D-GLUCOSE COMBINED CHRONIC TOXICITY AND CARCINOGENICITY STUDIES IN SPRAGUE-DAWLEY RATS AND SYRIAN GOLDEN-HAMSTERS

After an initial period of 16 weeks with increasing concentrations, D- glucose was administered at 30% in the diet to 50 male and 50 female S prague-Dawley rats from the 17(th) to the 112(th) study week. Addition al 10 male and 10 female animals were treated for 14 months and then s acrificed for interim examination. Groups of 60 male and 60 female Syr ian golden hamsters received D-glucose in the form of 20% solution in tap water for a period of 80 weeks. In each case, groups consisting of an equal number of untreated animals served as controls. General beha vior and mortality were not affected by the treatment. The rats and ha msters treated with glucose showed significantly higher body weights o f up to a maximum of 16% in male and 26% in female rats, or 15% in mal e and female hamsters. In rats, the increase was evident by week 14, a nd in the hamsters by week 10. Glucose-dosed rats displayed a slightly increased feed intake and a reduced water intake. Both parameters, ho wever, were not influenced in hamsters. Hematological and histopatholo gical examination showed no pertinent changes in hematopoetic tissue. Sharply increased blood glucose and renal glucose excretion values wer e present in rats beginning with 18 months and were indicative of the development of non-insulin-dependent diabetes mellitus (NIDDM). The in sulin concentrations in peripheral blood were not appreciably affected although there was a trend to higher values in males at all evaluatio n times and in females only at 3 months. Pathological evaluation did n ot show any compound related non-neoplastic lesions. The incidences of islet cell adenomas in the pancreas of male rats were significantly i ncreased and the cortical adenomas in the adrenals of females were dec reased. In addition, the mammary gland adenomas (in females) and the L eydig cell tumors of the testes were decreased. In hamsters, the incid ence of adrenocortical adenomas were increased in the females. No othe r pertinent neoplastic changes were observed In conclusion, the increa ses and decreases in benign neoplasms of hormone-sensitive tissues, ap pear to be the result of nutritionally/metabolism-induced modulation o f the homeostasis in these 4 tissues in both species, and not the resu lt of chronic glucose administration.