title: Three-generation reproduction study of rats ingesting up to 10% sorbitol in the diet--and a brief review of the toxicological status of sorbitol.
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)
mesh_terms: D000313:Adrenal Medulla / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000097:blood; D004032:Diet; D004435:Eating / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects; D008099:Liver / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012098:Reproduction / Q000187:drug effects*; D013012:Sorbitol / Q000633:toxicity*; D013963:Thyroid Hormones / Q000097:blood
chemical_list: D013963:Thyroid Hormones; D013012:Sorbitol; D002118:Calcium