Ascorbyl palmitate

414.53300

414.53

205-305-4

QN83US2B0N

DTXSID3041611

White or yellowish white powder

2932190090

113.29000

6.3

White to yellowish powder

1.15 g/cm3

116 °C

512.7±50.0 °C(Predicted)

178.1ºC

22.5 ° (C=1, EtOH)

Slightly soluble in ethyl alcohol.

3.32E-14mmHg at 25°C

LD50 orally in Rabbit: > 5000 mg/kg

Citrus-like

Henry's Law constant = 1.40X10-7 atm-cu m/mol at 25 °C (est)

204.8 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Weight/volume conversion: 16.92 mg/cu m approximately equal to 1 ppm|Base-catalyzed second-order hydrolysis reaction rate constant = 2.85X10-2 L/mol-sec at 25 °C (est)

NONH for all modes of transport

1

R20/21/22

S26-S36

CI7671040

Xn

Ascorbyl palmitate is stable in the dry state, but is gradually oxidized and becomes discolored when exposed to light and high humidity. During processing, temperatures greater than 658℃ should be avoided.

P264, P273, P280, P305+P351+P338, P337+P313, P501

H319

SRP: Criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Ascorbyl palmitate used as a chemical preservative in food for human consumption is generally recognized as safe when used in accordance with good manufacturing practice.|Ascorbyl palmitate used as a chemical preservative in animal drugs, feeds, and related products is generally recognized as safe when used in accordance with good manufacturing or feeding practice.

|Warning|H319 (43.87%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]|P264, P273, P280, P305+P351+P338, P337+P313, and P501|Aggregated GHS information provided by 416 companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Male MEl mice in which hepatotoxicity had been induced by the feeding of 600 mg/kg acetaminophen had covalent binding of acetaminophen metabolites to hepatic proteins, a depletion of hepatic nonprotein sulphydryl groups after 2 hours, and a dramatic increase in plasma alanine aminotransferase activity after 24 hours. The coadministration of acetaminophen and ascorbyl palmitate reduced this binding within 2 and 4 hours (to 31% and 22%, respectively), reduced the depletion in nonprotein sulfhdryl groups and aminotransferase activity, and completely prevented the 35% mortality observed at 24 hours after acetaminophen treatment alone. Ascorbyl palmitate appeared to prevent hepatic damage by removing the reactive acetaminophen metabolites and by having a sparing action on reduced hepatic glutathione.|Ascorbyl palmitate when topically applied at small doses inhibited 12-O-tetradecanoylphorbol-13-acetate-induced (TPA-induced) ornithine decarboxylase activity, tumor production, and DNA synthesis in mouse epithelial cell. A dose of 4 umol of ascorbyl palmitate inhibited by 60-70% after one topical application of 2 nmol TPA. When 5 nmol TPA was administered with 5 pmol ascorbyl palmitate twice weekly to previously initiated mice, 91% of tumors were inhibited per mouse.|... This work ... sought to determine the antioxidative properties of a lipid-soluble derivative of ascorbic acid, ascorbic acid-6-palmitate. ... Ascorbic acid-6-palmitate reduced cellular levels of reactive oxygen species following ultraviolet B irradiation. Treatment of keratinocytes with ascorbic acid-6-palmitate inhibited ultraviolet-B-mediated activation of epidermal growth factor receptor, extracellular regulated kinases 1 and 2, and p38 kinase because of its ability to prevent reduced glutathione depletion and scavenge hydrogen peroxide. Ascorbic acid-6-palmitate strongly promoted ultraviolet-B-induced lipid peroxidation, c-Jun N-terminal kinase activation, and cytotoxicity, however. End products of lipid peroxidation, such as 4-hydroxy-2-nonenal, have been reported to mediate stress-activated protein kinase activation and cell toxicity in epithelial cells. The lipid component of ascorbic acid-6-palmitate probably contributes to the generation of oxidized lipid metabolites that are toxic to epidermal cells. /The/ data suggest that, despite its antioxidant properties, ascorbic acid-6-palmitate may intensify skin damage following physiologic doses of ultraviolet radiation.|... The effects of various antioxidants, including ascorbyl palmitate, on rabbit platelet functions /were studied/ by means of thromboxane B2 synthesis and enzyme immunoassay. Ascorbyl palmitate inhibited A-23187-induced thromboxane B2 synthesis at 1.0 X 10-5 M and above, and thrombin-induced synthesis at 1. X 10-7 M when added simultaneously. The pretreatment of platelets with ascorbyl palmitate also inhibited both agonist-induced syntheses unless the platelets had been stimulated with thrombin. When the rabbits were fed ADI concentrations of ascorbyl palmitate for 5 days, agonist-induced activation of platelets also was reduced considerably.|For more Interactions (Complete) data for Ascorbyl palmitate (14 total), please visit the HSDB record page.

