DL-α-Tocopherol

430.71

430.71

94012

233-466-0

7QWA1RIO01

755839|82623|20812

DTXSID8021355

C74578

Slightly viscous, pale yellow oil

29.5

log Kow = 12.2 (est)

Liquid

0.950 g/mL at 20 °C(lit.)

2-4°C

205-210 °C @ Press: 0.02 Torr

240°C

n20/D 1.506

Miscible with chloroform, vegetable oils, ether, acetone and alcohol. Immiscible with water.

2-8°C

1.4X10-8 mm Hg at 25 °C (est)

[α]D/25 0° ± 0,05° (1 in 10 solution in chloroform)

Henry's Law constant = 7.9X10-5 atm-cu m/mole 25 °C (est)

pKa = 10.8 (hydroxy) (est)

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

Hydroxyl radical reaction rate constant = 2.3X10-10 cu cm/molec-sec at 25 °C (est)

UN1230 - class 3 - PG 2 - Methanol, solution

1

36/37/38-39/23/24/25-23/24/25-11

26-37/39-45-36/37-16-7

GA8746000

Xi,T,F

Exposure to light. Stable under recommended storage conditions.

P210-P260-P280-P301 + P310-P311

H225-H301 + H311 + H331-H370

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.|Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contaminated packaging :Dispose of as unused product.

Strong oxidizing agents

Substance added directly to human food affirmed as generally recognized as safe (GRAS).

Not Classified| |Warning|H317 (99.44%): May cause an allergic skin reaction [Warning Sensitization, Skin]|P261, P272, P280, P302+P352, P321, P333+P313, P363, and P501|Aggregated GHS information provided by 2175 companies from 10 notifications to the ECHA C&L Inventory.

Skin protection: Handle with gloves.|Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).|Respiratory protection: Respiratory protection not required. For nuisance exposures use type OV/AG (US) or type ABEK (EU EN 14387) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).|Body Protection: Impervious clothing. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Wear self contained breathing apparatus for fire fighting if necessary.|Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures Avoid breathing vapors, mist or gas. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Keep in suitable, closed containers for disposal.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

IDENTIFICATION AND USE: dl-alpha-Tocopherol is a slightly viscous, pale yellow oil. This is a synthetic form of alpha tocopherol. The activity of natural alpha-tocopherol on an equal weight basis, is at least twice as high as the synthetic form. dl-alpha-Tocopherol is used as an antioxidant in fats and oils and in animal feed. It is also used as experimental medication and as a dietary supplement. HUMAN EXPOSURE AND TOXICITY: Of 23,908 patients patch tested, 219 (0.9%) had sunscreen coded as an allergen source. The top 3 most frequent allergens in sunscreens were benzophenone-3, dl-alpha-tocopherol, and fragrance mix. Dietary supplementation with moderate dosage synthetic dl-alpha-tocopherol acetate did not significantly prolong bleeding or platelet aggregation in healthy volunteers. dl-alpha-Tocopherol provided protection against exercise-induced oxidative injury in healthy volunteers according to several reports. In vitro experiments demonstrated general inhibition of cell proliferation by dl-alpha-tocopherol, with breast and prostate cancer cells distinctly more sensitive than erythroleukemia cells. ANIMAL STUDIES: In chicks exposed to dl-alpha-tocopherol acetate for 3-8 weeks it caused prolonged prothrombin times, reticulocytosis, and a reduced hematocrit value. Supplementation of dl-alpha-tocopherol increased alpha-tocopherol concentration in cows; however, effects on reproductive efficiency were minimal. The addition of dl-alpha-tocopherol to leucocyte cultures reduced the number of chromosome breaks induced by 7,12-dimethylbenz(a)anthracene. dl-alpha-Tocopherol markedly reduced the mutagenic effect of malonaldehyde and beta-propiolactone in five strains of Salmonella typhimurium, which mutated with a frameshift mechanism.

