DOCSLIB.ORG

Food and Drug Administration, HHS § 172.842

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Food and Drug Administration, HHS § 172.842 Food and Drug Administration, HHS § 172.842 (b) The additive meets the specifica- (a) The food additive is manufactured tions of the Food Chemicals Codex, 7th by reacting stearic acid (usually con- ed. (2010), pp. 811–814, which is incor- taining associated fatty acids, chiefly porated by reference. The Director of palmitic) with sorbitol to yield essen- the Office of the Federal Register ap- tially a mixture of esters. proves this incorporation by reference (b) The food additive meets the fol- in accordance with 5 U.S.C. 552(a) and 1 lowing specifications: CFR part 51. You may obtain copies Saponification number, 147–157 from the United States Pharmacopeial Acid number, 5–10 Convention, 12601 Twinbrook Pkwy., Hydroxyl number, 235–260 Rockville, MD 20852 (Internet address (c) It is used or intended for use, http://www.usp.org). Copies may be ex- alone or in combination with poly- amined at the Food and Drug Adminis- sorbate 60 as follows: tration’s Main Library, 10903 New (1) As an emulsifier in whipped edible Hampshire Ave., Bldg. 2, Third Floor, oil topping with or without one or a Silver Spring, MD 20993, 301–796–2039, or combination of the following: at the National Archives and Records (i) Polysorbate 60; Administration (NARA). For informa- (ii) Polysorbate 65; tion on the availability of this mate- (iii) Polysorbate 80; rial at NARA, call 202–741–6030 or go to: whereby the maximum amount of the http://www.archives.gov/federal-register/ additive or additives used does not ex- cfr/ibr-locations.html. ceed 0.4 percent of the weight of the (c) When standards of identity estab- finished whipped edible oil topping; ex- lished under section 401 of the act do cept that a combination of the additive not preclude such use, polydextrose with polysorbate 60 may be used in ex- may be used in accordance with cur- cess of 0.4 percent: Provided, That the rent good manufacturing practices as a amount of the additive does not exceed bulking agent, formulation aid, humec- 0.27 percent and the amount of poly- tant, and texturizer in all foods, except sorbate 60 does not exceed 0.77 percent meat and poultry, baby food, and in- of the weight of the finished whipped fant formula. edible oil topping. (d) If the food containing the additive (2) As an emulsifier in cakes and cake purports to be or is represented for spe- mixes, with or without one or a com- cial dietary uses, it shall be labeled in bination of the following: compliance with part 105 of this chap- (i) Polysorbate 65. ter. (ii) Polysorbate 60. (e) The label and labeling of food a When used alone, the maximum single serving of which would be ex- amount of sorbitan monostearate shall pected to exceed 15 grams of the addi- not exceed 0.61 percent of the cake or tive shall bear the statement: ‘‘Sen- cake mix, on a dry-weight basis. When sitive individuals may experience a used with polysorbate 65 and/or poly- laxative effect from excessive con- sorbate 60, it shall not exceed 0.61 per- sumption of this product’’. cent, nor shall the polysorbate 65 ex- [46 FR 30081, June 5, 1981, as amended at 59 ceed 0.32 percent or the polysorbate 60 FR 37421, July 22, 1994; 60 FR 54425, Oct. 24, exceed 0.46 percent, and no combina- 1995; 61 FR 14480, Apr. 2, 1996; 62 FR 30985, tion of the emulsifiers shall exceed 0.66 June 6, 1997; 63 FR 57597, Oct. 28, 1998; 65 FR percent of the weight of the cake or 64605, Oct. 30, 2000; 65 FR 79719, Dec. 20, 2000; cake mix, calculated on a dry-weight 72 FR 46564, Aug. 21, 2007; 78 FR 71464, Nov. 29, basis. 