1,4:3,6-dianhydro-2,5-di-O-methyl-D-glucitol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Only limited information regarding the animal environmental conditions is available. Test animals were observed for 7 days post-application, which is a deviation from the OECD guideline.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1957

Report date:

1957

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Animals were observed for clinical signs and mortality for only 7 days post-application.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,4:3,6-dianhydro-2,5-di-O-methyl-D-glucitol

EC Number:

226-159-8

EC Name:

1,4:3,6-dianhydro-2,5-di-O-methyl-D-glucitol

Cas Number:

5306-85-4

Molecular formula:

C8H14O4

IUPAC Name:

1,4:3,6-dianhydro-2,5-di-O-methyl-D-glucitol

Test material form:

other: liquid

Test animals

Species:

rat

Strain:

other: Albino (Holtzman strain)

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 104 – 120 g
- Fasting period before study: 3 - 4 h prior to dosing
- Housing: Animals were housed by groups in metal cages suspended above the droppings.
- Diet: ad libitum
- Water: ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10 and 100% (v/v)

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

1.47, 2.15, 3.16, 4.61, 6.81 and 10 mL/kg b.w.

No. of animals per sex per dose:

5 (males)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Animals were observed closely for gross signs of systemic toxicity at frequent intervals during the day of administration of the test material and daily thereafter for a period of seven days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Statistical analysis of the mortality data done by the moving average method (Horn, 1956).

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LD50

Effect level:

5.63 mL/kg bw

Based on:

test mat.

Remarks on result:

other: All animals dosed with 6.81 and 10.0 mL/kg bw of the test material died within 2 days and 4 h post-application.

Mortality:

Animals died 1 hour (1/5), 4 hours (3/5) and 48 hours (1/5) post-administration with 6.81 mL/kg bw of the test material. Mortality of animals treated with the highest dose level of 10 mL/kg bw occurred 1 hour (3/5) and 4 hours (2/5) post-administration of the test material.

Clinical signs:

other: Within 5 – 10 min following oral administration of the test material the animals at each dose level tested appeared depressed and showed lacrimation, labored respiration, tachycardia and ataxia. During the reminder of the day the animals at the lowest dos

Gross pathology:

Gross pathology performed upon the animals that died showed hyperemic and inflated lungs, slight irritation of the small intestine, and congested kidneys and adrenals. In addition, the blood appeared to have a thin consistency and did not clot readily. A gross autopsy of the surviving animals revealed no gross pathological findings.

Any other information on results incl. tables

Table 1: Mortality

Dose [mL/kg bw]

Concentration of solution [%]

Time of Death

Hours

Days

Immediate

1

2

4

24

2

3

4

5

6

7

1.47

10

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

2.15

10

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

3.16

100

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

4.04

100

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

6.81

100

0/5

1/5

1/5

4/5

4/5

5/5

-

-

-

-

-

10.0

100

0/5

3/5

3/5

5/5

-

-

-

-

-

-

-

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

In this acute oral toxicity study a LD50 value of 5.63 mL/kg (corresponding to 6565 mg/kg bw based on a density of 1.166 g/cm³) bw was calculated in male rats.