DE LAS FACULTADES DE LAS AUTORIDADES EN MATERIA DE DEUDA

In the United States, sorbate is considered a GRAS compound, and because it is a metabolizable fatty acid, the World Health Organization has set the acceptable daily intake for sorbate at 25 mg/kg body weight per day. The relative nontoxicity of sorbates was established early in their testing as food preservatives. The compounds were fed to various animal species for determination of acute toxicity, as well as influence on metabolism, carcinogenicity, and teratogenicity after short- or long- term exposure. Overall, these studies demonstrated the relative harmlessness of sorbates and their relative superiority in safety compared to other chemical additives.

Acute toxicity studies with rats have determined LD50 (mean lethal dose) values for sorbates

in the range of 4.2 to 10.5 g/kg body weight (Smyth and Carpenter, 1948; Deuel et al., 1954a). For comparison, the LD50 for common salt (NaCl) is 5 g/kg body weight. Thus, based on acute toxicity,

sorbate is considered one of the least harmful preservatives in use.

Rat feeding studies have indicated that a dosage of 10% sorbic acid in the diet could be tolerated for 40 days (Lück, 1980). On extending the feeding period to 120 days, however, the growth rate and liver weight of the animals increased (Demaree et al., 1955). Additional studies with rats and dogs have shown no damage with feeding 5% sorbic acid for 90 days, but 8% sorbic acid resulted in an increase in liver weight (Deuel et al., 1954a; Demaree et al., 1955; Lück, 1976). The increase in liver weight has not been associated with histopathologic changes and has been interpreted as functional hypertrophy as a result of the caloric utilization of sorbic acid (Deuel et al., 1954a; Food and Drug Research Laboratories, 1973; Lück, 1980; Sofos, 1989).

Chronic toxicity studies have involved feeding rats and mice through the life span of one or two generations with sorbic acid concentrations as high as 90 mg/kg body weight or diets containing 10% sorbic acid. No abnormalities have been observed, and in some instances the growth rate of sorbate-fed animals increased significantly, apparently because of an increased caloric intake result- ing from the metabolizable sorbic acid. No carcinogenic or mutagenic effects have been observed with sorbate alone (Dickens et al., 1968; Shtenberg and Ignat’ev, 1970; Litton Biometrics, 1974, 1977; Food and Drug Research Laboratories, 1975; Gaunt et al., 1975; Hendy et al., 1976; Lück, 1980; Sofos and Busta, 1981, 1993; Sofos, 1994).

An allergic-type response has been reported for sorbic acid in one study in which bacon samples with sorbate–nitrite combinations were tested against C. botulinum. Some taste panelists reported certain “allergic-type” symptoms after tasting uninoculated experimental bacon (U.S. Department of Agriculture, 1979b; Berry and Blumer, 1981). Although it was implied that sorbate might have been involved in producing those symptoms, no direct relation could be proved between symptoms and specific ingredients used in formulating the bacon (U.S. Department of Agriculture, 1979b). In addition, no such symptoms were observed by other individuals who tasted sorbate–nitrate experimental bacon from other studies, and Robach and Adam (1980) were able to induce such symptoms from panelists consuming commercial bacon manufactured without sorbate. This, of course, does not rule out the possibility that high concentrations of sorbate may act as irritants to certain susceptible individuals (Sofos, 1989).

As preservatives for cosmetics and pharmaceutical products, sorbates have been extensively examined for skin tolerance (Lück, 1976; Patrizi et al., 1999). The literature is contradictory, but it indicates that most people are not affected by sorbic acid applied to the skin. Some sensitive individuals, however, show skin irritations when exposed to sorbic acid (National Academy of Sciences, 1982; Dejobert et al., 2001). Average sorbic acid concentrations for skin irritations are in the range of 1%, and some very sensitive individuals may show irritations even at lower levels (Lück, 1976). Considering the average use levels of 0.10% to 0.30% in food processing, the potential for such irritations in commercial products is minor.

There has been some concern about possible sorbate–nitrite reactions when added to the same substrate (Sofos, 1981; National Academy of Sciences, 1982). Because there is evidence of reactions between nitrite and fatty acids (Benedict, 1980) and because sorbic acid is an unsaturated fatty acid, it may react with nitrite in products such as cured meats. The products of such reactions have the potential of being mutagenic (Sofos, 1989). In general, however, various studies have indicated the following: (1) nitrite reacts with sorbic acid to form mutagens optimally at pH 3.5, not at 6.0, which is the average pH of most meat products; (2) formation of the c-nitroso mutagens requires the presence of excess nitrite; and (3) mutagen formation is inhibited by such ingredients as ascorbic acid, cysteine, and vegetable juices and is inactivated by heat (Kada, 1974; Kito et al., 1978; Osawa et al., 1979, 1980, 1982, 1986; Robach et al., 1980a; Namiki, 1979, 1980, 1981, 1983; Khoudokor- moff, 1981; Osawa and Namiki, 1982). Thus, the requirements for the reactions to proceed and the instability of the products make it unlikely for mutagens to be formed at detectable or harmful concentrations in foods treated with nitrite and sorbate (Sofos, 1981, 1989). Walker (1990) con- cluded that sorbate use, in general, does not appear to create toxicologic problems.

It has been regarded that amino-compounds, including lysine and glutamate, may undergo nonenzymatic browning reactions when stored with sorbic acid at a favorable range of aw and

temperature (Quattrucci and Masci, 1992). This reaction was demonstrated in model systems but, to some extent, it may apply also to more complex systems such as foods, leading to decreased amino acid availability (Quattrucci and Masci, 1992). Sorbates were found to react easily with proteins, forming high-molecular-weight products that do not seem to result in a nutritional loss, probably because the acid environment of the stomach leads to the breakdown of the sorbic-protein adducts (Quattrucci and Masci, 1992).

Sorbic acid has a conjugated system of double bonds, which makes it susceptible to nucleophilic attack, sometimes giving mutagenic products (Ferrand et al., 2000a,b). Under conditions typical of

Sorbic Acid and Sorbates 73

food processing (50°C to 80°C) cyclic derivatives resulting from a double addition reaction between sorbic acid and various amines were analyzed. The formation of new products by addition reactions using ethyl sorbate and various amines led, at 20°C, to linear monoadducts and, at 50°C, to cyclic derivatives resulting from double addition (Ferrand et al., 2000a,b). Mutagenesis studies, involving the Ames test and genotoxicity studies with HeLa cells and on plasmid DNA, in cyclic interaction products, showed that none of the products studied presented mutagenic or genotoxic activities (Ferrand et al., 2000a,b). It should be noted, however, that certain studies have reported inhibition by sorbate of carcinogenic nitrosamine formation in model systems (Tanaka et al., 1978; Chung, 1981; Lathia and Schellhoeh, 1981; Massey et al., 1982; Rao et al., 1982; Yamamoto et al., 1988). Sorbic acid, however, had no effect on nitrosamine formation from aminopyrine and sodium nitrite in animal stomachs (Kawanishi et al., 1981a,b; Sofos, 1989). Potential injury in cell hepatocytes induced by potassium sorbate was prevented by antioxidants (Sugihara et al., 1997).

No synergism in acute toxicity has been detected for combinations of sorbic acid with various other additives, including parabens, benzoate, and propionate (Sofos, 1989). Sorbate, however, did not protect against the toxic effects of other substances (Daoud and Griffin, 1980). The derivatives of sorbic acid are also relatively nontoxic. Overall, sorbates appear to be one of the safest food preservatives available.