Data on chronic toxicity and carcinogenicity are available for microcrystalline cellulose (E 460), methyl cellulose (E 461) hydroxypropyl cellulose (E 463), HPMC (E 464) and sodium carboxymethyl cellulose (E 466). Some studies were unfit for evaluation due to methodological shortcomings. In the only relevant study, the dietary administration of even high doses of microcrystalline cellulose (E 460) (30%, 15,000 mg/kg bw) to rats for 72 weeks did not affect survival, feed efficiency or haematology. Apart from some dystrophic calcification in renal tubules, no other relevant lesions were noted and tumour incidence did not differ with that of controls. Several studies were conducted in rats with methyl cellulose (E 461) via feed or drinking water or by gavage at concentrations up to 5% (2,500 mg methyl cellulose/kg bw per day) and for up to 2 years. For all examined parameters, no adverse effects were reported and also the observed tumours did not differ in type and number in treated and control groups. In the only identified study, the daily dosing of male and female rats (0, 1,500, 3,000 or 6,000 mg hydroxypropyl cellulose/kg bw) via gavage for 6 months did not cause adverse effects (including carcinogenicity) apart from a decrease in body weight in high-dosed rats (statistically significant in females only). Apart from a decrease in body weights of high-dosed males, no other significant adverse findings were reported and there was no indication of a carcinogenic effect in rats of either sex dietary exposed to HPMC (E 464) up to 20% (10,000 mg/kg bw per day) for 1 year. Carboxy methylcellulose (E 466) was tested in mice and rats at dosages of 0, 10,000 or 100,000 mg/kg diet (equivalent to 0, 1,500 or 15,000 mg/kg bw per day for mice and to 0, 500 or 5,000 mg/kg bw per day for rats) for up to 104 weeks. Despite the increase in feed intake, a treatment related decrease in body weight was noted at the end of the treatment. Histological examination revealed no intestinal abnormality or evidence of the passage of the additive across the intestinal wall in either species and the tumour incidences were comparable among groups.

ALL NATURAL? IS HPMC (E464) A CREDIBLE ALTERNATIVE TO GELATIN?

Substitution of cellulose with ethyl-, methyl-, hydroxypropyl-, hydroxypropyl-methyl- and carboxymethyl groups may increase the resistance of cellulose to degradation. Resistance increases with the degree of substitution and is greatest when the substituent groups are evenly dispersed along the polymer chain. Most cellulose of the additive under assessment will therefore pass the intestine undigested and will excreted unchanged via faeces. Even when a high cellulolytic activity is present, as in the rumen, ethyl cellulose remains sufficiently resistant to degradation to be used as enteric coatings designed to protect methionine from rumen release (EFSA FEEDAP Panel, 2012c). Subsequent degradation in the post-ruminal tract is most likely to lead to high molecule weight breakdown products, with little probability of absorption.