Registration Dossier

Diss Factsheets

Administrative data

Link to relevant study record(s)

Description of key information

Key value for chemical safety assessment

Additional information

Basic toxicokinetics

There are no studies available on the toxicokinetic behaviour of Reaction mass of 1-O-α-D-glucopyranosyl-D-fructose and 6-O-α-D-glucopyranosyl-D-fructose and fructose and glucose and sucrose. In accordance with Regulation (EC) 1907/2006, Annex VIII, Column 1, Section 8.8.1 and with Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2012), assessment of the toxicokinetic behaviour of the substance is conducted to the extent that can be derived from the relevant available information. This comprises a qualitative assessment of the available specific data on physicochemical and toxicological properties of the main components isomaltulose (CAS 13718-94-0) and trehalulose (CAS 51411-23-5) according to the relevant Guidance (ECHA, 2012).

Reaction mass of 1-O-α-D-glucopyranosyl-D-fructose and 6-O-α-D-glucopyranosyl-D-fructose and fructose and glucose and sucrose is the aqueous solution (syrup) of isomaltulose (CAS 13718-94-0), trehalulose (CAS 51411-23-5), fructose (CAS 57-48-7), glucose (CAS 50-99-7), sucrose (CAS 57-50-1), isomaltose (CAS 499-40-1) and oligosaccharides.

Fructose, (CAS 57-48-7), glucose (CAS 50-99-7) and sucrose (CAS 57-50-1) are well characterized in regard to their toxicokinetic behaviour and sufficient information is known to consider them as non-hazardous because of their intrinsic properties. Therefore, fructose, glucose and sucrose are included in Annex IV of Regulation (EC) 1907/2006. Moreover, they are essential components of human daily diet.

The residual disaccharide isomaltose (CAS 499-40-1), α-linked glucosyl-glucose, occurs naturally at branch sites within amylopectin in starches and is thus present in commercially available starch hydrolysates and maltodextrines, which are both included in Annex IV.

Information on the representative main components is given below.


Isomaltulose (6-O-α-D-glucopyranolsyl-D-fructose) is a reducing disaccharide consisting of glucose and fructose joined by a 1,6-glycosidic bond. Due to its chemical nature, isomaltulose represents an isomer of sucrose. The substance is a fine white powder at 20°C with a molecular weight of 342.3 g/mol, a vapour pressure of < 1E-10 Pa (Nagel, 2012a) with a water solubility of 320 g/L (O´Brian Nabors, 2012) and a log Pow of -3.57 (Nagel, 2012b). For commercial purposes, isomaltulose is synthesized by the enzymatic conversion of sucrose through the biocatalyst sucrose-glucosylmutase isolated from the microorganism Protaminobacter rubrum (CBS 574.44), which was shown to be non-hazardous in animals after intravenous injection (Porter et al., 1991). Naturally, isomaltulose occurs at low levels in honey and sugar cane extract (Siddiqui and Furgala, 1967; Takazoe, 1985; Eggleston and Grisham, 2003).


Trehalulose (1-O-α-D-glucopyranosyl-D-fructose) is a reducing disaccharide made from sucrose by enzymatic conversion of the α -1,2-linkage of glucose and fructose into the α -1,1-linkage. The substance has a molecular weight of 342.3 g/mol, a vapour pressure of < 1E-09 Pa (Nagel, 2012c) with a log Pow of -3.57 (Nagel, 2012d). Commercially, trehalulose is obtained by enzymatic conversion of sucrose by the α-glucosidase isolated from the microorganism Protaminobacter rubrum (CBS 574.44), which was shown to be non-hazardous in animals after intravenous injection (Porter et al., 1991). 


