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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1987-05-14 until 1987-06-22
Reliability:
1 (reliable without restriction)
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1994

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
Adopted: 12 may 1981
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
Directive 84/449/EEC
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Disodium disilicate
EC Number:
237-623-4
EC Name:
Disodium disilicate
Cas Number:
13870-28-5
Molecular formula:
Na2Si2O5
IUPAC Name:
disodium disilicate
Details on test material:
- Name of test material (as cited in study report): Natriumschichtsilikat Na-SKS-6 kristallin
- Physical state and appearance: white powder
- Analytical purity: >99%
- Storage condition of test material: Darkness at room temperature in a fume cupboard

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: HOECHST AG, Kastengrund, SPF breeding colony
- Age at study initiation: Male animals: Approx. 7 weeks and female animals: Approx. 8 weeks
- Weight at study initiation: Mean weight of male animals: 189 g ± 7 g and mean weight of female animals: 178 g ±6 g
- Fasting period before the study: About 16 hours
- Housing: In fully air-conditioned rooms in Makrolon cages (Type 4) on soft wood granulate in groups of 5 animals.
- Diet: Altromin 1324 rat diet (Altromin GmbH, Lage/Lippe), ad libitum
- Water: Tap water in plastic bottles, ad libitum
- Acclimation period: At least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 50 ± 20%
- Photoperiod (hrs dark / hrs light): 12 hours dark/ 12 hours light


IN-LIFE DATES: The animals were killed at the end of the observation time, 28 or 35 days after treatment.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 12.5, 20.0, 31.5, 50.0% (w/ v)
- Amount of vehicle (if gavage): 10 mL/kg body weight

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

DOSAGE PREPARATION: Disodium disilicate (delta-crystalline) was suspended in the stated concentrations in deionized water with the aid of mortar and pestle and distributed homogeneously by means of a magnetic stirrer.

Doses:
1250, 2000, 3150, 5000 mg/kg body weight
Female rats were not applied with the lowest dose used in the study (1250 mg/kg bw), the lowest dose applied to the female rats was 2000 mg/kg bw.
No. of animals per sex per dose:
5 animals per sex per dose.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14, 28 or 35 days
- Frequency of observations and weighing: Symptoms and lethality were recorded twice every day, on weekends and holidays only once. The animals were weighed weekly.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weight, inner organs were examined macroscopically for visible changes.
Statistics:
The LD50, the 95% limits of confidence and the equation of the probit line were established in male animals on the basis of the lethality rates by probit analysis. Calculation of the LD50 was not possible in females due to the lethality ratios.
Method of FIELLER and SIDAK, programs supplied by the department for practical mathematics, HOECHST AG).

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
2 507 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
2 000 - 3 150 mg/kg bw
Sex:
male/female
Dose descriptor:
LD0
Effect level:
1 250 mg/kg bw
Mortality:
In the 1250 mg/kg b.w dose group: No mortality occurred.
In the 2000 mg/kg b.w dose group: 3 out of 5 male rats (60%) died during the observation time. No female rats from this dose group died during the observation time.
In the 3150 mg/kg b.w dose group: 2 out of 5 male rats (40%) and 4 out of 5 female rats (80%) died during the observation time.
In the 5000 mg/kg b.w dose group: All male and female rats of this dose group died during the observation time.
Clinical signs:
other: The following clinical signs were observed after the application of the test substance: A few minutes after application the animals showed decreased spontaneous activity, sunken flanks, irregular breathing, uncoordinated gait, squatting posture, prone/lat
Gross pathology:
Macroscopic examination of the animals who were found dead revealed the following findings:
Lung: discoloured brightly red
Liver: partially discoloured light
Part adjacent to the stomach dis-coloured white
Spleen: Partially discoloured light
Kidneys: Partially discoloured light
Adrenals: Partially discoloured light
Stomach: Bleeding at the inner wall, mucosa discoloured white, partial detachment of the mucosa, filled with white-red mass, filled with red liquid (blood), wall glossy and gelatinous, taut filled.
Gut: Filled with reddish-brown mass or liquid (blood)
Cavities: Peritoneum filled with red liquid (2-3 mL)
The animals who were sacrificed at the end of the observation period showed partial fusion of liver lobules and parts of the small intestine with the stomach. The stomach wall was indurated and showed white or black discolouration.
Other findings:
No other findings

Any other information on results incl. tables

No remarks

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
LD50 (male animals): 2507 mg/kg body weight
LD50 (female animals): 2000- 3150 mg/kg body weight
Executive summary:

The test substance, disodium disilicate (delta-crystalline) was applied in single dose by gavage to 5 male and 5 female Wistar rats at the following doses:1250 (only for male rats), 2000, 3150, 5000 mg/kg body weight. The animals were observed up to 28 or 35 days. Mortality occurred at the 2000 mg/kg bw dose group (only in male animals) and above it. The lethaly intoxicated animals died after prefinal spasms. Different clinical signs of intoxification were observed in animals of the lowest dose group and onwards. Most of the surviving animals were free from clinical signs of intoxication after 8- 14 days but symptoms of stilted gait and sunken flanks were observed in individual animals until the end of the observation period. Development of body weight was impaired in all dose groups.

After the animals were sacrificed at the end of the observation period, the gross pathology examination showed partial fusion of liver lobules and parts of the small intestine with the stomach. The stomach wall was indurated and showed white or black discolouration.

The LD50 was determined to be 2507 mg/kg bw for male animals and between 2000 to 3150 mg/kg bw for female animals.