Registration Dossier

Toxicological information

Carcinogenicity

Currently viewing:

Administrative data

Description of key information

Considering that gluconate is an endogenously occurring compound that is utilized by the body in a normal physiological process, studies addressing the mutagenicity/genotoxicity of gluconate are not deemed necessary as it is expected that the compound is not carcinogenic.

Key value for chemical safety assessment

Additional information

In accordance with section 1 of REACH (REGULATION (EC) No 1907/2006) Annex XI, the carcinogenicity study (required in section 8.9.1) does not need to be conducted as there is sufficient weight of evidence from several independent sources of information leading to the conclusion that the substance is not carcinogenic.

Gluconate is an oxidative metabolite of glucose best known to occur in microorganisms, but also occurring in mammals (Rezzi, et al., 2009). Glucose is oxidized to gluconate by glucose 1-dehydrogenase, which occurs in mammalian tissues (Harrison, 1932). Gluconate enters the pentose phosphate pathway via conversion to 6-phosphogluconate, a metabolic route of glucose catabolism. The formation of 6-phosphogluconate from exogenous gluconate has been demonstrated in mammals, demonstrating mammalian enzymatic capabilities for metabolizing gluconate (Leder, 1957; Hakim & Moss, 1974). Gluconokinase is the enzyme responsible for catalyzing the phosphorylation of gluconate to 6-phosphogluconate and has been identified in mammalian tissues, such as the brain and kidneys (Hakim & Moss, 1974). Thus, gluconate occurs endogenously from the oxidative metabolism of glucose and is utilized in a well-known biochemical pathway (the pentose phosphate pathway) of glucose catabolsim via the action of gluconokinase. Considering that gluconate is an endogenously occurring compound that is utilized by the body in a normal physiological process, studies addressing the mutagenicity/genotoxicity of gluconate are not deemed necessary as it is expected that the compound is not carcinogenic.

Finally, D-gluconic acid (E 574) / D-glucono-1,5 lactone (E 575) are permitted food additives under European Union law and can be used without restrictions according to the ‘quantum satis’ principle according to Commission Regulation 1129/2011 amending Annex II to Regulation 1333/2008 by establishing a Union list of food additives. Commission Regulation 231/2012 laying down specifications for food additives listed in Annexes II and III to Regulation 1333/2008 sets out the purity criteria to be respected.  The substance(s) have in the past been assessed for their safety by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 1999http://www.inchem.org/documents/jecfa/jecmono/v042je12.htmand found as safe.  The ADI (Acceptable Daily Intake) was set as ‘not specified’

Reference List:

Hakim, A. & Moss, G., 1974. The effect of ether anesthesia on cerebral glucose metabolism - The pentose phosphate pathway. Anesthesiology, 34(3), pp. 261-267.

Harrison, D., 1932. The product of the oxidation of glucose by glucose dehydrogenase. Biochem J, 26(4), pp. 1295-1299.

Leder, I., 1957. Hog kidney gluconokinase. J Biol chem, Volume 255, pp. 125-136.

Rezzi, S. et al., 2009. Metabolic shifts due to long-term caloric restrion revealed in nonhuman primates. Exp Gerontol, 44(5), pp. 356-372.

Justification for classification or non-classification

The substance does not meet the criteria for classification and labelling for this endpoint, as set out in Regulation (EC) NO. 1272/2008.