Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30.06.1987 to 31.07.1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
No information on the purity of the TS, only two doses tested.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Degussa-Silane Si 108
- Substance type: Alkoxysilane
- Physical state: Colourless liquid
- Stability under test conditions: Stable
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann Versuchstierzucht GmbH & Co. KG., D-4799 Borchen
- Age at study initiation: Males: 26-29 weeks; Females: 27-29 weeks
- Weight at study initiation: Males: 332-429 g; Females: 212-247 g
- Fasting period before study: 16 hours
- Housing: Individually in Makrolon cages Type II
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 2
- Humidity (%): 55 15
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: Not given but study period was 30.06.1987 to 31.07.1987

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 5.11 ml/kg
Doses:
3236 and 4752 mg/kg
No. of animals per sex per dose:
Ten
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days for low dose and 21 days for high dose
- Frequency of observations and weighing: Behaviour and general condition were noted for the first 4-8 hours after dosing and then once daily. Mortality was checked twice daily. Body weights were recorded at the beginning and also 7, 14 and 21 days after administration.
- Necropsy of survivors performed: yes, a gross necropsy was performed on all animals. Macroscopic examination included external appearance, body orifices, body cavities and their contents.
Statistics:
None. LD50s estimated.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 5 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 3 500 mg/kg bw
Based on:
test mat.
Mortality:
See Table 1. Deaths occurred between day 4 and 17 after administration.
Clinical signs:
See Table 2. Following a dose of 3236 mg/kg bw there were coordination disturbances, piloerection, chromodacryorrhea, increased salivation and red nasal discharge. Following a dose of 4752 mg/kg bw there was additionally decreased muscle tone, loss of righting reflexes and increased diuresis. Individually also, tremor, vocalisation on handling, lacrimation, opacity of the cornea and green discoloured urine occurred. The development of toxic effects was protracted, with coordination disturbances detected after two hours, and all other symptoms from days 2-5. In the high dose group the effects were still apparent after 14 days, so the observation period was extended until they disappeared (three weeks).
Body weight:
Body weights were reduced following administration of both doses. In the highest dose group five animals were watered from day 2 or 3 because of their bad general condition, however the food intake was severely decreased. This lead to a severe decrease in body weight.
Gross pathology:
At necropsy of the deceased female animals the small intestine was filled with a red liquid. The deceased male animals showed cryptorchism (incidental finding).

Any other information on results incl. tables

Table 1 Mortality data

 Dose group (mg/kg bw)     Mortality rate     Time of death
   x/n  %  Hours post application  Days post application
             Males
 3236  0/5  0    
 4752  2/5  40    16 and 17
             Females
 3236  0/5  0    
 4752  3/5  60    Two on day 14 and one on day 8

Table 2 Clinical signs of toxicity

  Symptom Dose (mg/kg bw)          
   Male 3236  Male 4752  Female 3236  Female 4752
 Coordination disturbance 3  3  3  3
 Slight tremor    1    1
 Decrease of muscle tone AP    1    3
 Loss of righting reflex LP/DP    1    3/3
 Lacrimation        1
 Chromodacryorrhea    2  1  2
 Increased salivation  1    1  2
 Red nasal discharge  1  2  1  2
 Strenuous respiration    1    3
 Piloerection  1  3  4  4
 Diuresis/green urine        1/1
 Vocalisation on handling    1    
 Opacity of the cornea        1

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity study that was comparable to the now deleted OECD 401, but not to GLP (reliability score 2) the LD50 was at least 3500 mg/kg bw for male and female rats. Following a dose of 3236 mg/kg bw there were coordination disturbances, piloerection, chromodacryorrhea, increased salivation and red nasal discharge. Following a dose of 4752 mg/kg bw there was additionally decreased muscle tone, loss of righting reflexes and increased diuresis. Individually also, tremor, vocalisation on handling, lacrimation, opacity of the cornea and green discoloured urine occurred. The development of toxic effects was protracted, with coordination disturbances detected after two hours, and all other symptoms from days 2-5. All symptoms disappeared by day 21 of the observation period.