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Saccharin: Title and subTitle BreakReview of Safety Issues FREE

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This report was adopted as amended by the House of Delegates of the American Medical Association at the Annual Meeting, June 1985.

This report is not intended to be construed or to serve as a standard of medical care. Standards of medical care are determined on the basis of all the facts and circumstances involved in an individual case and are subject to change as scientific knowledge and technology advance and patterns of practice evolve. This report reflects the views of scientific literature as of 1984.

Reprint requests to Council on Scientific Affairs, Division of Drugs and Technology, American Medical Association, 535 N Dearborn St, Chicago, IL 60610 (John C. Ballin, PhD).


JAMA. 1985;254(18):2622-2624. doi:10.1001/jama.1985.03360180126039
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This report reviews the experimental and epidemiologic data related to the carcinogenicity of saccharin. The results of animal studies suggest a species and organ effect. In single-generation studies in rats, mice, hamsters, and monkeys, saccharin did not induce cancer in any organ. In two-generation studies involving rats, however, there was evidence that the incidence of bladder tumors was significantly greater in saccharin-treated males of the second generation than in controls; the development of bladder tumors in rats seems to be a species- and organ-specific phenomenon for which there is currently no explanation. In humans, available evidence indicates that the use of artificial sweeteners, including saccharin, is not associated with an increased risk of bladder cancer. Until there is firm evidence of its carcinogenicity in humans, saccharin should continue to be available as a food additive, and reports of adverse health effects associated with its use should be monitored.

(JAMA 1985;254:2622-2624)

REFERENCES

Aspartame:  Commissioner's final decision . Federal Register 1981;;46( (July 24) ):38283-38308.
 Food additives permitted for direct addition to food for human consumption: Aspartame . Federal Register 1983;;48( (July 8) ):31376-31382.
 The multiple sweetener concept . Calorie Control Commentary , (June) 1983;, pp 1-4.
O'Brien L, Gelardi RC:  Alternative sweeteners . Chemtech 1981;;11:274-278.
Arnold DL, Moodie CA, Grice HC, et al:  Long-term toxicity of ortho-toluenesulfonamide and sodium saccharin in the rat . Toxicol Appl Pharmacol 1980;;52:113-152.
Riggin RM, Kinzer GW:  Characterization of impurities in commercial lots of sodium saccharin produced by the Sherwin-Williams Process: I. Chemistry . Food Chem Toxicol 1983;;21:1-10.
Riggin RM, Margard WL, Kinzer GW:  Characterization of impurities in commercial lots of sodium saccharin produced by the Sherwin-Williams Process: II. Mutagenicity . Food Chem Toxicol 1983;;21:11-17.
Committee for a Study on Saccharin and Food Safety Policy: Saccharin: Technical Assessment of Risks and Benefits (Report No. 1) . Washington, DC, Assembly of Life Sciences/ Institute of Medicine, National Research Council/National Academy of Sciences, 1978;.
Nakanishi K, Hagiwara A, Shibata M, et al:  Dose response of saccharin in induction of urinary bladder hyperplasias in Fischer 344 rats pretreated with N-butyl-N-(4-hydroxybutyl) nitrosamine . JNCI 1980;;65:1005-1010.
Fukushima S, Hagiwara A, Ogiso T, et al:  Promoting effects of various chemicals in rat urinary bladder carcinogenesis initiated by N-nitroso-N-butyl-(4-hydroxybutyl) amine . Food Chem Toxicol 1983;;21:59-68.
Cohen SM, Arai M, Jacobs JB, et al:  Promoting effect of saccharin and DL-tryptophan in urinary bladder carcinogenesis . Cancer Res 1979;;39:1207-1217.
Nakanishi K, Fukushima S, Hagiwara A, et al:  Organ-specific promoting effects of phenobarbital sodium and sodium saccharin in the induction of liver and urinary bladdertumors in male F344 rats . JNCI 1982;;68:497-500.
Saccharin:  Current status . Food Chem Toxicol , 1985;, vol 23, No. (4) /5.
Howe GR, Burch JD, Miller AB, et al:  Artificial sweeteners and human bladder cancer . Lancet 1977;;2:578-581.
Kessler II, Clark JP:  Saccharin, cyclamate, and human bladder cancer . JAMA 1978;;240:349-355.
Hoover RN, Strasser PH:  Artificial sweeteners and human bladder cancer . Lancet 1980;; 1:837-840.
Walker AM, Dreyer NA, Friedlander E, et al:  An independent analysis of the National Cancer Institute study on non-nutritive sweeteners and bladder cancer . Am J Public Health 1982;;72:376-381.
Morrison AS, Buring JE:  Artificial sweeteners and cancer of the lower urinary tract . N Engl J Med 1980;;302:537-541.
Morrison AS, Verhoek WG, Leck I, et al:  Artificial sweeteners and bladder cancer in Manchester, U.K., and Nagoya, Japan . Br J Cancer 1982;;45:332-336.
Jensen OM, Kamby C:  Intra-uterine exposure to saccharine and risk of bladder cancer in man . Int J Cancer 1982;;29:507-509.
Moller-Jensen O, Knudsen JB, Sorensen BL, et al:  Artificial sweeteners and absence of bladder cancer risk in Copenhagen . Int J Cancer 1983;;32:577-582.
Najem GR, Louria DB, Seebode JJ, et al:  Life time occupation, smoking, caffeine, saccharine, hair dyes and bladder carcinogenesis . Int J Epidemiol 1982;;11:212-217.
Cranmer MF: Saccharin . Park Forest South, Ill, Pathotox Publishers Inc, 1980;.
Hannigan KJ:  The sweetener report, 1982-1987 . Food Eng , (July) 1982;, pp 75-85.
 AMA Council on Scientific Affairs: Aspartame: Review of Safety Issues . JAMA 1985;; 254:400-402.

