Although sodium benzoate tested negative in a cytogenetic assay with WI-38 cells in the absence of metabolic activation (US FDA, 1974), consistently positive results (in contrast to the negative results of benzoic acid) were obtained in tests on sister chromatid exchange and chromosome aberrations with CHL/CHO and DON cells or human lymphocytes without metabolic activation (Abe & Sasaki, 1977; Ishidate & Odashima, 1977; Ishidate et al., 1984, 1988; Xing & Zhang, 1990).
8.5.1 Benzoic acid Benzoic acid tested negative in several Ames tests and in one DNA damage assay with different Salmonella typhimurium strains in the presence or absence of metabolic activation (McCann et al., 1975; Ishidate et al., 1984; Nakamura et al., 1987; Zeiger et al., 1988).
Therefore, the ingestion of benzoic acid or its salts affects any body function or metabolic process in which glycine is involved; for example, it leads to a reduction in creatinine, glutamine, urea, and uric acid levels (US FDA, 1972a, 1973; Kubota & Ishizaki, 1991; WHO, 1996).
The rate of biotransformation in humans is high: after oral doses of 40, 80 or 160 mg sodium benzoate/kg body weight, the transformation to hippuric acid was independent of the dose -- about 17-29 mg/kg body weight per hour, corresponding to about 500 mg/kg body weight per day (Kubota & Ishizaki, 1991).
In other species, this metabolite appears only after higher doses of about 500 mg/kg body weight (see above) of benzoic acid or sodium benzoate, resulting in a depletion of the glycine pool (Bridges et al., 1970; US FDA, 1972a; Kubota et al., 1988).
Species; strain; Treatment Duration Organs examined in Resultsa Reference number of animals (days) histopathology, clinical per dosea chemistry, haematology Benzoic acid cat; 4 m 0 or 0.5% 3-4 liver, kidney, heart, mild hyperaesthesia, Bedford & Clarke in diet stomach, lung, brain, apprehension, and (1972) (approx.
However, due to the differences in the metabolism of benzoic acid in cats compared with other experimental animals and humans, this study was not taken into further consideration (see section 7).
In a maximization test, none of 15 guinea-pigs reacted positively after induction and challenge with a 10-20% solution of benzoic acid in water (Gad et al., 1986).
In an acute eye irritation/corrosion study with rabbits conducted according to OECD Guideline 405, some eye irritation was reported after application of benzoic acid in the form of a paste.
Species; strain; Treatment Duration Examinations; Resultsa Reference number of animals organs in per dosea histopathology, clinical chemistry, haematology Benzoic acid rat; Wistar; 0 or 1.5% in diet 18 months no data available reduced weight gain with Marquardt (1960) dose group: (approx.
In different experiments with rabbits, which have not been performed according to current guidelines, benzoic acid applied as dry powder or in the form of a paste was not irritating to slightly irritating to the skin (score 1.66/8: Bio-Fax, 1973; no score given: Bayer AG, 1978; primary skin irritation index 0.5 [no further information available]: RCC Notox, 1988a).
8.2.1 Benzoic acid Although there is a wide range of results from mostly non-standardized tests using various scoring systems, it can be concluded that benzoic acid is slightly irritating to the skin and irritating to the eyes.
8.4.3 Carcinogenicity of benzyl acetate, benzyl alcohol, and benzaldehyde As benzyl acetate, benzyl alcohol, and benzaldehyde are practically quantitatively metabolized via benzoic acid (see section 7.1), data on their carcinogenicity from 2-year studies may be used as supportive evidence in the assessment of the hazards associated with benzoic acid.
The authors attributed the higher toxicity of benzoic acid in cats compared with other species to the low capacity of cats for glucuronidation (see section 7).
With oral LD50 values of 2100-4070 mg sodium benzoate/kg body weight in rats, the acute toxicity of sodium benzoate is similar to that of benzoic acid, as are the symptoms (Smyth & Carpenter, 1948; Deuel et al., 1954; Bayer AG, 1977).