Document nkNwLJaLLk64GaEVRkmEZNjoX

FILE NAME Talc TALC DATE 1994 Jan 27 DOC TALC198 DOCUMENT DESCRIPTION Memo RE Talc Symposium - Suggested Cosmetic Comments Revised 1-27-94 January 27 1994 Note To : From : John E. Bailey Director Ph.D. 100 Office of Cosmetics and Colors Director Stanley R. Milstein Ph.D. Special Assistant to the Director SRM Office of Cosmetics and Colors OCAC Subject : TALC SYMPOSIUM - SUGGESTED COSMETIC COMMENTS This note provides you with suggested comments for Dr. Gilbertson's ISRTP Workshop presentation on Talc dealing with cosmetic perspectives Background Talc a complex hydrated magnesium silicate mineral has been mined since the time of the ancient Greeks Hildick and has a history of being mined in several regions of the world including Europe esp France and Italy the Orient including Manchuria and Japan India and the United States including California Montana North Carolina and Alabama The cosmetic literature reports whether accurately or not that Italian cosmetic talc has been the western world's standard for centuries Mulryan According to a dated U.S. Bureau of Mines estimate from 1979 the world's talc industry produced nearly 6.9 million tons of talc per year with a market value of ca. $ 435,000,000 Othmer Of this total ca. 17 of which could be expected to be of cosmetic quality Mulryan Because cosmetic and pharmaceutical OTC product matrices that employ cosmetic talc are also expected to possess desirable aesthetic characteristics that will find widespread consumer acceptance high quality cosmetic regardless of their geographic source share three 3 common characteristics high chemical purity a clean white color and good slip in addition to softness Mohs Mineralogical Scale grade of 1 and acceptable texture It has been said that a good quality talc should have such particle fineness that 98 of it goes through a standard mesh sieve i.e. 98 of the particles are sized < 74 microns however ultrafine grades of talc can also be produced and micronized talcs having particle sizes of only a few microns are also commercially available Martin Uses of Talc Talc is used in cosmetic products for the special feel shine and appearance esp transparency in face powders that it imparts to the cosmetic formulation A good talc should adhere to the skin evenly and aid in concealing superficial skin imperfections Because of its softness and slip lubricity the John E. Bailey Ph.D. - Page 2 talc may also have an emollient effect on the skin resisting mechanical abrasion and chafing of the skin due to the rubbing of skin or clothing The surface area of a talc also affects its ability to reflect light incident on the skin and therefore may also relate to its ability to reduce the perceived intensity or tint of a colorant Chemically treated ultra fine talcs can also afford water resistance in a cosmetic or OTC formulation Under the Federal Food Drug and Cosmetic Act FDCA of 1938 there is no requirement for premarket approval of cosmetics or with the exception of color additives and a short negative list of prohibited substances given at 21 CFR 700 their constituent raw materials Because there is no mandatory reporting requirement FDA does not know exactly how many products are on the market that contain talc as an ingredient However FDA does maintain a Voluntary Registration Program CVRP for cosmetics c.f. 21 CFR 720 in which companies can report their finished products and qualitative disclosures of ingredient composition current CVRP database indicates that there are about 2000 products in some 45 different cosmetic product categories that are voluntarily registered with FDA A few examples may be illustrative There are only 7 products registered as baby products baby lotions oils powders and creams while under the more generic powders category we find 425 products 21 registered More still are registered under the heading of blushers face powders and foundations where we find an additional 665 products 33.2 Finally there are 9 men's talcum products and 35 foot powders It should be emphasized that this is not an exhaustive recounting of all cosmetic products or even of all product categories known to utilize talc Nor does it represent the total universe of products or manufacturers of containing cosmetic products in the industry It is likely however that these registrations represent a significant portion of the volume of cosmetic products utilizing talc and distributed in the United States Based upon the figures given as one surveys the product categories reported in which talc has been to be used it seems clear that a significant number of cosmetic products are marketed at present for which there is a clear possibility of inhalation or perineal exposure Talc - Chemistry and Specifications | Talc has been described rather poetically as resulting ... during intense geologic