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Aspartame:  Commissioner's final decision . Federal Register 1981;;46( (July 24) ):38283-38308.
 Food additives permitted for direct addition to food for human consumption: Aspartame . Federal Register 1983;;48( (July 8) ):31376-31382.
 The multiple sweetener concept . Calorie Control Commentary , (June) 1983;, pp 1-4.
O'Brien L, Gelardi RC:  Alternative sweeteners . Chemtech 1981;;11:274-278.
Arnold DL, Moodie CA, Grice HC, et al:  Long-term toxicity of ortho-toluenesulfonamide and sodium saccharin in the rat . Toxicol Appl Pharmacol 1980;;52:113-152.
Riggin RM, Kinzer GW:  Characterization of impurities in commercial lots of sodium saccharin produced by the Sherwin-Williams Process: I. Chemistry . Food Chem Toxicol 1983;;21:1-10.
Riggin RM, Margard WL, Kinzer GW:  Characterization of impurities in commercial lots of sodium saccharin produced by the Sherwin-Williams Process: II. Mutagenicity . Food Chem Toxicol 1983;;21:11-17.
Committee for a Study on Saccharin and Food Safety Policy: Saccharin: Technical Assessment of Risks and Benefits (Report No. 1) . Washington, DC, Assembly of Life Sciences/ Institute of Medicine, National Research Council/National Academy of Sciences, 1978;.
Nakanishi K, Hagiwara A, Shibata M, et al:  Dose response of saccharin in induction of urinary bladder hyperplasias in Fischer 344 rats pretreated with N-butyl-N-(4-hydroxybutyl) nitrosamine . JNCI 1980;;65:1005-1010.
Fukushima S, Hagiwara A, Ogiso T, et al:  Promoting effects of various chemicals in rat urinary bladder carcinogenesis initiated by N-nitroso-N-butyl-(4-hydroxybutyl) amine . Food Chem Toxicol 1983;;21:59-68.
Cohen SM, Arai M, Jacobs JB, et al:  Promoting effect of saccharin and DL-tryptophan in urinary bladder carcinogenesis . Cancer Res 1979;;39:1207-1217.
Nakanishi K, Fukushima S, Hagiwara A, et al:  Organ-specific promoting effects of phenobarbital sodium and sodium saccharin in the induction of liver and urinary bladdertumors in male F344 rats . JNCI 1982;;68:497-500.
Saccharin:  Current status . Food Chem Toxicol , 1985;, vol 23, No. (4) /5.
Howe GR, Burch JD, Miller AB, et al:  Artificial sweeteners and human bladder cancer . Lancet 1977;;2:578-581.
Kessler II, Clark JP:  Saccharin, cyclamate, and human bladder cancer . JAMA 1978;;240:349-355.
Hoover RN, Strasser PH:  Artificial sweeteners and human bladder cancer . Lancet 1980;; 1:837-840.
Walker AM, Dreyer NA, Friedlander E, et al:  An independent analysis of the National Cancer Institute study on non-nutritive sweeteners and bladder cancer . Am J Public Health 1982;;72:376-381.
Morrison AS, Buring JE:  Artificial sweeteners and cancer of the lower urinary tract . N Engl J Med 1980;;302:537-541.
Morrison AS, Verhoek WG, Leck I, et al:  Artificial sweeteners and bladder cancer in Manchester, U.K., and Nagoya, Japan . Br J Cancer 1982;;45:332-336.
Jensen OM, Kamby C:  Intra-uterine exposure to saccharine and risk of bladder cancer in man . Int J Cancer 1982;;29:507-509.
Moller-Jensen O, Knudsen JB, Sorensen BL, et al:  Artificial sweeteners and absence of bladder cancer risk in Copenhagen . Int J Cancer 1983;;32:577-582.
Najem GR, Louria DB, Seebode JJ, et al:  Life time occupation, smoking, caffeine, saccharine, hair dyes and bladder carcinogenesis . Int J Epidemiol 1982;;11:212-217.
Cranmer MF: Saccharin . Park Forest South, Ill, Pathotox Publishers Inc, 1980;.
Hannigan KJ:  The sweetener report, 1982-1987 . Food Eng , (July) 1982;, pp 75-85.
 AMA Council on Scientific Affairs: Aspartame: Review of Safety Issues . JAMA 1985;; 254:400-402.
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