Registration Dossier

Administrative data

Description of key information

In the key skin irritation study, a mixture of the two structurally analogous substances 2,4,6,8,10-pentamethylcyclopentasiloxane (CAS 6166-86-5) and 2,4,6,8-tetramethylcyclotetrasiloxane (CAS 2370-88-9) was tested for skin irritancy according to OECD Test Guideline 404 and in compliance with GLP. No signs of skin irritation were observed and the test mixture was concluded to be not irritating to skin (Dow Corning Corporation, 2001).

In the key eye irritation study, the mixture of structurally analogous substances 2,4,6,8,10-pentamethylcyclopentasiloxane (CAS 6166-86-5) and 2,4,6,8-tetramethylcyclotetrasiloxane (CAS 2370-88-9) was tested in an in vivo eye irritation test according to OECD Test Guideline 405 and in compliance with GLP. The mixture produced minimal conjunctival redness at 4, 24 and 48 hours fully reversible within 72 hours and the mixture was concluded to be not irritating to eyes (Dow Corning Corporation, 2002).

Both studies were done with a mixture (approximately 50/50) of the structural analogues 2,4,6,8,10-pentamethylcyclopentasiloxane (CAS 6166-86-5) and 2,4,6,8-tetramethylcyclotetrasiloxane (CAS 2370-88-9).

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:
Dec 18, 2000 to Jan 10, 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Remarks:
No sentinel animal, not yet required in 2001
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
Test substance identified as mixture of 2,4,6,8,10-pentamethylcyclopentasiloxane (CAS 6166-86-5) (45%) and 2,4,6,8-tetramethylcyclotetrasiloxane (CAS 2370-88-9) (54%) and the impurity 0.9% hexamethylcyclohexasiloxane.
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
- three young adult females, at least 12 weeks old
- weight 3025g-3137g at initiation
- identification by eartag & cage card
- housed in individual suspended cages
- inspection upon arrival; acclimatisation for at least 7 days, observed twice daily
- Diet: Certifeid Rabbit LabDiet(r) 5322 ~a50 gr/animal/day. Tap water at lib. Food and water regularly analysed
- controlled temperature (69-71 degr. F), humidity (50-64%) light (12/12) and ventilation (10-15 changes / days)
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml / site
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
application to skin area approx 2.5 x 2.5, covered with 8-ply surgical gauze held in place with surgical porous tape. Overwrapped with gauze bandaging and secured with non-irritating tape; Animals were given restraint collars.
Duration of application 4 hours, after which bandages were removed and sites wiped clean with disposable paper towels moistened with deionized water.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No animals showed any signs of irritation at any point in time
Other effects:
slight weight loss (,1%) in one animal, not uncommmon in animals of this weight range and strain; not considered to be substance-related
no mortality.

Individual Irritation scores


Erythema


Edema


Animal nr.

Sex

1 hr

24 hrs

48 hrs

72 hrs


1 hr

24 hrs

48 hrs

72 hrs


34044

female

0

0

0

0


0

0

0

0


34045

female

0

0

0

0


0

0

0

0


34046

female

0

0

0

0


0

0

0

0



Total

0

0

0

0


0

0

0

0


PPI calculated for all timepoints: ppi = (0+0+0)/9 + (0+0+0) /9 = 0 + 0 = 0

Individual body weights (in grams):

Animal nr.

Sex

Initiation (day 0)

Termination (day 3)

34044

female

3137

3289

34045

female

3025

3067

34046

female

3034

3020

Interpretation of results:
GHS criteria not met
Conclusions:
The mixture of structurally analogous substances 2,4,6,8,10-pentamethylcyclopentasiloxane (CAS 6166-86-5) and 2,4,6,8-tetramethylcyclotetrasiloxane (CAS 2370-88-9) showed no signs of skin irritation.
Executive summary:

A mixture of the two structurally analogous substances 2,4,6,8,10-pentamethylcyclopentasiloxane (CAS 6166-86-5) and 2,4,6,8-tetramethylcyclotetrasiloxane (CAS 2370-88-9) was tested for skin irritancy according to OECD 404 test method under GLP . The mixture showed no signs of skin irritation. Based on structural analogy, the conclusion applies directly to the registered substance as well as from read-across from the analogue.

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:
Dec 18, 1201 to Jan 10, 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
Test substance identified as mixture of 2,4,6,8,10-pentamethylcyclopentasiloxane (CAS 6166-86-5) (45%) and 2,4,6,8-tetramethylcyclotetrasiloxane (CAS 2370-88-9) (54%) and the impurity 0.9% hexamethylcyclohexasiloxane.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
- three young adult rabbits, 2 females, one male, at least 12 weeks old
- weight 2531-2749 at study initiation
- identification by eartag & cage card
- housed in individual suspended cages
- inspection upon aarival; acclimatisation for at least 7 days, observed twice dayly
- Diet: Certified Rabbit LabDiet(r) 5322 ~a50 gr/animal/day. Tap water at lib. Food and water regularly analysed
- controlled temperature (69-71 degr. F), humidity (50-64%) light (12/12) and ventilation (10-15 changes / days)
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 ml /eye
Duration of treatment / exposure:
undefined. eyes were not washed at 1 hr post-treatment or later.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
OBSERVATIONS
- twice daily for mortality
- body weights at beginning and end of study.
Ocular Observations:
before dosing and at 1, 24, 48 and 72 hrs, both eyes were observed by means of an ophthalmoscope for ocular abnormalities Pre-dosing and at 72 hrs observation included use of sodium fluoerescein for detection of corneal defects. Scoring according to Draize. Only animals without any ocular abnormalities were used in the study
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
3
Reversibility:
not fully reversible within: 72 hrs
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 hrs
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 hrs
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
minimal redness of the coniunctivae in all animals at 4,24 and 48 hrs after instillation, completely reversible at 72 hrs
minimal chemosis at 4 hrs after instillation, completely reversible within 24 hrs
Other effects:
No other effects were observed at any timepoint . No weight loss, no mortality