1. Oral route

After oral ingestion, isomaltulose and trehalulose are enzymatically hydrolysed by the isomaltase-sucrase complex to the monosaccharides glucose and fructose in the small intestine (Goda and Hosoya, 1983; Goda et al., 1991, Yamada et al., 1985). In the free monosaccharide form, glucose is rapidly absorbed in the small intestine by an active process, while fructose is absorbed more slowly (Hyams et al., 1988; Rumessen and Gudmand-Høyer, 1988) by two separate mechanisms, namely glucose-independent facilitated transport and glucose-dependent fructose co-transport (Rumessen and Gudmand-Høyer, 1986; Smith et al., 1995) in which the presence of glucose facilitates the transport of fructose across the brush-border membrane of the small intestine, thereby increasing the absorption rate of fructose (Rumessen and Gudmand-Høyer, 1986; Smith et al., 1995). The absorptive capacity for fructose in humans has not been established conclusively (Riby et al., 1993); however, according to early perfusion studies conducted by Holdsworth and Dawson (1964), the total intestinal capacity for fructose absorption in adult males was estimated to be tremendous (approximately 4,800 g/day). Further, passive diffusion is possible which depends on the concentration of glucose in the intestinal lumen (Rugg-Gunn, 1991). In addition, it has been hypothesized that monosaccharides resulting from the enzymatic hydrolysis of disaccharides like isomaltulose and sucrose are absorbed through the brush-border membrane directly without being released into the luminal space by the disaccharidase-related transport system, which further facilitates absorption (Ugolev et al., 1986; Fujisawa et al., 1991).

Since isomaltulose and trehalulose are almost completely hydrolyzed in the small intestine, total exposure to glucose is similar to that achieved with sucrose. However, the lower peak glucose concentrations associated with the slower rate of absorption results in a reduction of both peak and total systemic (AUC) insulin levels in comparison to similar treatments with sucrose.

Overall, systemic bioavailability of components of Reaction mass of 1-O-α-D-glucopyranosyl-D-fructose and 6-O-α-D-glucopyranosyl-D-fructose and fructose and glucose and sucrose and/or the respective cleavage products is considered as possible in humans after oral uptake.

2. Inhalation

Reaction mass of 1-O-α-D-glucopyranosyl-D-fructose and 6-O-α-D-glucopyranosyl-D-fructose and fructose and glucose and sucrose is produced and marketed as an aqueous solution of carbohydrates with an expected low vapour pressure (<1E-05 Pa at 25°C) considering the surrogate substances isomaltulose and trehalulose.Therefore, under normal use and handling conditions, inhalation exposure and thus availability for respiratory absorption of the substance in the form of vapours, gases, or mists is not expected to be significant.

However, the substance may be available for respiratory absorption in the lung after inhalation of aerosols, if the substance is sprayed.In humans, particles with aerodynamic diameters below 100 µm have the potential to be inhaled. Particles with aerodynamic diameters below 50 µm may reach the thoracic region and those below 15 µm the alveolar region of the respiratory tract (ECHA, 2012). As the components of Palatec M represent hydrophilic compounds, that are soluble in water, passive transfer through cell membranes in the respiratory tract without transport systems is impeded. However, as passive diffusion was shown possible in the gastrointestinal tract for monosaccharides (Rugg-Gunn, 1991), absorption across the respiratory epithelium cannot be excluded for monosaccharides but for disaccharides, which in general require digestion to monosaccharides prior to absorption.

3. Dermal route

The smaller the molecule, the more easily it may be taken up. In general, a molecular weight below 100 favours dermal absorption, above 500 the molecule may be too large (ECHA, 2012). As the molecular weight of components of Reaction mass of 1-O-α-D-glucopyranosyl-D-fructose and 6-O-α-D-glucopyranosyl-D-fructose and fructose and glucose and sucrose ranges between 180.16 to 342.30 g/mol, a dermal absorption of the molecule remains possible.

If the substance is a skin irritant or corrosive, damage to the skin surface may enhance penetration (ECHA, 2012). As Reaction mass of 1-O-α-D-glucopyranosyl-D-fructose and 6-O-α-D-glucopyranosyl-D-fructose and fructose and glucose and sucrose and its components are not considered as skin irritants for humans, an enhanced penetration of the substance due to local skin damage can be excluded.

QSAR calculations regarding the molecular weight, log Kow and water solubility, estimated the following dermal absorption rates (calculated with DERMWIN, v.2.01, 2011, modified considering the Fick´s first law):

Isomaltulose: 0.08 µg/cm2/h (calculated with log Kow: -3.57, water solubility: 1E+06 mg/L).

Trehalulose: 0.03 µg/cm2/h (calculated with log Kow: -4.17, water solubility: 1E+06 mg/L

Thus, isomaltulose and trehalulose are considered to have a low dermal absorption potential of not more than 10%.