LD50 Guinea pig dermal >3 g/kg|LD50 Mouse oral >2 g/kg /33% suspension/|LD50 Rat oral >5 g/kg /33% suspension/

Ascorbyl palmitate's production and use as an antioxidant and as a chemical preservative food additive(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 450(SRC), determined from a structure estimation method(2), indicates that ascorbyl palmitate is expected to have moderate mobility in soil(SRC). Volatilization of ascorbyl palmitate from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.4X10-7 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Ascorbyl palmitate is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.09X10-15 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Biodegradation data in soil were not available(SRC, 2010).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 450(SRC), determined from a structure estimation method(2), indicates that ascorbyl palmitate is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.4X10-7 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 180(SRC), from an estimated log Kow of 6.0(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is high, provided the compound is not metabolized by the organism(SRC). Biodegradation data in water were not available(SRC, 2010).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), ascorbyl palmitate, which has an estimated vapor pressure of 2.09X10-15 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase ascorbyl palmitate may be removed from the air by wet or dry deposition(SRC). Ascorbyl palmitate does not contain chromophores that absorb at wavelengths >290 nm(3), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

A base-catalyzed second-order hydrolysis rate constant of 2.85X10-2 L/mole-sec(SRC) was estimated using a structure estimation method(1); this corresponds to half-lives of 7.7 years and 280 days at pH values of 7 and 8, respectively(1). Ascorbyl palmitate does not contain chromophores that absorb at wavelengths >290 nm(2), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 180 was calculated in fish for ascorbyl palmitate(SRC), using an estimated log Kow of 6.0(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is high(SRC), provided the compound is not metabolized by the organism(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of ascorbyl palmitate can be estimated to be 450(SRC). According to a classification scheme(2), this estimated Koc value suggests that ascorbyl palmitate is expected to have moderate mobility in soil.

The Henry's Law constant for ascorbyl palmitate is estimated as 1.4X10-7 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that ascorbyl palmitate is expected to be essentially nonvolatile from water surfaces(2). Ascorbyl palmitate is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.09X10-15 mm Hg(SRC), determined from a fragment constant method(3).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 3,051 workers (1,122 of these were female) were potentially exposed to ascorbyl palmitate in the US(1). Occupational exposure to ascorbyl palmitate may occur through inhalation and dermal contact with this compound at workplaces where ascorbyl palmitate is produced or used. Use data indicate that the general population may be exposed to ascorbyl palmitate via ingestion of food and via use of pharmaceutical products and antioxidants containing ascorbyl palmitate. (SRC)