upheavals underground which cause torrents of magnesia hot waters to alter basic rocks to hydrous magnesium silicate Mulryan The type of parent rock and the degree of alteration determine the purity and particle structure John E. Bailey Ph.D. > Page 3 of the talc According to the CTFA specification for cosmetic talc the balance of the talc may consist of other naturally occuring minerals such as calcite chlorite dolomite kaolin and magnesite Prior to the early 1970's there was some concern that talc mined and processed commercially could be contaminated by asbestos or asbestiform minerals Since that time however the cosmetic industry specification for talc has been tightened to virtually eliminate that concern For example a 1977 investigation of 46 talc samples by FDA revealed only 3 to contain asbestos tremolite or anthophyllite and even then the level was only 0.1 or less As mentioned earlier there are no premarket approval requirements under FDCA for cosmetics or their constituent raw materials Accordingly there are no mandated regulatory standards or specifications for the grade of talc that may be used in formulating cosmetic products However the Agency did note in its discussion concerning talc as a Category I skin protectant ingredient for the prevention of diaper rash c.f. 55 FR 25224 June 20 1990 ) that cosmetic talc should contain at least 90 platy talc having flat as opposed to fibrous particles that is free of detectable amounts of fibrous minerals including asbestos Other general talc specifications have been published by the Pharmacopoeia which specifies impurity limits and by the Cosmetic Toiletry and Fragrance Association which now U.S. CTFA also dictates that there should be no detectable fibrous amphiboles such as asbestiform tremolite OSHA defines fibers as particles of the relevant minerals which are 5 micometers or longer and having an aspect ratio of at least 1 c.f. 57 FR 24315 June 8 1992 There is also a Food Chemicals Codex FCC talc specification but the Agency has no way of knowing whether any given company in the cosmetic industry employs talc conforming to the USP CTFA or FCC specification Parenthetically we might note that ASTM has also | published a talc standard for paints Standard . 605-69 Acute and Chronic Medical Consequences of Talc Use The literature records that some pediatric authorities have recommended that the use of talcum powder one of whose main constituents is talc should be discouraged on neonates due to the possibility of acute massive associated infant death Some recent epidemiological studies which have generated considerable public interest have suggested an association between chronic female perineal talc dusting and the subsequent development of ovarian cancer Also there have been occasional occupational reports of chronic inhalation of talc dusts associated with the subsequent development of pulmonary fibrosis John E. Bailey Ph.D. - Page 4 It is beyond the scope of this presentation to do more than take note of these medical and occupational consequences alleged or proven that may be associated with talc usage and which have come to FDA's attention as well as to the attention of the American Public We look forward to the full and authoritative discussion of these issues and others which will take place at this Symposium I recognize that there may be aspects of these comments that Dr. Gilbertson may wish to avoid as an FDA spokesperson but I believe that there is enough given herein under the heading of cosmetic perspectives to allow for some judicious editing as you may think best SRMilstein ie - USP XXII Official Monographs / Talc 1309 -Pyrimidinetrione methylpropyl -5- propenyl butylbarbituric acid 115-44-6 Talbutal contains not less than 98.0 not more than 102.0 percent of C H16N2O3 C H16N2O3C lated on the dried basis percent and H16N2O3calcu- Packaging and storage -Preserve in tight containers Reference standard Talbutal Reference Standard in vacuum at 60 for 4 hours before using Dry Identification-- A The infrared absorption spectrum of a potassium bromide dispersion of it previously dried exhibits maxima only at the same wavelengths as that of a similar preparation of USP Tal- butal RS B The ultraviolet absorption spectrum of a 1 in 67,000 solution in pH 9.6 alkaline borate buffer see under Solutions in the section Reagents Indicators and Solutions exhibits maxima and minima at the same wavelengths as that of a similar solution of USP Talbutal RS concomitantly measured and the respective absorptivities calculated on the dried basis at the wavelength of maximum absorbance at about 241 nm do not differ by more than 3.0 Loss on drying Dry it in vacuum at 60 for 4 hours it loses not more than 1.0 of its weight Residue on ignition 281 not more than 0.2 Assay - Standard preparation Dissolve an accurately weighed quan- tity of