Overall, in contrast to the efficient absorption after ingestion, components of Reaction mass of 1-O-α-D-glucopyranosyl-D-fructose and 6-O-α-D-glucopyranosyl-D-fructose and fructose and glucose and sucrose like isomaltulose and trehalulose are only poorly absorbed through the skin based on the calculated low dermal absorption potential and the fact that the substances are not irritating to skin.Therefore, dermal uptake of Reaction mass of 1-O-α-D-glucopyranosyl-D-fructose and 6-O-α-D-glucopyranosyl-D-fructose and fructose and glucose and sucrose and its ingredients is considered as limited in humans.

In summary, experimental and calculated data show that the main components of Reaction mass of 1-O-α-D-glucopyranosyl-D-fructose and 6-O-α-D-glucopyranosyl-D-fructose and fructose and glucose and sucrose are mostly absorbed in the small intestine after oral exposure whereas absorption after dermal contact or inhalation can nearly be neglected.


Upon absorption, glucose and fructose are transported to the liver via the portal vein, where they are metabolized and subsequently distributed to all the tissues (Glinsmann et al., 1986). Due to a slower rate of hydrolysis of isomaltulose and trehalulose, and hence absorption from the small intestine, a blunted or attenuated increase in serum glucose and insulin levels, in comparison to a similar treatment with sucrose, is expected for trehalulose and isomaltulose which is confirmed for isomaltulose by clinical trials (MacDonald and Daniel, 1983; Kawai et al., 1985, 1989; Liao et al., 2001) and several animal studies (MacDonald and Daniel, 1983; Kawai et al., 1986).

An unpublished pig study in which ileal chyme was analyzed following treatment with a diet containing 20% isomaltulose, demonstrated nearly no passage of unhydrolyzed isomaltulose into the large intestine. Only 3% of the intake was detected at the terminal ileum which is indicative for an almost complete digestion in the small intestine (van Weerden, 1983). As trehalulose is hydrolysed by the isomaltase-sucrase complex such as isomaltulose (Goda and Hosoya, 1983; Goda et al., 1991, Yamada et al., 1985), a complete digestion in the small intestine is expected also for trehalulose.

Metabolism / Hydrolysis

Disaccharades like isomaltulose, trehalulose and sucrose are enzymatically hydrolysed at the glycosidic bond between the monosaccharide units to equal parts in glucose and fructose (Cheetham, 1982; Goda and Hosoya, 1983; MacDonald and Daniel, 1983; Yamada et al., 1985, Ziesenitz, 1986; Goda et al ., 1991; Würsch, 1991; Günther and Heymann, 1998). Specifically, the hydrolysis is catalysed by the isomaltase-sucrase complex present in the intestinal mucosa, of which the isomaltase subunit is reported to carry out most of the hydrolysis of isomaltulose and trehalulose (Goda and Hosoya, 1983; Goda et al., 1991, Yamada et al., 1985) whereas the sucrase subunit hydrolyses sucrose (Cheetham, 1982). Studies in animals (Dahlquist et al ., 1963; MacDonald and Daniel, 1983; Kawai et al., 1986; Okuda et al ., 1986, Tsuji et al., 1986) and in humans (MacDonald and Daniel, 1983; Kawai et al ., 1985, 1989) indicate that the rate of hydrolysis of isomaltulose is only one-fifth to one-fourth that of sucrose, at dose levels likely to be encountered by humans (i.e ., in the 1 g/kg body weight/day range). The rate of hydrolysis in intestinal mucosal homogenate isolated from the small intestine of pigs, accounted for 2 to 5% of the rate of hydrolysis of maltose and 10 - 20% of the rate of hydrolysis for sucrose (Dahlqvist, 1961). Further, isomaltulose is hydrolysed less efficiently than maltose or saccharose in homogenates from human jejunal mucosa (Grupp and Siebert, 1978). The Vmax for the hydrolysis of isomaltulose was 11 and 45% of that for maltose and saccharose, respectively, leading to a significant reduction in postpranial glycaemic and insulinaemic responses (EFSA 2011). For trehalulose, the rate of hydrolysis was established to be about three-fourths that of sucrose. Thus, the hydrolysing activity decreases from sucrose over trehalulose to isomaltulose (Tsuji et al., 1986).

