Food additive carrageenan: Part II: A critical review of carrageenan in vivo safety studies.

Carrageenan (CGN) is a seaweed-derived high molecular weight (Mw) hydrocolloid, primarily used as a stabilizer and thickener in food. The safety of CGN regarding its use in food is reviewed. Based on experimental studies in animals, ingested CGN is excreted quantitatively in the feces. Studies have shown that CGN is not significantly degraded by low gastric pH or microflora in the gastrointestinal (GI) tract. Due to its Mw, structure and its stability when bound to protein, CGN is not significantly absorbed or metabolized. CGN also does not significantly affect the absorption of nutrients. Subchronic and chronic feeding studies in rodents indicate that CGN at doses up to 5% in the diet does not induce any toxicological effects other than soft stools or diarrhea, which are a common effect for non-digestible high molecular weight compounds. Review of several studies from numerous species indicates that food grade CGN does not produce intestinal ulceration at doses up to 5% in the diet. Effects of CGN on the immune system following parenteral administration are well known, but not relevant to food additive uses. The majority of the studies evaluating the immunotoxicity potential were conducted with CGN administered in drinking water or by oral gavage where CGN exists in a random, open structured molecular conformation, particularly the lambda form; hence, it has more exposure to the intestinal mucosa than when bound to protein in food. Based on the many animal subchronic and chronic toxicity studies, CGN has not been found to affect the immune system, as judged by lack of effects on organ histopathology, clinical chemistry, hematology, normal health, and the lack of target organ toxicities. In these studies, animals consumed CGN at orders of magnitude above levels of CGN in the human diet: ≥1000 mg/kg/d in animals compared to 18-40 mg/kg/d estimated in the human diet. Dietary CGN has been shown to lack carcinogenic, tumor promoter, genotoxic, developmental, and reproductive effects in animal studies. CGN in infant formula has been shown to be safe in infant baboons and in an epidemiology study on human infants at current use levels.