Food consumption and body weight changes with neotame, a new sweetener with intense taste: Differentiating effects of palatability from toxicity in dietary safety studies

Regulatory Toxicology and Pharmacology

Volumn 38, Issue 2, 2003, Pages 124-143

  Mayhew, Dale A ^a   Comer, C Phil ^b   Stargel, W Wayne ^a  

^a NutraSweet Company   (United States)

^b Graystone Associates Inc   (United States)

Author keywords

Allometric growth; Dog; Food consumption; Neotame; Palatability; Preference; Rat; Sprague Dawley; Sweeteners

Indexed keywords

NEOTAME; SWEETENING AGENT;

ANIMAL BEHAVIOR; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BODY GROWTH; BODY WEIGHT DISORDER; CHRONIC TOXICITY; CLINICAL OBSERVATION; CONTROLLED STUDY; DIETARY INTAKE; DOG; FEMALE; FLUID INTAKE; FOOD INTAKE; FOOD POISONING; FOOD PREFERENCE; FOOD SAFETY; MALE; MAXIMUM TOLERATED DOSE; MORBIDITY; MORTALITY; MOUSE; NONHUMAN; PALATABILITY; PHYSICAL EXAMINATION; PRIORITY JOURNAL; RAT; RAT STRAIN; SWEETNESS; WEIGHT GAIN;

ANIMALIA; CANIS FAMILIARIS;

EID: 0141480798     PISSN: 02732300     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0273-2300(03)00074-6     Document Type: Article

References (59)