Inflammatory bowel disease is often associated with iron deficiency anemia and oral iron supplementation may be required. However, iron may increase oxidative stress through the Fenton reaction and thus exacerbate the disease. This study was designed to determine in rats with dextran sulfate sodium (DSS)-induced colitis whether oral iron supplementation increases intestinal inflammation and oxidative stress and whether the addition of an antioxidant, vitamin E, would reduce this detrimental effect. Four groups of rats that consumed 50 g/L DSS in drinking water were studied for 7 d and were fed: a control, nonpurified diet (iron, 270 mg, and dl-alpha-tocopherol acetate, 49 mg/kg); diet + iron (iron, 3000 mg/kg); diet + vitamin E (dl-alpha-tocopherol acetate, 2000 mg/kg) and the diet + both iron and vitamin E, each at the same concentrations as above. Body weight change, rectal bleeding, histological scores, plasma and colonic lipid peroxides (LPO), plasma 8-isoprostane, colonic glutathione peroxidase (GPx) and plasma vitamin E were measured. Iron supplementation increased disease activity as demonstrated by higher histological scores and heavier rectal bleeding. This was associated with an increase in colonic and plasma LPO and plasma 8-isoprostane as well as a decrease in colonic GPx. Vitamin E supplementation decreased colonic inflammation and rectal bleeding but did not affect oxidative stress, suggesting another mechanism for reducing inflammation. In conclusion, oral iron supplementation resulted in an increase in disease activity in this model of colitis. This detrimental effect on disease activity was reduced by vitamin E. Therefore, the addition of vitamin E to oral iron supplementation may be beneficial.|Previous studies have shown that beta-carotene and alpha-tocopherol can act synergistically to inhibit the growth of experimentally induced oral cancer. The initial studies on the synergistic anticancer activity of antioxidants have been extended to include reduced glutathione and ascorbic acid. Sixty male hamsters (4-5 wks old) were divided into six equal groups. Groups 1-6 were treated with 7,12-dimethylbenz[a]anthracene (DMBA) (0.5% solution). Group 2 received a mixture containing equal amounts of beta-carotene, dl-alpha-tocopherol (vitamin E), glutathione, and l-ascorbic acid (vitamin C) (12.5 micrograms) delivered orally by pipette. Groups 3-6 were treated with beta-carotene alone (50 micrograms), vitamin E alone (50 micrograms), glutathione (50 micrograms) alone, and vitamin C alone (50 micrograms). Animals were euthanized at 12 and 14 weeks. Tumors were counted and measured, and tumor burden was calculated for each experimental group. The mixture of antioxidants significantly reduced tumor burden, whereas the beta-carotene, vitamin E, and reduced glutathione treatments also reduced tumor burden. beta-Carotene and glutathione provided greater levels of chemoprevention than vitamin E as single agents. In contrast, vitamin C treatment produced no antitumor effect but increased tumor burden by Week 14. This mixture of antioxidants produced a significant synergistic chemoprevention of oral cancer.|Ferric nitrilotriacetate (Fe-NTA) is a potent nephrotoxic agent. In this communication, we show the modulatory effect of DL-alpha-tocopherol (Vitamin-E) on ferric nitrilotriacetate (Fe-NTA)-induced renal oxidative stress, toxicity and hyperproliferative response in rats. Fe-NTA-treatment enhances the susceptibility of renal microsomal membrane for iron-ascorbate-induced lipid peroxidation and hydrogen peroxide generation which are accompanied by a decrease in the activities of renal antioxidant enzymes, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase and depletion in the level of renal glutathione. Parallel to these changes, a sharp increase in blood urea nitrogen and serum creatinine has been observed. In addition, Fe-NTA-treatment also enhances renal ornithine decarboxylase activity (ODC) and increases [(3)H]thymidine incorporation in renal DNA. Prophylactic treatment of animals with /vitamin E/ Vit.E daily for 1 week prior to the administration of Fe-NTA resulted in the diminution of Fe-NTA-mediated damage. Enhanced susceptibility of renal microsomal membrane for lipid peroxidation induced by iron-ascorbate and hydrogen peroxide generation were significantly reduced (P < 0.05). In addition, the depleted level of glutathione and inhibited activities of antioxidant enzymes recovered to significant levels (P < 0.05). Similarly, the enhanced blood urea nitrogen and serum creatinine levels which are indicative of renal injury showed a reduction of about 50% at a higher dose of Vit.E. The pretreatment of rats with Vit.E reduced the Fe-NTA-mediated induction in ODC activity and enhancement in [(3)H]thymidine incorporation in DNA. The protective effect of Vit.E was dose dependent. In summary, our data suggest that Vit.E is an effective chemopreventive agent in kidney and may suppress Fe-NTA-induced renal toxicity.|Ultraviolet (UV) irradiation of C3H/HeN mice induces skin cancer and an immunosuppression that prevents the host from rejecting antigenic UV-induced tumors. The capacity of topical vitamin E (dl-alpha-tocopherol) to prevent photocarcinogenesis or the immunosuppression induced by UV irradiation was assessed. Skin cancer incidence in UV-irradiated mice was 81% at 33 weeks after the first UV exposure; application to mice of 25 mg vitamin E three times per week for three weeks before UV irradiation, and throughout the experiment, reduced this incidence to 42% (p = 0.0065, log rank test). Immunoenhancement by vitamin E was assessed by comparing levels of immunosuppression by splenocytes from normal or UV-irradiated mice, with and without topical vitamin E treatment. Transfer of splenocytes from UV-irradiated mice to naive mice prevented the recipients from rejecting a UV-induced tumor challenge, whereas splenocytes from UV-irradiated mice treated with vitamin E did not prevent recipients from rejecting a similar tumor challenge. Phenotypic analysis of splenocytes used in the passive transfer assay, conducted with a biotin-avidin-immunoperoxidase technique, revealed that vitamin E treatment of mice undergoing UV irradiation prevented the UV-induced down regulation of Ia expression in splenocytes and increased the proportion of Lyt-2+ and L3T4+ splenocytes. Therefore, chronically applied vitamin E can effectively reduce cancer formation and immunosuppression induced by UV irradiation. Prevention of UV-induced down regulation of Ia expression may have contributed to this immunomodulation.|For more Interactions (Complete) data for dl-alpha-Tocopherol (9 total), please visit the HSDB record page.