USP Talbutal RS in 5 mL of alcohol contained in a 100- mL volumetric flask dilute with pH 9 6 alkaline borate buffer see under Solutions in the section Reagents Indicators and Solutions to volume mix and dilute quantitatively and stepwise with the same alcohol mixture to obtain a solution having a known concentration of about 10 gper ml Assay preparation Weigh and finely powder not less than 20 Talbutal Tablets Transfer an accurately weighed portion of the powder equivalent to about 50 mg of talbutal to a separator with the aid of 15 ml of water and add 5 mL of & hydrochloric acid Extract with four mL portions of chloroform filter cach portion through chloroform cotton into a 250 volumetric flask dilute with chloroform to volume and mix Transfer 50 mL of this solution to a beaker and evaporate just to dryness Transfer the residue to a 100 volumetric flask with the aid of first 5 ml of alcohol and then pH 9 6 alkaline borate buffer Dilute with the buffer to volume and mix Concomitantly determine the absorbances of the Standard preparation and the Assay preparation in cm cells at the wavelength of maximum absorbance at about 241 nm with a suitable spectrophotometer using a 1 in 20 solution of alcohol in pH 9.6 alkaline borate buffer as the blank Calculate the quantity in mg of H inNthe porOtion of Tablets taken by the formula SC / As Heavy metals Method II 231 0002 in which C is the concentration in gper mL of USP Talbutal Transfer about 500 mg of Talbutal accurately weighed to mL conical flask and dissolve in 25 mL of dimethyl- formamide Add 5 drops ofa freshly prepared 1 in 1000 solution of azo violet in dimethylformamide and titrate with 0.1 lithium RS in the Standard preparation and A ' and As are the absorbances of the Assay preparation and the Standard preparation respectively methoxide VS to a violet point taking precautions against the absorption of atmospheric carbon dioxide Perform a blank determination and make any necessary correction Each mL of Talc 01 lithium methoxide is equivalent to 22.43 mg of C H CN O H N O Talbutal Tablets Talc is a native hydrous magnesium silicate sometimes containing a small proportion of aluminum silicate Talbutal Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of CH 16N2O3 Packaging and storage - Preserve in tight containers Reference standard Talbutal Reference Standard in vacuum at 60 for 4 hours before using Dry Identification Shake a quantity of finely powdered Tablets equivalent to about 200 mg of talbutal with 10 mL of pentane for 5 minutes and filter through a porosity sinteredglass filter Discard the filtrate and shake the residue with 10 mL of chloroform for 15 minutes Filter through the same filter evaporate the filtrate with the aid of gentle heat to dryness and use the residue of talbutal so obtained for the following tests A A portion of the residue responds to Identification test 4 under Talbutal B To the remainder of the residue add 1 mL of glacial acetic acid and 10 mL of water mix then add bromine TS dropwise the bromine color is discharged on shaking Dissolution 711 - Medium water 900 ml Apparatus 2 50 rpm Time 45 minutes Procedure Determine the amount of CH dNissolvOed from ultraviolet absorbances at the wavelength of maximum ab- sorbance at about 241 nm of filtered portions of the solution under test suitably diluted with pH 9 6 alkaline borate buffer see under Buffer Solutions in the section Reagents Indicators and So- lutions in comparison with a Standard solution having a known concentration of USP Talbutal RS in the same medium Tolerances Not less than 75 Q of the labeled amount of CHNCHisN dissolved in 45 minutes Uniformity of dosage units 905 meet the requirements Packaging and storage = Preserve in closed containers Identification Mix about 200 mg of anhydrous sodium carbonate with 2 g of anhydrous potassium carbonate and melt in platinum crucible To the melt add 100 mg of the substance under test and continue heating until fusion is complete Cool and transfer the fused mixture to a dish or beaker with the aid of about 50 mL of hot water Add hydrochloric ac d to the liquid until effervescence ceases then add 10 mL more of the acid and evaporate the mixture on steam bath to dryness Cool add 20 mL of water boil and filter the mixture an insoluble residue of silica remains Dissolve in the filtrate about 2 g of ammonium chloride and add 5 mL of 6 \ ammonium hydroxide Filter if necessary and add dibasic sodium phosphate TS to the filtrate a white crystalline precipitate of magnesium ammonium phosphate separates Microbial limit -- The total bacterial count does not exceed 500 per g Loss on ignition 733 Weigh accurately about 1 g and ignite at 1000 to constant weight it loses not more than 65 % of its weight soluble substances Digest 1.00 g with 20 mL of 3. hy- drochloric acid at 50 for 15 minutes add water to restore