Assessment of the genotoxicity of calcium cyclamate and cyclohexylamine.
Calcium cyclamate and its major metabolite cyclohexylamine have been subjected to numerous evaluations for genetic activity. With the exception of studies for chromosome damage, the results have been negative. Results from a wide range of in vitro and in vivo cytogenetic assays ranged from clearly negative to various degrees of clastogenicity. Interpretation of the cytogenetic studies has been complicated by the conflicting responses, although some of the positive effects seem to be the consequence of secondary effects produced by high ion levels and excessive toxicity. In the studies presented here calcium cyclamate and cyclohexylamine were tested for mutagenic activity using an in vitro mammalian cells assay for gene mutation and an in vitro unscheduled DNA synthesis assay in rat hepatocytes with the Drosophila sex-linked recessive lethal assay. Calcium cyclamate was not genetically active in any of the three assays when tested to the maximum possible concentrations. The compound was largely nontoxic but did show some evidence of cytotoxicity in rat hepatocytes at concentrations of 1 mg/ml and higher. Cyclohexylamine was also negative in the three assays, but was considerably more cytotoxic at the concentrations used. The results from the three studies conducted in this evaluation are in general agreement with the majority of published genetic toxicology data for these two chemicals and indicated that the calcium cyclamate and cyclohexylamine have no direct, intrinsic genotoxicity of the type measured by these assays.
Brusick
D
D
Department of Molecular Toxicology, Hazleton Laboratories America, Inc., Kensington, Maryland 20895.
Cifone
M
M
Young
R
R
Benson
S
S
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003494:Cyclamates / Q000633:toxicity*; D003514:Cyclohexylamines / Q000633:toxicity*; D004260:DNA Repair / Q000187:drug effects; D004331:Drosophila melanogaster / Q000235:genetics; D005804:Genes, Lethal; D005808:Genes, Recessive; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000187:drug effects; D009152:Mutagenicity Tests; D009153:Mutagens; D051381:Rats
D003494:Cyclamates; D003514:Cyclohexylamines; D009153:Mutagens; D007041:Hypoxanthine Phosphoribosyltransferase