Registration Dossier

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

Constituent 1
Chemical structure
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:
(3R,3aR,6S,6aR)-3,6-dimethoxy-hexahydrofuro[3,2-b]furan
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:
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 dosage level tested continued to show the above-listed gross signs of systemic toxicity. Within one hour or less dosage, and generally during the reminder of the day, the remaining animals showed the following additional signs: bloody discharge from the eyes, slow and labored respiration and depressed and absent placement, righting and pain reflexes, while the animals at the three higher dosage levels also showed bloated abdomens. Mortality was immediately preceded by coma and a profuse discharge from the eyes. 24 hour post-administration and daily during the reminder of the observation period the animals at the lower dosage levels exhibited normal appearance and showed a bloody discharge around the eyes and labored respiration, while those at the 4.61 and 6.81 mL/kg bw levels also showed bloated abdomens, tachycardia, and depressed or absent placement and righting reflexes. These animals gradually recovered within an additional one to three days, after which they appeared normal.
Body weight:
The average body weights of the animals at each of the four lower dosage levels showed an increase over the respective initial average body weights at the end of the study period.
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.