dl-alpha-Tocopherol is a totally synthetic formulation of alpha-tocopherol(1); therefore, it is not naturally occurring(SRC).

dl-alpha-Tocopherol's production and use as a biological antioxidant(1), as a nitrosamine blocker in meat curing(1), as an antioxidant in cosmetics(2), as a dietary supplement(3) and chemical intermediate(4) 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 2.5X10+7(SRC), determined from a structure estimation method(2), indicates that dl-alpha-tocopherol is expected to be immobile in soil(SRC). Volatilization of dl-alpha-tocopherol from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.9X10-5 atm-cu m/mole(SRC), using a fragment constant estimation method(2). However, adsorption to soil is expected to attenuate volatilization(SRC). dl-alpha-Tocopherol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.4X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Naturally occurring alpha-tocopherol was biodegraded by aerobic bacterial communities isolated from marine sediment(3). However, biodegradation data on dl-alpha-tocopherol relevant to environmental importance in soil were not available.(SRC, 2015). dl-alpha-Tocopherol has a UV absorption maxima at 294 nm(4) and, therefore, may be susceptible to direct photolysis on soil surfaces exposed to sunlight(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2.5X10+7(SRC), determined from a structure estimation method(2), indicates that dl-alpha-tocopherol is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 7.9X10-5 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 29 hours and 15 days, respectively(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column(SRC). The estimated volatilization half-life from a model pond is >10 years if adsorption is considered(4). According to a classification scheme(5), an estimated BCF of 39(SRC), from an estimated log Kow of 12.2(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Naturally occurring alpha-tocopherol was biodegraded by aerobic bacterial communities isolated from marine sediment(5). However, biodegradation data on dl-alpha-tocopherol relevant to environmental importance in water were not available.(SRC, 2015). dl-alpha-Tocopherol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), dl-alpha-tocopherol, which has an estimated vapor pressure of 1.4X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases (in the ambient atmosphere. Vapor-phase dl-alpha-tocopherol is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 1.7 hours(SRC), calculated from its rate constant of 1.7X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Particulate-phase dl-alpha-tocopherol may be removed from the air by wet and dry deposition(SRC). dl-alpha-Tocopherol has a UV absorption maxima at 294 nm(3), and therefore, may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of dl-alpha-tocopherol with photochemically-produced hydroxyl radicals has been estimated as 2.3X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 1.7 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). dl-alpha-Tocopherol has a UV absorption maxima at 294 nm(2), and therefore, may be susceptible to direct photolysis by sunlight(SRC). dl-alpha-Tocopherol is reported to gradually darken on exposure to light(2). It is slowly oxidized by atmospheric oxygen(2). dl-alpha-Tocopherol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3).