Antimutagenic Agents; Antioxidants|Ascorbyl palmitate has a vitamin C activity approximately equal to that of L-ascorbic acid. ... Vitamin C is an essential cofactor for prolyl and lysyl hydroxylases, the enzymes involved in the intracellular biosynthesis of collagen.|/Experimental Therapy/ QR-333, a topical compound that contains quercetin, a flavonoid with aldose reductase inhibitor effects, ascorbyl palmitate, and vitamin D(3), was formulated to decrease the oxidative stress that contributes to peripheral diabetic neuropathy and thus alleviate its symptoms. ... This randomized, placebo-controlled, double-blind trial included 34 men and women (21-71 years of age) with Type 1 or 2 diabetes and diabetic neuropathy who applied QR-333 or placebo (2:1 ratio), three times daily for 4 weeks, to each foot where symptoms were experienced. ... QR-333 reduced the severity of numbness, jolting pain, and irritation from baseline values. Improvements were also seen in overall and specific quality-of-life measures. QR-333 was well tolerated. Eleven patients in the QR-333 group reported 23 adverse events (all mild or moderate); 4 in the placebo group reported 5 events (all moderate). One patient who applied QR-333 noted a pricking sensation twice, the only adverse event considered possibly related to study treatment...|The presence of ascorbyl palmitate in oral supplements contributes to the ascorbic acid content of the supplement and probably helps protect fat-soluble antioxidants in the supplement.

Agents that reduce the frequency or rate of spontaneous or induced mutations independently of the mechanism involved. (See all compounds classified as Antimutagenic Agents.)|Substances that inhibit or prevent the proliferation of NEOPLASMS. (See all compounds classified as Antineoplastic Agents.)|Naturally occurring or synthetic substances that inhibit or retard oxidation reactions. They counteract the damaging effects of oxidation in animal tissues. (See all compounds classified as Antioxidants.)

When incorporated into the cell membranes of human red blood cells, ascorbyl palmitate has been found to protect them from oxidative damage and to protect alpha-tocopherol (a fat-soluble antioxidant) from oxidation by free radicals. However, the protective effects of ascorbyl palmitate on cell membranes have only been demonstrated in the test tube. Taking ascorbyl palmitate orally probably doesn't result in any significant incorporation into cell membranes because most of it appears to be hydrolyzed (broken apart into palmitate and ascorbic acid) in the human digestive tract before it is absorbed. The ascorbic acid released by the hydrolysis of ascorbyl palmitate appears to be as bioavailable as ascorbic acid alone.|When applied topically to guinea pigs, ascorbyl palmitate penetrated the skin barrier so that ascorbic acid content in the skin, liver, and blood increased eight-, seven-, and four-fold, respectively, when compared to control animals that did not receive ascorbyl palmitate.|(14)C-Ascorbyl palmitate was applied to the skin of scorbutic (affected by scurvy) guinea pigs. Following the topical application, ascorbic acid concentrations in the skin, liver, kidneys, and blood were four to eight times greater than in the control.|Ascorbyl palmitate dissolved in a sodium taurocholate solution was hydrolyzed by homogenates of the liver, pancreas, and intestines of guinea pigs. Approximately 80% of ascorbyl palmitate was hydrolyzed to free ascorbic acid by homogenates of the small intestine and pancreas. ... Ascorbyl palmitate (the equivalent of 20 mg of ascorbic acid) was orally administered to guinea pigs, and the amount of free ascorbic acid excreted in the urine was measured. Greater amounts of acid were excreted at 0-24 hours than at 24-48 hours. A similar trend was found in these organs of free ascorbic acid content when L-ascorbic acid was administered instead, but a reverse tendency was observed with ascorbyl palmitate.

