Three-generation reproduction study of rats ingesting up to 10% sorbitol in the diet--and a brief review of the toxicological status of sorbitol |
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| Authors: | K M MacKenzie W N Hauck A G Wheeler F J Roe |
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| Affiliation: | 1. Department of Medicine, Einstein Medical Center, Klein Building, Suite 300, 5501 Old York Road, Philadelphia, PA 19141, USA;2. Infectious Disease Fellowship Program, Internal Medicine Residency Program, Einstein Medical Center, Klein Building, Suite 300, 5501 Old York Road, Philadelphia, PA 19141, USA;3. Infection Prevention and Control, Einstein Medical Center, Klein Building, Suite 300, 5501 Old York Road, Philadelphia, PA 19141, USA;1. Interfacultary Research Center of Biomaterials (CEIB), University of Liège, Institute of Chemistry, Building B6C, Sart-Tilman, Liège (ZIP code 4000), Belgium;2. Cardiovascular Research Center, Avenue de l''hôpital 13, Liège (ZIP code 4000), Belgium;3. Hemostasis and Thrombosis center, CHU, Avenue de l''hôpital 13, Liège (ZIP code 4000), Belgium;4. Centre for Pharmaceutical Nanotechnology and Nanotoxicology, Department of Pharmacy, Faculty of Health and Medical Sciences and NanoScience Centre, University of Copenhagen, Universitetsparken 2, Copenhagen (ZIP code 2100), Denmark;5. Department of Physiology, CARIM, Maastricht University, Universiteitssingel 50, ER Maastricht (ZIP code 6229ER),The Netherlands;1. Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ, 07677, USA;2. Columbia University Medical Center, Department of Dermatology, 161 Fort Washington Ave., New York, NY, 10032, USA;3. Malmo University Hospital, Department of Occupational & Environmental Dermatology, Sodra Forstadsgatan 101, Entrance 47, Malmo, SE-20502, Sweden;4. School of Natural Resources & Environment, University of Michigan, Dana Building G110, 440 Church St., Ann Arbor, MI, 58109, USA;5. Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Strasse 1, 30625, Hannover, Germany;6. University of Sao Paulo, School of Veterinary Medicine and Animal Science, Department of Pathology, Av. Prof. Dr. Orlando Marques de Paiva, 87, Sao Paulo, CEP 05508-900, Brazil;7. Member RIFM Expert Panel, University of Wuerzburg, Department of Toxicology, Versbacher Str. 9, 97078, Würzburg, Germany;8. Oregon Health Science University, 3181 SW Sam Jackson Park Rd., Portland, OR, 97239, USA;9. Vanderbilt University School of Medicine, Department of Biochemistry, Center in Molecular Toxicology, 638 Robinson Research Building, 2200 Pierce Avenue, Nashville, TN, 37232-0146, USA;10. University of Pennsylvania, Perelman School of Medicine, Center of Excellence in Environmental Toxicology, 1316 Biomedical Research Building (BRB) II/III, 421 Curie Boulevard, Philadelphia, PA, 19104-3083, USA;11. The University of Tennessee, College of Veterinary Medicine, Department of Comparative Medicine, 2407 River Dr., Knoxville, TN, 37996- 4500, USA;12. Department of Pharmacology, University of Arizona, College of Medicine, 1501 North Campbell Avenue, P.O. Box 245050, Tucson, AZ, 85724-5050, USA;13. Department of Dermatology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan;1. Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Japan;2. Odawara Research Center, Nippon Soda Co., Ltd, Japan;1. Center for Integrative Genomics, University of Lausanne, Genopode Building, CH-1015 Lausanne, Switzerland;2. ULB Center for Diabetes Research, Université Libre de Bruxelles (ULB), Brussels, Belgium;1. Livestock Issues Research Unit, USDA-ARS, Lubbock, TX 79403, United States;2. Diamond V, Cedar Rapids, IA 52404, United States |
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| Abstract: | Groups of 12 male and 24 female 5-wk-old Charles River CD (SD) BR rats (F0) were fed a sucrose-containing ground cereal-based diet in which 0, 2.5, 5.0 and 10.0% (w/w) sorbitol was included at the expense of sucrose. The rats were first mated after 14 wk on the diet. F1a litters were born 19 wk after the start of the study and F1b litters at wk 30. Groups of 12 male and 24 female F1b rats were first mated when 18 wk old. They gave rise to F2a litters after 3 wk and to F2b litters 10 wk later. Likewise, groups of 12 male and 24 female F2b rats were first mated when 18 wk old, producing F3a and F3b litters 3 wk and 10 wk later, respectively. F0 rats were killed 33 wk after the start of the study, F1a in wk 22, F1b in wk 68, F2a in wk 57, F2b in wk 92 and F3a in wk 96. Apart from slight reductions in food consumption in sorbitol-fed F1b males and in body-weight gain in sorbitol-fed F0, F1b and F2b rats of both sexes, treatment was associated with no clinically observed effects. There were no deaths attributable to treatment and no adverse effects on mating performance or pregnancy rates in the parent animals of any generation. Treatment was associated with no consistent adverse effect on any measure of reproductive performance or behaviour during gestation or lactation. No abnormal pups were observed in any generation. Not unexpectedly, caecal enlargement was consistently observed at necropsy of sorbitol-treated rats of all generations and significant rises in serum calcium were observed in F0 males and females exposed to 10% sorbitol and in F1b males exposed to either 5 or 10% sorbitol. Differences between treated and control F3a rats in respect of T3 and TSH levels were probably spurious as they followed no consistent pattern. Similarly, between-group variations in gonadal weight were considered to have no toxicological significance because they lacked consistency and were not accompanied by any histologically-evident changes. Microscopic examination of lesions from F1a and F2a animals, of gonads from F1b and F2b and of selected tissues from the F3a generation revealed no changes of toxicological significance.(ABSTRACT TRUNCATED AT 400 WORDS) |
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