An estimated BCF of 39 was calculated in fish for dl-alpha-tocopherol(SRC), using an estimated log Kow of 12.2(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(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 dl-alpha-tocopherol can be estimated to be 2.5X10+7(SRC). According to a classification scheme(2), this estimated Koc value suggests that dl-alpha-tocopherol is expected to be immobile in soil.

The Henry's Law constant for dl-alpha-tocopherol is estimated as 7.9X10-5 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that dl-alpha-tocopherol is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 29 hours(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 15 days(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column(SRC). The estimated volatilization half-life from a model pond is >10 years if adsorption is considered(3). dl-alpha-Tocopherol's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC), but volatilization from soil is expected to be attenuated by adsorption(SRC). dl-alpha-Tocopherol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.4X10-8 mm Hg(SRC), determined from a fragment constant method(1).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 114 workers (0 of these were female) were potentially exposed to dl-alpha-tocopherol in the US(1). Occupational exposure to dl-alpha-tocopherol may occur through dermal contact with this compound at workplaces where dl-alpha-tocopherol is produced or used. Monitoring and use data indicate that the general population may be exposed to dl-alpha-tocopherol via ingestion of food and food supplements, and dermal contact with consumer products containing dl-alpha-tocopherol(SRC).

EXPL THER We evaluated the effects of vitamin E (dl-alpha-tocopherol) on mutagen sensitivity levels in a randomized placebo-controlled pilot trial. In brief, a dietary supplement of 1000 mg/day vitamin E or a placebo was randomly administered for 3 months to melanoma outpatients clinically free of the disease. Plasma vitamin E and mutagen sensitivity levels were measured at baseline and at the end of the trial after 3 months. At baseline, we found no significant differences in plasma vitamin E and mutagen sensitivity levels between the two groups. We also measured dietary intake at baseline and found dietary vitamin E to be a poor predictor of plasma levels of vitamin E. After 3 months of supplementation, we found that plasma levels of alpha-tocopherol increased significantly (P = 0.0005) in the vitamin E compared to the placebo group. We also found a non-significant, but consistent decrease in plasma gamma-tocopherol concentrations in the vitamin E supplemented compared to the placebo group. We did not find any significant difference between the vitamin E and placebo groups in mutagen sensitivity levels either at baseline or after 3 months of supplementation. We conclude that short term vitamin E supplementation, although it causes increased blood levels of alpha-tocopherol, does not provide protection against bleomycin-induced chromosome damage.|EXPL THER Epidemiological studies have demonstrated an inverse relationship between vitamin E intake and cardiovascular disease (CVD) risk. In contrast, randomized controlled trials have reported conflicting results as to whether vitamin E supplementation reduces atherosclerosis progression and CVD events. The study population consisted of men and women > or =40 years old with an LDL cholesterol level > or =3.37 mmol/L (130 mg/dL) and no clinical signs or symptoms of CVD. Eligible participants were randomized to DL-alpha-tocopherol 400 IU per day or placebo and followed every 3 months for an average of 3 years. The primary trial end point was the rate of change in the common carotid artery far-wall intima-media thickness (IMT) assessed by computer image-processed B-mode ultrasonograms. A mixed effects model using all determinations of IMT was used to test the hypothesis of treatment differences in IMT change rates. Compared with placebo, alpha-tocopherol supplementation significantly raised plasma vitamin E levels (P<0.0001), reduced circulating oxidized LDL (P=0.03), and reduced LDL oxidative susceptibility (P<0.01). However, vitamin E supplementation did not reduce the progression of IMT over a 3-year period compared with subjects randomized to placebo. The results are consistent with previous randomized controlled trials and extend the null results of vitamin E supplementation to the progression of IMT in healthy men and women at low risk for CVD.