Multigeneration Reproduction Study of Lactitol in Rats

Abstract

Lactitol is a disaccharide sugar alcohol (polyol) which holds promise as a reduced calorie, noncariogenic sugar substitute. In a multigeneration reproduction study, lactitol was fed to Wistar-derived Cpb:WU rats of both sexes throughout three successive generations at dietary concentrations of 0, 2, 5, and 10%. A comparison group receiving a diet with 20% lactose was included during the F., generation. The initial mating comprised 20 male and 40 female rats per group. For subsequent matings, 10 males and 20 females were used. In each generation, two litters were reared until they were at least 3 weeks old. Fertility was uniformly high in all treatment groups throughout the study and the feeding of lactitol was not associated with any adverse effects on fertility and reproductive performance. However, growth rates and survival were slightly decreased in pups of the 10% lactitol group, except in F₃ litters where no effect of lactitol on survival was seen. In the 20% lactose group of the F, generation, a similar growth retardation and decreased survival was seen. The second litter of third-generation rats (F_3b) was subjected to gross and histopathological examination 4 weeks after weaning. F_3b rats fed 5 or 10% lactitol showed cecal enlargement which was not associated with any morphological alterations and which is commonly seen in rodents fed polyols or slowly digestible carbohydrates. In some F_3b males of all dosage groups, an opaque appearance of the liver cell cytoplasm was noted. However, this effect was not dose related and was not accompanied by any other hepatic changes in the lactitol groups. Since this phenomenon was not seen in older rats or after chronic administration of lactitol, it was considered to be a transient manifestation of an altered metabolism in young rats. All other histopathological findings were equally distributed between control and test animals, or occurred in one or a few rats only. It is concluded that lactitol administered in the diet to three successive generations of rats at levels up to 10%, has no adverse effects on reproductive performance in either sex. The slight developmental delay which occurred in some generations, has been observed earlier with other polyols and may be attributed to the poor digestibility of these compounds.

References

1. Den Uyl, C.H. (1987). Technical and commercial aspects of the use of lactitol in foods as a reduced calorie bulk sweetener. In: Developments in Sweeteners 3. T.H. Grenby (ed.). London: Elsevier Applied Science, pp. 65–81.

2. Nilsson, U. and JÄGerstad, M. (1987). Hydrolysis of lactitol. maltitol and Palatinit by human intestinal biopsies. Br. J. Nutr. 58, 199–206.

3. Grimble, G.K. , Patil, D.H. , and Silk, D.B.A. (1988). Assimilation of lactitol, an “unabsorbed” disaccharide in the normal human colon. Gut 29, 1666–1671.

4. Til, H.P. , Bosland, M.C. , Hollanders, V.M.H. , and BÄR. A. (1992). Subchronic toxicity study of lactitol in dogs. J. Am. Coll. Toxicol. 11(2), 219–232.

5. Sinkeldam, E.J. , Woutersen, R.A. , Hollanders, V.M.H. , Til, H.P. , Van Garderen-Hoetmer, A. , and Bär, A. (1992). Subchronic and chronic toxicity/cancerogenicity feeding studies with lactitol in rats. J. Am. Coll. Toxicol. 11(2), 165–188.

6. El-Harith, E.A. , Dickerson, J.W.T. , and Walker R. (1976). Potato starch and cecal hypertrophy in the rat. Food Cosmet. Toxicol., 14, 115–121.

7. Leegwater, D.C. , De Groot, A.P. , and Van Kalmthout-Kuyper, M. (1974). The aetiology of caecal enlargement in the rat. Food Cosmet. Toxicol. 12, 687–697.

8. Leichter, J. Tolensky, A.F. (1975). Effect of dietary lactose on the absorption of protein, fat and calcium in the post-weaning rat. Am. J. Clin. Nutr. 28, 238–241.

9. Moser, R.L. , Peo, E.R. , Crenshaw, T.D. , and Cunningham, P.J. (1980). Effect of dietary lactose on gain, feed conversion, blood, bone and intestinal parameters in postweaning rats and swine. J. Anim. Sci. 51, 89–99.

10.

