TOCOPHEROL

Single Dose (Acute) Toxicity From the original report on Tocopherols In rats, the dermal LD 50 is >3 g/kg for tocopherol and >2 g/kg for tocophersolan. The oral LD 50 of tocopherol, tocopheryl ace- tate, tocopheryl nicotinate, tocopheryl succinate, and tocophersolan are greater than 4, 16, 10, 7, and 7 g/kg, respectively, in rats. In mice, the oral LD 50 of tocopherol is >25 ml/kg and of tocopheryl acetate is >4 g/kg.1 Dermal Tocopheryl Acetate According to robust summary data submitted to ECHA, the dermal LD 50 of tocopheryl acetate is > 3 g/kg bw in albino rats.42 Five animals per group were dosed with 1 or 3 g/kg bw undiluted tocopheryl acetate in vegetable oil under an occlusive patch for 24 h. Slight erythema was observed 24-48 h after exposure. Slight abrasion was observed in one low-dose female, two high-dose females, and two high-dose males. Tocopheryl Phosphate The acute dermal toxicity of mixed tocopheryl phosphates (MTP) was determined in New Zealand rabbits; the dermal LD 50 was greater than 1130 mg/kg bw MTP in female rabbis.46 MTP is a mixture of α-tocopheryl phosphate and α-di-tocopheryl phosphate, and is produced by phosphorylating d-α-tocopherol with P 4 O 10 ; the final composition typically contained α- tocopheryl phosphate, α-di-tocopheryl phosphate, and α-tocopherol in the ratio of 1:0.49:0.08 (w/w/w). (Unless indicated otherwise, this is the composition of MTP tested in various studies that are summarized throughout this report.) An aq. gel containing 1130 mg/kg bw MTP (918 mg/kg bw α-tocopherol equivalents) was applied to the clipped dorsal skin of five male and five female rabbits for 24 h using surgical gauze. The test site was washed upon patch removal, and evaluated for irrita- tion at 24 h, 7 days, and 14 days. At 24 h, slight to well-defined erythema was observed in 4/5 males and all females, and slight to moderate edema was observed in 2/5 males and all females. Signs of irritation were not observed at days 7 and 14. … [kırpıldı - bölüm toplam 37160 karakter]

Definition and Structure Tocopherols and tocotrienols are amphiphilic lipids that share in common a substituted chromanol core.2 Together, the tocopherols and tocotrienols comprise vitamin E, differing structurally by substitution on the polar, chromanol core by either a lipophilic saturated, phytyl side chain, or by an unsaturated, isoprenoid (geranylgeranyl) side chain, respectively. Tocoph- erols have three stereocenters (*) which are all of the R-configuration (D-form) when obtained from natural sources. Synthet- ically produced tocopherols, however, are commonly racemic mixtures.3 Tocotrienols have one stereocenter and three double bonds, which are in the R-configuration and are all trans-geometries, respectively, when obtained from natural sources. Synthetically produced tocotrienols, however, can potentially have any combination of stereochemistry and double bond geometries, or mixtures thereof. Figure 1. Tocopherols and Tocotrienols In addition to possible stereochemistries and double bond geometries, vitamin E is comprised of eight naturally occurring structural analogs: four tocopherols (α-, β-, γ-, and δ-analogs) and four tocotrienols (α-, β-, γ-, and δ-analogs).3 These analogs differ structurally by the presence and placement of additional methyl groups around the aromatic ring of the chromanol core. All four of the tocopherol analogs are listed in the definition for Tocopherol. According to the definition for the cosmetic ingredient, however, Tocotrienols only contains the α-, γ-, and δ-analogs (i.e., no β-tocotrienol). Figure 2. α-, β-, γ-, and δ-analogs  Distributed for Comment Only -- Do Not Cite or Quote -wherein methyl groups C and D are present in the case of α-tocotrienol, only C for β-tocotrienol, only D for γ- tocotrienol, and neither for δ- tocotrienol -wherein R is hydrogen or, in the case of the tocopheryl ingredients, constitutes, together with the attached oxygen, an ester … [kırpıldı - bölüm toplam 33042 karakter]