|EXPL THER The glycation of proteins and elevated triglyceride (TG) levels are two of the major risk factors in the development of complications of diabetes. Previous studies have found some beneficial effects of supplementation of pharmacological doses (900-2000 IU/day) of vitamin E in Type II diabetic patients. This study examined whether supplementation with a modest dose of vitamin E (100 IU/day) had any effect on blood glucose, glycated hemoglobin (GHb), TG or red cell counts in Type I diabetic patients. 35 diabetic patients were supplemented with either DL-alpha-tocopherol (vitamin E) capsules (orally, 100 IU/day) or a placebo for 3 months in a double-blind clinical trial. Fasting blood was collected from each diabetic patient before and after vitamin E or placebo supplementation. Data were analyzed using paired "t" tests and the Wilcoxon Signed Rank Test. Levels of GHb (mean +/- SEM) were 11.5 +/- 0.4 and 12.8 +/- 0.9% (p < 0.05); glucose, 8.8 +/- 1.2 and 11.6 +/- 1.3 mM; and TG, 2.2 +/- 0.2 and 2.9 +/- 0.3 mM (p < 0.03) after vitamin E supplementation versus before supplementation. There were no differences in these parameters after supplementation with the placebo. There was no effect on blood RBC, hematocrit, and hemoglobin levels after supplementation of vitamin E or the placebo. There were no differences in ages and duration of diabetes between placebo and vitamin E-supplemented groups. This study suggests that modest vitamin E supplementation (100 IU/day) can significantly lower blood GHb and TG levels and does not have any effect on red cell indices in Type I diabetic patients.|EXPL THER Dietary components may be both causal and protective in cases of pancreatic carcinoma, but the preventive potential of single constituents has not been evaluated. The /study/ report the effects of alpha-tocopherol and beta-carotene supplementations on the rates of incidence of and mortality from pancreatic carcinoma in a randomized, controlled trial. The 29,133 participants in the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study were male smokers who were ages 50-69 years at the time they were randomized into 1 of the following 4 intervention groups: dl-alpha-tocopherol (AT; 50 mg/day), beta-carotene (BC; 20 mg/day), both AT and BC, and placebo. The daily supplementation lasted for 5-8 years. Incident cancers were identified through the national Finnish Cancer Registry and death certificates of the Statistics Finland. Results were analyzed by supplementation with Cox regression models. Effects of both supplementations were statistically nonsignificant. The rate of incidence of pancreatic carcinoma was 25% lower for the men who received beta-carotene supplements (n = 38) compared with the rate for those who did not receive beta-carotene (n = 51) (95% CI, -51% to 14%). Supplementation with alpha-tocopherol (n = 51) increased the rate of incidence by 34% (95% CI, -12% to 105%) compared with the rate for those who did not receive alpha-tocopherol. Mortality from pancreatic carcinoma during the follow-up, adjusted for stage and anatomic location of the tumor, was 19% (95% CI, -47% to 26%) lower among those who received beta-carotene and 11% (95% CI, -28% to 72%) higher among those who received alpha-tocopherol as compared with those who did not receive supplementation. Supplementation with beta-carotene or alpha-tocopherol does not have a statistically significant effect on the rate of incidence of pancreatic carcinoma or the rate of mortality caused by this disease.|For more Therapeutic Uses (Complete) data for dl-alpha-Tocopherol (7 total), please visit the HSDB record page.

