A dietary two-generation reproductive toxicity study of (2R,4R)-monatin salt in Crl:CD(SD) rats |
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Institution: | 1. Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail), UMR_S 1085, F-35000 Rennes, France;2. Department of Pathology and Cytology, Rennes University Hospital, 35033 Rennes, France;3. Department of Thoracic, Cardiac and Vascular Surgery, Rennes University Hospital, 35033 Rennes, France;4. Boehringer Ingelheim Pharma GmbH & Co, KG, Biberach an der Riss, Germany;5. Department of Respiratory Diseases, Competence Center for Rare Pulmonary Disease, Rennes University Hospital, 35033, Rennes, France |
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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. |
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Keywords: | Reproductive toxicity Rat Oral AAALAC"} {"#name":"keyword" "$":{"id":"kwrd0035"} "$$":[{"#name":"text" "_":"Assessment and Accreditation of Laboratory Animal Care BSA"} {"#name":"keyword" "$":{"id":"kwrd0045"} "$$":[{"#name":"text" "_":"bovine serum albumin bw"} {"#name":"keyword" "$":{"id":"kwrd0055"} "$$":[{"#name":"text" "_":"body weight D"} {"#name":"keyword" "$":{"id":"kwrd0065"} "$$":[{"#name":"text" "_":"diestrus FDA"} {"#name":"keyword" "$":{"id":"kwrd0075"} "$$":[{"#name":"text" "_":"US Food and Drug Administration GD"} {"#name":"keyword" "$":{"id":"kwrd0085"} "$$":[{"#name":"text" "_":"gestation day GLP"} {"#name":"keyword" "$":{"id":"kwrd0095"} "$$":[{"#name":"text" "_":"Good Laboratory Practice LD"} {"#name":"keyword" "$":{"id":"kwrd0105"} "$$":[{"#name":"text" "_":"lactation day M"} {"#name":"keyword" "$":{"id":"kwrd0115"} "$$":[{"#name":"text" "_":"metestrus NOAEL"} {"#name":"keyword" "$":{"id":"kwrd0125"} "$$":[{"#name":"text" "_":"no-observed-adverse-effect level OECD"} {"#name":"keyword" "$":{"id":"kwrd0135"} "$$":[{"#name":"text" "_":"Organisation for Economic Cooperation and Development PND"} {"#name":"keyword" "$":{"id":"kwrd0145"} "$$":[{"#name":"text" "_":"postnatal day |
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