Studies in which isomaltulose was administered intravenously have demonstrated that any isomaltulose absorbed intact is hydrolysed in plasma and in peripheral tissues to glucose and fructose: male Wistar rats administered bolus intravenous injections of 0.5 g isomaltulose/kg body weight, showed elevated blood glucose and insulin levels which are indicative of parenteral hydrolysis (Okuda et al.,1986). As hydrolysis of trehalulose is catalyzed by the same enzyme complex (Goda and Hosoya, 1983; Goda et al., 1991, Yamada et al., 1985), a similar parenteral metabolism is expected.

Subsequent to the hydrolysis, glucose and fructose are utilized by well-characterized carbohydrate metabolic pathways (Lina et al., 2002).

Glucose is an essential substrate for the synthesis of ATP, which provides energy for cellular functions via the pentose phosphate shunt pathways and the Krebs cycle (Glinsmann et al., 1986). The liver plays a major role in regulating blood glucose levels (Glinsmann et al., 1986). Excess glucose is converted to glycogen, which is stored in the liver and skeletal muscle tissues, or to fat in a process called lipogenesis (Glinsmann et al., 1986). Glycogen, as well as fat, provides a readily available source of energy for both liver and skeletal tissues during starvation or when increased energy needs arise (Glinsmann et al., 1986). Blood glucose levels also are regulated through insulin and glucagon secretion by the pancreas (Glinsmann et al., 1986). Similarly, the general disposition of fructose metabolism is altered by changes in nutritional and endocrine status (Van den Berghe, 1978).For instance, during periods of starvation and ethanol or glucagon administration, gluconeogenesis from fructose is increased (Van den Berghe, 1978).

In addition to the liver, the small intestine and the kidney contain enzymes necessary for the metabolism of fructose (Van den Berghe, 1986); however, the utilization of fructose in extrahepatic tissues is minimal (Hallfrisch, 1987). In the liver, fructose is rapidly phosphorylated by adenosine triphosphate (ATP) to form fructose-1-phosphate, a reaction catalysed by the fructose-specific enzyme, fructokinase (Hers, 1952).The ability of the liver to extract the majority of the fructose that passes through it is primarily due to the high activity of fructokinase (Mayes, 1993). Fructose-1-phosphate is then broken down into glyceraldehyde and dihydroxyacetone phosphate by the liver enzyme aldolase B (Mayes, 1993; Levi and Werman, 1998). Finally, the third enzyme of the fructose pathway, triokinase, catalyses the phosphorylation of glyceraldehyde by ATP to form glyceraldehyde-3-phosphate (Hers, 1962).Glyceraldehyde-3-phosphate and dihydroxyacetone phosphate subsequently join the glycolytic pathway at the triose phosphate stage of metabolism and from this point on, the metabolism of glucose and fructose becomes qualitatively similar (Mayes, 1993). Therefore, glucose, glycogen, and lactate are the major end products of fructose, and consequently of isomaltulose and trehalulose, while carbon dioxide, ketone bodies, or triacylglycerol are the minor products (Extron and Park, 1967; Mayes and Laker, 1986; Levi and Werman, 1998). 


Recent studies show that no intact isomaltulose reaches the colon, and thus is not available for fermentation to short-chain fatty acids (Dahlquist et al., 1963; MacDonald and Daniel, 1983; van-Weerden, 1983; Kawai et al., 1986; Okuda et al., 1986; Tsuji et al., 1986, MacDonald and Daniel, 1983; Kawai et al., 1985, 1989). In rats only small amounts of radioactivity were detected in the faeces and urine (up to 2.5 and 3.6% in the urine and faeces, respectively) whereas over 50% of the radioactivity was identified in the expired air within the first 72 hours following administration of single oral doses of up to 0.5 g C-isomaltulose/kg body weight (MacDonald and Daniel, 1983; Lina et al ., 2002). In pigs fed 20% isomaltulose, no sugar was detected within the faeces (van Weerden, 1983) thereby confirming that isomaltulose digestion is not fermentative.Regarding a comparable digestion of trehalulose due to the hydrolysis via the isomaltase-sucrase complex in the small intestine, fermentation can be excluded for trehalulose as well.

Further studies demonstrated excretion in the urine after intravenously administration: clinically healthy beagle dogs intravenously exposed to 2 g isomaltulose excreted approximately 83% of the dose in the urine within 24 hours following treatment (Hall and Batt, 1996). In humans, unmetabolized isomaltulose was found in the urine, with approximately 65% excreted within the first 2.5 hours following infusion. These results are representative of rapid and more complete excretion of intact isomaltulose in humans as compared to that observed in dogs.