The 2R-stereoisomers are the only forms of alpha-tocopherol that are maintained in human plasma and tissue. The activity of natural or natural-source alpha-tocopherol (RRR alpha-tocopherol), on an equal weight basis, is at least twice as high as synthetic alpha-tocopherol. This is mainly because half of the stereoisomers of synthetic alpha-tocopherol are not maintained in human plasma and are, therefore, not bioavailable.

The main impurities resulting from the synthesis consist of tocopherol-related products (impurity A: all-rac-trans-2,3,4,6,7-pentamethyl-2-(4,8,12-trimethyltridecyl)-2,3-dihydrobenzofuran-5-ol; impurity B: all-rac-cis-2,3,4,6,7-pentamethyl-2-(4,8,12-trimethyltridecyl)-2,3-dihydrobenzofuran-5-ol; impurity C: 4-methoxy-2,3,6-trimethyl-5-[(all-RS,E)-3,7,11,15-tetramethylhexadec-2-enyl]phenol; impurity D: (all-RS, all-E)-2,6,10,14,19,23,27,31-octamethyldotriaconta-12,14,18-triene). On average from five batches,they amount to approximately 1.7 %.

/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 TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) 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/ To investigate the in vivo effect of short-term, moderate dosage synthetic dl-alpha-tocopherol acetate supplementation on platelet aggregation, coagulation profile, and simulated bleeding time in healthy individuals. alpha-tocopherol is the most biologically active isomer of Vitamin E, traditionally promoted as an antioxidant and therapeutic agent in cardiovascular disease. In vitro studies have suggested that alpha-tocopherol plays a role in the inhibition of platelet aggregation. However, further investigations into the effect of alpha-tocopherol on bleeding in vivo have not duplicated these findings. A total of 42 healthy volunteers complied with a 2-week abstinence period from the use of anti-platelet agents followed by determination of baseline platelet aggregation properties and coagulation studies using citrated whole blood. Moderate dosage Vitamin E (800 IU of dl-alpha-tocopherol acetate) was then self-administered for 14 days with reevaluation of platelet aggregation and coagulation profile, and simulated bleeding time after 14 days of Vitamin E supplementation. Forty subjects completed the 4-week study period. All 40 subjects demonstrated normal baseline coagulation studies and all had collagen-stimulated platelet aggregation assessment performed in triplicate. After Vitamin E supplementation, no significant difference was demonstrated in any study parameter. Dietary supplementation with moderate dosage synthetic dl-alpha-tocopherol acetate did not significantly prolong bleeding or platelet aggregation in vivo. The affect of Vitamin E on platelet aggregation in vitro does not appear to be reproducible in vivo. Therefore, peri-operative discontinuation of Vitamin E may not be necessary.|/HUMAN EXPOSURE STUDIES/ The protective effect of vitamin E supplementation on exercise-induced oxidative damage was tested in 21 male volunteers. Nine young (22-29 yr) and 12 older (55-74 yr) sedentary male subjects participated in a double-blind protocol and received either 800 IU dl-alpha-tocopherol or a placebo daily. After 48 days, vitamin E supplementation significantly increased alpha-tocopherol in plasma and skeletal muscle. Subjects then performed a bout of eccentric exercise at 75% of their maximum heart rate by running down an inclined treadmill for 45 min. All vitamin E-supplemented subjects excreted less (P < 0.05) urinary thiobarbituric acid adducts after the exercise bout than placebo subjects at 12 days postexercise (35 and 18% above baseline in young and old supplemented groups, respectively, vs. 60 and 80% in young and old placebo groups, respectively). After exercise, the initial difference in alpha-tocopherol concentration of muscle between young placebo and vitamin E-supplemented groups was diminished and muscle lipid conjugated dienes tended to increase (P = 0.09) in placebo subjects. Placebo subjects had a significant decrease in major fatty acids of muscle biopsy taken immediately after exercise. When normalized for the hemoconcentration effects of exercise, the plasma concentration of vitamins E and C and uric acid showed no significant change. The alterations in fatty acid composition, vitamin E, and lipid conjugated dienes in muscle and in urinary lipid peroxides in controls after eccentric exercise are consistent with the concept that vitamin E provides protection against exercise-induced oxidative injury.|/HUMAN EXPOSURE STUDIES/ Expired pentane, an index of lipid peroxidation, and pulmonary function were measured as a function of exercise for 1 hr with and without exposure to 0.3 ppm ozone. In experiment 1, 10 subjects who exercised on a bicycle ergometer at 50% of maximal oxygen consumption while being exposed to 0.3 ppm ozone had increased lung residual volume and decreased vital capacity, maximal midexpiratory flow rate, and forced expiratory volume in 1 s. In experiment 2, breath collected into a spirometer filled with hydrocarbon-scrubbed air showed increased pentane from the stress of exercise but no effect of ozone. During rest and exercise in experiment 3, two of six subjects had higher pentane levels than the other subjects. Following daily supplementation with 1,200 IU dl-alpha-tocopherol for 2 wk, the mean production of pentane during rest and exercise was significantly lowered, and there was no difference in pentane production among the subjects. It was concluded that lipid peroxidation occurs during exercise and that it is attenuated by vitamin E.|/HUMAN EXPOSURE STUDIES/ Free radical-mediated oxidative stress has been implicated in the pathogenesis of numerous chronic diseases. Vitamin E is known to play an important role in the free-radical quenching process. However, clinical trials with vitamin E have yielded contrasting results in the prevention of several diseases related to oxidative stress. This study was undertaken to investigate the antioxidative and humoral immunologic effects of vitamin E supplementation in three different age groups: young (mean age 32.7 +/- 5.7 y), middle-aged (mean age 47.0 +/- 5.0 y) and elderly (67.6 +/- 4.7 y) women. Volunteer subjects were given a supplement of 400 IU dl-alpha-tocopherol acetate for 6 wk. Thiobarbituric acid reacting substances (TBARS) in the plasma significantly decreased with vitamin E supplementation. In addition, the radical scavenger activities (RSA) of red blood cells significantly increased with vitamin E supplementation in all age groups. However, humoral immune response modulation was not observed following vitamin E supplementation. Even though there is no clear indication that vitamin E supplementation is necessary to improve the humoral immune functions, vitamin E supplementation may be beneficial to all adult age groups as a preventive measure for complications related to oxidative damage.|For more Human Toxicity Excerpts (Complete) data for dl-alpha-Tocopherol (7 total), please visit the HSDB record page.

