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Short description of key information on bioaccumulation potential result: 
Tharandt et al. (1979) evaluated the absorption, distribution, metabolism, and excretion of D-glucono-δ-lactone and sodium-D-gluconate in a series of experiments conducted in Wistar rats. The compound D-glucono-δ-lactone was shown to be rapidly absorbed, utilized in the pentose phosphate pathway, and incorporated into liver glycogen. The intestinal absorption of D-glucono-δ-lactone and of sodium-D-gluconate was rapid following oral administration with a higher degree of absorption reported for the lactone. Following the oral administration of D-glucono-δ-lactone and sodium-D-gluconate, excretion occurred via the feces, urine, and expired air. The volume of distribution was determined to be 50.55 and 40.97% of the total body weight for D-glucono-δ-lactone and sodium-D-gluconate, respectively. Based on the results of this study, the bioaccumulation potential of D-glucono-δ-lactone and sodium-D-gluconate cannot be determined.

Key value for chemical safety assessment

Additional information

Gluconic acid and salts of gluconic acid (e.g., calcium, magnesium, and sodium) are freely ionisable in aqueous solution, and may thus be assessed on the basis of data on the gluconate anion [9]. Gluconate also may be derived from D-glucono-δ-lactone (the cyclic ester of gluconic acid), considering that this compound forms an equilibrium mixture with lactone and gluconic acid in aqueous solution. Additionally, since gluconate and its various salts, D-glucono-δ-lactone, and gluconic acid all exist in equilibrium in aqueous solution, each compound may be used as a surrogate for another when data availability is limited.


The high water solubility of D-glucono-δ-lactone and its existence in aqueous solution primarily as the gluconate anion (between pH 4 and 9) suggests that the compound would be poorly absorbed. However, The International Programme on Chemical Safety (IPCS) has noted that gluconate is likely absorbed in its protonated form (i.e., gluconic acid), with which it exists in equilibrium. In addition, specific toxicokinetic data on sodium gluconate and D-glucono-δ-lactone, suggest that D-glucono-δ-lactone would be absorbed from the oral route of exposure both in the intact and hydrolyzed form. The results of the toxicokinetic study indicated that at least 70.5% (intact and hydrolyzed forms) of an orally administered dose of D-glucono-δ-lactone and at least 55.1% of an orally administered dose of (sodium) gluconate is systemically absorbed. Following intravenous administration, the volumes of distribution of D-glucono-δ-lactone and (sodium) gluconate were determined to be approximately 50 and 41% of total body weight, respectively, in both healthy and diabetic rats. Both compounds were absorbed to a greater degree in diabetic than in healthy rats [11]. Upon absorption, gluconate is incorporated into hepatic glycogen, with a greater degree of incorporation obtained from D-glucono-δ-lactone than with sodium gluconate, as demonstrated in fasted male rats. D-glucono-δ-lactone also enters the pentose phosphate pathway in the liver, as demonstrated in fasted healthy and diabetic male rats [11]. Additionally, stabilization of the lactone ring with 20% Tris buffer was shown to increase absorption of intact D-glucono-δ-lactone [7]. The use of gluconate as an energy source is supported by the results of a study by Anon (1973) [11], who demonstrated that growth in rats fed a low-calorie diet and supplemented with D-glucono-δ-lactone was 191 to 213% greater than rats fed a low-calorie diet alone. The bulk of an administered dose of D-glucono-δ-lactone and sodium gluconate is rapidly excreted in feces, urine, and expired air, with the major route of excretion being expired air.


Clinical signs, such as hunching, sluggishness, weight loss, and evidence of gastrointestinal irritation (i.e., local inflammation, diarrhea, and vomiting), were observed following oral administration of potassium gluconate or D-glucono-δ-lactone in acute or repeated-dose toxicity studies in rodents; however, these effects were attributed to local and not systemic effects. Moreover, no gross or histopathological effects were observed in these studies. Therefore, sites of tissue distribution other than the liver could not be concluded based on the results of the oral toxicity studies. No systemic effects were reported in the available reproductive toxicity studies, in which pregnant rats, mice, hamsters, and rabbits were orally exposed to D-glucono-δ-lactone. Therefore, although the toxicokinetic study described above demonstrated that D-glucono-δ-lactone and sodium gluconate are absorbed following oral exposure, whether these compounds cross the placental barrier cannot be deduced from the available reproductive toxicity studies. 


