2,4,6,8-tetramethylcyclotetrasiloxane

Endpoint summary

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 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

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Remarks:

No sentinel animal, not yet required in 2001

GLP compliance:

yes (incl. QA statement)

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 test system 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

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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 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, showed 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, 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 (Dow Corning Corporation, 2002).

Following 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 showed 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 read-across data, 2,4,6,8-tetramethylcyclotetrasiloxane does not require classification for skin or eye irritation according to Regulation (EC) No 1272/2008.