DL-ALPHA-TOCOPHERYL SUCCINATE; dl-Apha-tocopheryl succinate is not available as a nutritional supplement. The reason for this is that it does not crystallize well but forms a paste. However, it is available for research purposes.|DL-ALPHA-TOCOPHERYL ACETATE; dl-Alpha-tocopheryl acetate is available as a stand-alone supplement and in combination products. Typical doses for supplementation range from 100 to 400 IU daily (as alpha-tocopherol).

All other chemical product and preparation manufacturing|2H-1-Benzopyran-6-ol, 3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-: ACTIVE|All-rac-alpha-tocopherol has also vitamin E activity; 1 mg of all-rac-alpha-tocopherol is equivalent to 1.10 IU of vitamin E.|The 2R-stereoisomers are the only forms of alpha-tocopherol that are maintained in human plasma and tissue. The activity of natural or natural-source alpha-tocopherol (RRR alpha-tocopherol), on an equal weight basis, is at least twice as high as synthetic alpha-tocopherol. This is mainly because half of the stereoisomers of synthetic alpha-tocopherol are not maintained in human plasma and are, therefore, not bioavailable.|The active substance is all-rac-alpha-tocopherol (Chemical Abstracts Service (CAS) number 10191-41-0; European Inventory of Existing Commercial chemical substances (EINECS) number 233--466-0; chemical formula C29H50O2) consisting of eight stereoisomers (RRR, RRS, RSS, RSR, SRR, SSR, SRS and SSS) in equal quantities.

