Evaluation of E 460(i), E 460(ii), E 461, E 462, E 463, E 464, E 465, E 466, E 468 and E 469 as food additives

At the request of the European Commission, the EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) conducted a scientific re-evaluation of the safety of microcrystalline cellulose (E460(i)), powdered cellulose (E460(ii)), methyl cellulose (E461), ethyl cellulose (E462), hydroxypropyl cellulose (E463), hydroxypropyl methyl cellulose (E464), ethyl methyl cellulose (E465), sodium carboxymethyl cellulose (E466), enzymatically hydrolysed carboxymethyl cellulose (E469), and cross-linked carboxymethyl cellulose (E468).

Cellulose is a linear polysaccharide consisting of glucopyranose units linked by β-1,4-glycosidic bonds. Its molecular formula is (C₆H₁₀O₅)n, and its molecular weight ranges from 50,000 to 2,500,000 depending on the source.

Modified celluloses are produced by substituting hydroxyl groups with methyl, ethyl, or hydroxypropyl groups, altering their physicochemical properties for technological use in the food industry.

Microcrystalline cellulose (E460(i)) and powdered cellulose (E460(ii)) were evaluated by the Scientific Committee on Food (SCF) in 1999, which confirmed the status of "ADI not specified". It was recommended that particle size should not be less than 5 μm.

The limited toxicological data for some modified celluloses are compensated by the structural, physicochemical, and biological similarities among them, which allows for a read-across approach.

Studies demonstrated that microcrystalline and powdered cellulose are partially fermented by the gut microbiota, whereas modified celluloses (E461–E469) are not absorbed, not fermented, and are excreted intact.

Toxicity studies showed that acute oral intake of these additives is associated with low toxicity. In short-term and subchronic studies, the primary effect observed at high doses (up to 10% in the diet) was reduced body weight gain, attributed to nutritional limitations rather than toxicity.

Genotoxicity studies (Ames test, chromosomal aberration assays) showed negative results for microcrystalline cellulose, methyl cellulose, and sodium carboxymethyl cellulose. Similarly, negative results were obtained for cross-linked and enzymatically hydrolysed carboxymethyl cellulose.

Chronic toxicity studies did not reveal carcinogenic properties of cellulose additives. The NOAEL for most of them is 9,000 mg/kg body weight per day.

Regarding reproductive and developmental toxicity, studies did not show adverse effects even at doses exceeding 1,000 mg/kg body weight.

Human consumption data also indicate good tolerability: intake of up to 35 g of microcrystalline or powdered cellulose per day did not affect blood biochemical parameters, and modified celluloses (up to 6,000 mg/day for 8 months) were well tolerated by patients with diarrhoea or constipation.

However, in mouse experiments, sodium carboxymethyl cellulose (E466) was associated with alterations in gut microbiota, inflammation, obesity, and impaired glycaemic control.

The EFSA Panel concluded that:

• Microcrystalline, powdered, and modified celluloses do not raise concerns for genotoxicity.
• The available toxicological data allow the application of the read-across approach to all forms of cellulose.
• There is no need to establish a numerical ADI.
• Intake levels up to 660–900 mg/kg body weight per day do not pose a health concern.

However, regarding the use of E466 in special medical purpose foods for infants and young children (categories 13.1.5.1 and 13.1.5.2), EFSA noted the absence of adequate data to assess safety for these population groups. Nevertheless, the actual use of E466 in such products appears to be negligible.

EFSA also recommended revising the permissible limits of toxic impurities (arsenic, lead, mercury, cadmium) in the EU specifications for cellulose additives to reduce their contribution to overall dietary exposure to these elements.