Definition and Structure Tocopherols and tocotrienols are amphiphilic lipids that share in common a substituted chromanol core.3 Together, the tocopherols and tocotrienols comprise vitamin E, differing structurally by substitution on the polar, chromanol core by either a lipophilic saturated, phytyl side chain, or by an unsaturated, isoprenoid (geranylgeranyl) side chain, respectively. Tocoph- erols have three stereocenters (*) which are all of the R-configuration (D-form) when obtained from natural sources. Synthet- ically produced tocopherols, however, are commonly racemic mixtures.4 Tocotrienols have one stereocenter and three double bonds, which are in the R-configuration and are all trans-geometries, respectively, when obtained from natural sources. Synthetically produced tocotrienols, however, can potentially have any combination of stereochemistry and double bond geometries, or mixtures thereof. 1  Distrbuted for comment only -- do not cite or quote Tocopherols CH3 CH3 O CH3 * * * CH3 CH3 CH3 HO chromanol core phytyl side chain Tocotrienols CH3 CH3 O CH3 … [kırpıldı - bölüm toplam 43043 karakter]

Single Dose (Acute) Toxicity From the original report on Tocopherols In rats, the dermal LD 50 is >3 g/kg for tocopherol and >2 g/kg for tocophersolan. The oral LD 50 of tocopherol, tocopheryl ace- tate, tocopheryl nicotinate, tocopheryl succinate, and tocophersolan are greater than 4, 16, 10, 7, and 7 g/kg, respectively, in rats. In mice, the oral LD 50 of tocopherol is >25 ml/kg and of tocopheryl acetate is >4 g/kg.1 Dermal Tocopheryl Acetate According to robust summary data submitted to ECHA, the dermal LD 50 of tocopheryl acetate is > 3 g/kg bw in albino rats.44 Five animals per group were dosed with 1 or 3 g/kg bw undiluted tocopheryl acetate in vegetable oil under an occlusive patch for 24 h. Slight erythema was observed 24-48 h after exposure. Slight abrasion was observed in one low-dose female, two high-dose females, and two high-dose males. Tocopheryl Phosphate The acute dermal toxicity of mixed tocopheryl phosphates (MTP) was determined in New Zealand rabbits; the dermal LD 50 was greater than 1130 mg/kg bw MTP in female rabbits.49 MTP is a mixture of α-tocopheryl phosphate and α-di-tocopheryl phosphate, and is produced by phosphorylating d-α-tocopherol with P 4 O 10 ; the final composition typically contained α-to- copheryl phosphate, α-di-tocopheryl phosphate, and α-tocopherol in the ratio of 1:0.49:0.08 (w/w/w). (Unless indicated otherwise, this is the composition of MTP tested in various studies that are summarized throughout this report.) An aq. gel containing 1130 mg/kg bw MTP (918 mg/kg bw α-tocopherol equivalents) was applied to the clipped dorsal skin of five male and five female rabbits for 24 h using surgical gauze. The test site was washed upon patch removal, and evaluated for irrita- tion at 24 h, 7 days, and 14 days. At 24 h, slight to well-defined erythema was observed in 4/5 males and all females, and … [kırpıldı - bölüm toplam 39376 karakter]

EPA ToxValDB skin/eye data - endpoint: skin irritation: in vivo, classification: Studies Indicate No Significant Irritation, species: rabbit, study: skin irritation, guideline: OECD Guideline 404 (Acute Dermal Irritation / Corrosion) equivalent or similar to, year: 1982. Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.

EPA ToxValDB skin/eye data - endpoint: eye irritation: in vivo, classification: Studies Indicate No Significant Irritation, species: rabbit, study: eye irritation, guideline: OECD Guideline 405 (Acute Eye Irritation / Corrosion) equivalent or similar to, year: 1982. Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.

EPA ToxValDB skin/eye data - endpoint: skin sensitisation: in vivo (non-LLNA), classification: Not likely to be sensitizing, species: guinea pig, study: skin sensitization, guideline: equivalent or similar to OECD Guideline 406 (Skin Sensitisation), year: 1988. Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.

EPA ToxValDB skin/eye data - endpoint: Skin Irritation, classification: SkinIrr2. Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.