Registration Dossier

Administrative data

Description of key information

The key study for skin irritation finds the registered substance not irritating to the skin of rabbits, in a study equivalent to current OECD guideline but not compliant with GLP (Haruna 2001). The key study for eye irritation finds the registered substance not irritating to the eyes of rabbits, in a study equivalent to current OECD guideline but not compliant with GLP (Haruna 2001).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17 May 2001 - 23 July 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
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
Species:
rabbit
Strain:
other: Japanese White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Oriental Bio Service Kanto Co., Ltd.
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 1.9 - 2.15 kg
- Housing: Animals were housed individually in aluminium cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/-15
- Air changes (per hr): minimum 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
occlusive
Preparation of test site:
other: intact and abraded skins, clipped of fur
Vehicle:
other: olive oil
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): 90% and 50% solution

VEHICLE
- Lot/batch no. (if required): 32264
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: On the back of rabbits previously clipped of fur, 4 application sites were set in two symmetrically left and right. Of the 4 application sites, 2 served as intact skin and the other 2 as abraded skin. 0.5 mL of 90% and 50% test substance/olive oil solutions were uniformly spread on 2.5x2.5 cm patches, which were then applied to 2 intact and 2 abraded skins, respectively.

- % coverage:
- Type of wrap if used: Each patch was covered with adhesive elastic bandage and the whole application area was covered with gauze, which was occluded by 'Silky Tex' and surgical tape.

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, intact skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, intact skin
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, intact skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, intact skin
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, abraded skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, abraded skin
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, abraded skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, abraded skin
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, intact skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, intact skin
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, intact skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, intact skin
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, abraded skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, abraded skin
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, abraded skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, abraded skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, intact skin
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, intact skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, intact skin
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, intact skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, abraded skin
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, abraded skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, abraded skin
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, abraded skin
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, intact skin
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, intact skin
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, intact skin
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, intact skin
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, abraded skin
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, abraded skin
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, abraded skin
Irritation parameter:
edema score
Basis:
animal #4
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, abraded skin
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, intact skin
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, intact skin
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, intact skin
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, intact skin
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, abraded skin
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, abraded skin
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, abraded skin
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, abraded skin
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, intact skin
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, intact skin
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, intact skin
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, intact skin
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, abraded skin
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution, abraded skin
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, abraded skin
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution, abraded skin
Irritant / corrosive response data:
In any intact and abraded skins treated with 90% test substance solution, no skin reactions were observed in any animals at any observation time points of 1, 24, 48 and 72 hours after removal of the patches. In any intact and abraded skins treated with 50% test substance solution, no skin reactions were similarly observed in any animals at any observation time points.
Other effects:
No clinical signs were observed in any animals throughout the observation period. The body weights of all animals increased satisfactorily throughout the observation period.
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was found not to be irritating, in response to 50% and 90% solution applied onto intact and abraded skin of rabbits. The study was equivalent to current OECD guideline, but not conducted in compliance with GLP.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17 May 2001 - 23 July 2001
Reliability:
1 (reliable without restriction)
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
Species:
rabbit
Strain:
other: Japanese White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Oriental BioService Kanto Co., Ltd.
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 1.93-2.07 kg
- Housing: Animals were housed individually in aluminium cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/-15
- Air changes (per hr): minimum 10
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
other: olive oil
Controls:
yes, concurrent vehicle
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1mL
- Concentration (if solution): 50% or 90%

VEHICLE
- Concentration (if solution): 90(v/v)% or 50(v/v)%
- Lot/batch no. (if required): 32264
Duration of treatment / exposure:
single instillation, 24 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no


SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: 50% solution
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: 50% solution
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: 90% solution
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: 90% solution
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: 90% solution
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: 50% solution
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: 50% solution
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: 50% solution
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: 50% solution
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 50% solution
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: 90% solution
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: 90% solution
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: 90% solution
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: 90% solution
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 90% solution
Irritant / corrosive response data:
No eye irritation was observed in the cornea, iris or conjunctivae of the 3 animals at any observation time point in response to 50% or 90% solution, or in response to vehicle control of olive oil, applied to the other eye of the animals.
Other effects:
No clinical signs were observed in any animals throughout the observation period. The body weights of all animals increased satisfactorily throughout the observation period.
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was found not irritating to rabbit eye in response to 50% or 90% solution in olive oil. The study was conducted according to a protocol equivalent to OECD guideline, but not in compliance to GLP.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In the key study for skin irritation, test animals were administered 50% or 90% solution of test material in olive oil onto intact or abraded skin (Haruna 2001). No signs of irritation were observed in any of the animals at either dose, at any observation time points of 1, 24, 48 and 72 hours after removal of the patches. No clinical signs were observed in any animals throughout the observation period. The body weights of all animals increased satisfactorily throughout the observation period.

As supporting study for skin irritation was also available (Haruna 2001), in which two application sites, symmetrically left and right against the back median line, were set on the previously clipped skin of 3 rabbits. 0.25 mL of 90% and 50% test substance solution was applied once daily for 2 weeks, 14 times in total, by open dermal administration. The application sites were observed for signs of erythema and edema according to the Draize's evaluation standard for skin reactions and evaluated for the cumulative skin irritation potential of 90% and 50% test substance solution. No skin reactions or clinical signs were observed in any animals at any observation time points throughout the study period.

A second supporting study was also available in which human volunteers (26 women; age range 30-57, mean 42.1 years and 14 men; age range 28-49 years, mean 37.9 years) were subjected to a patch test (Haruna 2001). A 50% or 90% solution of test material was applied onto a patch which was attached to the upper back of the volunteers for 24 hours. After the end of the application, the patches were removed and assessed at 1 and 24 hours after the patch removal. No positive responses to test material in olive oil were evident in subjects after patch removal. A mild erythematous reaction to test material in 90% olive oil was observed on 2 subjects after patch removal, which was seen to be negative by 24 hours.

The findings of the supporting studies support the key study for skin irritation.

In the key study for eye irritation, test animals received a single instillation of 50% or 90% solution of test material in olive oil into the eye (Haruna 2001). No eye irritation was observed in the cornea, iris or conjunctivae of the 3 animals at any observation time point in response to 50% or 90% solution, or in response to vehicle control of olive oil, applied to the other eye of the animals. No clinical signs were observed in any animals throughout the observation period and the body weights of all animals increased satisfactorily throughout the observation period.


Justification for classification or non-classification

Based on the available information, 1,1,1,3,5,5,5 -Heptamethyl-3 -[(trimethylsilyl)oxyl]trisiloxane does not require classification for skin or eye irritation in accordance with current Regulation (EC) No 1272/2008.