3,4-Dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-benzopyran-6-ol

Insoluble in water, freely soluble in ethanol, miscible in ether

Practically insoluble in water; freely soluble in oils, fats, acetone, alcohol, chloroform, ether, other fat solvents

[n]D/20 1,503-1,507

Index of refraction: 1.5045 at 25 °C/D

Liquid

Slightly yellow to amber, nearly odourless, clear, viscous oil which oxidises and darkens on exposure to air or light

Pale yellow liquid; Darkened gradually by light; [Merck Index]

Exposure to light. Stable under recommended storage conditions.

The shelf-life of the additive has been investigated in three commercial batches, stored in aluminium bottles under argon at 15 and at 25 °C. After 3 years of storage, a decrease in the concentration of all-rac-alpha-tocopherol of 3 % or less was observed.

209.75 Ų [M-H]- [CCS Type: DT; Method: stepped-field]

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

This chemical does not meet GHS hazard criteria for 25.2% (567 of 2247) of reports.

Warning

H317 (74.3%): May cause an allergic skin reaction [Warning Sensitization, Skin]

P261, P272, P280, P302+P352, P321, P333+P317, P362+P364, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 2247 reports by companies from 11 notifications to the ECHA C&L Inventory.；Reported as not meeting GHS hazard criteria per 567 of 2247 reports by companies.；There are 10 notifications provided by 1680 of 2247 reports by companies with hazard statement code(s).；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

Chemical: 2H-1-Benzopyran-6-ol, 3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-

Regulation (EC) No 178/2002 (amended)

Regulation (EC) No 1831/2003 (amended)

2H-1-Benzopyran-6-ol, 3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of 2H-1-Benzopyran-6-ol, 3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)- are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 26-08-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/11866

DL-alpha-tocopherol: Does not have an individual approval but may be used under an appropriate group standard

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.

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.

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.

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.

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.

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).

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.

Although all forms of Vitamin E exhibit antioxidant activity, it is known that the antioxidant activity of vitamin E is not sufficient to explain the vitamin's biological activity. <br/>Vitamin E's anti-atherogenic activity involves the inhibition of the oxidation of LDL and the accumulation of oxLDL in the arterial wall. It also appears to reduce oxLDL-induced apoptosis in human endothelial cells. Oxidation of LDL is a key early step in atherogenesis as it triggers a number of events which lead to the formation of atherosclerotic plaque. In addition, vitamin E inhibits protein kinase C (PKC) activity. PKC plays a role in smooth muscle cell proliferation, and, thus, the inhibition of PKC results in inhibition of smooth muscle cell proliferation, which is involved in atherogenesis. <br/>Vitamin E's antithrombotic and anticoagulant activities involves the downregulation of the expression of intracellular cell adhesion molecule(ICAM)-1 and vascular cell adhesion molecule(VCAM)-1 which lowers the adhesion of blood components to the endothelium. In addition, vitamin E upregulates the expression of cytosolic phospholipase A2 and cyclooxygenase (COX)-1 which in turn enhances the release of prostacyclin. Prostacyclin is a vasodilating factor and inhibitor of platelet aggregation and platelet release. It is also known that platelet aggregation is mediated by a mechanism involving the binding of fibrinogen to the glycoprotein IIb/IIIa (GPIIb/IIIa) complex of platelets. GPIIb/IIIa is the major membrane receptor protein that is key to the role of the platelet aggregation response. GPIIb is the alpha-subunit of this platelet membrane protein. Alpha-tocopherol downregulates GPIIb promoter activity which results in reduction of GPIIb protein expression and decreased platelet aggregation. Vitamin E has also been found in culture to decrease plasma production of thrombin, a protein which binds to platelets and induces aggregation. A metabolite of vitamin E called vitamin E quinone o

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.

/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-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).

PURE CULTURE: alpha-Tocopherol was biodegraded by aerobic bacterial communities (genera Idiomarina and Bacillus) isolated from marine sediment and microbial mat sample. Biodegradation appeared to involve an initial omega-oxidation of the isoprenoid side chain and subsequent beta-oxidation, affording 2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman(1). /alpha-Tocopherol/

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).

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).

Chemical: 2H-1-Benzopyran-6-ol, 3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-

Regulation (EC) No 178/2002 (amended)

Regulation (EC) No 1831/2003 (amended)

2H-1-Benzopyran-6-ol, 3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of 2H-1-Benzopyran-6-ol, 3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)- are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 26-08-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/11866

DL-alpha-tocopherol: Does not have an individual approval but may be used under an appropriate group standard

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 natural form of vitamin E found in green vegetables, grains, and oils; Used in antioxidants and as a vitamin E supplement; [Merck Index] Used as an antioxidant and nutritional additive in animals feeds; [ExPub: EFSA] Permitted for use as an inert ingredient in non-food pesticide products; [EPA]

Farming (Feed Additives) [Category: Industry]

MEDICATION

All-rac-alpha-tocopherol is mainly used as an antioxidant in fats and oils and in feedingstuffs rich in oils and fats.

There are several forms of vitamin E available commercially /including dl-alpha-tocopherol/. These are available as nutritional supplements or in functional and fortified foods.

Laboratory chemicals; manufacture of substances

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 %.

It is synthesised from a mixture of toluene and 2,3,5-trimethyl-hydroquinone that reacts with isophytol to all-rac-alpha-tocopherol using iron in the presence of hydrogen chloride gas as catalyst. The reaction mixture obtained is filtered and extracted with aqueous caustic soda. Toluene is removed by evaporation and the residue (all-rac-alpha-tocopherol) is purified by vacuum distillation.

It is chemically synthesized by condensing racemic isophytol with trimethyl hydroquinone.

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).

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

Fragrance Ingredients

Food Additives -> ANTIOXIDANT -> JECFA Functional Classes

Food Additives -> ANTIOXIDANT; NUTRIENT_SUPPLEMENT -> JECFA Functional Classes

All Other Basic Organic Chemical Manufacturing；Plastics Product Manufacturing；Soap, Cleaning Compound, and Toilet 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.