Reaction products of sodium glucoheptonate with manganese sulfate and sodium hydroxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable well documented peer-reviewed reports.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

2004

Reference 2

Reference Type:

publication

Title:

Glucono-Delta-Lactone and the Calcium, Magnesium, Potassium and Sodium salts of Gluconic acids.

Author:

WHO

Year:

1999

Bibliographic source:

World Health Organization, Geneva, 1999. IPCS - International Programme on Chemical Safety (vaialble via: http://www.inchem.org/documents/jecfa/jecmono/v042je12.htm; 2015-07-16).

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Summary of acute toxicity data in animals.

GLP compliance:

not specified

Test type:

other: Summary of acute toxicity data in animals.

Test material

Test material information

Constituent 1

Reference substance name:

Gluconic acid and its derivatives

IUPAC Name:

Gluconic acid and its derivatives

Details on test material:

Sodium Gluconate, CAS 527-07-1
Potassium Gluconate, CAS 299-27-4

Purity (%) of :

Sodium gluconate: 98-102%

Potassium gluconate: 97-103%

Test animals

Species:

other: rats and dogs

Strain:

other: rats: Sprague Dawley; dogs: no data

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Concentration in vehicle:
- Amount of vehicle (if gavage):
- Justification for choice of vehicle:
- Lot/batch no. (if required):
- Purity:

MAXIMUM DOSE VOLUME APPLIED:

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:

Doses:

Rats: 500, 1000, 2000 mg/kg bw (Mochizuki, 1995) and 3000, 3600, 4320, 5190, 6210 mg/kg bw (TNO, 1978);
Dogs: 1000 and 2000 mg/kg bw (Okamoto, 1995).

No. of animals per sex per dose:

Rats: 5 sex/dose;
Dogs: no data

Details on study design:

Rats:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on days 1, 2, 3, 7, 10, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, and gross pathological changes in brain, pituitary, thyroid, salivary gland, thymus, heart, lung, liver, spleen, kidney, adrenals, stomach, small and large intestine, pancreas, gonads, urinary bladder, and lymph nodes.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks:

sodium gluconate

Remarks on result:

other: for rats and dogs (Mochizuki, 1995; Okamoto, 1995).

Effect levels 2

Sex:

not specified

Dose descriptor:

LD50

Effect level:

6 060 mg/kg bw

Based on:

test mat.

Remarks:

potassium gluconate

Remarks on result:

other: for rats (TNO, 1978)

Mortality:

No mortality was observed (Mochizuki, 1995; Okamoto, 1995). One animal died in the 5190 mg/kg bw group and four animals in the 6210 mg/kg bw group. Deaths occurred between 5 and 21 hours after treatment. Survivors recovered gradually (TNO, 1978).

Clinical signs:

other: Soft faeces and diarrhoea, seen in one male and three females at 2000 mg/kg bw, were the only clinical effects observed 2-3 h after treatment (Mochizuki, 1995).

Gross pathology:

No gross abnormalities were observed at necropsy (Mochizuki, 1995).

Other findings:

The minimum lethal dose was > 2000 mg/kg bw, although a transient, initial laxative effect was observed in rats at doses > 1000 mg/kg bw (Mochizuki, 1995).

Any other information on results incl. tables

Data on acute oral toxicity for sodium gluconate in rat (Mochizuki, M, Bozo Research Center 1995) (doses: 500, 1000, 2000 mg/kg) and dog (Okamoto M., 1995) (doses: 1000 and 2000 mg/kg) fed by gavage showed no death at any dose, hence the minimum lethal dose was estimated > 2000 mg/kg for both species.

Rats were fed by gavage 3000, 3600, 4320, 5190, 6210 mg/kg bw (30% (w/v) aqueous solution) potassium gluconate and were observed for signs of toxicity during a 14-day period. One animal died in the 5190 mg/kg bw group and four animals in the 6210 mg/kg bw group. Deaths occurred between 5 and 21 hours after treatment. Survivors recovered gradually. The LD50 was calculated (according to the method of Weil) to be 6060 mg/kg bw. However, the effects that were observed occurred at doses that exceed the accepted limit dose of 5000 mg/kg bw and the LD₅₀ may be related to high dosing (TNO, 1978). No relevant oral toxicity data were found in the literature for the other substances of the category. Conclusion Studies with sodium gluconate in the rat and dog report LD₅₀ values > 2000 mg/kg bw for both species. A gavage study with potassium gluconate and rats reported an LD₅₀ of 6060 mg/kg bw.

Applicant's summary and conclusion

Conclusions:

Oral LD50 > 2000 mg/kg bw was established for rats and dogs for gluconates.

Executive summary:

Data on acute oral toxicity for sodium gluconate in rat (doses: 500, 1000, 2000 mg/kg) and dog (doses: 1000 and 2000 mg/kg) fed by gavage showed no death at any dose, hence the minimum lethal dose was estimated > 2000 mg/kg for both species.

Rats were fed by gavage 3000, 3600, 4320, 5190, 6210 mg/kg bw (30% (w/v) aqueous solution) potassium gluconate and were observed for signs of toxicity during a 14-day period. One animal died in the 5190 mg/kg bw group and four animals in the 6210 mg/kg bw group. Deaths occurred between 5 and 21 hours after treatment. Survivors recovered gradually. The LD50 was calculated (according to the method of Weil) to be 6060 mg/kg bw. However, the effects that were observed occurred at doses that exceed the accepted limit dose of 5000 mg/kg bw and the LD50 may be related to high dosing (TNO, 1978). No relevant oral toxicity data were found in the literature for the other substances of the category. In conclusion, the studies with sodium gluconate in the rat and dog report LD50 values > 2000 mg/kg bw for both species. A gavage study with potassium gluconate and rats reported an LD50 of 6060 mg/kg bw.