Food consumption and body weight changes with neotame, a new sweetener with intense taste: differentiating effects of palatability from toxicity in dietary safety studies.
Safety studies done with neotame, a sweetener with intense taste, demonstrate that changes in bodyweight (BW) and BW gain (BWG) are due to reduced food consumption (FC) rather than toxicity. When offered a choice, rats preferred basal diet to diet with relatively low concentrations of neotame. When no choice was available, rats ate less as concentrations increased, demonstrating reduced palatability. Changes in dietary concentrations of neotame resulted in changes in FC. The maximum tolerable doses (MTDs) in rats, dogs, and mice were due to decreases in BWG secondary to poor palatability of diets when neotame concentrations exceeded approximately 35,000 ppm. Concentrations were increased as animals grew to maintain constant dosing on a "mg/kg bw/day" basis. Food conversion efficiency (FCE) was not changed in rats during periods of active growth. The only consistent findings across safety studies were reductions in BW, BWG, and FC with no dose-response in rats, mice, and dogs. In definitive safety studies, there were no adverse findings related to neotame treatment from clinical observations, physical examinations, water consumption, or clinical pathology evaluations; nor was there morbidity, mortality, organ toxicity, macroscopic or microscopic postmortem findings. Analysis of data from long-term studies in Sprague-Dawley rats support the conclusion that changes in FC alone can cause the observed changes in BWG in neotame studies when changes are scaled allometrically [Regul. Toxicol. Pharmacol. (2003)]. Consequently, BW parameters are not appropriate endpoints for setting no-observed-effect levels (NOELs) for neotame.
Mayhew
Dale A
DA
Regulatory Affairs, The NutraSweet Company, 1801 Maple Street, Evanston, IL 60201, USA. dale.a.mayhew@nutrasweet.com
Comer
C Phil
CP
Stargel
W Wayne
WW
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D015197:Carcinogenicity Tests; D004032:Diet; D004151:Dipeptides / Q000008:administration & dosage / Q000633:toxicity*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005518:Food Preferences; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013549:Sweetening Agents / Q000008:administration & dosage / Q000633:toxicity*; D013649:Taste; D036401:Toxicity Tests, Chronic
D004151:Dipeptides; D013549:Sweetening Agents; C404525:neotame