When the capacity for sugar absorption in the small intestine is exceeded, a substantial amount of the malabsorbed carbohydrate enters the large intestine where it acts as an osmotic laxative, resulting in the production of gas and organic acids (Hyams et al., 1988; Rumessen and Gudmand-Høyer, 1988). Therefore, typical symptoms of carbohydrate malabsorption include diarrhoea, flatulence, borborygmus, abdominal distention, and abdominal cramps (Lifshitz et al., 1992).

In summary, all studies indicate that isomaltulose is almost completely hydrolyzed to fructose and glucose which are subsequently utilized in well-characterized carbohydrate pathways. Nutritionally, the compound is equivalent to sucrose with a slower rate of hydrolysis. Considering the similarity of the metabolism pathways of trehalulose and isomaltulose, an equal toxicokinetic behaviour in humans can be assumed for trehalulose.


References not included in IUCLID:

Cheetham, P.S.J. 1982. The human sucrase-isomaltase complex: Physiological, biochemical, nutritional and medical aspects. In: Lee, C.K.; Lindley, M.G. (Eds.). Developments in Food Carbohydrate—3. Disaccharidases.  Applied Science Publishers; London, Engl./Englewood, New Jersey, pp. 107-140.

Dahlquist A.; Auricchio, S.; Semenza, G.; Prader, A. 1963. Human intestinal disaccharidases and hereditary disaccharide intolerance. The hydrolysis of sucrose, isomaltose, palatinose (isomaltulose), and a 1,6-α -oligosaccharide (isomaltoligosacch aride) preparation. J Clin Invest 42(4):556-562.

Dahlqvist A. 1961. Hydrolysis of Palatinose (isomaltulose) by pig intestinal glycosidases. Acta Chem Scand 15:808-816 .

ECHA. 2012. Guidance on information requirements and chemical safety assessment – Chapter 7c: Endpoint specific guidance. European Chemicals Agency, HelsinkiSiddiqui, I.R; Furgala, B. 1967. Isolation and characterization of oligosaccharides from honey. Part I Disaccharides. J Apicult Res 6:139-145. Cited In: Irwin & Sträter

EFSA. 2011. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to the sugar replacers xylitol, sorbitol, mannitol, maltitol, lactitol, isomalt, erythritol, D-tagatose, isomaltulose, sucralose and polydextrose and maintenance of tooth mineralisation by decreasing tooth demineralisation (ID 463, 464, 563, 618, 647, 1182, 1591, 2907, 2921, 4300), and reduction of post-prandial glycaemic responses (ID 617, 619, 669, 1590, 1762, 2903, 2908, 2920) pursuant to Article 13(1) of Regulation (EC) no 1924/2006 (question no EFSA-Q-2008-1404, EFSA-Q-2008-1406, EFSA-Q-2008-1456, [etc.], adopted on 12 November 2010, and EFSA-Q-2008-1250, EFSA-Q-2008-1251, EFSA-Q-2008-1350, EFSA-Q-2008-1405, [etc.], adopted on 28 January 2011, adopted on 28 January 2011 by European Food Safety Authority). EFSA J 9(4):2076. [25 pp.]. doi:10.2903/j.efsa.2011.2076. Available at:

Eggleston G, Grisham M (2003). Oligosaccharides in cane and their formation on cane deterioration. In: Eggleston G, Coté GL, editors. Oligosaccharides in Food and Agriculture. (ACS Symposium Series 849). Oxford, Engl. / New York (NY): Oxford University Press, pp. 211-232.

Extron, J.H.; Park, C.R. 1967. Control of glucon eogenesis in liver. I. General features of gluconeogenesis in the perfused livers of rats. J Biol Chem 242:2622-2636. Cited In: Mayes, 1993.

Fujisawa, T.; Riby, J.; Kretchmer, N. 1991. Intestinal absorption of fructose in the rat. Gastroenterology 101:360-367. Cited In: Riby et al., 1993.

Glinsmann, W.H.; Irausquin, H.; Park, Y.K. 1986. Evaluation of health aspects of sugars contained in carbohydrate sweeteners. Report of Sugar Task Force, 1986. J Nutr 116(11, Suppl):S1, S17 & S48-S92.