the original volume mix mL of 2 A sulfuric constant weight the mg 20 % and filter To 10 mL of the filtrate add | acid evaporate to dryness and ignite to weight of the residue does not exceed 10 Reaction and soluble substances Boil 10 g with 50 ml of water for 30 minutes adding water from time to time to maintain ap- proximately the original volume and filter the filtrate is neutral to htmus paper Evaporate half of the filtrate filtrate to dryness and dry at 105 for 1 hour the weight of the residue does not exceed 5 mg ) soluble iron Slightly acidify with hydrociloric hydrociloric acid the remaining half of the filtrate obtained in the test for Reaction d 1310 Tamoxifen / Official Monographs and soluble substances and add 1 mL of potassium ferrocyanide TS the liquid does not acquire a blue color Arsenic Heavy metals and Lead-- Test Transfer 10.0 g to a 250 flask and add 50 mL of 0.5 N hydrochloric acid Attach a reflux condenser to the flask heat on a steam bath for 30 minutes cool transfer the mixture to a beaker and allow the undissolved material to settle Decant the supernatant liquid through thick strong mediumspeed filter paper into a 100 volumetric flask retaining as much as possible of the insoluble material in the beaker Wash the slurry and beaker with three mL portions of hot water decanting each washing through the filter into the flask Finally wash the filter paper with 15 mL of hot water cool the filtrate to room temperature dilute with water to volume and mix Use this Test solution for the following tests Arsenic Method I -Use 10 mL of the Test solution in preparing the Test Preparation The limit is 3 ppm Heavy metals -Use 5 mL of the Test solution in pre- paring the Test Preparation The limit is 0.004 Lead 251 mL portion of the Test solution contains not more than 5 gof lead 0.001 Tamoxifen Citrate 2NCH2NCH 2NCH CCHH O O SdCH C O = C Coby . CH2COOH CH2COOH CH2COH + COOH r) CH2COOH CH2COOH C26H29NO.C6H O 563.65 Ethanamine diphenyl phenoxy methyl- Z hydroxy propanetricarboxylate ) dimethyleth- ylamine citrate ) 54965-24-1 Tamoxifen Citrate contains not less than 99.0 per- cent and not more than 101.0 percent of C26H29NO.C6H8O7 calculated on the dried basis Packaging and Preserve in closed resistant containers Reference standard Tamoxifen Citrate Reference Standard at 105 for 4 hours before using Identification- A The infrared absorption spectrum of a potassium bromide dispersion of it exhibits maxima only at the same wavelengths as that of a similar preparation of USP Tamoxifen Citrate RS exhibiting a single band in the 1700 to 1740 cmflregion of the spectrum B The ultraviolet absorption spectrum of a 1 in 50,000 so- lution in methanol exhibits maxima and minima at the same wavelengths as that of a similar solution of USP Tamoxifen Citrate RS concomitantly measured Melting range 741 melts at about 142 with decomposition Loss on drying -Dry it at 105 for 4 hours it loses not more than 0.5 of its weight Residue on ignition 281 not more than 0.2 isomer- Mobile Prepare a methanol solution containing in each liter 320 mL of water 2 mL of glacial acetic acid and 1.08 g of sodium octanesulfonate Standard preparation a suitable quantity accurately weighed of USP Tamoxifen Citrate RS in Mobile phase to obtain a solution having a known concentration of about 600 ...gper mL Citrate Test preparation about 30 mg of Tamoxifen Citrate accurately weighed proceed as directed under Standard prep- aration Chromatographic system see Chromatography The liquid chromatograph is equipped with a 254 detector and a mm ^ cm column that contains packing L11 The flow rate is about 0.7 mL per minute Chromatograph five replicate injections of the Standard preparation and record the respons of the major peak the relative standard deviation is not than 3.0 and the relative retention time of the minor E peak to that of the isomer peak is not greater than 0.93 NO.C6H8O7 NO.C6H8O7 sampling Separately introduce equal volumes about 20 of the Test preparation and the Standard preparation into liquid chromatograph by means of a suitable Measure the minor peak responses for the isomer obtained the Standard preparation and the Assay preparation Calcu the quantity in mg of isomer C26H29 portion of Tamoxifen Citrate taken by the formula inf 0.05C C in which is the concentration in gper mL of the ison as the citrate based on its declared content in USP Tamon Citrate RS in the Standard preparation and the ry and r the minor peak responses obtained from the Assay prepara and the Standard preparation respectively The isomer tent is not more than 1.0 of tamoxifen citrate C26H29 C6H8O7 Related impurities Test preparation Disperse about 3 g in 100 mL of in a separator Over a minute period add 50 mL of 0 sodium hydroxide with mixing Extract with two mL port of ether and combine the extracts Wash with 20 mL of nitrogen