A reliable analytical method for the simultaneous determination of dl-alpha-tocopherol acetate and dl-alpha-tocopherol in foods was established by HPLC using post-column photochemical reaction with UV and fluorescence detection. For low-fat food such as fruit juice and vegetable sauce, the tocopherols were extracted with methanol containing 0.1% ascorbic acid and the extract solution was injected into the HPLC. For fatty foods such as butter and margarine, the tocopherols were extracted with a mixed solvent of acetonitrile-2-propanol (9:1) containing ascorbic acid. The extract was cleaned up using a Sep Pak plus C18 cartridge and the eluent from the cartridge was injected into the HPLC. The peaks corresponding to tocopherols on the chromatogram were confirmed by comparing their UV spectra with those of the standard mixture at lamp-on and lamp-off of the photochemical reactor. The recoveries of tocopherols from low-fat foods (orange juice and barbecue sauce) fortified at levels of 10 and 100 microg/kg each were 88.3 to 105.8% (RSD 0.5 to 6.0%) and those from the fatty foods (peanut butter and margarine) fortified at 100 microg/kg each were 57.1 to 88.3% (RSD 3.0 to 6.4%). The determination limits corresponded to 10 microg/kg of the tocopherols in the low-fat foods and 20 microg/kg in the fatty foods.|A collaborative study was conducted to evaluate a method for identifying d- or dl-alpha-tocopherol in pharmaceuticals, food supplements, or feed supplements. The sample is extracted and saponified, the extraneous color is removed by chromatography, and the sample is assayed for vitamin E. Optical rotations are determined before and after formation of the ferricyanide oxidation product. The specific optical rotation of the oxidation product is negligible for the dl-form and +25.5 degrees for the d-form. Statistical analysis of the data reported by 8 collaborators for the standard d-alpha-tocopheryl acetate and for 6 unknown samples indicates a significant interaction between laboratories and samples. The mean coefficients of variation among laboratories for the determinations of the corrected specific optical rotation of the standard and the rotation ratio for the unknown samples containing d-alpha-tocopherol were 11.7 and 21.6%, respectively, for all laboratories and 5.8 and 11.8%, respectively, for experienced laboratories. This identification test for vitamin E is acceptable for determining the form of vitamin E as either d or dl /alpha-tocopherol/, but is not acceptable for accurately determining mixtures of the 2 forms. The method has been adopted as official first action for the identification of d- or dl-alpha-tocopherol.|The free radical scavenger properties of vitamin E (DL-alpha-tocopherol), a natural antioxidant, and derivatives were studied using an original in vitro method consisting of free radical production by photoirradiation of pheomelanin and direct detection of the free radicals by a physical, specific technique, electron spin resonance. Validation of this method has been realized using well-known biological free radical scavengers, superoxide dismutase and reduced glutathione. DL-alpha-Tocopherol, tocopheryl acetate, tocopheryl linoleate, and tocopheryl polyoxyethylene (POE) succinate induced a significant diminution of the free radical production. In order of efficiency, tocopheryl POE succinate was the best scavenger (37.6% inhibition at 0.25%) followed by tocopheryl linoleate (25.6% inhibition at 1%) and tocopheryl acetate (23.9% inhibition at 0.5%) and finally DL-alpha-tocopherol (16.2% inhibition at 0.05%). The results reported a decrease of the inhibitory effect for high concentrations of DL-alpha-tocopherol (0.1%) and tocopheryl acetate (1%), showing a tendency of this compound to act as a prooxidant. Used in optimal concentrations in cosmetologic or dermatologic formulations, Vitamin E and these derivatives should prevent or reduce the harmful activity of free radicals in the skin.

EPA Safer Chemical Functional Use Classes -> Preservatives and Antioxidants|Safer Chemical Classes -> Green circle - The chemical has been verified to be of low concern|Food additives|Cosmetics -> Antioxidant; Skin conditioning

Food Additives -> ANTIOXIDANT;