2013] (3) As an emulsifier, alone or in com- bination with polysorbate 60 in non- § 172.842 Sorbitan monostearate. standardized confectionery coatings The food additive sorbitan monostea- and standardized cacao products speci- rate, which is a mixture of partial ste- fied in §§ 163.123, 163.130, 163.135, 163.140, aric and palmitic acid esters of sorbitol 163.145, and 163.150 of this chapter, as anhydrides, may be safely used in or on follows: food in accordance with the following (i) It is used alone in an amount not prescribed conditions: to exceed 1 percent of the weight of the 97 VerDate Mar<15>2010 13:59 Jul 24, 2014 Jkt 232072 PO 00000 Frm 00107 Fmt 8010 Sfmt 8010 Y:\SGML\232072.XXX 232072 pmangrum on DSK3VPTVN1PROD with CFR § 172.844 21 CFR Ch. I (4–1–14 Edition) finished nonstandardized confectionery (ii) A statement of the concentration coating or standardized cacao product. or strength of the additive in any in- (ii) It is used with polysorbate 60 in termediate premixes. any combination of up to 1 percent sor- (2) The label or labeling shall bear bitan monostearate and up to 0.5 per- adequate directions to provide a final cent polysorbate 60 provided that the product that complies with the limita- total combination does not exceed 1 tions prescribed in paragraph (c) of this percent of the weight of the finished section. nonstandardized confectionery coating or standardized cacao product. [42 FR 14491, Mar. 15, 1977, as amended at 43 (4) As an emulsifier in cake icings FR 2871, Jan. 20, 1978] and cake fillings, with or without one § 172.844 Calcium stearoyl-2-lactylate. or a combination of the following: (i) Polysorbate 65. The food additive calcium stearoyl-2- (ii) Polysorbate 60. lactylate may be safely used in or on food in accordance with the following When used alone, the maximum prescribed conditions: amount of sorbitan monostearate shall (a) The additive, which is a mixture not exceed 0.7 percent of the weight of of calcium salts of stearoyl lactylic the cake icing or cake filling. When acids and minor proportions of other used with polysorbate 65 and/or poly- calcium salts of related acids, is manu- sorbate 60, it shall not exceed 0.7 per- factured by the reaction of stearic acid cent, nor shall the polysorbate 65 ex- ceed 0.32 percent or the polysorbate 60 and lactic acid and conversion to the exceed 0.46 percent, and no combina- calcium salts. tion of these emulsifiers shall exceed 1 (b) The additive meets the following percent of the weight of the cake icing specifications: or cake filling. Acid number, 50–86. (5) As an emulsifier in solid-state, ed- Calcium content, 4.2–5.2 percent. ible vegetable fat-water emulsions in- Lactic acid content, 32–38 percent. tended for use as substitutes for milk Ester number, 125–164. or cream in beverage coffee, with or without one or a combination of the (c) It is used or intended for use as following: follows: (i) Polysorbate 60. (1) As a dough conditioner in yeast- (ii) Polysorbate 65. leavened bakery products and prepared mixes for yeast-leavened bakery prod- The maximum amount of the additive ucts in an amount not to exceed 0.5 or additives shall not exceed 0.4 per- part for each 100 parts by weight of cent by weight of the finished edible flour used. vegetable fat-water emulsion. (2) As a whipping agent in: (6) It is used alone as a rehydration (i) Liquid and frozen egg white at a aid in the production of active dry level not to exceed 0.05 percent. yeast in an amount not to exceed 1 per- (ii) Dried egg white at a level not to cent by weight of the dry yeast. exceed 0.5 percent. (7) As an emulsifier, alone or in com- bination with polysorbate 60, in the (iii) Whipped vegetable oil topping at minimum quantity required to accom- a level not to exceed 0.3 percent of the plish the intended effect, in formula- weight of the finished whipped vege- tions of white mineral oil conforming table oil topping. with § 172.878 and/or petroleum wax (3) As a conditioning agent in dehy- conforming with § 172.886 for use as pro- drated potatoes in an amount not to tective coatings on raw fruits and vege- exceed 0.5 percent by weight thereof. tables. (d) To assure safe use of the additive: (d) To assure safe use of the additive, (1) The label and labeling of the food in addition to the other information re- additive and any intermediate premix quired by the Act: prepared therefrom shall bear, in addi- (1) The label of the additive and any tion to the other information required intermediate premixes shall bear: by the act, the following: (i) The name of the additive. (i) The name of the additive. 98 VerDate Mar<15>2010 13:59 Jul 24, 2014 Jkt 232072 PO 00000 Frm 00108 Fmt 8010 Sfmt 8010 Y:\SGML\232072.XXX 232072 pmangrum on DSK3VPTVN1PROD with CFR.
