Safety of carrageenan in foods. (Correspondence).

A recent review of the toxicology of carrageenan by Tobacman (1) raised questions about the safety of carageenan-containing foods. Intact carageenan is a high molecular weight hydrocolloid (molecular weight 1.5-20 x [10.sup.6]). One concern has focused on the potential for degraded (low molecular weight) carageenan to be formed by acid hydrolysis in the stomach and the possibility that this material could promote cancer of the colon (1). Rats fed degraded carrageenan have been shown to develop colorectal tumors (2). Studies involving initiation with the genotoxic carcinogen azoxymethane, followed by quantitation of the number of aberrant intestinal crypts formed in response to subsequent carrageenan exposure, have also suggested that degraded carageenan has the potential to promote colon cancer in rats (3).

These findings have led to degraded carrageenan being classified by the International Agency for Research on Cancer (IARC) as 2B, a possible human carcinogen, based on animal study data. Native carrageenan has been classified by IARC as 3, unclassifiable with respect to carcinogenicity in humans.

In a recent paper, Tache et al (4) used a well-established and highly sensitive aberrant crypt assay to examined the potential for carrageenan to promote azoxymethane-induced colonic cancer; they found no promoting effect when a humanized gut flora was used. Because the carrageenan was administered in the drinking water, it was available for degradation in the acidic environment of the stomach. The use of normal rodent microbiologic flora produced a promoting effect of carrageenan in this model system (4), confirming positive results of previous studies, in contrast with the negative effect that occurred using humanized intestinal flora in the rat. Thus, the conclusion must be that this colon cancer-promoting effect is a rodent-specific phenomenon, requiring a rodent intestinal microbiologic flora, and that carrageenan would not promote colon cancer in humans.

The concerns with regard to the induction of ulcerative colitis expressed by Tobacman (1) are also inappropriately extrapolated from animal data with regard to human risk. There have been many studies carried out with carrageenan in animals, and carrageenan has been used to induce inflammation in susceptible species and to test the anti-inflammatory properties of new candidate drugs. Although guinea pigs are very sensitive to the induction of colitis by carrageenan, primates--a more appropriate species for comparison to humans--are resistant to the induction of colitis by carrageenan.

The safety of carrageenan for use in foods was confirmed at the 57th meeting of the Joint Food and Agriculture Organization of the United Nations/World Health Organization Expert Committee on Food Additives (JECFA) in Rome in June 2001 (5). The JECFA recommended an acceptable daily intake (ADI) of "not specified," the most favorable ADI for a food additive. This recommendation was made after a review of all of the current toxicology and carcinogenicity studies on carrageenan by two world experts in this field, S. Cohen (University of Nebraska Medical Center, Omaha, NE, USA) and N. Ito (Nagoya City University  Medical School, Nagoya, Japan). It included consideration of studies not cited by Tobacman (1) in her evaluation.

Phil Carthew
Unilever Safety and Environmental
Assurance Centre
Sharnbrook, Bedfordshire, United Kingdom
E-mail: [e-mail]

REFERENCES AND NOTES

(1.) Tobacman JK. Review of harmful gastrointestinal effects of carrageenan in animal experiments. Environ Health Perspect 109:983-994 (2001).

(2.) Ishioka T, Kuwabara N, Oohashi Y, Wakabayashi K. Induction of colorectal tumors in rats by sulfated polysaccharides. CRC Crit Rev Toxicol 17:215-244 (1987).

(2.) Corpet DE, Tache S, Preclaire M. Carrageenan given as a jelly, does not initiate, but promotes the growth of aberrant crypt foci in the rat colon. Cancer Lett 114:53-55 (1997).

(4.) Tache S, Peiffer G, Millet AS, Corpet DE. Carrageenan gel and aberrant crypt foci in the colon of conventional and human flora-associated rats. Nutr Cancer 37:193-198 (2000).

(5.) Joint FAO/WHO Expert Committee on Food Additives Fifty-seventh Meeting, Rome, 5-14 June, 2001. Summary and Conclusions. Available: http://www.fao.org/es/ ESN/Jecfa/57corr.pdf [cited 15 February 2002],