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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
See attachment to Section 13 for justification of read-across.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
read-across source
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: Crl: CD (SD) IGS BR
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: ca. 11 weeks
- Weight at study initiation: 220-241 g
- Fasting period before study: over night
- Housing: Individually housed in suspended wire mesh cages
- Diet: Lab diet 5002 Certified Rodent Diet, ad libitum, except the night prior to dosing and approximately 4 hours post-dosing
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1 -22.2
- Humidity (%): 46-65
- Air changes (per hr): 10.2-11.3
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg
Doses:
2000 mg/kg
No. of animals per sex per dose:
3F
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Animals were observed for clinical abnormalities immediately after dosing and then approximately 30 minutes, 90 minutes, four hours post dose and daily thereafter. The animals were examined for a minimum of the following changes in the skin and fur, eyes and mucous membranes, respiratory system, circulatory system, autonomic and central nervous system, motor activity and behaviour pattern. The body weights were recorded on study day 0 prior to dosing, on study day 7 and on study day 14 prior to terminal sacrifice.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: The gross necropsy included examination of the external surface, all orifices of the body and the cranial, thoracic and abdominal cavities and their contents.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no mortalities.
Clinical signs:
All animals appeared normal throughout the study.
Body weight:
All animals gained weight from study day 0 to 14.
Gross pathology:
No significant macroscopic findings were noted.
Other findings:
None reported.
Interpretation of results:
GHS criteria not met
Conclusions:
An LD50 value of >2000 mg/kg was determined in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.
Reason / purpose for cross-reference:
read-across source
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
not in compliance with GLP.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Hilltop-Wistar albino rats, weighing between 200 and 300 g, received the test material by stomach intubation with a ball-end stainless steel needle.  The sample was injected through the needle by means of a syringe and doses were varied by adjusting the volume of the test material.  The rats were fasted overnight before dosing.  Five males and 5 females were included on each level (16.0 and 8.0 ml/kg). 
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Hilltop-Wistar albino
Sex:
male/female
Details on test animals or test system and environmental conditions:
weighing between 200 and 300 g
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE: Not applicable

MAXIMUM DOSE VOLUME APPLIED: Not stated
Doses:
8.0 and 16.0 ml/kg
No. of animals per sex per dose:
5/sex/group
Control animals:
no
Details on study design:
Hilltop-Wistar albino rats, weighing between 200 and 300 g, received the test material by stomach intubation with a ball-end stainless steel needle.  The sample was injected through the needle by means of a syringe and doses were varied by adjusting the volume of the test material.  The rats were fasted overnight before dosing.  Five males and 5 females were included on each level (16.0 and 8.0 ml/kg).  The animals were maintained on appropriate commercial diet and municipal water.  Both were available ad libitum except during period of fasting, manipulation or restraint.   Animal weights were recorded at 0 days (before dose), 7 days and 14 days (just prior to sacrifice).  At death or sacrifice, each animal was subjected to gross pathologic evaluation.
Statistics:
 LD50s were calculated by the moving average method (Thompson, 1947) and were based on a 14-day observation period.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 16 mL/kg bw
Based on:
test mat.
Remarks on result:
other: corresponding to 12.16 g/kg
Mortality:
MALES:
 16.0 ml/kg Dead/Dosed: 0/5
8.0 ml/kg Dead/dosed: 1/5

FEMALES:
 16.0 ml/kg Dead/Dosed: 0/5
8.0 ml/kg Dead/Dosed: 0/5
Clinical signs:
MALES:
16.0 ml/kg  None noted.
 8.0 ml/kg: In the animal that died, sluggishness, unsteady gait at 4 min; death at 15 min.  In survivors, none noted.

FEMALES:
 16.0 ml/kg None noted.
8.0 ml/kg  None noted.
Body weight:
MALES:
16.0 ml/kg Weight change (g) at 7 days: 64 to 60 (mean = 67); Weight change (g) at 14 days: 101 to 121 (mean = 113)
8.0 ml/kg Weight change (g) at 7 days: 72 to 81 (mean = 76); Weight change (g) at 14 days: 96 to 107 (mean = 102)

FEMALES:
 16.0 ml/kg Weight change (g) at 7 days: 30 to 42 (mean = 36) Weight change (g) at 14 days: 35 to 59 (mean = 49)
8.0 ml/kg Weight change (g) at 7 days: 24 to 39 (mean = 33) Weight change (g) at 14 days: 33 to 43 (mean = 38)
Gross pathology:
MALES:
 16.0 ml/kg : Nothing remarkable.
 8.0 ml/kg  In animal that died, lungs with dark spots; liver dark; stomach liquid-filled, injected; intestines and kidneys red.  In survivors, nothing remarkable.

FEMALES:
 16.0 ml/kg : Nothing remarkable.
8.0 ml/kg  Nothing remarkable.
Other findings:
No other findings reported.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral LD50 was determined to be > 16.0 ml/kg, dosed as received, in both male and female rats.

Data source

Materials and methods

Test material

Constituent 1
Chemical structure
Reference substance name:
Dodecamethylpentasiloxane
EC Number:
205-492-2
EC Name:
Dodecamethylpentasiloxane
Cas Number:
141-63-9
Molecular formula:
C12H36O4Si5
IUPAC Name:
2,2,4,4,6,6,8,8,10,10-decamethyl-3,5,7,9-tetraoxa-2,4,6,8,10-pentasilaundecane

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Remarks:
L2
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Remarks:
L3
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.

Applicant's summary and conclusion