remove the water layer and dry the ether layer over anhydro sodium sulfate Evaporate the ether layer under dry in vacuum at room temperature for 2 hours Accurat weigh 1.5 g of the residue into a mL volumetric flask 5.0 mL of a mixture of 5 volumes of acetic anhydride and volumes of pyridine and heat at 60 for 10 to 15 minutes @ dilute with the same solvent mixture to volume and mix - i Test preparation Using the same acetic anhydride anhydride dine mixture prepare a 200 dilution of Test preparation Chromatographic system see Chromatography 621 ically the gas chromatograph is equipped with a ionizati detector and contains a m ^ mm glass column packed w 5 percent liquid phase G17 on 100- to mesh support S1 conditioned at 300 for 24 hours The column and injection f are maintained at about 260 and the detector at about 3000 about Dry helium is used as the carrier gas at a flow rate of mL per minute In a suitable chromatogram five replicate jections of Test preparation B show a relative standard deviation of not more than 3.0 : Procedure equal portions about 2 Laccurat measured of Test preparation A and Test preparation B the chromatograph and record the chromatograms from 5.0 relative to the retention time of the major peak Measure chromatograms obtained individual areas of the peaks other than those produced by solvent and the tamoxifen on the To Test preparation A and calculate their sum No single peak an is greater than total area of the tamoxifen peak on the gh the matogram obtained from Test preparation B 0.5 and of the peak areas is not greater than twice the total area of tamoxifen peak on the chromatogram obtained from Test aration B 1.0 Iron Accurately weigh 1.0 g and transfer to a suit crucible Add sufficient sulfuric acid to wet the substance carefully ignite at a low temperature until thoroughly char char The crucible may be loosely covered with a suitable lid du mL nitric the charring Add to the carbonized mass 2 of and 5 drops of sulfuric acid and heat cautiously until white no longer are evolved Ignite preferably in a muffle furnace 500 to 600 until the carbon is completely burned off add 10 mL of warm 0.1 N hydrochloric acid and digest for 5 minutes Transfer the contents of the crucible with the small portions of water to a mL volumetric flask dilute water to volume and mix Pipet 10 mL from the volumetricad into a comparison tube dilute with water to 45 mL 0.005 mL of hydrochloric acid and mix The limit is F sulfuric Arsenic Method II Us 10e mL of dilute aci in 2 instead of 5 mL of sulfuric acid The limit is 2 ppmo Heavy metals Method II 231 0.001 Citrate Weigh accurately about 1 g of Tamoxifen dissolve in 150 mL of glacial acetic acid Titrate the with 0.1 N perchloric acid VS determining the pointpopo 0.54 0.54 1.36 4.76 4.7615.9 18.2 2.82.8 Osorbable : Sutures of mono- Suture is lan laid out the strand ure as didiameter rescribed 21. the : less than re greater 1 less than -Surgical ne average mpanying ire swaged Attachment quirements in the test ure but iner the flask flask at the ume by the by evapora USP XX Talbutal i = N 40 CHCH NH CH CH CCHH Sr CH 0 CHNO 224.26 -Pyrimidinetrionc methylpropyl propenyl butylbarbituric acid 115-44-6 115-44-6 Talbutal contains not less than 98.0 percent and not more than 102.0 percent of C H1ca6 lculated on the dried basis Packaging and Preserve in tight containers Reference standard Talbutal Reference Standard in vacuum at 60 for 4 hours before using Identification A The infrared absorption spectrum of a potassium bromide dispersion of it previously dried exhibits maxima only at the same wavelengths as that of a similar preparation of USP Talbutal B The ultraviolet absorption spectrum of a 1 in 67,000 solution in pH 9.6 alkaline borate buffer see under Solutions in the section Reagents Indicators and Solutions exhibits maxima and minima at the same wavelengths as that of a similar solution of USP Tal- butal RS concomitantly measured and the respective absorptivities calculated on the dried basis at the wavelength of maximum absorbance at about 241 nm do not differ by more than 3.0 Loss on drying -Dry it in vacuum at 60 for 4 hours not more than 1.0 of its weight it loses Residue on ignition 281 not more than 0.2 Heavy metals Method II 231 0.002 Transfer about 500 mg of Talbutal accurately weighed to 125 conical flask and dissolve in 25 ml of dimethylformamide Add 5 drops of a freshly prepared I in 1000 solution of azo violet in dimethylformamide and titrate with 0.1 N lithium meth- oxide VS to a violet point taking precautions against the absorption of atmospheric carbon dioxide Perform a blank de- termination and make any necessary correction Each ml of 0.1 lithium methoxide is equivalent to 22.43 mg of C 16N2O3 Talbutal Tablets Talbutal Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of CH16N2O3 CH16N2O3 CH16N2O3 CH16N2O3 