10. Staudacher, W. and Kirchgessner, M. (1984). Protein- und Fettansatz sowie Energieverwertung bei Verfülterung von Palatinit an wachsenden Ratten. Z. Tierphysiol., Tieremährg. u. Futtermittelkd. 52, 272–283.

11.

11. Maranesi, M. , Gentili, P. , and Carenini, G. (1984). Nutritional studies on maltitol. Part 1: Acceptability, energetic yield, effects on growth and blood biochemical parameters. Acta Vitaminol. Enzymol. 6, 3–9.

12.

12. Mackenzie, K.M. , Hauck, W.N. , Wheeler, A.G. , and Roe, F.J.C. (1986). Three-generation reproduction study of rats ingesting up to 10% sorbitol in the diet—and a brief review of the toxicological status of sorbitol. Fd. Chem. Toxicol. 24, 191–200.

13.

13. Newberne, P.M. , Conner, M.W. , and Estes, P. (1988). The influence of food additives and related materials on lower bowel structure and function. Toxicol. Pathol. 16, 184–197.

14.

14. Smits-Van Prooije, A.E. , Degroot, A.P. , Dreef-Van Der Meulen, H.C. , and Sinkeldam, E.J. (1990). Chronic toxicity and carcinogenicity study of isomalt in rats and mice. Food Chem. Toxicol. 28, 243–251.

15.

15. Woutersen, R.A. (1987). Chronic toxicity and carcinogenicity of lactitol in rats: Comparison with lactose. In: Low Digestibility Carbohydrates. D.C. Leegwater , V.J. Feron , and R.J.J. Hermus (eds.), Wageningen: Pudoc, pp. 51–60.

16.

16. De Groot, A.P. , Til, H.P. , Feron, V.J. , Dreef-Van Der Meulen, H.C. , and Willems, M.I. (1974). Two-year feeding and multigeneration studies in rats on five chemically modified starches. Food Cosmet. Toxicol. 12, 651–697.

17.

17. IPCS/WHO (1983). Toxicological evaluation of certain food additives and contaminants. WHO Food Additives Series, 18, 82–94 (lactitol).

18.

18. IPCS/WHO (1987). Toxicological evaluation of certain food additives and contaminants. WHO Food Additives Series, 20, 207–237 (isomalt).

19.

19. IPCS/WHO (1983). Toxicological evaluation of certain food additives and contaminants. WHO Food Additives Series, 18, 161–174 (xylitol).

20.

20. IPCS/WHO (1987). Principles for the safety assessment of food additives and contaminants in food. Environ. Health Criteria 70, 39–59.

21.

21. Dehmel, K.H. , Foerster, H. , and Menhnert, H. (1969). Absorption of xylitol. In: International Symposium on Metabolism, Physiology, and Clinical Use of Pentoses and Pentitols. B.L. Horecker , K. Lang , and Y. Takagi (eds.). Berlin, Heidelberg: Springer-Verlag, pp. 177–181.

22.

22. Dahlqvist, A. and Thompson, D.L. (1964). The digestion and absorption of lactose by the intact rat. Acta Physiol. Scand. 61, 20–33.

23.

23. Karimzadegan, D. , Clifford, A.J. , and Hill, F.W. (1979). A rat bioassay for measuring the comparative availability of carbohydrates and its application of legume foods, pure carbohydrates and polyols. J. Nutr. 109, 2247–2259.

24.

24. Koëter, H.B.W.M. and Bär, A. (1992). Embryotoxicity and teratogenicity studies with lactitol in rats. J. Am. Coll. Toxicol. 11(2), 249–257.

25.

25. Feron, V.J. , De Groot, A.P. , Spanjers, M.T. , and Til, H.P. (1973). An evaluation of the criterion “organ weight” under conditions of growth retardation. Food Cosmet. Toxicol. 11, 85–94.

26.

26. Salminen, S.J. (1982). Investigations of the toxicological and biological properties of xylitol. Thesis. University of Surrey. U.K.

27.

27. FAO/WHO (1978). Summary of toxicological data of certain food additives and contaminants. WHO Food Additives Series 13, 20–25 (sorbitol).