Oxidation products of D-Glucose with nitric acid, sodium salts

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August - September 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Oxidation products of D-Glucose with nitric acid, sodium salts

Molecular formula:

Reaction products consisting mainly of sodium salts of D-glucarate, mono, di and tri carboxylic acids and keto gluconates. See remarks

IUPAC Name:

Oxidation products of D-Glucose with nitric acid, sodium salts

Test material form:

liquid

Specific details on test material used for the study:

Composition: Sodium glucarate (40 - 50%), other Sodium Salts of Sugar Acids (25 - 30%), other ingredients, Impurities (2 – 5%)

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Canada, Saint Constant, Quebec
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 213.1-221.0 g
- Fasting period before study: overnight
- Housing: individual
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 16 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): minimum 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The animals were dosed at 5000 mg/kg (7.51 mL/kg by volume of the test item). The individual doses of the test item were individually calculated for each animal based on the body weight of the animal. All doses were administered orally using a feeding cannula inserted into the stomach of the animals.

Doses:

5000 mg/kg ba

No. of animals per sex per dose:

3 females

Control animals:

no

Details on study design:

The animals were individually observed during the first 30 minutes after dosing and periodically during the first 24 hours following dosing (with special attention given during the first 4 hours). Observations once daily were carried out for the remainder of the study. The animals were observed for 14 days after the dosing. Cage side observations were directed towards any changes in the skin and fur; eyes and mucous membranes; respiratory, circulatory, autonomic and central nervous system; and also somatomotor activity and behaviour pattern. Particular attention was directed to any observation of tremors, convulsions, and salivation. The body weights of the animals were determined prior to test item administration (i.e., Day 1), on Day 8 and on Day 15. Body weight gains were calculated. Gross necropsy was performed on each rat that was sacrificed at the end of the 14-day observation period. Necropsy included an examination of: external surfaces of the body; all orifices; cranial cavity; external surfaces of the brain and spinal cord; nasal cavity and paranasal sinuses; thoracic, abdominal and pelvic cavities and viscera.

Statistics:

Not required

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths occurred at the limit dose of 5000 mg/kg bw

Mortality:

No mortalities were observed post dosing and throughout the 14-day observation period.

Clinical signs:

All animals appeared normal after dosing and throughout the 14-day observation period.

Body weight:

All animals gained body weight by Day 8 and at the end of the study.

Gross pathology:

Gross necropsy of all animals sacrificed at the end of the 14-day observation period revealed no abnormal findings.

Any other information on results incl. tables

No effects of treatmnet were observed in this study at the limit dose of 5000 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The acute oral LD50 in rats of D-Glucose, reaction products with Nitric Acid and Sodium Nitrite (1:1), Sodium Salts was found to be >5000 mg/kg bw under the condtions of this study. The substance is therefore classified in Category 5 for acute oral toxicity according to the GHS criteria, and does not require classification for acute oral toxicity according to the CLP Regulation.

Executive summary:

The acute oral toxicity of [D-Glucose, reaction products with Nitric Acid and Sodium Nitrite (1:1), Sodium Salts] was investigated in an OECD 423 and GLP-compliant study. Three female Crl:CD(SD)BR rats were gavaged with the undiluted test material at a dose level of 5000 mg/kg bw and observed for 14 days. No deaths occurred and no signs of toxicity were observed. All animals gained weight over the study period. Gross necropsy did not reveal any effects of treatment. The acute oral LD50 was therefore found to be >5000 mg/kg bw under the conditions of this study. The substance is therefore classified in Category 5 for acute oral toxicity according to the GHS criteria, and does not require classification for acute oral toxicity according to the CLP Regulation.