Prepared at the 74th JECFA (2011) and published in FAO JECFA Monographs 11 (2011), superseding the specifications prepared at the 63rd JECFA (2004), published in the Combined Compendium of Food Additive Specifications, FAO JECFA Monographs 1 (2005). A group ADI ”not specified” for modified celluloses (ethyl cellulose, ethyl hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, methyl cellulose, methyl ethyl cellulose, and sodium carboxymethyl cellulose) was established at the 35th JECFA (1989).
INS No. 464
Hydroxypropylmethyl cellulose is a methyl cellulose modified by treatment with alkali and propylene oxide by which a small number of 2-hydroxypropyl groups are attached through ether links to the anhydroglucose units of the cellulose. The article in commerce may be further specified by viscosity.
Hydroxypropylmethyl cellulose, 2-hydroxypropyl ether of methyl cellulose
z = 0.07 - 0.34
y = 1.12 - 2.03
x = 3-(z + y): (z + y = degree of substitution)
where R = H or CH3 or CH2CHOHCH3
Unsubstituted structural unit: 162.14.
Structural unit with 1.19 degree of substitution: approx. 180.
Structural unit with 2.37 degree of substitution: approx. 210.
Macromolecules: from about 13,000 (n about 70) up to about 200,000 (n about 1000)
Not less than 19% and not more than 30% of methoxylgroups (-OCH3) and not less than 3% and not more than 12% hydroxypropoxyl groups (-OCH2CHOHCH3), on the dried basis
Hygroscopic white or off-white powder, or granules or fine fibres
Emulsifier, thickening agent, stabilizer
Swells in water, producing a clear to opalescent, viscous colloidal solution; insoluble in ethanol
A 0.1% solution of the sample is shaken vigorously. A layer of foam appears. This test permits the distinction of sodium carboxymethyl cellulose from other cellulose ethers.
To 5 ml of a 0.5% solution of the sample, add 5 ml of a 5% solution of copper sulfate or of aluminium sulfate. No precipitate appears. This test permits the distinction of sodium carboxymethyl cellulose from other cellulose ethers.
See description under METHOD OF ASSAY
Loss on drying
Not more than 10% (105o to constant weight)
Not less than 5 and not more than 8 (1 in 100 soln)
Not more than 1.5% for products with viscosities of 50 centipoises or above, and not more than 3% for products with viscosities below 50 centipoises
Test 1 g of the sample
Not more than 0.1 mg/kg
See description under TESTS
Not more than 2 mg/kg
Determine using an AAS/ICP-AES technique appropriate to the specified level. The selection of sample size and method of sample preparation may be based on the principles of the methods described in Volume 4 (under “General Methods, Metallic Impurities”).
Determine by Gas Chromatography–Mass Spectrometry (GC-MS) (Vol. 4) using the following procedure.
Note: Propylene chlorohydrins (PCH) are present as 2 isomers namely: 1-chloro-2-propanol (1C2P) and 2-chloro-1-propanol (2C1P).
Internal Standard Stock Solution #1 (1 mg/ml): Weigh 0.1 g to nearest 0.1 mg (approximately 100 μl) of o-xylene-d10 (CAS 56004-61-6) into a 100 ml volumetric flask and make up to volume with methanol.
Internal Standard Stock Solution #2 (100 μg/ml): Pipette 5ml of Internal Standard Stock Solution #1 into a 50 ml volumetric flask and make up to volume with methanol.
Internal Standard Stock Solution #3 (4 μg/ml): Pipette 1 ml of Internal Standard Stock Solution #2 into a 25 ml volumetric flask and make up to volume with methanol:
Internal Standard Solution #4 (16 ng/ml): Add 1 ml of Internal Standard Stock Solution #3 into a 250 ml volumetric flask and dilute to volume with diethyl ether.
Internal Standard Solution #5 (8 ng/ml): Pipette 25 ml of Internal Standard Stock Solution #4 into a 50 ml volumetric flask and dilute to volume with diethyl ether.
Stock Standard Solution #2 (100 μg/ml): Pipette 5 ml of Standard Stock Solution #1 into a 50 ml volumetric flask and make up to volume with diethyl ether
Stock Standard Solution #3 (10 μg/ml): Pipette 5 ml of Standard Stock Solution #2 into a 50 ml volumetric flask and make up to volume with
Stock Standard Solution #4 (500 ng/ml): Pipette 5 ml of Standard Stock Solution #3 into a 100 ml volumetric flask and make up to
Note: All standard solutions should be prepared with diethyl ether of the highest purity available.
Prepare working standard solutions by pipetting the volumes shown in the table below in to a 10 ml volumetric flask and make up to volume with diethyl ether.