1. Ackroff K., Sclafani A. Palatability and foraging cost interact to control caloric intake. J. Exp. Psychol.: Anim. Behav. 25:1999;28-36.
2. Adolph E.F. Urges to eat and drink in rats. Am. J. Physiol. 151:1947;110-125.
3. ANZFA, 2001. Inquiry Report and Regulatory Impact Statement, Permission for Use of Neotame, Australia New Zealand Food Authority (ANZFA) 30 May, 2001, p. 9.
4. Chowaniec J., Hicks R.M. Response of the rat to saccharin with particular reference to the urinary bladder. Br. J. Cancer. 39:1979;355-375.
5. Christian M.S., Hoberman A.M., Johnson M.D., Brown W.R., Bucci T.J. Effect of dietary optimization on growth, survival, tumor incidences and clinical pathology parameters in CD Sprague-Dawley and Fischer-344 rats: a 104-week study. Drug Chem. Toxicol. 21:1998;97-117.
6. Duffy P.H., Seng J.E., Lewis S.M., Mayhugh M.A., Aidoo A., Hattan D.G., Casiciano D.A., Feuers R.J. The effects of different levels of dietary restriction on aging and survival in the Sprague-Dawley rat: implications for chronic studies. Aging Clin. Exp. Res. 13:2001;263-272.
7. Duffy P.H., Lewis S.M., Mayhugh M.A., McCracken A., Thom B.T., Reeves P.G., Blakely S.A., Casciano D.A., Feuers R.J. Effect of the AIN-93M purified diet and dietary restriction on survival in Sprague-Dawley rats: implications for chronic studies. J. Nutr. 132:2002;101-107.
8. Dunnett C.W. New tables for multiple comparisons with a control. Biometrics. 20:1964;482-491.
9. Eaton D., Klaassen C.D. Klaassen Curtis D. Casarett & Doull's Toxicology. sixth ed. 2001;16-17 McGraw-Hill, New York. 29.
10. Ferrell F. Preference for sugars and nonnutritive sweeteners in young beagles. Neurosci. Biobehav. Rev. 8:1984;199-203.
11. Flamm, G., 2002. A proposed policy for assessing palatability issues based on lessons learned. Toxicology Forum symposium, Aspen, Colorado, USA, July 8, 2002. Toxicology Forum Proceedings, Summer Meeting, 2002.
12. Flamm, W.G., Blackburn, G.L., Comer, C.P., Mayhew, D.A., Stargel, W.W., 2003. Long-term food consumption and body weight changes in neotame safety studies are consistent with the allometric relationship observed for other sweeteners and during dietary restrictions. Regul. Toxicol. Pharmacol. 38.
13. FDA, 1982. Toxicological principles for the safety assessment of direct food additives and color additives used in food: "Redbook." Washington, DC.
14. FDA, 1988. Food additives permitted for direct addition to food for human consumption; acesulfame potassium. Fed. Regist. 53 (145), 20379-26383.
15. FDA, 1993. Toxicological principles for the safety assessment of direct food additives and color additives used in food: "Redbook II." Washington, DC.
16. FDA, 1998a. Food additives permitted for direct addition to food for human consumption; sucralose. Fed. Regist. 63 (64), 16417-16433.
17. FDA, 1998b. Monsanto Co.: Filing a food additive petition. Fed. Regist. 63 (27), 6762. Study reports available by Freedom of Information (FOI) request from US FDA.
18. FDA, 1999a. Food additives permitted for direct addition to food for human consumption; sucralose. Fed. Regist. 64 (155), 43908-43909.
19. FDA, 1999b. Monsanto Co.: Filing a food additive petition. Fed. Regist. 64 (25), 6100. Study reports available by Freedom of Information (FOI) request from US FDA.
20. FDA, 2002. Food additives permitted for direct addition to food for human consumption; neotame. Fed. Regist. 67 (131), 45300-45310.
21. Glaser D., Tinti J., Nofre C. Evolution of the sweetness receptor in primates. Chem. Senses. 20:1995;573-584.
22. Grice H.C., Goldsmith L.A. Sucralose - an overview of the toxicity data. Food Chem. Toxicol. 38(Suppl. 2):2000;S1-S6.
23. Hubert M.F., Laroque P., Gillet J.P., Keenan K.P. The effects of diet, ad libitum feeding, and moderate and severe dietary restriction on body weight, survival, clinical pathology parameters, and cause of death in control Sprague-Dawley rats. Toxicol. Sci. 58:2000;195-207.
24. Jakubczak L.F. Age differences in the effects of palatability of diet on regulation of calorie intake and body weight of rats. J. Gerontol. 32:1977;49-57.
25. Jakubczak L.F. Calorie and water intakes as a function of strain, age, and caloric-density of diet. Physiol. Behav. 20:1978;273-278.
26. Keenan K.P., Smith P.F., Hertzog P., Soper K., Ballam G.C., Clark R.L. The effects of overfeeding and dietary restriction on Sprague-Dawley rat survival and early pathology biomarkers of aging. Toxicol. Pathol. 22:1994;300-315.
27. Keenan K.P., Laroque P., Ballam G.C., Soper K.A., Dixit R., Mattson B.A., Adams S.P., Coleman J.B. The effects of diet, ad libitum overfeeding, and moderate dietary restriction on the rodent bioassay: the uncontrolled variable in safety assessment. Toxicol. Pathol. 24:1996;757-768.
28. Kennedy G.C. The hypothalamic control of food intake in rats. Proc. R. Soc. 137:1950;535-549.
29. Kennedy G.C. Ontogeny of mechanisms controlling food and water intake. Code C.F. Handbook of Physiology. Section 6, Alimentary Canal. vol. 1:1967;337-351 American Physiological Society, Washington, DC.
30. Kratz C.M., Levitsky D.A., Lustick S. Differential effects of quinine and sucrose octa acetate on food intake in the rat. Physiol. Behav. 20:1978;665-667.
