Registration Dossier

Administrative data

Description of key information

Information on the acute oral toxicity of D-glucono-1,5-Lactone was obtained from data on read across substance, potassium gluconate. Potassium gluconate is associated with low acute toxicity in rats following oral administration. The reported oral LD50 of potassium gluconate was 6060 mg/kg body weight in male and female Wistar rats in a study performed to test guidelines (Spanjers and Til, 1978). Transient clinical signs included sluggishness, humpback behavior, and severe diarrhea and 7 animals died at the high dose level between 5 and 21 hours after administration of the test article. There were no macroscopic findings at necropsy. 
Information on the acute dermal toxicity effects of D-glucono-1,5-Lactone was obtained from data on the read across substance, gluconic acid. Gluconic acid is associated with low acute toxicity following dermal administration in rats. The dermal LD50 value for gluconic acid was determined to be greater than 2000 mg/kg body weight in rats in a study performed according to test guidelines and good laboratory practice (Mortier, 2009). There were no mortalities, adverse clinical effects, body weight effects, dermal reactions, or adverse findings in organ or tissue at necropsy.
In accordance with column 2 of REACH Annex VIII, the acute toxicity by inhalation study (required in section 8.5.2) does not need to be conducted as acute toxicity studies are available for the oral and dermal routes of exposure.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
6 060 mg/kg bw

Additional information

Acute Toxicity: Oral

Information on the acute oral toxicity of D-glucono-1,5-Lactone was obtained from data on the read across substance, potassium gluconate.

The potential acute oral toxicity of potassium gluconate was assessed in Wistar rats in accordance with OECD Guidelines for the Testing of Chemicals No. 401 (Spanjers and Til, 1978). Groups of 5 male and 5 female rats were administered 3000, 3600, 4320, 5190, or 6210 mg/kg body weight of potassium gluconate in water (vehicle) by gavage. Animals were observed for clinical signs of toxicity for 14 days and macroscopic examination of the survivors at autopsy was performed. Within a few hours of dosing, sluggishness, humpback behavior, and severe diarrhea was reported. Two and 7 animals died in the 5109 and 6210 mg/kg body weight groups, respectively, between 5 and 21 hours after treatment. Afterwards, the survivors recovered gradually and appeared healthy again at the end of the observation period. Macroscopic examination of the survivors did not reveal any test article-related gross alterations. Based on mortality figures, the LD50 in male and female rats was calculated to be 6060 mg/kg body weight with 95% confidence intervals of 5640 to 6510 mg/kg body weight. Potassium gluconate was not classified as acutely toxic according to CLP.

Acute Toxicity: Dermal

Information on the acute dermal toxicity of D-glucono-1,5-Lactone was obtained data from the read across substance, gluconic acid.

The potential acute dermal toxicity of gluconic acid was assessed in Sprague-Dawley rats in accordance with OECD Guidelines for the Testing of Chemicals No. 402 and Good Laboratory Practice (Mortier, 2009). Five male and 5 female rats were administered 2000 mg/kg body weight of the undiluted test article with a semiocclusive wrapping to the dorsal part of the rat for 24 hours. The animals were examined clinically before treatment, twice on the day of application, and daily for the following 14 days. In addition, skin lesion evaluation was performed once daily. Body weights were recorded on Days 1, 7, 14, and 15. All surviving animals underwent necropsy at the end of the observation period. No mortalities, no clinical signs of toxicity, and no dermal reactions were observed. Mean body weight gain in treated animals was normal when compared with historical data. No organ or tissue findings were seen at necropsy. The acute dermal LD50 of the undiluted test material in rats was greater than 2000 mg/kg body weight. Gluconic acid was not classified as acutely toxic according to CLP.

Acute Toxicity: Inhalation

In accordance with column 2 of REACH Annex VIII, the acute toxicity by inhalation study (required in section 8.5.2) does not need to be conducted as acute toxicity studies are available for the oral and dermal routes of exposure.

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.

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.