A gas chromatograph with a mass selective detector (GCMS) in Selective Ion Monitoring (SIM) mode, Electron impact ionisation (EI) source, pulsed-splitless injector and a data station.
Inlet temperature 225°
Deactivated fused silica, 10 m x 0.25 mm i.d. x 0.35 mm o.d.
Initial temperature 40°
Ion source temperature. 230°
o-Xylene-d10 Target ion m/z = 116, Qualifier ion m/z = 98
o-Xylene-d10 13.7 min
AR(std) is the ratio of detector response for 1C2P or 2C1P versus the detector response for o-xylene-d10 in the standard;
AR(sample) = R(Sample)/R(IS)
METHOD OF ASSAY
Determination of the hydroxypropoxyl group
The apparatus for hydroxypropoxyl group determination is shown in the accompanying diagram. The boiling flask, D, is fitted with an aluminium foil-covered Vigreux column, E, on the sidearm and with a bleeder tube through the neck and to the bottom of the flask for the introduction of steam and nitrogen. A steam generator, B, is attached to the bleeder tube through Tube C, and a condenser, F, is attached to the Vigreux column. The boiling flask and steam generator are immersed in an oil bath, A, equipped with a thermo-regulator such that a temperature of 155o and the desired heating rate may be maintained. The distillate is collected in a 150-ml beaker, G, or other suitable container.
Transfer about 100 mg of the sample, previously dried at 105o for 2 h and accurately weighed, into the boiling flash, and add 10 ml of chromium trioxide solution (60 g in 140 ml of water). Immerse the steam generator and the boiling flask in the oil bath (at room temperature) to the level of the top of the chromium trioxide solution. Start cooling water through the condenser and pass nitrogen gas through the boiling flask at the rate of one bubble per sec. Starting at room temperature, raise the temperature of the oil bath to 155o over a period of not less than 30 min, and maintain this temperature until the end of the determination. Distil until 50 ml of the distillate is collected. Detach the condenser from the Vigreux column, and wash it with water, collecting the washings in the distillate container. Titrate the combined washings and distillate with 0.02 N sodium hydroxide to a pH of 7.0, using a pH meter set at the expanded scale.
NOTE: Phenolphthalein TS may be used for this titration, if it is also used for all standards and blanks.
Record the volume, Va of the 0.02 N sodium hydroxide used. Add 500 mg of sodium bicarbonate and 10 ml of dilute sulfuric acid TS, and then after evolution of carbon dioxide has ceased, add 1 g of potassium iodide. Stopper the flask, shake the mixture, and allow it to stand in the dark for 5 min. Titrate the liberated iodine with 0.02 N sodium thiosulfate to the sharp disappearance of the yellow colour, confirming the end-point by the addition of a few drops of starch TS. Record the volume of 0.02 N sodium thiosulfate required as Ya.
Make several reagent blank determinations, using only the chromium trioxide solution in the above procedure. The ratio of the sodium hydroxide titration (Vb) to the sodium thiosulfate titration (Yb), corrected for variation in normalities, will give the acidity-to-oxidizing ratio, Vb/Yb= K, for the chromium trioxide carried over in the distillation. The factor K should be constant for all determinations.
Make a series of blank determinations using 100 mg of methyl-cellulose (containing no foreign material) in place of the sample, recording the average volume of 0.02 N sodium hydroxide required as Vm and the average volume of 0.02 N sodium thiosulfate required as Ym.
Calculate the hydroxypropoxyl content of the sample, in mg, by the formula:
75.0 x [N1 (Va-Vm) – k N2 (Ya – Ym)]
N1 = the exact normality of the 0.02 N sodium hydroxide solution
N2 = the exact normality of the 0.02 N sodium thiosulfate solution
k = VbN1/YbN2
Chart for converting percentage of substitution, by weight, of hydroxypropoxyl groups to molecular substitution per glucose unit.
Determination of the methoxyl group
Volume 4, under ASSAY METHODS, Cellulose Derivatives Assay, Ethoxyl and Methoxyl Group Determination. See Apparatus and Procedure in Ethoxy and Methoxy Group Determination and determine the content of methoxy groups (-OCH3).
Calculate as percentage. Correct the % of methoxy groups thus determined by the formula:
A - (B x 0.93 x 31 / 75)
A is the total % of -OCH3 groups determined;
A - (B x 0.93 x 31 / 75)
A = the total % of -OCH3 groups determined
B = the % of -OCH2CHOHCH3 determined in the Method of Assay for Hydroxypropoxyl group content
0.93 = an average obtained by determing, on a large number of samples, the propylene produced from the reaction of hydriodic acid with hydroxypropoxyl groups during the Method of Assay for metoxyl groups (-OCH3).