Toxicological aspects of cyclamate and cyclohexylamine.
In the late 1960s the artificial sweetener cyclamate was implicated as a bladder carcinogen in rats. This finding and other concerns about its safety ultimately led to a ban on cyclamate in the U.S. and restrictions on its use in many other countries. Since that time, the carcinogenic potential of cyclamate and cyclohexylamine, its principal metabolite, has been reevaluated in a group of well-controlled, well-designed bioassays that have failed to substantiate the earlier findings. This review of the published and unpublished literature on cyclamate attempts to evaluate the carcinogenicity question and other important aspects of the toxicity of cyclamate and cyclohexylamine, including their effects on various organ systems, their genotoxic potential, and their effects on reproduction. In addition, the physiological disposition of cyclamate is reviewed, with particular attention directed toward the site and extent of its conversion to cyclohexylamine.
B A
BA
Bopp
R C
RC
Sonders
J W
JW
Kesterson
D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000042:Absorption; D000311:Adrenal Glands / Q000187:drug effects; D000818:Animals; D001419:Bacteria / Q000378:metabolism; D001769:Blood / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D002642:Chick Embryo; D002869:Chromosome Aberrations; D003043:Cocarcinogenesis; D006224:Cricetinae; D003494:Cyclamates / Q000378:metabolism / Q000633:toxicity*; D003514:Cyclohexylamines / Q000378:metabolism / Q000633:toxicity*; D004064:Digestive System / Q000187:drug effects; D005260:Female; D005854:Germ Cells / Q000187:drug effects / Q000648:ultrastructure; D006321:Heart / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007422:Intestines / Q000382:microbiology; D007668:Kidney / Q000187:drug effects; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects; D008113:Liver Neoplasms / Q000139:chemically induced; D008175:Lung Neoplasms / Q000139:chemically induced; D008228:Lymphoma, Non-Hodgkin / Q000139:chemically induced; D008253:Macaca mulatta; D008297:Male; D008770:Methylnitrosourea; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D009374:Neoplasms, Experimental / Q000139:chemically induced; D010179:Pancreas / Q000187:drug effects; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012098:Reproduction / Q000187:drug effects; D013566:Sympathomimetics / Q000633:toxicity; D013737:Testis / Q000187:drug effects; D013961:Thyroid Gland / Q000187:drug effects; D014018:Tissue Distribution; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced
D001786:Blood Glucose; D003494:Cyclamates; D003514:Cyclohexylamines; D009153:Mutagens; D013566:Sympathomimetics; D008770:Methylnitrosourea