For hydroxypropyl cellulose (E 463), the identified NOAEL corresponded to the highest dose 6,000 mg hydroxypropyl cellulose/kg bw per day (by gavage). The most relevant feeding studies with HPMC (E 464) were performed in rats which tolerated up to 10%, corresponding to 9,000 mg test item/kg bw per day. Rabbits tolerated up to 7,500 mg HPMC/kg bw per day administered via the diet (30 day exposure) and dogs up to 1,500 mg HPMC/kg bw per day, in either case being the highest tested dosages. More studies were conducted using sodium carboxy methylcellulose (E 466). The most relevant ones were conducted in rats, with NOAEL values ranging from 4,500 to 9,000 mg test item/kg bw per day (in all cases the highest dose tested). In these studies, some effects (caecum and colonic enlargement, urothelial hyperplasia, nephrocalcinosis, diffuse epithelial hyperplasia in the urinary bladder) were observed, however, not considered of toxicological concern: the findings in the gastrointestinal tract were considered to be a consequence of the accumulation of poorly absorbed water-soluble material and the findings in kidneys and urinary bladder were attributed to the up to fourfold higher concentration of sodium in the test diet compared with the basal diet. In one further study, rats were daily exposed (gavage) to doses equivalent to 0, 500, 2,500 or 5,000 mg/kg bw per day. Animals treated with ≥ 2,500 mg/kg bw per day had soft and pale faeces, which was attributed to the presence of test material and not considered of toxicological relevance. In the absence of any other adverse effects, also for this study, the identified NOAEL was the top dose (5,000 mg/kg bw per day).
Manufacturers must monitor the heavy metal content of HPMC and take appropriate measures to reduce its levels if necessary Manufacturers must monitor the heavy metal content of HPMC and take appropriate measures to reduce its levels if necessary
