title: A two-year dietary carcinogenicity study of (2R,4R)-monatin salt in mice.
abstract: Groups of Crl:CD-1 (ICR) mice (60/group/sex) were fed 0 (2 control groups), 5000, 20,000, or 40,000 ppm of enzymatically sourced (2R,4R)-monatin salt ("R,R-monatin") in the diet for up to two years. There were no adverse effects on survival, incidence of palpable masses and tumors, feed consumption, hematology or serum chemistry parameters, organ weights, or ophthalmic, macroscopic, and microscopic examinations. The only notable effect was statistically significantly lower mean body weights and body weight gains in all treated groups, which generally occurred throughout the study and were most likely a result of caloric dilution of the test diets and not considered adverse. There were no test article-related changes in the incidence or occurrence of neoplastic diseases in mice on this study. The no-observed-effect-level (NOEL) for carcinogenicity of R,R-monatin fed to mice for 24 months was 40,000 ppm, the highest dietary concentration tested, which was equivalent to approximately 6502 and 7996 mg/kg bw/day in males and females, respectively.
authors.affiliation: Cargill Limited, 300-240 Graham Avenue Winnipeg, MB, R3C 4C5, Canada. Electronic address: witty_brathwaite@cargill.com.
authors.forename: Witty A
authors.initials: WA
authors.lastname: Brathwaite
authors.affiliation: Cargill, Incorporated, 15407 McGinty Rd West, Wayzata, MN, 55391, USA. Electronic address: christine_crincoli@cargill.com.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Crincoli
authors.affiliation: Cargill, Incorporated, 15407 McGinty Rd West, Wayzata, MN, 55391, USA. Electronic address: alex_eapen@cargill.com.
authors.forename: Alex K
authors.initials: AK
authors.lastname: Eapen
authors.affiliation: Toxicology Regulatory Services, 2365 Hunters Way, Charlottesville, VA 22911, USA. Electronic address: mrihner@toxregserv.com.
authors.forename: Marisa O
authors.initials: MO
authors.lastname: Rihner
authors.affiliation: Toxicology Regulatory Services, 2365 Hunters Way, Charlottesville, VA 22911, USA. Electronic address: anikiforov@toxregserv.com.
authors.forename: Andrey I
authors.initials: AI
authors.lastname: Nikiforov
authors.affiliation: WIL Research, 310 Millstone Drive, Hillsborough, NC, 27278, USA. Electronic address: catherine.picut@wilresearch.com.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Picut
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004032:Diet; D005260:Female; D018698:Glutamic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D007211:Indoles / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012492:Salts
chemical_list: C414924:4-hydroxy-4-(indol-3-ylmethyl)glutamic acid; D002273:Carcinogens; D007211:Indoles; D012492:Salts; D018698:Glutamic Acid
keywords: Carcinogenicity; Dietary; Mice; R,R-Monatin; Safety