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

• Published in: Mutation research Vol. 68; no. 4; p. 367
• Main Authors: Srám, R J, Rössner, P, Zhurkov, V S, Kodýtková, I
• Format: Journal Article
• Language: English
• Published: Netherlands 01.12.1979
• Subjects: Acrylates - pharmacology; Animals; Body Weight - drug effects; Bone Marrow - drug effects; Bone Marrow - physiology; Chromosome Aberrations - drug effects; Drinking Behavior - drug effects; Female; Genes, Dominant; Genes, Lethal; Humans; Lymphocytes - drug effects; Lymphocytes - physiology; Male; Mice; Mutation - drug effects; Nitrofurans - pharmacology
• ISSN: 0027-5107

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 concentration of 10, 100 and 1000 mg 5-FNA/1 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 [trix-(1-aziridinyl)phosphine oxide] per kg revealed that, at a concentration of 1000 mg 5-NFA/1, 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/1 reduced TEPA-induced dominant lethality to within control values. A reduction in male fertility was observed after the single or repeated 5-NFA doses, but no changes when 5-NFA was applied in drinking water. The cytogenetic analysis of human peripheral lymphocytes exposed in vitro for the last 24 h of culture to concentrations of 1--100 micrograms 5-NFA/Ml did not show any compound-related chromosomal changes. The results of dominant-lethal and bone-marrow cytogenetic studies in mice after consumption of drinking water containing 1000 mg of 5-NFA/1 for 12 weeks and dosed subsequently with TEPA suggests that 5-NFA has some antimutagenic activity. Because none of the studies reported revealed any compound-related genetic activity, the results suggest that 5-NFA is not a chromosome-breaking agent in mammals.