Load more

Recommended publications
  • Safety Assessment of Sorbitan Esters As Used in Cosmetics
    Safety Assessment of Sorbitan Esters as Used in Cosmetics Status: Re-Review for Panel Review Release Date: August 18, 2014 Panel Meeting Date: September 8-9, 2014 The 2014 Cosmetic Ingredient Review Expert Panel members are: Chairman, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Ronald A. Hill, Ph.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; James G. Marks, Jr., M.D., Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Director is Lillian J. Gill, D.P.A. This safety assessment was prepared by Monice M. Fiume, Assistant Director/Senior Scientific Analyst and Bart Heldreth, Ph.D., Chemist. © Cosmetic Ingredient Review 1620 L Street, NW, Suite 1200 ♢ Washington, DC 20036-4702 ♢ ph 202.331.0651 ♢ fax 202.331.0088 ♢ [email protected] Commitment & Credibility since 1976 Memorandum To: CIR Expert Panel Members and Liaisons From: Monice M. Fiume MMF Assistant Director/Senior Scientific Analyst Date: August 18, 2014 Subject: Safety Assessment of Sorbitan Esters as Used in Cosmetics Enclosed is the Re-Review of the Safety Assessment on Sorbitan Esters as Used in Cosmetics. (It is identified as sorbes092014rep_final for posting in the pdf document.) In 1985, the Panel determined that a group of seven sorbitan esters were safe as used in cosmetic ingredients. In 2002, the Panel reviewed the safety of an additional 10 sorbitan ester, and issued an addendum to that report, concluding that the sorbitan fatty acid esters were safe as used in cosmet- ic ingredients.
    [Show full text]
  • Gad Compounds Assessed
    Name CAS # ((5-Amino-2-carboxyphenyl)thio)gold sodium salt 17010-23-0 (2-Hydroxypropyl)-γ-cyclodextrin 128446-34-4 (4-hydroxy-4-isobutylpiperidin-1-yl)(1H-imidazol-1-yl)methanone (5aR, 9aR)-octahydrobenzo[e][1,3,2]dioxathiepine 3,3- (LMPC) 1-myristoyl-2-hydroxy-sn-glycero-3-phosphocholine 20559-16-4 (Trimethylsilyl)acetic acid 2345-38-2 (Z) 7-Hexadecenal 56797-40-1 (Z)-2-chloro-4-(diethylamino)but-2-en-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate (Z)-3-chloro-4-(diethylamino)but-2-en-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate (Z,Z,Z) 8,11,14-Eicosatrienoic acid 1783-84-2 1-(2-butoxyethoxy)-ethanol 5446-78-5 1,1,1,3,5,5,7,7,7-Nonamethyl-3-(trimethylsiloxy) tetrasiloxane 38146-99-5 1,10-decanedithiol 1191-67-9 1,1'-bicyclohexyl-4,4'-diol 20601-38-1 1,1-bis(p-ethoxyphenyl)-2,2-dimethylpropane 27955-87-9 1,1-carbonyldiimidazole (CDI) 530-62-1 1,1-cyclohexanedithiol 3855-24-1 1,2,3,4-Tetrahydronaphthalene 119-6-2 1,2,3-trichloro-2-methylpropane 1871-58-5 1,2,3-triethylbenzene 42205-08-3 1,2,4-benzenetriol 533-73-3 1,2,4-triethylbenzene 877-44-1 1,2-cyclohexanediamine 694-83-7 1,2-cyclohexanedicarboxylic acid 1687-30-5 1,2-cyclohexanediol 931-17-9 1,2-dichlorobenzene 95-50-1 1,2-Ethanediamine 107-15-3 1,2-ethanedithiol 540-63-6 1,2-propanediol, monobutyl ether 29387-86-8 1,3,5-Tributyl-2,4,6-trioxo-hexahydro-striazine 846-74-2 1,3,5-triethylbenzene 102-25-0 1,3,5-Trioxane 110-88-3 1,3:2,4-Bis(3,4-dimethylbenzylidene)sorbitol 135861-56-2 1,3-Bis(diallylamino)-2-propanol 4831-46-3 1,3-butanediol 107-88-0 1,3-cycloheptadiene 4054-38-0 1,3-cyclohexanedicarboxylic
    [Show full text]
  • Polysorbates 20, 60, 65 and 80)
    Original: Japanese Provisional translation Evaluation Report of Food Additives Polysorbates (Polysorbates 20, 60, 65 and 80) June 2007 Food Safety Commission Contents History of deliberation.......................................................................................................1 Members of the Food Safety Commission.........................................................................1 Expert members of the Expert Committee on Food Additives, Food Safety Commission.…………1 Evaluation results on the Health Risk Assessment of Polysorbate 20, Polysorbate 60, Polysorbate 65 and Polysorbate 80 as food additives...................................................................................................2 Summary.............................................................................................................................................. 2 1. Introduction...................................................................................................................................... 3 2. Background...................................................................................................................................... 3 3. Outline of the designation of food additives.................................................................................... 3 4. Name, etc. ........................................................................................................................................ 3 (1) Polysorbate 20 ......................................................................................................................
