Reaction mass of 1-O-α-D-glucopyranosyl-D-mannitol and 6-O-α-D-glucopyranosyl-D-glucitol

Endpoint summary

Additional information

No experimental data on toxicity of Isomalt towards terrestrial organisms are available. In general, based on the molecular structure of the constituents of Isomalt, and their natural occurrence and role in common metabolic pathways, toxic effects on terrestrial organisms are not expected.

One QSAR result available for earthworms did not indicate any toxicity of the substance towards terrestrial macroorganisms (LC50 (14 d) = 3932.315 mg/L). Both disaccharides are not fully compliant with the applicability domain of the model (see details in the attached QSAR reports). However, the result is used in a weight of evidence approach, in accordance to the REACh Regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2.

Isomalt belongs to the group of polyols and is a mixture of hydrogenated mono- and disaccharides whose principal components are both the disaccharides 1-O-α-D-glucopyranosyl-D-mannitol (1,1-GPM) and 6-O-α-D-glucopyranosyl-D-glucitol (=6-O-α-D-glucopyranosyl-D-sorbitol) (1,6-GPS). These disaccharides are composed of a pyranose, i.e. a six membered ring with 5 carbon atoms and one oxygen atom, connected to glucitol (also known as sorbitol) or to mannitol. Glucitol and mannitol are sugar alcohols that are isomers of each other. Isomalt is manufactured in a two-stage process in which sucrose is first transformed into Isomaltulose, a reducing disaccharide (6-O-α-D-glucopyranosyl-D-fructose). The Isomaltulose is then hydrogenated to yield Isomalt, using a nickel catalyst.

Complete hydrolysis of Isomalt yields glucose, sorbitol, and mannitol (2:1:1) (JECFA, 1985). Glucose is a common monosaccharide that feeds into glycolysis. Glycolysis is a well described metabolic pathway used by virtually all cells, both eukaryotic and prokaryotic, to produce energy in form of ATP. Mannitol is known to be metabolically inert in humans and occurs naturally, as a sugar or sugar alcohol, in fruits and vegetables. It is rapidly excreted in the urine. Sorbitol also occurs naturally in fruits and will either be excreted in the urine by the kidneys, or metabolized to carbon dioxide and dextrose, the latter of which will feed into glycolysis again (Wishart et al., 2018). The monosacharides are metabolized following the classical route (Lina, Jonker and Kozianowski, 2002; and references therein).

Moreover, based on a ready biodegradability study available for Isomaltulose (=6-O-alpha-D-glucopyranosyl-D-fructose), used as source substance in a read-across approach as detailed in the analogue justification attached to IUCLID section 13, and QSAR calculations done for both of the main components, i.e. 1-O-α-D-glucopyranosyl-D-mannitol (1,1-GPM) and 6-O-α-D-glucopyranosyl-D-glucitol (=6-O-α-D-glucopyranosyl-D-sorbitol) (1,6-GPS), Isomalt is expected to be rapidly degraded in the environment. Therefore long-term exposure is generally not expected.

Glucose, D-glucitol, and D-mannitol are included in Annex IV of Regulation (EC) No 1907/2006, as sufficient information is known about these substances, and they are considered to cause minimum risk because of their intrinsic properties.

All environmental toxicity data and evidence available (QSAR results, read across, literature data and OECD QSAR Toolbox profiling) for Isomalt indicate that there is no toxicity at all and consequently the substance is not classified for any hazard. Isomalt is widely used as a food additive. It is produced in compliance with applicable German and European Food Law (e.g. Regulation (EC) No 178/2002, Regulation (EC) No 852/2004) as well as international quality standards including ISO 9001 and IFS Food. The specifications cover the requirements for Isomalt of Codex Alimentarius, Food Chemicals Codex (FCC) and Regulation (EU) No 231/2012. The product is an evaluated and as safe classified food additive (E953). By the responsible “Joint Expert Committee on Food Additives” (JECFA, an advisory body of WHO/FAO) an ADI (acceptable daily intake for man) for ISOMALT was not established (ADI: “not specified”). ADI „not specified“ means that, on the basis of the available data (chemical, biochemical, toxicological, and other) the intake of the substance arising from its use (at the levels necessary to achieve the desired effect) does not represent a hazard to health.

In conclusion, with all the information available as detailed above, and for reasons of animal welfare, testing with terrestrial organisms is not considered justified.

References:

JECFA (1985) Isomalt. International Programme on Chemical Safety, World Health Organization. Toxicological Evaluation of Certain Food Additives and Contaminants. Who Food Additives Series 20. WHO, Geneva.

Wishart, D.S. et al. (2018) DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Research, 46: D1074–D1082, doi: 10.1093/nar/gkx1037.https://www.drugbank.ca/drugs/DB00742accessed for Mannitol,https://www.drugbank.ca/drugs/DB01638accessed for Sorbitol