Registration Dossier

Administrative data

Description of key information

No skin irritation or eye irritation studies were available on D-glucono-1,5-lactone; however, data on the read-across substance, gluconic acid are available. A skin irritation study on gluconic acid in rabbits, performed according to test guidelines and in compliance with GLP, has demonstrated that the test compound is not a skin irritant. An eye irritation study on gluconic acid in rabbits,  performed according to test guidelines and in compliance with GLP, has demonstrated that the test compound is not an eye irritant. Therefore, no skin irritation or eye irritation potential is expected for D-glucono-1,5-lactone.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

No skin irritation or eye irritation studies were available on D-glucono-1,5-lactone; however, data on the read-across substance, gluconic acid are available.

Skin Irritation/Corrosion

The skin irritation potential of gluconic acid was assessed in rabbits in a GLP-compliant study performed according to OECD Guidelines for the Testing of Chemicals No. 404 (Mortier, 2009). In this study, New Zealand White rabbits were exposed to 0.5 mL of undiluted gluconic acid on the clipped dorsal under semi-occlusive conditions. The adjacent non-treated areas served as controls. Gluconic acid was applied to one rabbit three times successively for a period of three minutes, one hour, and four hours, respectively, followed by the single application of gluconic acid to two additional animals for a period of 4 hours. Any cutaneous lesions were evaluated at approximately 1, 24, 48, and 72 hours after removal of the dressing. Skin reactions were scored according to a prescribed numerical system. No erythema or edema were observed in any animals tested throughout the observation period. Under the experimental conditions adopted, gluconic acid was reported to be non-irritant for the skin of the rabbit. Gluconic acid is not classified as a skin irritant according to CLP (EC 1272/2008).

 

Eye Irritation

 

An eye irritation study on gluconic acid has been performed in accordance with OECD Guidelines for the Testing of Chemicals No. 405 and in compliance with GLP (Mortier, 2009). In this study, 0.1 mL of undiluted gluconic acid was instilled into the eye lids of each of 3 New Zealand White rabbits. Ocular changes were assessed and recorded immediately at 1, 24, 48, and 72 hours after treatment. Scoring was performed according to guideline methods. Signs of irritation persisted in one animal and observations up to Day 8 were recorded. No observations indicative of systemic toxicity or ill health were noted for any rabbit during the course of this study. One hour after instillation, all animals had slight to moderate chemosis and moderate to severe redness of the conjunctivae. Two animals also had lacrimation, lesions of iris, and one of them had corneal lesions. Twenty-four hours after instillation, one animal had severe chemosis with lacrimation and severe redness of the conjunctivae, lesions of iris, and cornea. The two other animals had slight chemosis and slight redness of conjunctivae, and one of them also had lacrimation and lesions of the iris. Forty-eight hours after instillation, only one animal had signs (severe chemosis with lacrimation and severe redness of the conjunctivae, lesions of iris, and of the cornea). Seventy-two hours after instillation, only slight chemosis and slight redness of the conjunctivae persisted in one animal. No ocular lesion persisted in any animal at the end of the exposure period (i.e., reversibility by 72 hours for two animals and by Day 8 for one animal). Based on the results, gluconic acid was found to be slightly irritating to rabbit eyes. Gluconic acid is not classified as an eye irritant according to CLP (EC 1272/2008).

 

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.


Effects on eye irritation: slightly irritating

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.