Vitamin C (ascorbic acid) is a non-enzymatic antioxidant important in protecting the lung against oxidative damage and is decreased in lung lining fluid of horses with airway inflammation. To examine possible therapeutic regimens in a species with ascorbate-synthesising capacity, ... Te effects of oral supplementation of two forms of ascorbic acid, (each equivalent to 20 mg ascorbic acid per kg body weight) on the pulmonary and systemic antioxidant status of six healthy ponies in a 3 x 3 Latin square design. Two weeks supplementation with ascorbyl palmitate significantly increased mean plasma ascorbic acid concentrations compared to control (29 +/-- 5 and 18 +/- 7 umol/L, respectively; p < 0.05). Calcium ascorbyl-2-monophosphate, a more stable form of ascorbic acid, also increased mean plasma ascorbic acid concentrations, but not significantly (23 +/- 1 umol/L; p = 0.07). The concentration of ascorbic acid in bronchoalveolar lavage fluid increased in five out of six ponies following supplementation with either ascorbyl palmitate or calcium ascorbyl-2-monophosphate compared with control (30 +/- 10, 25 +/- 4 and 18 +/- 8 umol/L, respectively; p < 0.01). Neither supplement altered the concentration of glutathione, uric acid or alpha-tocopherol in plasma or bronchoalveolar lavage fluid. In conclusion, the concentration of lung lining fluid ascorbic acid is increased following ascorbic acid supplementation (20 mg/kg body weight) in an ascorbate-synthesising species.|It has been known that solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have occlusive effects, but ascorbyl palmitate (AP) incorporation moisturized skin significantly better than placebo in short-term (p < 0.001) and long-term trials (p < 0.01) for both SLN and NLC. In the second part of the study, SLN and NLC were found to sustain the penetration of AP through excised human skin about 1/2 and 2/3 times compared to NE (p < 0.001 and p < 0.01), respectively...|6-O-Palmitoyl-L-ascorbic acid dissolved in a sodium taurocholate solution was hydrolyzed by homogenates of the pancreas, liver, and intestines of guinea pigs.

... Whether L-ascorbic acid 6-palmitate (AAP), an amphipathic derivative of AA, has chemopreventive effects /was examined/ using a gap-junctional intercellular communication (GJIC) model. AAP and ascorbic acid (AA) exhibited dose-dependent free radical-scavenging activities and inhibited hydrogen peroxide (H(2)O(2))-induced intracellular reactive oxygen species (ROS) production in normal rat liver epithelial cells. Unexpectedly, however, AAP did not protect against the inhibition of GJIC induced by H(2)O(2); instead, it inhibited GJIC synergistically with H(2)O(2). AAP inhibited GJIC in a dose-dependent and reversible manner. This inhibitory effect was not due to the conjugated lipid structure of AAP, as treatment with palmitic acid alone failed to inhibit GJIC under the same conditions. The inhibition of GJIC by AAP was restored in the presence of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor U0126, but not in the presence of other signal inhibitors and antioxidant (PKC inhibitors, EGFR inhibitor, NADPH oxidase inhibitor, catalase, vitamin E, or AA), indicating the critical involvement of MEK signaling in the GJIC inhibitory activity of AAP. Phosphorylation of ERK and connexin 43 (Cx43) was observed following AAP treatment, and this was reversed by U0126. These results suggest that the AAP-induced inhibition of GJIC is mediated by the phosphorylation of Cx43 via activation of the MEK-ERK pathway.

