zinc carrier protein CRIP. Zinc can also bind to metallothionein, thus preventing excessive absorption. Zinc is widely distributed in all tissues and tissue fluids, with higher concentrations in the liver, gastrointestinal tract, kidneys, skin, lungs, brain, heart, and pancreas. In the blood, zinc binds to carbonic anhydrase in red blood cells, as well as to albumin, β2-macroglobulin, and amino acids in plasma. Zinc bound to albumin and amino acids can diffuse across tissue membranes. Zinc is ultimately excreted through urine and feces. (L49)

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Biological Half-Life
Half-life: 3 hours

Toxicity Summary
The CIR expert panel concluded that the following 27 zinc salts, when formulated as non-irritating solutions under current usage methods and concentrations, are safe for use in cosmetics… Zinc sulfate… Safe for use in cosmetics under specific conditions. Anemia is caused by excessive zinc absorption inhibiting the absorption of copper and iron, likely through competitive binding with intestinal mucosal cells. An imbalance in the binding levels of copper and zinc with Cu,Zn-superoxide dismutase is associated with amyotrophic lateral sclerosis (ALS). Gastric acid can dissolve metallic zinc to form corrosive zinc chloride, thereby damaging the gastric mucosa. Metal fume fever is thought to be an immune response following zinc inhalation. (L48, L49, A49)

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Protein Binding
Zinc is 60% bound to albumin; 30% to 40% bound to α-2 macroglobulin or transferrin; and 1% bound to amino acids, mainly histidine and cysteine.

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Interactions
This study investigated the effects of intraperitoneal injection of zinc sulfate (22, 44, or 88 mg/kg) 48 hours later on gastric ulceration, gastric acid secretion, and mast cell count changes 4 hours after intraperitoneal injection of reserpine (5 mg/kg) in intact (without pyloric occlusion) or pyloric occlusion rats. The results showed that zinc sulfate dose-dependently antagonized the gastric effects of reserpine, through mechanisms including preventing ulceration in the rumen and glandular segments, reducing gastric acid secretion, and inhibiting mast cell degranulation, primarily occurring in the glandular mucosa. The relationship between these findings and the effects of zinc on gastric mast cells is discussed.
Concomitant intake of large amounts of dietary fiber, phosphorus, or phytates with zinc supplements may reduce zinc absorption by forming non-absorbable complexes; zinc supplements should be taken at least 2 hours after consuming foods containing fiber, phosphorus, or phytates. /Zinc Supplements/
Some studies have found that folic acid reduces zinc absorption, but not in cases of zinc overdose; other studies have not found an inhibitory effect. /Zinc Supplements/
High doses of iron supplements can inhibit the absorption of zinc in the intestines; this used to be a problem for people taking over-the-counter multivitamin and mineral supplements or infant formula with a high iron-zinc ratio; however, most companies in the United States have restructured their products; zinc supplements should be taken at least 2 hours apart from iron supplements. /Zinc Supplements/
For more complete data on interactions of zinc sulfate (16 types), please visit the HSDB records page.

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Non-Human Toxicity Values
Oral LD50 in rats: 2949 mg/kg
Oral LD50 in rats: 623 mg Zn/kg /from table/
Oral LD50 in male rats: 920 mg/kg body weight
Oral LD50 in mice: 57 mg/kg
For more complete data on non-human toxicity values of zinc sulfate (8 types), please visit the HSDB record page.

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Toxicity Data
LD50: 57 mg/kg (oral, mouse) (T13)

LD50: 71.7 mg/kg (intraperitoneal, mouse) (T13)

LD50: 40 mg/kg (intravenous, rat) (T81)

