4-O-β-D-galactopyranosyl-D-glucitol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Reference 2

Reference Type:

other: Published secondary source

Title:

Lactitol

Author:

WHO/FAO

Year:

1983

Bibliographic source:

WHO/FAO: Expert Committee on Food Additives Summary of Toxicological Data of Certain Food Additives Series 18 (http://www.inchem.org/documents/jecfa/jecmono/v18je10.htm)

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

only 2 rabbits/sex/dose; abraded and non-abraded skin

GLP compliance:

not specified

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

4-O-β-D-galactopyranosyl-D-glucitol

EC Number:

209-566-5

EC Name:

4-O-β-D-galactopyranosyl-D-glucitol

Cas Number:

585-86-4

Molecular formula:

C12H24O11

IUPAC Name:

4-O-beta-D-galactopyranosyl-D-glucitol

Specific details on test material used for the study:

di-saccharide alcohol lactitol (4-B-D-galactopyranosyl­D-sorbitol)

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.34 to 2.86 kg
- Housing: individually caged
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): approx. 18°C

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- % coverage: 10%
- Type of wrap if used: The treated area was covered with a thin layer of cellulose sheet and wrapped in polyethylene foil.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the test substance was removed from the skin with water and the animals were wiped dry with towels
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): All dose levels were applied in the same volume of 9 ml/kg body weight by appropriate dissolving in water

Part of the trunk of the animals was freed from hair the day before the start of the experiment using electric clippers. Half the number of animals received the material on the intact skin, the other half on the abraded skin.

Duration of exposure:

24 hours

Doses:

0.0, 1.5, 3.0 and 4.5 g/kg body weight

No. of animals per sex per dose:

2/sex/dose

Control animals:

yes

Details on study design:

Duration of observation period following administration: 2 weeks
- Frequency of observations and weighing: Body weights were recorded on day 0 and at the end of weeks 1 and 2. Food and water consumption was recorded weekly. Clinical signs and local skin reactions were recorded.
- Necropsy of survivors performed: yes
- Other examinations performed: haematological endpoints (Hb, PCV, RBC, and WBC) and histopathological endpoints (liver, kidney, spleen, treated and untreated skin)

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 4 500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: highest dose tested

Mortality:

In the course of the subsequent observation period one female rabbit of the 3.0 g/kg group died on day 3. The animal that died at day 3 of the study showed signs of peritonitis and pericarditis, which probably caused the death of this animal.

Clinical signs:

other: None observed

Gross pathology:

At autopsy, no gross lesions were found that could be related to treatment. At microscopic examination, no treatment-related changes were seen

Other findings:

Dermal effects included slight scaliness at 1.5 and 3.0 g/kg. No dermal effects were observed at 4.5 g/kg.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test substance is > 4.5 g/kg.

Executive summary:

Lactitol was examined for its acute dermal toxicity in an experiment with albino rabbits. Lactitol was applied at dose levels of 0.0 (control), 1.5, 3.0 and 4.5 g/kg body weight. All dose levels were applied in the same volume of 9 ml/kg body weight by appropriate dissolving in water. Half the number of animals received the material on the intact skin, the other half on the abraded skin. The treated area was covered with a thin layer of cellulose sheet and wrapped in polyethylene foil. After an exposure time of 24 hours the test substance was removed from the skin with water and the animals were wiped dry with towels. Subsequently they were caged individually in a room of constant temperature and provided ad libitum with the standard laboratory diet and tap water. The rabbits were observed for two weeks with regard to general appearance and behaviour, mortality, local skin reactions, growth, food and water intake. At the end of the two-week period, examinations were carried out for possible changes in blood composition and macroscopic appearance of several organs. Samples of the liver, kidneys, spleen, treated and untreated skin were collected for histological examination. Dermal application of lactitol caused slight skin reactions at 1.5 g/kg, and 3.0 g/kg and no skin reactions at 4.5 g/kg. Growth, food and water intake, and haematology were not affected by lactitol. Gross and microscopic examination conducted terminally did not reveal any treatment-related changes. The dermal LD50 of lactitol was found to be higher than 4.5 g/kg body weight.