Individual scores and mean scores over 24,48 an d 72 hrs:



1 hr

24 hr

48 hr

72 hr

Mean score 24,48,72 hrs

Animal nr 34586, M

Cornea opacity

0

0

0

0

0

Cornea area

0

0

0

0

0

Iris

0

0

0

0

0

Conjunctivae

redness

1

1

1

0

0,7

Conjunctivae

chemosis

1

0

0

0

0

Conjunctivae

discharge

0

0

0

0

0

Animal nr. 34595, F

Cornea opacity

0

0

0

0

0

Cornea area

0

0

0

0

0

Iris

0

0

0

0

0

Conjunctivae

redness

1

1

1

0

0,7

Conjunctivae

chemosis

1

0

0

0

0

Conjunctivae

discharge

0

0

0

0

0

Animal nr. 34594, F

Cornea opacity

0

0

0

0

0

Cornea area

0

0

0

0

0

Iris

0

0

0

0

0

Conjunctivae

redness

1

1

1

0

0,7

Conjunctivae

chemosis

1

0

0

0

0

Conjunctivae

discharge

0

0

0

0

0

Individual body weights:

Animal nr

Sex

At initation

At 72 hrs

34586

male

2744

2834

34596

Female

2531

2720

34594

Female

2684

2695

Interpretation of results:
GHS criteria not met
Conclusions:
The mixture of structurally analogous substances 2,4,6,8,10-pentamethylcyclopentasiloxane (CAS 6166-86-5) and 2,4,6,8-tetramethylcyclotetrasiloxane (CAS 2370-88-9) produced minimal conjunctival redness at 4, 24 and 48 hrs fully reversible within 72 hours. There were no other sings of irritation and the test material was concluded to be not irritating to eyes.
Executive summary:

The mixture of structurally analogous substances 2,4,6,8,10-pentamethylcyclopentasiloxane (CAS 6166-86-5) and 2,4,6,8-tetramethylcyclotetrasiloxane (CAS 2370-88-9) was tested in an in vivo eye irritation test according to OECD 405 under GLP. The mixture produced minimal conjunctival redness at 4, 24 and 48 hrs and minimal chemosis at 4 hrs, all fully reversible. The conclusion applies directly to the registered substance as well as indirectly by read-across from the structural analogue which is also present in the mixture.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In the key skin irritation study, a mixture of the two structurally analogous substances 2,4,6,8,10-pentamethylcyclopentasiloxane (CAS 6166-86-5) and 2,4,6,8-tetramethylcyclotetrasiloxane (CAS 2370-88-9) was tested for skin irritancy according to OECD Test Guideline 404 and in compliance with GLP (Dow Corning Corporation, 2001).

Following a single topical application of the mixture 2,4,6,8,10-pentamethylcyclopentasiloxane (CAS  6166-86-5) and 2,4,6,8-tetramethylcyclotetrasiloxane (CAS  2370-88-9) to the skin of 3 rabbits, there were no signs of erythema or edema. No signs of skin irritation were observed and the test mixture was concluded to be not irritating to skin.

In the key eye irritation study, a mixture of structurally analogous substances 2,4,6,8,10-pentamethylcyclopentasiloxane (CAS 6166-86-5) and 2,4,6,8-tetramethylcyclotetrasiloxane (CAS 2370-88-9) was tested in an in vivo eye irritation test according to OECD Test Guideline 405 and in compliance with GLP (Dow Corning Corporation, 2002).

Following a single instillation of 0.1 ml of the mixture 2,4,6,8,10-pentamethylcyclopentasiloxane (CAS  6166-86-5) and 2,4,6,8-tetramethylcyclotetrasiloxane (CAS  2370-88-9) to the eyes of 3 rabbits, there was minimal conjunctival irritation which was reversible within 72 hours. No other signs of eye irritation were observed during the 72-hour observation period. The test material was concluded to be not irritating to eyes.

See attachment to IUCLID Section 13 for justification of using data for the mixture of 2,4,6,8,10-pentamethylcyclopentasiloxane (CAS 6166-86-5) and 2,4,6,8-tetramethylcyclotetrasiloxane (CAS 2370-88-9).



Justification for classification or non-classification

Based on the available data for the mixture (approximately 50/50) of the structural analogues 2,4,6,8,10-pentamethylcyclopentasiloxane (CAS 6166-86-5) and 2,4,6,8-tetramethylcyclotetrasiloxane (CAS 2370-88-9), no classification is required for skin and eye irritation for the registered substance 2,4,6,8,10-pentamethylcyclopentasiloxane (CAS 6166-86-5) according to Regulation (EC) No 1272/2008.