The National Formulary states that ascorbyl palmitate must contain between 95.0% and 100.5% of C22H3807, based on the dried weight. Depending on the method of manufacture, ascorbyl palmitate could contain stearic acid, because palmitic acid samples contain large quantities of stearic acid.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ One hundred nineteen subjects were enrolled in a modified Draize assay for skin sensitization potential. Of those, 106 completed the study. Ascorbyl palmitate at concentrations of 1%, 3%, and 5% in petrolatum (0.025 g) was applied under occlusive conditions to the scapular back using a Finn Chamber. The test materials were applied three times per week for 3 consecutive weeks, and once in the 4th week (10 applications). The patch sites were evaluated 48 or 72 hours after application. Twelve days after the last patch was removed, a challenge patch was applied to an untreated skin site on the scapular back. The patch was removed at 48 hours, and the site was scored at patch removal and at 96 hours. One subject had a rash on his torso during the 3rd week of the study, but this was attributed to exclusionary medication that was not reported on the subject's personal and medical history, and was not related to the test substances. During induction, the 1 % preparation caused seven 1 + reactions in a single subject. No reactions were noted for the 3% preparation, and one subject had five 1 + reactions after being treated with the 5% preparation. Under the conditions of this study, the investigators concluded that 1-5% ascorbyl palmitate was not sensitizing.|/HUMAN EXPOSURE STUDIES/ A maximization test using 15 female and 13 male subjects was performed to determine the contact sensitization potential of an eye cream containing 0.2% ascorbyl palmitate. Skin sites on the upper outer arm, volar forearm, or back of each subject were pretreated with 0.1 mL of sodium lauryl sulfate (SLS) at a concentration of 0.25% and covered with occlusive patches for 24 hours. At patch removal, 0.1 mL of the test eye cream was applied to the same site and covered with occlusive tape. This induction patch remained in place for 48 hours, after which it was removed and the test site was examined for signs of irritation. If no irritation was observed, the pretreatment-treatment procedure was repeated at the same skin site for a total of five induction exposures. If irritation was observed, the treatment patch only was applied for the duration of the study. Ten days after the last induction patch application, 0.1 mL of SLS (5.0%) was applied to an untreated skin site under an occlusive patch for 1 hour. The SLS patch was removed and replaced with a challenge patch containing the eye cream. At 48 h and 72 hours, the skin sites were examined for sensitization. Twenty-six subjects completed the study; the remaining 2 subjects withdrew for reasons unrelated to the study. No adverse reactions or signs of dermal sensitization were observed during this study.|/ALTERNATIVE and IN VITRO TESTS/ Rapidly growing tumor cells in rodents and humans have high glutathione S-transferase (GST) activity, and GST can be involved in tumor cell drug resistance. Ascorbyl palmitate significantly inhibited human term placental and fetal liver GST activity towards its second substrate, 1-chloro-2, 4-dinitrobenzene (K=10.0 uM). The I50 (uM) for ascorbyl palmitate was 45 +/- 0.3 when tested using cultures of human fetal liver, and 6 +/- 1.5 using cultures of rat liver.|/OTHER TOXICITY INFORMATION/ Glutathione-S-transferase (GST) activity from human term placenta and human fetal liver towards 1-chloro-2,4-dinitrobenzene as the second substrate was significantly inhibited by the saturated fatty acids, stearic (SA) and palmitic (PA) acids and fatty acid esters, ascorbyl stearate (Asc-S) and ascorbyl palmitate (Asc-P). The nature of inhibition of human placental GST was competitive towards CDNB with Ki values of 3.1, 10.0, 13.5 and 18.5 uM for Asc-S, Asc-P, PA and SA, respectively. The inhibitory effect of Asc-S on human term placental GST was reversible. I50 values for Asc-S, Asc-P, SA and PA were 15, 45, 83 and 78 uM, respectively, for partially purified human fetal liver GSTs and 21, 6, 88 and 117 uM, respectively, for partially pure rat liver GSTs...

6-O-palmitoylascorbate

100% AS AN ANTIOXIDANT SYNERGIST IN FATS & OILS (1973)

Grade: FCC (Foods Chemical Codex).

L-Ascorbic acid, 6-hexadecanoate: ACTIVE|Ascorbyl palmitate is an antioxidant in foods containing vegetable oil and animal fats; more recently it has appeared in the neutraceutical pantheon under the name "ester-C."|Active compounds can be protected against degradation by incorporation into colloidal carrier systems. The stabilizing effect of carrier systems for ascorbyl palmitate (AP) was investigated using microemulsions (ME), liposomes and solid lipid nanoparticles (SLN). Analysis of chemical stability by HPLC showed that AP is most resistant against oxidation in non-hydrogenated soybean lecithin liposomes, followed by SLN, w/o and o/w ME, and hydrogenated soybean lecithin liposomes...|Ascorbic acid (AA), also known as vitamin C, is a very popular skin-whitening agent used in cosmetics. However, the use of AA (and also its sodium or magnesium salts) in cosmetic products is limited owing to its labile oxidative properties. In order to avoid its early degradation, different derivatives have been designed, such as ascorbyl phosphate (APH; as magnesium or sodium salts) and ascorbyl palmitate (AP), and more recently the ascorbyl glucoside (AG).

EPA Safer Chemical Functional Use Classes -> Preservatives and Antioxidants|Safer Chemical Classes -> Green half-circle - The chemical is expected to be of low concern|Food additives|Food Additives -> ANTIOXIDANT; -> JECFA Functional Classes|Cosmetics -> Antioxidant

Food Additives -> ANTIOXIDANT;