    [Show full text]
  • Summary Report for Polyoxyethylene Sorbitan Monooleate and Triolate
    European Medicines Agency Veterinary Medicines and Inspections EMEA/CVMP/72503/2006-FINAL March 2006 COMMITTEE FOR MEDICINAL PRODUCTS FOR VETERINARY USE POLYOXYETHYLENE SORBITAN MONOOLEATE AND TRIOLEATE SUMMARY REPORT 1. Polyoxyethylene sorbitan monooleate (CAS number: 9005-65-6) and polyoxyethylene sorbitan trioleate (CAS number: 9005-70-3) are oleate esters of sorbitol. The chemical name polyoxyethylene sorbitan monooleate covers the substances known by the commercial names Polysorbate 80, and Polysorbate 81. Polyoxyethylene sorbitan trioleate covers the substance known by the commercial name Polysorbate 85. The substances are used as excipients (emulsifiers and dispersing agents) in medicinal products. They are also widely used as a emulsifiers in foods products and cosmetics. Polysorbate 80 was included in Annex II of Council Regulation (EC) No 2377/90 for all food producing animals under the group “Substances Generally Recognised as Safe” for which no individual assessment was carried out. For the inclusion of substances in the group “Substances Generally Recognised as Safe” the Committee for Medicinal Products for Veterinary Use (CVMP) took into account the following aspects: • pharmacologically active substances used in veterinary medicinal products rapidly metabolised to simple organic metabolites such as carbon dioxide, acetic acid and ethanol; • pharmacologically active substances used in veterinary medicinal products having a low oral bioavailability; • conditions of use of veterinary medicinal products. The Annex II entry for Polysorbate 80 was subsequently modified following a request from a company to include the similar substance Polysorbate 81. The CVMP agreed that Polysorbate 81 would be covered by the assessment and Annex II entry for Polysorbate 80 and recommended that the name be replaced by the chemical name polyoxyethylene sorbitan monooleate for the substances known as Polysorbate 80 and Polysorbate 81.
    [Show full text]
  • Revision Date: February 2021 1 SORBITAN MONOOLEATE
    SORBITAN MONOOLEATE POLYOXYETHYLENE DERIVATIVE This dossier on sorbitan monooleate polyoxyethylene derivative presents the most critical studies pertinent to the risk assessment of sorbitan monooleate polyoxyethylene derivative in its use in drilling muds. This dossier does not represent an exhaustive or critical review of all available data. The information presented in this dossier was obtained from the ECHA database that provides information on chemicals that have been registered under the EU REACH (ECHA), and the European Food and Safety Authority (EFSA, 2015). Where possible, study quality was evaluated using the Klimisch scoring system (Klimisch et al., 1997). Screening Assessment Conclusion – Sorbitan monooleate polyoxyethylene is classified as a tier 1 chemical and requires a hazard assessment only. 1 BACKGROUND Sorbitan monooleate polyoxyethylene derivative is a hydrophilic, non-ionic surfactant used as an emulsifier. It is considered a UVCB substance (substance of unknown or variable composition, complex reaction products or biological materials). Based on the substance group types evaluated, the substance is likely to biodegrade, has a low potential to bioaccumulate and, based on its non- ionic surfactant properties will adsorb to soils. Based on read across from a similar substance (sorbitan monolaurate, ethoxylated (1-6.5 moles ethoxylated) [CAS No. 9005-64-5]), acute and chronic toxicities are relatively low. 2 CHEMICAL NAME AND IDENTIFICATION Chemical Name (IUPAC): Sorbitan monooleate polyoxyethylene derivative CAS RN: 9005-65-6 Molecular formula: Not available (UVCB substances) Molecular weight: Not available (UVCB substances) Synonyms: See below. The composition of sorbitan monooleate polyoxyethylene derivative (CAS No. 9005-65-6) is unknown. The CAS No. 9005-65-6 is a generic CAS No.