Zinc sulfate is a colorless crystalline solid. It can also be prepared as a hexahydrate (ZnSO₄·6H₂O) and a heptahydrate (ZnSO₄·7H₂O). All forms of zinc sulfate are soluble in water and are non-flammable. Its main hazard lies in its environmental threat. Immediate measures should be taken to limit its spread into the environment. Zinc sulfate can be used in the production of rayon, as a feed additive, and as a fertilizer ingredient. Zinc sulfate is a metal sulfate compound with zinc ions (Zn²⁺) as its counter ion. It is a fertilizer. It is a zinc molecular entity and also a metal sulfate. It contains zinc ions (Zn²⁺).
The CIR expert group concluded that the following 27 zinc salts are safe for use in cosmetics described in this safety assessment, provided they are formulated to be non-irritating under current cosmetic application methods and concentrations… Zinc sulfate…
Zinc sulfate is an inorganic compound with the chemical formula ZnSO₄, historically known as “alum”. It is listed in the World Health Organization's Essential Medicines List, which lists the most important medicines needed by basic health systems. Zinc sulfate is a salt of zinc, an essential trace metal for the human body. Zinc participates in tissue repair and is an important component of certain proteins, including those related to taste and smell. Zinc sulfate supplementation may help prevent radiation-induced aphasia. (NCI04) Zinc ore is a mineral with the chemical formula Zn2+S6+O4 or Zn(SO4). Its IMA symbol is Zin. Zinc sulfate is used as a malting/fermentation aid and a nutritional supplement. Zinc sulfate (ZnSO4) is a colorless, crystalline, water-soluble compound. Its hydrated form, ZnSO4·7H2O, is the mineral zinc sulfate ore, historically known as alum, and can be prepared by reacting zinc with an aqueous solution of sulfuric acid. It can also be prepared by adding solid zinc to a solution of copper(II) sulfate. Zinc sulfate has been shown to have antibacterial and anti-spectrally properties (A7766, A7767). Zinc sulfate belongs to the transition metal sulfate class of compounds. In these inorganic compounds, the largest oxyanion is sulfate, and the heaviest atoms besides oxyanions are transition metals. Zinc sulfate can be used to treat diseases associated with zinc deficiency, such as enteropathic acrodermatitis. For external use, zinc sulfate can be used as an astringent in lotions and eye drops. (Reynolds JEF (ed.): Martindale Pharmacopeia (electronic version). Micromedex, Englewood, Colorado, 1995)
See also: Calcium sulfate (related); Ferrous sulfate (related); Ammonium sulfate (related)...See more...

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Drug Indication
This product is a mineral used alone or in combination with oral rehydration therapy (ORT) to treat or prevent hypozincemia. It can also be used as a local astringent. Zinc sulfate injection (USP) is indicated as a supplement to intravenous infusions in total parenteral nutrition (TPN).

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Mechanism of Action
In vitro rat ileum studies have shown that zinc inhibits cAMP-induced chloride-dependent fluid secretion by suppressing basolateral potassium (K) channels. This study also demonstrates that zinc is specific for cAMP-activated K channels, as it does not block calcium (Ca)-mediated K channels. Since this study was not conducted in zinc-deficient animals, these results suggest that zinc may be effective in non-zinc-deficient conditions. Furthermore, zinc improves water and electrolyte absorption, promotes intestinal epithelial regeneration, increases brush border enzyme levels, and enhances immune responses, thereby improving pathogen clearance.

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Therapeutic Uses
Grid Title: Astringents
Dietary Supplement Ingredients (Minerals and Trace Elements) Used Before October 15, 1994 / Effective Date of the 1994 Dietary Supplement Health and Education Act /..
Veterinary Drug: Zinc sulfate (USP), applied topically as a 10% aqueous solution, is highly effective in treating foot rot in sheep.
Veterinary Drug: An effective ophthalmic antibacterial astringent, available in aqueous solution or ointment (0.25-0.5%). Spraying sheep with a 0.25% solution after shearing reduces the incidence of wound infection. A 1% solution has been used to treat particulate vaginitis in cows and balanitis in rams, and is an excellent odorless antibacterial egg wash. …As a white emulsion…for bruises, inflammation, and itchy skin areas in cattle and horses.
For more complete data on the therapeutic uses of zinc sulfate (26 in total), please visit the HSDB record page.

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Drug Warnings
Zinc sulfate is an effective emetic, but its potential hemolytic and nephrotoxic effects are too great to be recommended. Thiazide diuretics have been found to increase urinary zinc excretion. Zinc supplements: High doses of zinc may inhibit intestinal absorption of copper; zinc supplements should be taken at least 2 hours after copper supplements. Patients using zinc sulfate eye drops should discontinue use and consult a doctor if they experience eye pain or vision changes, persistent redness or irritation, or if their condition worsens or lasts for more than 3 days. For more complete data on drug warnings for zinc sulfate (15 total), please visit the HSDB records page.

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Pharmacodynamics
Zinc sulfate is a cofactor for more than 70 different enzymes, including alkaline phosphatase, lactate dehydrogenase, and RNA and DNA polymerases. Zinc helps with wound healing, maintaining normal growth rates, skin hydration, and the senses of taste and smell.

ZNSO4

161.44

159.881

7733-02-0

23713-49-7 (Parent) ; 7446-20-0 (heptahydrate)

24424

White to off-white solid powder

1.957

330ºC at 760 mmHg

212 °F (USCG, 1999) ; 680 °C (decomposes)

0.426

0

4

0

6

62.2

0

OS(=O)(=O)O.[Zn]

NWONKYPBYAMBJT-UHFFFAOYSA-L

InChI=1S/H2O4S.Zn/c1-5(2,3)4;/h(H2,1,2,3,4);/q;+2/p-2

zinc sulfate

Zinc sulfate

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)

H2O : ~50 mg/mL (~309.71 mM; with ultrasonication)

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.)