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Administrative data

Description of key information

The key study for acute oral toxicity reports an LD50 value of >2000 mg/kg bw in rat, conducted according to a protocol equivalent to current OECD guideline but not in compliance with GLP (Haruna 2001). In accordance with Column 2 of REACH Annex VIII, the acute toxicity study via the inhalation route (required in Section 8.5.2) does not need to be conducted as reliable data via the oral and dermal routes are available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 30 2001 - July 23 2001
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
according to
Guideline:
other: Guidance on Safety Assessment of New Cosmetics (Japan Cosmetic Industry Association, technical materials No.92, 1991
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crj:CD(SD)IGS
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Atsugi Breeding Center, Charles River Japan Inc.
- Age at study initiation:6 weeks
- Weight at study initiation: male 193-212 g, female 131-151 g
- Fasting period before study: ca. 18 hours
- Housing: Individually housed, in stainless steel bracket cages for rats
- Diet : ad libitum
- Water: ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 50 +/- 20
- Air changes (per hr): minimum 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 100 or 200 mg/mL


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: According to the Guidance on Safety Assessment of New Cosmetics, 2000 mg/kg was set for the high dose group, 1000 mg/kg for the low dose group, and olive oil for the control group.
Doses:
vehicle at 0 mg/kg, 1000 and 2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for clinical signs and mortality at 15, 30 minutes, 1, 3 and 6 hours after treatment on the day of treatment and thereafter once daily. Animals were weighed on the day of treatment and on days 2, 3, 4, 8, 11 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: The body surface and the intracranial, intrathoracic and intra-abdominal organs were macroscopically examined. Histopathological examination was not performed because necropsy did not reveal any abnormal changes.
Statistics:
The body weight measurements obtained in the study were averaged and standard deviation was calculated for each group, which were analysed for homogeneity of variance by F-test. Since the results showed homogenous variance, Student t-test was performed. There was no statistical significance noted.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred through the observation period in either males or females in all the groups including the control group in response to test article administration.
Clinical signs:
No clinical signs caused by the test substance were observed. Watery diarrhoea was observed in males and females in all groups, which ceased by day 2 of treatment, after which no special changes were observed.
Body weight:
During the observation period, there was no statistical difference in body weight measurements between the groups. The body weight of each group increased favourably.
Gross pathology:
There were no remarkable findings at necropsy in any group of animals.
Other findings:
None reported.
Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Not classified according to Regulation (EC) No 1272/2008
Conclusions:
An LD50 value of >2000 mg/kg bw in rats of both sexes is reported in a study equivalent to current OECD guideline, which was not GLP compliant.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

An oral LD50 value of >2000 mg/kg bw in rats of both sexes is reported in a GLP compliant study conducted according to a protocol equivalent to current OECD guideline (Haruna 2001). No deaths occurred through the observation period in either males or females in any of the groups including the control group in response to test article administration. No clinical signs in response to the test substance were observed. Watery diarrhoea was observed in males and females in all groups including control group, which ceased by day 2 of treatment, after which no special changes were observed. During the observation period, there was no statistical difference in body weight measurements between the groups. The body weight of all animals increased favourably. There were no remarkable findings at necropsy in any of the animals.

 


Justification for classification or non-classification

Based on the available information, no classification is required for acute toxicity of 1,1,1,3,5,5,5 -heptamethyl-3 -[(trimethylsilyl)oxy]trisiloxane in accordance with Regulation (EC) No 1272/2008.