    [Show full text]
  • Polysorbate 20 Polysorbate 65 Polysorbate 21 Polysorbate 80 Polysorbate 40 Polysorbate 81 Polysorbate 60 Polysorbate 85 Polysorbate 61
    Safety Assessment of Polysorbates as Used in Cosmetics Status: Tentative Amended Report for Public Comment Release Date: March 31, 2015 Panel Meeting Date: June 15-16, 2015 All interested persons are provided 60 days from the above date to comment on this safety assessment and to identify additional published data that should be included or provide unpublished data which can be made public and included. Information may be submitted without identifying the source or the trade name of the cosmetic product containing the ingredient. All unpublished data submitted to CIR will be discussed in open meetings, will be available at the CIR office for review by any interested party and may be cited in a peer-reviewed scientific journal. Please submit data, comments, or requests to the CIR Director, Dr. Lillian J. Gill. The 2015 Cosmetic Ingredient Review Expert Panel members are: Chair, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Ronald A. Hill, Ph.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; James G. Marks, Jr., M.D.; Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Director is Lillian J. Gill, D.P.A. This report was prepared by Lillian C. Becker, Scientific Analyst/Writer. © Cosmetic Ingredient Review 1620 L Street, NW, Suite 1200 Washington, DC 20036-4702 ph 202.331.0651 fax 202.331.0088 [email protected] ABSTRACT This is a safety assessment of polysorbates as used in cosmetics. These ingredients mostly function as surfactants in cosmetics.
    [Show full text]
  • Safety Assessment of Polysorbates As Used in Cosmetics
    Safety Assessment of Polysorbates as Used in Cosmetics Status: Draft Final Amended Report for Panel Review Release Date: May 22, 2015 Panel Meeting Date: June 15-16, 2015 The 2015 Cosmetic Ingredient Review Expert Panel members are: Chair, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Ronald A. Hill, Ph.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; James G. Marks, Jr., M.D.; Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Director is Lillian J. Gill, D.P.A. This report was prepared by Lillian C. Becker, Scientific Analyst/Writer. © Cosmetic Ingredient Review 1620 L Street, NW, Suite 1200 Washington, DC 20036-4702 ph 202.331.0651 fax 202.331.0088 [email protected] Commitment & Credibility since 1976 MEMORANDUM To: CIR Expert Panel and Liaisons From: Lillian C. Becker, M.S. Scientific Analyst and Writer Date: May 22, 2015 Subject: Draft Final Amended Report of Polysorbates as Used in Cosmetics Attached is the draft final amended report of Polysorbates as used in cosmetics. [PSorba_062015_Rep] In March, 2015, the Panel issued a tentative amended report with a conclusion of safe as used when formulated to be nonirritating. This safety assessment combined 3 previous reports and added new polysorbate ingredients. There were three polysorbate ingredients reported in the VCRP but were not listed in the Dictionary (PEG-20 sorbitan laurate, PEG-20 sorbitan stearate, and PEG-30 sorbitan beeswax). The Council has asserted that PEG-20 sorbitan laurate is another term for polysorbate 20 and PEG-20 sorbitan stearate is another term for polysorbate 60.
