V79 Chinese hamster lung cells were used to evaluate in vitro the cytotoxicity and genotoxicity of erythrosine (2', 4', 5', 7'-tetraiodofluorescein disodium salt; FD and C Red No. 3), a color additive used widely in foods, drugs and cosmetics. Erythrosine reduced colony size at 200 micrograms/ml and was lethal to 90% or more of the cells at 400 micrograms/ml. At dose levels of 100, 200 and 300 micrograms/ml of medium, erythrosine was non-mutagenic to V79 cells at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) and sodium, potassium ATPase (Na+, K+ -ATPase) gene loci and did not increase the frequency of sister-chromatid exchanges with or without rat hepatocyte-mediated activation. Erythrosine at 300 micrograms/ml, unlike lower dose levels, produced an increase in micronucleus frequency in the absence of hepatocytes. An erythrosine dose-related increase in the mitotic frequency was due to an increase in the number of first mitoses at the expense of later cell divisions. Hepatocytes moderated the effect of erythrosine treatment on micronucleus frequency, mitotic frequency and MII/MI ratio. These results demonstrate the advantage of a multiple end-point approach to the evaluation of cytotoxicity and genotoxicity within a single-assay system.

Animals↗

PubMedDate not supplied

Histopathological and radioautographical studies on the forestomach of F344 rats treated with butylated hydroxyanisole and related chemicals.

Butylated hydroxyanisole, when fed to male Fischer 344 rats for periods of 9 days or more, led to forestomach epithelial cell necrosis and regeneration. Both the induced proliferation and the histopathological changes were considerably more prevalent in the prefundic region of the forestomach than in the mid-region. Using [Me-3H]thymidine, a specific DNA precursor, and radioautography it was shown that the effect of the antioxidant was apparently threshold at 0.25% in the diet after both 9 days and 3 months of treatment and that the proliferation was dependent on the continuous presence of the antioxidant in the diet at 3 and 6 months. Some other phenols and acids were investigated after 9-27 days' feeding; most induced some degree of epithelial cell proliferation in the rat forestomach, although some had a greater effect on the mid-region than on the prefundic region. These observations are discussed in terms of the likely relevance of butylated hydroxyanisole-induced forestomach tumours to the possibility that the antioxidant may lead to cancer in humans exposed to lower levels in their diet.

Administration, Oral↗

PubMedDate not supplied

A 12-week study of BHA in the cynomolgus monkey.

Butylated hydroxyanisole (BHA) given by gavage to female cynomolgus monkeys on 5 days/wk for 84 days produced transient changes in selected serum chemistry and haematology parameters. Terminal observations revealed increased liver size, decreased hepatic monooxygenase activity and an increase in the mitotic index of the oesophageal epithelium. Several of these observations are similar to those reported for rodents also given BHA at or near the maximum tolerated dose. Gastroscopic evaluation of the stomach and oesophagus at monthly intervals and extensive gross and histopathological examination failed to reveal the proliferative effects seen in the forestomach of rats fed diets containing BHA.

Administration, Oral↗

PubMedDate not supplied

Panel discussion: Possible mechanisms of BHA carcinogenicity from a consideration of its chemical and biological properties.

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Animals↗