MacKenzie K M, Hauck W N, Wheeler A G, Roe F J
Food Chem Toxicol. 1986 Mar;24(3):191-200. doi: 10.1016/0278-6915(86)90228-0.
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)
将12只雄性和24只雌性5周龄的查尔斯河CD（SD）BR大鼠（F0）分为几组，喂食以谷物为基础的含蔗糖饲料，其中分别含有0%、2.5%、5.0%和10.0%（w/w）的山梨醇，蔗糖含量相应减少。大鼠在喂食该饲料14周后首次交配。在研究开始19周后出生F1a代幼崽，30周后出生F1b代幼崽。将12只雄性和24只雌性F1b大鼠在18周龄时首次交配。3周后产下F2a代幼崽，10周后产下F2b代幼崽。同样，将12只雄性和24只雌性F2b大鼠在18周龄时首次交配，分别在3周和10周后产下F3a和F3b代幼崽。F0大鼠在研究开始33周后处死，F1a在第22周处死，F1b在第68周处死，F2a在第57周处死，F2b在第92周处死，F3a在第96周处死。除了喂食山梨醇的F1b雄性大鼠食物消耗量略有减少，以及喂食山梨醇的F0、F1b和F2b两性大鼠体重增加略有减少外，该处理未观察到临床效应。没有因处理导致的死亡，对任何一代亲本动物的交配性能或妊娠率也没有不良影响。该处理对妊娠或哺乳期的任何生殖性能或行为指标均未产生持续的不良影响。在任何一代中均未观察到异常幼崽。不出所料，在所有世代经山梨醇处理的大鼠尸检时均持续观察到盲肠肿大，在暴露于10%山梨醇的F0雄性和雌性大鼠以及暴露于5%或10%山梨醇的F1b雄性大鼠中观察到血清钙显著升高。处理组和对照组F3a大鼠在T3和TSH水平上的差异可能是虚假的，因为它们没有一致的模式。同样，性腺重量的组间差异被认为没有毒理学意义，因为它们缺乏一致性且没有伴随任何组织学上明显的变化。对F1a和F2a动物的病变、F1b和F2b的性腺以及F3a代的选定组织进行显微镜检查，未发现具有毒理学意义的变化。（摘要截取自400字）