    [Show full text]
  • Food and Drug Administration, HHS § 172.836
    Food and Drug Administration, HHS § 172.836 (2) Direct esterification of glycerol accordance with the following pre- with a mixture of primarily stearic, scribed conditions: palmitic, and myristic acids; (a) The food additive is manufactured by reacting stearic acid (usually con- to yield a product with less than 0.3 taining associated fatty acids, chiefly acid number and less than 0.2 percent palmitic) with sorbitol to yield a prod- water, which is then reacted with uct with a maximum acid number of 10 ethylene oxide. and a maximum water content of 0.2 (b) The additive meets the following percent, which is then reacted with specifications: ethylene oxide. Saponification number, 65–75. (b) The food additive meets the fol- Acid number, 0–2. lowing specifications: Hydroxyl number, 65–80. Saponification number 45–55. Oxyethylene content, 60.5–65.0 percent. Acid number 0–2. (c) The additive is used or intended Hydroxyl number 81–96. for use in the following foods when Oxyethylene content 65 percent–69.5 percent. standards of identity established under (c) It is used or intended for use as section 401 of the Act do not preclude follows: such use: (1) As an emulsifier in whipped edible oil topping with or without one or a Use Limitations combination of the following: 1. As an emulsifier in pan-re- Not to exceed levels required (i) Sorbitan monostearate; lease agents for and as a to produce the intended ef- (ii) Polysorbate 65; dough conditioner in yeast- fects, total not to exceed (iii) Polysorbate 80; leavened bakery products.
    [Show full text]
  • Inert Reassessment - Members of the Sorbitan Fatty Acid Esters and The
    UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASIiINGTON, D.C. 20460 DATE: May 20,2005 ACTION MEMORANDUM SUBJECT: Inert Reassessment - Members of the Sorbitan Fatty Acid Esters and the FROM: sponse Branch TO: Lois A. Rossi, Director Registration Division I. FQPA REASSESSMENT ACTION Action: Reassessment of six inert ingredient exemptions from the requirement of a tolerance. The six tolerance exemptions are to be maintained. Chemicals: CFR Reference Number 40 CFR Tolerance Exemption Expression Limits Uses exemptions ** 1 180.920 Poly(oxyethylene)(5) sorbitan monooleate (none) Surfactants, related adjuvants of surfactants 1 180.910 Polyoxyethylene (20) sorbitan (none) Surfactants, related adjuvants monostearate of surfactants 1 180.920 Polysorbate 60, conformng to 21 CFR (none) Surfactant 172.836 1 180.910 Polysorbate 65, conforming to 21 CFR (none) Emulsifier 172.838, CFR Reference Number 40 CFR Tolerance Exemption Expression Limits Uses exemptions ** Sorbitan fatty acid esters (fatty acids (none) Surfactants, related adjuvants limited to C12, C14, C16, and C18 of surfactants containing minor amounts of associated fatty acids) and their derivatives; the poly(oxyethy1ene) content averages 5-20 moles. 180.930 Sorbitan fatty acid esters (fatty acids (none) Buffering agent, corrosion limited to C12, C14, C16, and C18 inhibition 1 containing minor amounts of associated fatty acids) and their poly(oxyethy1ene) derivatives of sorbitan fatty acid esters; the poly(oxyethy1ene) content averages 16-20 moles. **Residues listed in 40 CFR 180.910 (formerly 180.1001(c)) are exempt from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops or to raw agricultural commodities after harvest.
    [Show full text]
  • 01 Excipients Prelims 1..9
    Polyoxyethylene Sorbitan Fatty Acid Esters 549 41 Liebmann J et al. Cremophor EL, solvent for paclitaxel, and toxicity. 50 Lin SY et al. In vitro release, pharmacokinetic and tissue distribution Lancet 1993; 342: 1428. studies of doxorubicin hydrochloride (adriamycin HCl (R)) encapsu- 42 Badary OA et al. Effect of Cremophor EL on the pharmacokinetics, lated in lipiodolized w/o emulsions and w/o/w multiple emulsions. antitumor activity and toxicity of doxorubicin in mice. Anticancer Pharmazie 1992; 47: 439–443. Drugs 1998; 9: 809–815. 43 Sanchez H et al. Immunosuppressive treatment affects cardiac and 20 General References skeletal muscle mitochondria by the toxic effect of vehicle. J Mol Cell Cardiol 2000; 32: 323–331. BASF Corporation. Technical literature: Cremophor EL, Castor Oil, June 44 Bowers VD et al. The hemodynamic effects of Cremophor-EL. 2008. Transplantation 1991; 51: 847–850. BASF Corporation. Technical literature: Cremophor ELP, July 2008. 45 Verani R. Cyclosporin nephrotoxicity in the Fischer rat. Clin Nephrol BASF Corporation. Technical literature: Cremophor RH 40, November 1986; 25( Suppl 1): S9–13. 2008. 46 Thiel G et al. Acutely impaired renal function during the intravenous Rischin D et al. Cremophor pharmacokinetics in patients receiving 3, 6, and administration of cyclosporin A: a cremophore side-effect. Clin Nephrol 24 hour infusions of paclitaxel. J Natl Cancer Inst 1996; 88: 1297–1301. 1986; 25( Suppl 1): S40–42. 47 Windebank AJ et al. Potential neurotoxicity of the solvent vehicle for cyclosporin. J Pharmacol Exp Ther 1994; 268: 1051–1056. 21 Author 48 Kiorpes AL et al. Pulmonary changes in rats following the administra- KK Singh.
