title: Mutagenicity and genotoxicity studies of arruva, an R,R-monatin salt isomer.
abstract: Arruva, the R,R-isomer of monatin (sodium/potassium 2R,4R-2-amino-4-carboxy-4-hydroxy-5-(3-indolyl) pentanoate), an intense sweetener originally identified in root bark of the South African shrub Schlerochitin ilicifolius, was examined for its mutagenic and genotoxic potential via bacterial reverse mutation, mouse lymphoma and in vivo mouse micronucleus assays, all accomplished in the presence and absence of S9 metabolic activation. In the bacterial reverse mutation assay, arruva was determined to not cause reverse mutations in four Salmonella typhimurium strains and one Escherichia coli strain at concentrations up-cells did not exhibit concentration-related increases in mutant frequency at test concentrations up to 3200μg/ml. In the in vivo micronucleus test, arruva was administered to male mice via single gavage doses at 500, 1000 or 2000mg/kg bw. At 24 or 48h post-dose, the mice were euthanized and femoral bone marrow cells were collected for evaluation of micronucleated polychromatic erythrocyte (MPCE) presence. No statistically significant increases of MPEs were observed relative to the respective vehicle control groups. Under the conditions of these studies, arruva was concluded to be negative in all three assays, thereby indicating the absence of its potential mutagenicity or genotoxicity under the conditions tested.
authors.affiliation: Cargill, Inc., 15407 McGinty Road W., MS-163, Wayzata, MN 55391, United States. Electronic address: Phillip_casterton@cargill.com.
authors.forename: Phillip L
authors.initials: PL
authors.lastname: Casterton
authors.affiliation: Cargill, Ltd., 300-240 Graham Avenue, Winnipeg, Manitoba R3C 4C5, Canada. Electronic address: Witty_brathwaite@cargill.com.
authors.forename: Witty A
authors.initials: WA
authors.lastname: Brathwaite
authors.affiliation: Cargill, Inc., 15407 McGinty Road W., MS-163, Wayzata, MN 55391, United States. Electronic address: Christine_crincoli@cargill.com.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Crincoli
mesh_terms: D027901:Acanthaceae / Q000737:chemistry; D000818:Animals; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004926:Escherichia coli / Q000187:drug effects; D018698:Glutamic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D007211:Indoles / Q000633:toxicity*; D008223:Lymphoma / Q000139:chemically induced; D008297:Male; D051379:Mice; D015162:Micronucleus Tests / Q000379:methods; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity*; D010936:Plant Extracts / Q000633:toxicity; D018517:Plant Roots / Q000737:chemistry; D012486:Salmonella typhimurium / Q000187:drug effects; D013549:Sweetening Agents / Q000633:toxicity
chemical_list: C414924:4-hydroxy-4-(indol-3-ylmethyl)glutamic acid; D007211:Indoles; D009153:Mutagens; D010936:Plant Extracts; D013549:Sweetening Agents; D018698:Glutamic Acid
keywords: Arruva; Genotoxicity; Monatin; Mutagenicity; R,R-monatin salt