Mutagenicity studies with nitrofurans: I. Mutagenicity of nitrofurylacrylic acid for mammals

Abstract

Cytogenetic analysis of mouse bone-marrow cells, the dominant lethal test in mice and the cytogenetic analysis of human peripheral lymphocytes in vitro were used to study the mutagenicity of 3-(5-nitro-2-furyl)acrylic acid (5-NFA) for mammals. The bone-marrow cytogenetic analysis was performed in female mice exposed to 5-NFA administered intraperitoneally in single doses of 15–120 mg/kg and in 5 repeated doses of 15 and 30 mg/kg, intragastrically in single doses of 30–240 mg/kg and 5 repeated doses of 30 and 60 mg/kg, and perorally for 12 weeks to 5-NFA concentrations of 10, 100 and 1000 mg 5-NFA/l in drinking water. The bone-marrow analysis was performed in this case after 12 days, 3, 4, 6, 8, 10 and 12 weeks exposure. No increase in chromosome damage attributable to dosing with 5-NFA occurred in any of these experiments. Experiments in which mice were exposed to 5-NFA in drinking water for 12 weeks and then treated with a single i.p. dose of 2 mg of the mutagen TEPA [tris-(1-aziridinyl)phosphine oxide] per kg revealed that, at a concentration of 1000 mg 5-NFA/l, the clastogenic activity of TEPA was reduced to that in untreated animals. The dominant lethal test was performed in male mice exposed to 5-NFA applied intraperitoneally in single doses of 40–120 mg/kg and in 5 repeated doses of 10–30 mg/kg, intragastrically in 5 repeated doses of 20–60 mg/kg, and perorally for 4 weeks in drinking water containing 5-NFA at concentrations of 10, 100, 316 and 1000 mg/l. No significant differences were detected between the exposed and control groups of animals. Experiments in which male mice were exposed to 5-NFA in drinking water and treated after the 4-week exposure to 5-NFA with 1 mg TEPA/kg revealed that a concentration of 1000 mg 5-NFA/l reduced TEPA-induced dominant lethality to within control values. A reduction in male fertility was observed after the single or these results on microorganisms and the limited possibility of their direct extrapolation to mammals, it may be concluded that, in view of negative results on the mammalian level, there is no indication for genetic risk from 5-NFA for man. The results suggest that it may be safe to accept 0.1 mg 5-NFA/kg as the tentatively permissible maximal daily intake. Next, experiments should clear up the metabolism of 5-NFA in the organism, its effects on the repair of induced genetic damage and especially the finding of a possible antimutagenic effect.