D-mannose

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: U.S. FDA, Redbook 2000: IV.C.2: Acute Oral Toxicity Tests (1993)

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

D-mannose

EC Number:

222-392-4

EC Name:

D-mannose

Cas Number:

3458-28-4

Molecular formula:

C6H12O6

IUPAC Name:

D-mannose

Test material form:

solid: particulate/powder

Details on test material:

Purity: >99%

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approximately 10 weeks old
- Weight at study initiation: ranged from approximately 209.5 to 233.4 g
- Fasting period before study: yes
- Housing: housed individually in solid-bottom caging with bedding and appropriate species-specific enrichment
- Diet: PMI® Nutrition International, LLC Certified Rodent LabDiet® 5002, ad libitum
- Water: ad libitum
- Acclimation period: 6-day quarantine period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-26ºC
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): approximate 12-hour light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- A single oral dose of the test item was suspended in deionized water and adjusted for purity.

Doses:

5000 mg/kg

No. of animals per sex per dose:

5 rats at 5000 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: observed for clinical signs at the beginning of fasting, just before dosing (test day 1), once during the first 30 minutes after dosing and 2 more times on the day of dosing, and once each day thereafter. Clinical observations were inadvertently not recorded on test day 5.
-Frequency of weighing: test days -1, 1, 8, and 15
- Necropsy of survivors performed: yes
- Other examinations performed: no

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:

Remarks:

highest dose tested

Mortality:

No deaths occurred.

Clinical signs:

other: No clinical abnormalities were observed.

Gross pathology:

No gross lesions were present in the rats at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 is greater than 5000 mg/kg.
This study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).

Executive summary:

The test item was administered by oral gavage to five fasted female rats at a dose level of 5000 mg/kg. All rats were observed for mortality, body weight effects, and clinical signs for 14 days after dosing. The rats were necropsied to detect grossly observable evidence of organ or tissue damage.

No incidents of mortality, overall bodyweight losses or clinical abnormalities were observed. No gross lesions were present in the rats at necropsy. Under the conditions of this study, the oral LD50 for the test substance was greater than 5000 mg/kg for female rats.