D Biotin, Unpublished report from Covance Laboratories Inc., Madison, WIisconsin, USA Submitted to WHO by The NutraSweet Company, Illinois, USA. Radiolabel was not retained in any organ, and the amounts detected in several tissues (e.g. In addition to de-esterified neotame, three minor degradation products were detected, specifically N-[N-(3,3-dimethylbutyl)-L-aspartamidyl]-L-phenylalanine 1-methyl ester formed by cyclization of neotame, N-[N-(3,3-dimethylbutyl)-L-beta-aspartyl]-L-phenylalanine 1-methyl ester formed by beta-rearrangement of neotame, and N-[N-(3,3-dimethylbutyl)-L-aspartamidyl]-L-phenylalanine formed by methyl ester hydrolysis of N-[N-(3,3-dimethylbutyl)-L-aspartamidyl]-L-phenylalanine 1methyl ester. None of these clinical symptoms required medical intervention, and most were considered mild to moderate, although four headaches were documented as severe. Submitted to WHO by The NutraSweet Company, Illinois, USA. Similarly, N-[N-(3,3-dimethylbutyl)-L-aspartamidyl]-L-phenylalanine (NC-00779) was administered at a dose of 0, 0.3, 1.0, or 3.0 mg/kg bw per day. Absolute spleen weight was decreased in males in all groups (15–43%), and spleen weights were increased in females at 200 and 1200/2000 mg/kg bw per day only, although none of these changes were statistically significant. Neotame is sold under the brand name Newtame®, and is approximately 7,000 to 13,000 times sweeter than table sugar. Also can resist protein denaturation and keep good flavor in rich protein foods. Applications and Uses of Crystalline Fructose, Applications and Uses of Saccharin Sodium. Neotame was extensively metabolized to de-esterified neotame; approximately 14% of the administered dose was recovered in the urine as de-esterified neotame. [2], It is suitable for use in carbonated soft drinks, yogurts, cakes, drink powders, bubble gums among other foods. Kirkpatrick, D., Aikens, P., Nicholson, J. Kisicki, J., Combs, M. & Gao, X. Pharmacokinetic analysis of the data for plasma confirmed that neotame was rapidly absorbed (mean Tmax =0.4 h) and rapidly cleared from the body (mean t1/2 =0.6 h), mostly by conversion to de-esterified neotame. There were no differences in organ : body weight ratios, with the exception of spleen weight being lower and ratios for brain and testes being higher in males at 3000 mg/kg bw per day. Most of these were determined to be of mild or moderate severity, and were reported in all three treatment groups, with no dose–response relationship or statistically significant differences between groups. As average body weight was 100 kg, intake was 0, 60 or 150 mg/day. In females at 100 mg/kg bw per day, the difference in body weight compared with controls had decreased to 7% by the end of week 2. At termination, blood and urine samples were collected for analysis of clinical pathology parameters after an overnight fast. Body-weight gain in females was significantly decreased at 500 and 2000 mg/kg, but no dose–response relationship was evident. Litter size and survival were not affected by treatment, nor were there any treatment-related effects on sex ratio. Atterson, P. (1997a) NC-00723: Charcoal propulsion test in rats (oral administration). Biliary excretion accounted for 2% of the radiolabel. Most of the material recovered in the faeces was unabsorbed material. Low concentrations of an unidentified metabolite were also found, representing 0.7–1.2% of the administered dose (Kirkpatrick et al., 1997a). & Bunch, R. (1998) An evaluation of the potential of NC-00779 to induce micronucleated polychromatic erythrocytes in the bone marrow of mice (micronucleus test). The absolute organ weights of adrenals, heart, kidneys, liver, prostate, spleen, and thymus were decreased in males at 3000 mg/kg bw per day compared with controls. Balwierz, P. & Bunch, R. (1998a) Evaluation of the mutagenic potential of NC-00777 in the Ames Salmonella/microsome assay. Food consumption was decreased in week 1 in males at >100 mg/kg bw per day, and in females at 1000 mg/kg bw per day. Diet containing quinine sulfate at 5000 ppm was used as a positive control. Neotame E961 can be used in Food, Beverage, Pharmaceutical, Health & Personal care products, Agriculture/Animal Feed/Poultry. The plasma concentrations of neotame and de-esterified neotame were examined during a 2-year study of carcinogenicity in CD-1 mice at doses of up to 4000 mg/kg bw per day. Cabonce, M., Asbury, J., McAdams, J., Wagner, C. & Kier, L. (1998a) AS52/XPRT Gene mutation assay with NC-00764. The total combined amount (i.e. Unpublished report from Huntingdon Life Sciences Ltd., Huntingdon, Cambridgeshire, UK. These differences were considered to be normal variation and were not related to treatment with the test article. There were no macroscopic findings at necropsy that were considered to be related to treatment. In females, the absolute weight of the uterus was higher in all treatment groups than that of controls, with increases of 14% at 50 and 500 mg/kg bw per day, and of 34% at 1000 mg/kg bw per day. After oral administration, >90% of the radiolabel was recovered in urine and faeces within 48 h. Within 72 h after oral administration of [14C]neotame at a dose of 15 or 120 mg/kg bw, 8.5–10.8% and 84.5–87.2% of the radiolabel was excreted in the urine and faeces, respectively. Submitted to WHO by Food Standards Australia, New Zealand. Neotame E961 is of great stability, do not affect products’ features including drinks’ flavor,color after batch production, high temperature short time(HTST) sterilization and aseptic operation. On the basis of the data evaluated, the Committee considered that neotame is rapidly but only partially absorbed in all species studied, and that both absorbed and non-absorbed neotame are metabolized via well-characterized pathways to nontoxic metabolites. Submitted to WHO by The NutraSweet Company, Illinois, USA. Submitted to WHO by The NutraSweet Company, Illinois, USA. Methanol is distilled followed by addition of water. There were no treatment-related effects on mortality, nor were there any clinical signs of toxicity during daily and periodic physical examinations. There was a slight (not statistically significant) decrease in motor activity for F1 males at 1000 mg/kg bw per day. Study No. After a stabilization period, each dog was given a single intraduodenal dose of vehicle (0.5% methylcellulose/0.1% (v/v) polysorbate 80), followed by neotame at a dose of 5 or 15 mg/kg bw. These changes were generally within the ranges for historical controls and were not accompanied by microscopic changes. Nineteen healthy men (mean age ±SD, 28 ±6 years) were given single doses of 0.10, 0.25, or 0.50 mg/kg bw (seven, six, six men per dose, repectively) of neotame in solution. The NOEL was 200 mg/kg bw per day on the basis of changes in alkaline phosphatase activity (Thomford & Saunders, 1995). 1-306 Xinle yuan Xinkang Garden of Xintang town ,Guangzhou City, Guangdong P.R.China, Tel:+86 20 32919657 Mobile:+86 13533621907, @2009 -Food Ingredient & Plastic Additives Wellgo Chemical Technology Co.,LTD. There were no effects on food consumption, body weight, or body-weight gain at any interval during gestation, at any dose up to the highest dose administered in the diet. More than 95% of orally administered neotame is metabolized. Neotame is currently permitted for use in the United States, Australia, China, Costa Rica, the Czech Republic, Ecuador, Mexico, New Zealand, Peru, Poland, Romania, and Trinidad and Tobago. No radiolabel was detected in the fetus at any time. Unpublished report from Monsanto Company, Environmental Health Laboratory, St. Louis, Missouri, USA. The heads of one-third of the fetuses were fixed and examined after serial sectioning. The mean volume of distribution of neotame was approximately 1 l/kg bw, a value that is in excess of the average total volume of body water in beagle dogs and indicates some distribution to tissues, without extensive tissue binding. This observation was not associated with any effects on the gastrointestinal tract and was likely to be due to the presence of unabsorbed neotame. [8], Neotame is sweet because it binds to TAS1R2-receptors of mouth as an agonist. The possible effects of neotame on gastrointestinal motility were studied in male Sprague-Dawley rats using the charcoal propulsion test.