Goda, T.; Hoyosa, N. 1983. Hydrolysis of palatinose by rat intestinal sucrase-isomaltase complex. Nihon Eiyo Shokuryo Gakkaishi 36:169-173. Cited In: Würsch, 1991.

Goda, T.; Takase, S.; Hosoya, N. 1991. Hydrolysis of palatinose condens ates by rat intestinal disaccharidases. Nihon Eiyo Shokuryo Gakkaishi 44(5):395-398.

Grupp U, Siebert G (1978). Metabolism of hydrogenated palatinose, an equimolar mixture of alpha-D-glucopyranosido-1,6-sorbitol and alpha-D-glucopyranosido-1,6-mannitol. Res Exp Med (Berl) 173(3):261-278.

Günther, S.; Heymann, H. 1998. Di- and oligosaccharide substrate specificities and subsite binding engergies of pig intestinal glycoamylase-maltase. Arch Biochem Biophys 354(1):111-116.

Hall, E.J.; Batt, R.M. 1996. Urinary excretion by dogs of intravenously administered simple sugars.Res Vet Sci 60(3):280-282.

Hallfrisch, J. 1987. Metabolism. In: Reiser, S.; Hallfrisch, J. (Eds.).Metabolic Effects of Dietary Fructose. CRC Press; Boca Raton, Florida, pp. 25-40. Cited In: Levi and Werman, 1998.

Hers, H.G. 1952. Fructokinase of the liver. Biochim Biophys Acta 8:416-423. Cited In: Mayes, 1993.

Hers, H.G. 1962. Triokinase. In: Colowick, S.P.; Kaplan, N.O. (Eds.). Preparation and Assay of Enzymes. Academic Press; New York. Methods in enzymology, Vol. 5, pp. 362-364. Cited In: Mayes, 1993.

Holdsworth, C.D.; Dawson, A.M. 1964. The absorption of monosaccharides in man. Clin Sci 27:371-379. Cited In: Riby et al., 1993.

Hyams, J.S.; Etienne, N.L.; Leichtner, A.M.; Theuer, R.C. 1988. Carbohydrate malabsorption following fruit juice ingestion in young children. Pediatrics 82(1):64-68.

Kawai, K.; Okuda, Y.; Chiba, Y.; Yamashita, K. 1986. Palatinose as a potential parenteral nutrient: its metabolic effects and fate after oral and intravenous administration to dogs. J Nutr Sci Vitaminol 32:297-306.

Kawai, K.; Okuda, Y.; Yamashita, K. 1985. Changes in blood glucose and insulin after an oral palatinose administration in normal s ubjects. Endocrino l Jpn 32(6):933-936.

Kawai, K.; Yoshikawa, H.; Murayama, Y.; Okuda, Y.; Yamashita, K. 1989. Usefulness of palatinose as a caloric sweetener for diabetic patients. Horm Metab Res 21:338-340.

Levi, B.; Werman, M.J. 1998. Long-term fructose consumption accelerates glycation and several age-related variables in male rats. J Nutr 128(9):1442-1449.

Liao, Z.-H.; Li, Y.-B.; Yao, B.; Fan, H.-D.; Hu, G.-L.; Weng, J.-P. 2001. The effects of isomaltulose on blood glucose and lipids for diabetic subjects. Diabetes 50(Suppl. 2):A366 [Abstract No. 1530-P].

Lifshitz, F.; Ament, M.E.; Kleinman, R.E.; Klish, W.; Lebenthal, E.; Perman, J.; Udall, J.N. (Jr.). 1992. Role of juice carbohydrate malabsorption in chronic nonspecific diarrhea in children. J Pedi atr 120(5):825-829.

Lina, B.A.R.; Jonker, D.; Kozianowski, G. 2002. Isomaltulose (Palatinose® ): A review of biological and toxicological studies. Food Chem Toxicol 40(10):1375-1381.

MacDonald, I.; Daniel, J.W. 1983. The bioavailability of isomaltulose in man and rat. Nutr Rep Int 28(5):1083-1090.

Mayes, P.A. 1993. Intermediary metabolism of fructose. Am J Clin Nutr 58(5, Suppl.):754S-765S.

