Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

No skin sensitisation studies were available on D-glucono-1,5-lactone; however, data on the read-across substance, gluconic acid are available. The skin sensitisation potential of gluconic acid was assessed in a GLP-compliant study performed according to OECD Guidelines for the Testing of Chemicals No. 429 (local lymph node assay) (Bradshaw, 2009). In the main study, groups of 4 mice were tested with the undiluted test material or diluted test material at concentrations of 50 or 25% v/v in dimethyl formamide. The mice were treated daily with an application of 25 µL of the appropriate concentration of the test material to the dorsal surface of each ear for three consecutive days. Another group of four mice received the vehicle alone in the same manner. Five days following the first topical application of the test material all mice were injected via the tail vein with 250 µL of phosphate buffered saline containing 3H-methyl thymidine (3HTdR). Five hours following the administration of 3HTdR all mice were killed. A single cell suspension of pooled lymph node cells was prepared by gentle mechanical disaggregation. The incorporation of 3HTdR was counted by beta-scintillation. Since treatment with the test material did not result in at least a 3-fold or greater increase in 3HTdR incorporation compared to control values, the test substance was considered to be non-sensitising under the conditions of the test. In addition, there were no deaths and no signs of systemic toxicity reported, and body weight changes between Day 1 and Day 6 were similar among test and control animals. Therefore, no skin sensitisation potential is expected for D-glucono-1,5-lactone.

 

D-glucono-δ-lactone is a cyclic ester of gluconic acid which, in aqueous solution, forms an equilibrium mixture of the lactone and gluconic acid. Gluconic acid is a somewhat weak carboxylic acid with a dissociation constant of pKa = 3.6. The dissociation of an acid into a proton and an anion is an equilibrium, the reverse of which is the re-association of that same anion with a proton to reform the original acid. The pKa of 3.6 means that, when the ambient pH = 3.6, half the gluconic acid molecules will exist in the form of the uncharged acid, and half as the anion. At pH < 3.6, the undissociated form will predominate, and pH > 3.6 the anion will predominate. Sodium gluconate and potassium gluconate are both 1:1 salts of gluconic acid, which will each dissolve in water to generate separate sodium or potassium cations and gluconate anions. Sodium and potassium are both strong bases, and are therefore expected to remain ionized at essentially any pH, but the gluconate anions deriving from the salts will be subject to the same equilibrium as those deriving from the free acid. To be in equilibrium, both the forward and the backward reaction must possess the same pKa value, so the gluconate anion is predicted to posses the same pKa of 3.6 as the free acid. In this way, gluconic acid in aqueous solution is in equilibrium with its cyclic esters and its anion, according to the pH of the system, and in any system with sufficient buffering capacity, the effects of introducing equimolar amounts of gluconic acid, D-glucono-δ-lactone, sodium gluconate or potassium gluconate would be indistinguishable. Hence these four substances are considered to be appropriate surrogates for each other in sufficiently buffered aqueous systems, such as environmental waters, flora and fauna.


Migrated from Short description of key information:
No skin sensitisation studies were available on D-glucono-1,5-lactone; however, data on the read-across substance, gluconic acid are available. Gluconic acid was reported to be non-sensitising to skin in a local lymph node assay conducted in mice in a GLP-compliant study performed according to test guidelines.

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.