Saccharin mechanistic data and risk assessment: urine composition, enhanced cell proliferation, and tumor promotion

Pharmacol Ther. 1996;71(1-2):225-52. doi: 10.1016/0163-7258(96)00069-1.


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.

Publication types

  • Consensus Development Conference
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Carcinogenicity Tests
  • Carcinogens / metabolism*
  • Carcinogens / toxicity*
  • Cell Division / drug effects
  • Female
  • Humans
  • Male
  • Rats
  • Risk Assessment
  • Saccharin / metabolism*
  • Saccharin / toxicity*
  • Sweetening Agents / metabolism*
  • Sweetening Agents / toxicity*
  • Urinary Bladder Neoplasms / chemically induced*
  • Urinary Bladder Neoplasms / pathology
  • Urine / chemistry*


  • Carcinogens
  • Sweetening Agents
  • Saccharin