    [Show full text]
  • Determination of Sorbitan Tristearate in Vegetable Oils and Fats
    Determination of Sorbitan Tristearate in Vegetable Oils and Fats Karen Thyssen* and Karsten Stig Andersen Aarhus Oliefabrik A/S, Analytical Department, 8100 Aarhus C, Denmark ABSTRACT: A new method for analysis of Sorbitan Tristearate tive. All methods use lengthy and laborious procedures and (STS) in vegetable oils and fats has been developed. The method hazardous chemicals (e.g., chlorinated solvents, benzene). is based on isolation and hydrolysis of STS compounds in a sil- The GLC methods also use hazardous derivatization reagents ica cartridge. The polyalcohols are eluted from the silica car- [trimethylchlorosilane and N,N-bis(trimethylsilyl)trifluoro- tridge and the final separation and quantitation are done by acetamide]. high-performance liquid chromatography and refractive index The work described in this paper has focused on develop- detection. Linearity, precision, and recovery satisfy general de- ing a new method which is quantitative, environmentally ac- mands on quantitative methods. The detection limit and the quantitation limit are well below the concentrations normally ceptable, safe in the workplace, and which demands a mini- used to attain functional effects of STS in vegetable oils and fats. mum of manual work for the determination of Sorbitan Tris- JAOCS 75, 1855–1860 (1998). tearate in vegetable oils and fats in the legal concentration range. KEY WORDS: Bloom retardation, emulsifier, high-perfor- mance liquid chromatography, solid-phase extraction, sorbitan tristearate, STS, vegetable oil. EXPERIMENTAL PROCEDURES Materials. HPLC-grade tert-butyl methyl ether and heptane were supplied by Rathburn (Walkerburn, United Kingdom). Fatty acid esters of sorbitol and its anhydrides are approved HPLC-grade acetonitrile and pro analysis (p.a.) sulfuric acid as food additives in most of the world.
    [Show full text]
  • Polysorbates 20 and 80 Used in the Formulation of Protein Biotherapeutics: Structure and Degradation Pathways
    Polysorbates 20 and 80 Used in the Formulation of Protein Biotherapeutics: Structure and Degradation Pathways BRUCE A. KERWIN Department of Pharmaceutics, Amgen Inc., One Amgen Center Dr., Thousand Oaks, California 91320 Received 14 June 2007; revised 9 August 2007; accepted 8 September 2007 Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jps.21190 1 1 ABSTRACT: Polysorbates 20 and 80 (Tween 20 and Tween 80) are used in the formulation of biotherapeutic products for both preventing surface adsorption and as stabilizers against protein aggregation. The polysorbates are amphipathic, nonionic surfactants composed of fatty acid esters of polyoxyethylene sorbitan being polyoxyethy- lene sorbitan monolaurate for polysorbate 20 and polyoxyethylene sorbitan monooleate for polysorbate 80. The polysorbates used in the formulation of biopharmaceuticals are mixtures of different fatty acid esters with the monolaurate fraction of polysorbate 20 making up only 40–60% of the mixture and the monooleate fraction of polysorbate 80 making up >58% of the mixture. The polysorbates undergo autooxidation, cleavage at the ethylene oxide subunits and hydrolysis of the fatty acid ester bond. Autooxidation results in hydroperoxide formation, side-chain cleavage and eventually formation of short chain acids such as formic acid all of which could influence the stability of a biopharmaceutical product. Oxidation of the fatty acid moiety while well described in the literature has not been specifically investigated for polysorbate. This review focuses on the chemical structure of the polysorbates, factors influencing micelle formation and factors and excipients influencing stability and degradation of the polyoxyethylene and fatty acid ester linkages. ß 2007 Wiley-Liss, Inc.
    [Show full text]