No systemic effects were reported in the available inhalation and dermal toxicity studies. However, the lack of observed systemic effects following inhalation exposure does not preclude the possibility of absorption from these routes of exposure. The high water solubility and small particle size (<100 µm) of D-glucono-δ-lactone dust favour its dissolution in the mucous lining and absorption via the respiratory tract. Thus, the absorption of D-glucono-δ-lactone via the inhalation route of exposure is likely. Alternatively, the high molecular weight (178.14 g/mol) and high water solubility of D-glucono-δ-lactone do not favour its absorption via the dermal route of exposure. Based on the available data, and taking into consideration the high water solubility (and negative log Pow) of D-glucono-δ-lactone at physiological pH, D-glucono-δ-lactone is not expected to bioaccumulate.

Discussion on bioaccumulation potential result:

 In one experiment, D-glucono-δ-lactone (in combination with 20% Tris w/w) was orally administered to fasted healthy male rats at a single dose of 4 g/kg body weight to assess and compare the absorption of the compound and its subsequent incorporation into hepatic glycogen stores. D-glucono-δ-lactone is commonly believed to be metabolized to gluconic acid and lactone, which are intermediates in the oxidation of glucose through the pentose phosphate cycle. Liver samples were excised, and the levels of glycogen metabolites (glucose-6-phosphate and 6-phosphogluconate) were measured in groups of animals 5 hours following administration of D-glucono-δ-lactone. The measured levels of hepatic glucose-6-phosphate and 6-phosphogluconate 5 hours following administration of D-glucono-δ-lactone were 163 and 27 µmol/kg wet weight, respectively, similar to normal (i.e., untreated and fed) animals. Thus, the results of this experiment support the absorption, distribution to the liver, and incorporation into the pentose phosphate pathway of D-glucono-δ-lactone in healthy male rats. Of note, although D-glucono-δ-lactone is readily hydrolyzed to gluconic acid, the addition of 20% Tris buffer stabilized the lactone ring of D-glucono-δ-lactone, thus increasing the absorption of the intact compound. The authors noted that liver glycogen levels were greatest when D-glucono-δ-lactone, which is normally hydrolyzed in aqueous solution, was administered along with a 20% Tris buffer (w/w). 


In a second experiment, radiolabelled D-glucono-δ-lactone and sodium-D-gluconate were orally administered to fasted healthy male rats at single dosages of 0.8 g/kg body weight to compare its absorption, distribution, and excretion. Five hours after administration, radioactivity was measured in the feces and intestines, urine, exhaled carbon dioxide, and whole body (excluding the gastrointestinal tract) of the test animals. Radioactivity was also measured in blood samples. The amounts of radioactivity recovered from exhaled carbon dioxide, the whole body (excluding the gastrointestinal tract), the intestine and feces, and the urine following the administration of radiolabelled D-glucono-δ-lactone represented 25.0, 23.1, 29.5, and 7.0% of the administered dose, respectively. These results indicated that at least 70.5% (i.e., the remaining proportion of the dose after subtracting the amount recovered from the intestine and feces) of the dose of radiolabelled D-glucono-δ-lactone was absorbed following oral administration. The total recovered radioactivity of D-glucono-δ-lactone was reported to be approximately 84.6% of the dose. The radioactivity of sodium-D-gluconate was reported to be 12.1, 19.7, 44.9, and 5.0% from exhaled carbon dioxide, from the whole body (excluding the gastrointestinal tract), intestine and feces, and in the urine, respectively after 5 hours. The total recovered radioactivity of sodium-D-gluconate was reported to be approximately 81.7% of the dose. These results suggested that at least 55.1% of the dose of radiolabelled sodium-D-gluconate was absorbed after oral administration. According to the results observed in the blood, feces, and intestine, the authors reported rapid intestinal absorption following the oral administration of D-glucono-δ-lactone and that D-glucono-δ-lactone was absorbed to a greater degree than sodium D-gluconate.


In a third experiment, a single dose of radiolabelled D-glucono-δ-lactone or sodium-D-gluconate (0.655 μCi) was intravenously injected in healthy male rats to assess the volume of distribution. Five minutes following administration, gluconate and, even more so, D-glucono-δ-lactone were detected in considerable amounts intracellularly (exact amounts and specific tissues assessed not reported). Approximately 0.18 and 0.51% of the applied dose of sodium-D-gluconate and D-glucono-δ-lactone, respectively, was retained in the liver glycogen. The authors determined the volume of distribution of sodium-D-gluconate and D-glucono-δ-lactone to be 40.97 and 50.11% of the total body weight in rats, respectively.