31. Laroque P., Keenan K.P., Soper K.A., Dorian C., Gerin G., Hoe C.-M., Duprat P. Effect of early body weight and moderate dietary restriction on the survival of the Sprague-Dawley rat. Exp. Toxicol. Pathol. 49:1997;459-465.
32. LeBlanc J., Lupin D., Diamond P., Macari M., Richard D. Thermogenesis in response to various intakes of palatable food. Can. J. Physiol. Pharmacol. 64:1986;976-982.
33. Levene H. Robust tests for equality of variances. Olkin I.et al. Contributions to Probability and Statistics. 1960;278-292 Standford University Press, Standford, California.
34. Macdonald I. Non-linear relationship between reduced energy intake and rate of weight loss in rats. Ann. Nutr. Metab. 34:1990;213-215.
35. Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother. Rep. 50:1966;163-170.
36. Mitchell, D., Brown, M., 1995. NC-00723: Toxicity Study by Dietary Administration to CD Rats for 13-Weeks Followed by a 4-Week Reversibility Period. Study Number (PCR 0988). Unpublished Report from Huntingdon Life Sciences Ltd., Eye, Suffolk, England, UK.
37. Mitchell, D., Brown, M., 1997a. NC-00723: 52-Week Toxicity Study by Dietary Administration to CD Rats with Exposure In Utero and Followed by a 4-Week Reversibility Period. Study Number (PCR 1011). Unpublished Report from Huntingdon Life Sciences Ltd., Eye, Suffolk, England, UK.
38. Mitchell, D., Brown, M., 1997b. NC-00723: Oncogenicity Study by Dietary Administration to CD Rats with Exposure In Utero. Study Number (PCR 1000). Unpublished Report from Huntingdon Life Sciences Ltd., Eye, Suffolk, England, UK.
39. Nicholls, I., 1997a. NC-00723: Dietary Preference Study. Study Number (PCR 1150). Unpublished Report from Huntingdon Life Sciences Ltd., Eye, Suffolk, England, UK.
40. Nicholls, I., 1997b. NC-00723: Dietary Preference Feasibility Study. Study Number (PCR 1132). Unpublished Report from Huntingdon Life Sciences Ltd., Eye, Suffolk, England, UK.
41. Nofre C., Tinti J.M. In quest of hyperpotent sweeteners. Mathlouthi M., Kanters J.A., Birch G.G. Sweet-Taste Chemoreception. 1991;205-236 Elsevier, London.
42. Nolen G.A. Effect of various restricted dietary regimens on the growth, health, and longevity of albino rats. J. Nutr. 102:1972;1477-1494.
43. Oishi S., Oishi H., Hiraga K. The effect of food restriction for 4 weeks on common toxicity parameters in male rats. Toxicol. Appl. Pharmacol. 47:1979;15-22.
44. Peck J.W. Rats defend different body weights depending on palatability and accessibility of their food. J. Comp. Physiol. Psychol. 92:1978;555-570.
45. Peto R. Editorial: guidelines on the analysis of tumour rates and death rates in experimental animals. Br. J. Cancer. 29:1974;101-105.
46. Pizzi W.J., Holson R.R., Merkel G., Gough B. A study of taste preferences and polydipsic drinking elicited by saccharin but not aspartame in rat, mouse, and hamster. Soc. Neurosci. Abstr. 12(2):1986;1298.
47. Schärer K. The effect of chronic underfeeding on organ weights on rats. How to interpret organ weight changes in cases of marked growth retardation in toxicity tests? Toxicology. 7:1977;45-56.
48. Schoenig G.P., Goldenthal E.I., Geil R.G., Frith C.H., Richter W.R., Carlborg F.W. Evaluation of the dose response and in utero exposure to saccharin in the rat. Food Chem. Toxicol. 23:1985;475-490.
49. Sclafani A., Abrams M. Rats show only a weak preference for the artificial sweetener aspartame. Physiol. Behav. 37:1986;253-256.
50. Smith J.C., Sclafani A. Saccharin as a sugar surrogate revisited. Appetite. 38:2002;155-160.
51. Thomford, P., Saunders, W., 1995. 13-Week Dietary Toxicity Study of NC-00723 in Dogs Followed by a 4-Week Reversibility Period. Study Number (PCR 0990). Unpublished Report from Hazleton Wisconsin Inc., Madison, WI.
52. Thomford, P., Carter, J., 1997a. 104-Week Dietary Carcinogenicity Study with NC-00723 in CD-1 Mice. Study Number (PCR 1014). Unpublished Report from Covance Laboratories Inc., Madison, WI.
53. Thomford, P., Carter, J., 1997b. 52-Week Dietary Toxicity Study of NC-00723 in Dogs Followed by a 4-Week Reversibility Period. Study Number (PCR 1017). Unpublished Report from Covance Laboratories Inc., Madison, WI.
54. Thomsen M.W., Dalton J., Stewart C.N. Comparison of aspartame and 4-chloroaspartame taste characteristics in rats and monkeys. Chem. Senses. 13:1988;397-405.
55. WHO, 1983. Evaluation of certain food additives and contaminants. Acesulfame Potassium. 27th Report of the Joint/WHO/FAO Expert Committee on Food Additives (JECFA), World Health Organization (WHO) Technical Report Series No. 696.
56. WHO, 1991. Evaluation of certain food additives and contaminants. Trichlorogalactosucrose. WHO Food Additive Series 28. TRS 806, pp. 219-228.
57. WHO, 2003. Summary and conclusions, food additives evaluated toxicologically (JECFA/61/SC). Joint FAO/WHO Expert Committee on Food Additives (JECFA), Sixty-first meeting, Rome, 10-19 June 2003. (Toxicological monograph to be published in WHO Food Additives Series No. 52.).
58. Willoughby, C., 1997. NC-00723: Two Generation Reproductive Study by Dietary Administration to CD Rats. Study Number (PCR 1001). Unpublished Report from Huntingdon Life Sciences Ltd., Eye, Suffolk, England, UK.
59. Winer B.J. Design and analysis of single-factor experiments. Statistical Principles in Experimental Design. second ed. 1971;149-260 McGraw-Hill, New York.