A 90-day dietary study of a (2R,4R)-monatin salt in Beagle dogs.
(2R,4R)-Monatin salt (Na/K) [sodium/potassium (2R,4R)-2-amino-4-carboxy-4-hydroxy-5-(3-indolyl) pentanoate, hereafter "R,R-monatin"] was administered in the diets of groups of Beagle dogs (4/sex/group) at concentrations of 0 (basal diet), 5000, 20,000, or 35,000 ppm for 13 weeks. There were no effects on survival, clinical observations, body weight and body weight gain, feed consumption and feed efficiency, functional observational battery, ophthalmic examination, and electrocardiographic evaluation. No adverse effects on hematology, serum chemistry, and urinalysis parameters were reported. A statistically significant decrease in testicular weights associated with germ cell hypocellularity and reduced luminal sperm in the epididymides was reported in all treated male groups. Based on these findings, the dietary no-observed-adverse-effect level (NOAEL) of R,R-monatin for 90 days was considered 35,000 ppm for female dogs (approximately 1101 mg/kg bw/day) and <5000 ppm for male dogs (approximately <151 mg/kg bw/day).
Cargill, Incorporated, 15407 McGinty Rd West, Wayzata, MN 55391, USA. Electronic address: christine_crincoli@cargill.com.
Christine M
CM
Crincoli
Cargill Limited, 300-240 Graham Avenue, Winnipeg, MB R3C 4C5, Canada. Electronic address: witty_brathwaite@cargill.com.
Witty A
WA
Brathwaite
Toxicology Regulatory Services, 2365 Hunters Way, Charlottesville, VA 22911, USA. Electronic address: mrihner@toxregserv.com.
Marisa O
MO
Rihner
Toxicology Regulatory Services, 2365 Hunters Way, Charlottesville, VA 22911, USA. Electronic address: anikiforov@toxregserv.com.
Andrey I
AI
Nikiforov
ReproTox Consulting, Inc. d/b/a/ Stephen B. Harris Group, 6109 Madra Ave., San Diego, CA 92120, USA. Electronic address: steve@sbhgrp.com.
Stephen B
SB
Harris
WIL Research Laboratories, 1407 George Road Ashland, OH 44805, USA. Electronic address: melanie.greeley@wilresearch.com.
Melanie A
MA
Greeley
Cargill, Incorporated, 15407 McGinty Rd West, Wayzata, MN 55391, USA. Electronic address: alex_eapen@cargill.com.
Alex K
AK
Eapen
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D018698:Glutamic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D007211:Indoles / Q000008:administration & dosage*; D008297:Male; D009929:Organ Size / Q000187:drug effects
C414924:4-hydroxy-4-(indol-3-ylmethyl)glutamic acid; D007211:Indoles; D018698:Glutamic Acid
Dietary; Dog; R,R-monatin; Safety; Toxicity