Mayes, P.A.; Laker, M.E. 1986. Effects of acute and long-term fructose administration on liver lipid metabolism. In: Macdonald, I.; Vrana, A. (Eds.). Metabolic Effects of Dietary Carbohydrates. Progress in Biochemical Pharmacology, Vol. 21, pp. 33-58. Cited In: Mayes, 1993.

Okuda, Y.; Kawai, K.; Chiba, Y.; Koide, Y.; Yamashita, K. 1986. Effects of parenteral palatinose on glucose metabolism in normal and streptozotocin diabetic rats.Horm Metab Res 18:361-364.

Porter MC , Kuijpers MH, Mercer GD, Hartnagel RE Jr, Koeter HB (1991).Safety evaluation of Protaminobacter rubrum: Intravenous pathogenicity and toxigenicity study in rabbits and mice. Food Chem Toxicol 29(10):685-688.

Riby, J.E.; Fujisawa, T.; Kretchmer, N. 1993. Fructose absorption. Am J Clin Nutr 58(5, Suppl.):748S-753S.

Rugg-Gunn, 1991. Sugarless – The Way Forward: Proceedings of an International Symposium Held at the University of Newcastle at Tyne, U. K., September 1990. ISBN-10 / 13 :1851665986 / 9781851665983. Publisher: Elsevier Applied Science

Rumessen, J.J.; Gudmand-Høyer, E. 1986. Absorption capacity of fructose in healthy adults. Comparison with sucrose and its constituent monosaccharides. Gut 27(10):1161-1168.

Rumessen, J.J.; Gudmand-Høyer, E. 1988. Functional bowel disease: malabsorption and abdominal distress after ingestion of fructose, sorbitol, and fructose-sorbitol mixtures. Gastroenterology 95(3):694-700.

Smith, M.M.; Davis, M.; Chasalow, F.I.; Lifshitz , F. 1995. Carbohydrate absorption from fruit juice in young children. Pediatrics 95(3):340-344.

Takazoe, I. 1985. New trends on sweeteners in Japan. Int Dent J 35(2):58-65.

Tsuji, Y.; Yamada, K.; Hosoya, N.; Moriuchi, S. 1986. Digestion and absorption of sugars and sugar substitutes in rat small intestine. J Nutr Sci Vitaminol 32:93-100.

Ugolev, A.M.; Zaripov, B.Z.; Iezuitova, N.N.; Gruzdkov, A.A.; Rybin, I.S.; Voloshenovich, M.I.; Nikitina, A.A.; Punin, M.Yu.; Tokgaev, N.T. 1986. A revision of current data and views on membrane hydrolysis and transport in the mammalian small intestine based on a comparison of techniques of chronic and acute experiments: experimental re-investigation and critical review. Comp Biochem Physiol A 85(4):593-612. Cited In: Riby et al ., 1993.

Van den Berghe, G. 1978. Metabolic effects of fructose in the liver. Curr Top Cell Regul 13:97-135. Cited In: Mayes, 1993.

Van den Berghe, G. 1986. Fructose metabolism and short-term effects on carbohydrate and purine metabolism pathway. In: Macdonald, I.; Vrana, A. (E ds.). Metabolic Effects of Dietary Carbohydrates. Progress in Biochemical Pharmacology, Vol. 21, pp. 1-32. Cited In : Levi and Werman, 1998.

van Weerden, I.E.R.; Huisman, L.J.; Leeuwen, P. 1983.Digestion Processes of Palatinose® and Saccharose in the Small and Large Intestine of the Pig. ILOB-Report 320, June 20, 1983. Cited In: Irwin and Sträter, 1991.

Würsch, P. 1991. Metabolism and tolerance of sugarless sweeteners. In: Rugg-Gunn, A.J.(Ed.). Sugarless: The Way Forward. Else vier Applied Science; New York, pp. 32-51.

Yamada, K.; Shinohara, H.; Hosoya, N. 1985. Hydrolysis of 1-O-α-D-glucopyranosyl-D-fructofuranose (Trehalulose) by rat intestinal surcrase-isomaltase complex. Nutrition Reports International 32 (5): 1211 - 1220

Ziesenitz, S.C. 1986. Carbohydrasen aus jejunalmucosa des Menschen = [Carbohydrases from the human jejunal mucosa]. Z Ernährungswiss 25(4):253-258. Cited In: Würsch, 1991.