Pergamon - Food and Chemical Toxicology 36 (1998) 1139-1174
1. C. MUNRO!, W. O. BERNT2, J. F. BORZELLECN, G. FLAMM4, B. S. LYNCH!, E. KENNEPOHV'*, E. A. BARs and J. MODDERMAN6 'CanTox Inc" Consultants in Toxicology, Health and Environmental Sciences, 2233 Argentia Road, Suite 308, Mississauga, Ontario, Canada, L5N 2X7, 'University of Nebraska Medical Center, Nebraska's Health Science Center, 600 South 42nd Street, Box 986810, Omaha, NE 68198-6810, USA, 'Department of Pharmacology and Toxicology, Medical College of Virginia, Box 980613, Richmond, VA 23298-0613, USA, 'Flamm Associates, 4861 North AlA, Vero Beach, FL 32963, USA, 'Bioresco
AG, Hauptstrasse 63, Postfach 406, 4102 Binningen, Switzerland and 'Keller and Heckman, LLP, 1001 G Street, NW, Washington, DC 20001, USA (Accepted 12 June 1998).
Once erythritol is separated from the fermentation broth, it is purified to result in a crystalline product that is more than 99% pure. Its intended uses principally include confectionery, chewing gum, and beverage and bakery products.
Erythritol occurs widely in nature and has been found to occur naturally in several foods including wine, sake, beer, water melon, pear, grape and soy sauce at levels up to 0.13 % (w Iv) (Dubernet et al., 1974; Onishi and Saito, 1959, 1960; Shindou et al., 1988, 1989; Sponholz and Dittrich, 1985; Sponholz et al., 1986).
Evidence indicates that erythritol also exists endogenously in the tissues and body fluids of humans and animals (Goossens and Roper, 1994; Horning et al., 1974; Noda et al., 1994; Oku and Noda, 1990a,b; Spencer, 1967). It has been identified in human plasma at levels of approximately 1.2 mg/ litre (Niwa et al., 1993) as well as in foetal blood of animals (Britton, 1967; Roberts et al., 1976). Erythritol occurs normally in human urine (Goossens and Roper, 1994). Urinary concentrations have been reported to range from 10 to 100 mg/litre (Pitkiinen and Pitkiinen, 1964) or 42 to 65 mg creatinine/g (Pfaffenberger et al., 1976).
This critical and comprehensive review of the safety database on erythritol provides a well documented basis from which a safety evaluation of this product can be conducted. Numerous acute, subchronic, chronic and special toxicity studies have been conducted in rats, mice and dogs. The special studies consist of long-term feeding studies conducted to determine carcinogenic potential, intravenous and oral teratogenicity studies to determine the potential for effects on the foetus, oral studies administered over one or two generations to determine the potential for reproductive effects, and studies in bacterial and mammalian systems to determine mutagenic potential. The majority of the safety studies conducted were feeding studies in which erythritol was mixed into the diet at concentrations as high as 20%. All of the safety studies on erythritol have demonstrated that it is well tolerated and elicits no adverse toxicological effects. As erythritol is not systemically metabolized, some intravenous studies also have been conducted. Even when administered intravenously, erythritol did not produce any adverse toxicological effects. The safety database on erythritol provides no evidence that erythritol has any carcinogenic, mutagenic or teratogenic potential. In addition, no effects on reproductive performance or fertility have been reported in the studies.
In animals, at high doses (e.g. 20 g/kg body weight/day), erythritol treatment has been associated with some physiological changes consisting of transient diarrhoea, increased caecal and kidney weights, increased water consumption and urine output, and minor changes in certain urinary parameters. These effects are considered to be physiological responses (WHO, 1987), and are commonly observed in test animals treated with high oral doses of poorly metabolized, or poorly absorbed, low molecular weight compounds, including various carbohydrate compounds. Most importantly, no histopathological evidence of toxicity has been reported in any study conducted with erythritol Absorption, distribution, metabolism and excretion studies. |