Packaging and storage Preserve in tight containers Reference standard Talbutal Reference Standard in vacuum at 60 for 4 hours before using Identification a quantity of finely powdered Tablets equivalent to about 200 mg of talbutal with 10 ml of pentane for 5 minutes and filter through a porosity sintered filter Discard the filtrate and shake the residue with 10 ml of for evapo- chloroform for 15 minutes Filter through the same filter rate the filtrate with the aid of gentle heat to dryness and use the residue of talbutal so obtained the following tests A A portion of the residue responds to Identification test A under Talbutal responds B To the remainder of the residue add 1 ml of glacial acetic acid and 10 ml of water mix then add bromine TS dropwise the bromine color is discharged on shaking Disintegration 701 30 minutes Weight variation 931 meet the requirements for Tablets AssayAs-sayStandard preparation an accurately weighed quantity of USP Talbutal RS in 5 ml of alcohol contained in 100 volu- metric flask dilute with pH 9.6 alkaline borate buffer see under Solutions in the section Reagents Indicators and Solutions to volume mix and dilute quantitatively and stepwise with the same Official Monographs / Tape 761 alcohol mixture to obtain a solution having a known con- centration of about 10 gper ml Weigh Assay preparation and finely powder not less than 20 Talbutal Tablets Transfer an accurately weighed portion of the powder equivalent to about 50 mg of talbutal to a separator with 3 the aid of 15 ml of water and add 5 ml of N hydrochloric acid Extract with four ml portions of chloroform filter each portion through chloroform cotton into a 250 volumetric flask dilute with chloroform to volume and mix Transfer 5.0 ml of this solution to a beaker and evaporate just to dryness Transfer the residue to a 100 volumetric flask with the aid of first 5 ml of alcohol and then pH 9.6 alkaline borate buffer Dilute with the buffer to volume and mix Procedure Concomitantly determine the absorbances of the Standard preparation and the Assay preparation in cm cells at the wavelength of maximum absorbance at about 241 nm with a suitable spectrophotometer using a 1 in 20 solution of alcohol in pH 9.6 alkaline borate buffer as the blank Calculate the quantity in mg of CH6N2O3 in the portion of the Tablets taken by the formula Au in which C is the concentration in gper ml of USP Talbutal RS in the Standard preparation and A and As are the absorbances of the Assay preparation and the Standard preparation respectively Talc Talc is a native hydrous magnesium silicate sometimes containing a small proportion of aluminum silicate Packaging and storage Preserve in closed containers Mix Identification 500 mg with about 200 mg of anhydrous so- dium carbonate and 2 g of anhydrous potassium carbonate and heat the mixture in platinum crucible until fusion is complete Cool and transfer the fused mixture to a dish or beaker with the aid of about 50 ml of hot water Add hydrochloric acid to the liquid until effervescence ceases then add 10 ml more of the acid and evaporate the mixture on a steam bath to dryness Cool add 20 ml of water boil and filter the mixture an insoluble residue of silica remains Dissolve in the filtrate about 2 g of ammonium chloride and add 5 ml of 6 N ammonium hydroxide Filter if necessary and add sodium phosphate TS to the filtrate a white crystalline precipitate of magnesium ammonium phosphate separates Loss on ignition Weigh accurately about 1 g and ignite at red heat to constant weight it loses not more than 5.0 of its weight soluble substances Digest 1.00 g with 20 ml of 3 N hydrochloric acid at 50 for 15 minutes add water to restore the original of original volume mix and filter To 10 ml the filtrate add 1 ml of N sulfuric acid evaporate to dryness and ignite to constant weight the weight of the residue does not exceed 10 mg 2.0 Reaction and soluble substances Boil 10 g with 50 ml of water for 30 minutes adding water from time to time to maintain approximately the original volume and filter The filtrate is neutral to of the litmus paper Evaporate half filtrate to dryness and dry at 105 for 1 hour the weight of the residue does not exceed 5 mg 0.1 soluble Slightly acidify with hydrochloric acid the of remaining half the filtrate obtained in the test for Reaction and soluble substances and add 1 ml of potassium ferrocyanide TS the liquid does not acquire a blue color Adhesive Tape Adhesive Tape consists of fabric and film evenly coated on one side with a sensitive adhesive mixture Its length is not less than 98.0 percent of that declared on the label and its average width is not less than 95.0 percent of the declared width If Adhesive Tape has been rendered sterile it is protected from contamination by appropriate packaging Packaging and storage- - Preserve in closed containers and