title: A dietary two-generation reproductive toxicity study of (2R,4R)-monatin salt in Crl:CD(SD) rats.
abstract: (2R,4R)-Monatin salt [sodium/potassium 2R,4R-2-amino-4-carboxy-4-hydroxy-5-(3-indolyl) pentanoate] was fed at 5000, 15,000, or 35,000 ppm to Crl:CD(SD) rats over two generations. Reduced body weights were observed at all dose levels. Sustained effect on body weight gain at 35,000 ppm in the F0 and F1 parental animals was associated with lower feed efficiency, soft stool, and slightly lower numbers of implantation sites. Lower numbers of pups born and live litter size at 35,000 ppm were considered secondary to slightly lower numbers of former implantation sites in the dams. Spermatogenic endpoints, estrous cyclicity, reproductive performance, mean gestation length, and parturition were unaffected in the F0 and F1 generations. There were no effects on F1 and F2 generation postnatal survival. Reduced pre-weaning pup body weights at 35,000 ppm resulted in lower F1 and F2 body weights at study termination. Slight delays in pubertal landmarks in the F1 offspring were considered secondary to the reduced pup body weights. The no-observed-adverse-effect level (NOAEL) was 15,000 ppm for systemic, reproductive, and neonatal effects based on test article-related effects on body weight and food efficiency, slight decrease in maternal implantation sites and corresponding reduction in live litter size, and reductions in pre-weaning pup body weights at 35,000 ppm.
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 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: Caledonia, MI 49316, USA. Electronic address: philcasterton@gmail.com.
authors.forename: Phillip L
authors.initials: PL
authors.lastname: Casterton
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 Laboratories, 1407 George Road Ashland, OH 44805, USA. Electronic address: eddie.sloter@wilresearch.com.
authors.forename: Eddie D
authors.initials: ED
authors.lastname: Sloter
authors.affiliation: ReproTox Consulting, Inc. d/b/a/ Stephen B. Harris Group, 6109 Madra Ave., San Diego, CA, 92120, USA. Electronic address: steve@sbhgrp.com.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Harris
mesh_terms: D000818:Animals; D005247:Feeding Behavior; D005260:Female; D018698:Glutamic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D007211:Indoles / Q000633:toxicity*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*
chemical_list: C414924:4-hydroxy-4-(indol-3-ylmethyl)glutamic acid; D007211:Indoles; D018698:Glutamic Acid
keywords: (2R,4R)-monatin salt; Oral; Rat; Reproductive toxicity