Saccharin mechanistic data and risk assessment: urine composition, enhanced cell proliferation, and tumor promotion.
Sodium saccharin (NaSac) produces bladder tumors consistently in male rats only after lifetime exposure that begins at birth. NaSac is not metabolized and is negative in most genotoxicity tests. NaSac-induced cell damage and proliferation have been proposed as important factors in tumor promotion, and dose-response information demonstrating a threshold for these parameters is available. One theory proposes that high levels of NaSac, combined with protein in a high Na+, high pH environment found only in the male rat, form toxic microscopic crystals; therefore, NaSac-induced tumors may not be relevant to human carcinogenesis.
Whysner
J
J
Toxicology and Risk Assessment Program, American Health Foundation, Valhalla, NY 10595-1599, USA.
Williams
G M
GM
D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000378:metabolism* / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D051381:Rats; D018570:Risk Assessment; D012439:Saccharin / Q000378:metabolism* / Q000633:toxicity*; D013549:Sweetening Agents / Q000378:metabolism* / Q000633:toxicity*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000473:pathology; D014556:Urine / Q000737:chemistry*
D002273:Carcinogens; D013549:Sweetening Agents; D012439:Saccharin