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). Only in one recombination assay with Bacillussubtilis H17 and M45 was a positive result obtained (Nonaka, 1989). However, due
to missing experimental details (only results given), the validity of this
study cannot be judged. There was no indication of genotoxic activity (chromosome
aberrations, sister chromatid exchange) in tests with mammalian cells (Chinese
hamster CHL and CHO cells, human lymphoblastoid cells, human lymphocytes)
without metabolic activation (Oikawa et al., 1980; Tohda et al., 1980; Ishidate et al., 1984; Jansson et al., 1988). In vivo studies with benzoic acid were not identified in the literature.
Sodium benzoate also gave negative results in some Ames tests and in Escherichia coli in the presence or absence of metabolic activation (Ishidate et al., 1984; Prival et al., 1991). As with benzoic acid in recombination assays with Bacillus subtilis H17 and M45, positive results were obtained (Ishizaki & Ueno, 1989;
Nonaka, 1989). 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). However, from the limited information given in the publications (i.e., only results given), it cannot be judged if these positive results may
have been attributable to cytotoxic effects. In a valid in vivo study performed by the US FDA (1974), sodium benzoate tested negative
in a cytogenetic assay (bone marrow) in rats after single or multiple oral
application of doses up to 5000 mg/kg body weight. In a study with mice
(comparable dosing scheme), there was also no indication of mutagenic activity
in a host-mediated assay (US FDA, 1974). However, in a dominant lethal
assay with rats (comparable dosing scheme; males were mated with untreated
females following 7 or 8 weeks of dosing), some statistically significant
and dose-related findings were reported in week 7: decreased fertility
index for both treatment regimens and an increased number of preimplantation
losses after single dosing (US FDA, 1974). In summary, the in vitro studies with benzoic acid gave no indications for genotoxic effects, whereas in vivo studies were not identified. Sodium benzoate was also inactive in bacterial
test systems, whereas tests with mammalian cells gave consistently positive
results. In addition, in an in vivo study with sodium benzoate (dominant lethal assay in rats), a positive
result was obtained. As a result, a genotoxic activity of sodium benzoate
cannot be ruled out entirely at present.
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