2,4,6-trimethyl-2,4,6-tris(3,3,3-trifluoropropyl)cyclotrisiloxane

Endpoint summary

Description of key information

In the key skin irritation study for 2,4,6-trimethyl-2,4,6-tris(3,3,3-trifluoropropyl)cyclotrisiloxane, conducted according to OECD Test Guideline 404 and in compliance with GLP, the registered substance was concluded to be not irritating to rabbit skin (BSL Bioservice, 2013a).

In the key eye irritation study for 2,4,6-trimethyl-2,4,6-tris(3,3,3-trifluoropropyl)cyclotrisiloxane, conducted according to OECD Test Guideline 405 and in compliance with GLP, the registered substance was concluded to be not irritating to eyes (BSL Bioservice, 2013b).

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:

2012-10-21 to 2012-10-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Germany
- Age at study initiation: 21-22 weeks old
- Weight at study initiation: >2kg
- Housing: plastic rabbit cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +/- 3
- Humidity (%): 55 +/- 10
- Air changes (per hr): minimum 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: left side on the dorsal area
- Type of wrap if used: the test item was applied to a gauze patch, which was applied to the skin and held in place with non-irritating tape. The patch was fixed with semi-occlusive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not stated


SCORING SYSTEM: Draize

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:

Initial test in animal no. 1: no signs of irritation were seen immediately after the patch removal. Examination of the test site 1 hour after patch removal revealed erythema grade 1 which was fully reversible within 24 hours after the patch removal. No irritant or corrosive effects were observed on the intact skin of the two further female rabbits (strain NZW) of the main test after a contact time of 4 hours.

Under the conditions of the present study, the single dermal application of the test item F-D3 to three rabbits at a dose of 0.5 g showed irritant but no corrosive effects in animal no.1 which were fully reversible within 24 hours. Neither mortalities nor significant clinical signs of toxicity were observed.

Table: Dermal Irritation Evaluation

Animal No.	Application Site	Irritation (hours after patch removal)
		1 hour		24 hours		48 hours		72 hours
		T	C	T	C	T	C	T	C
1	Erythema	1	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0
2	Erythema	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0
3	Erythema	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0

T = test item;       C = control;        0 – 3 = grade

Table: Individual Data

Individual Systemic and Local Findings - Animal No. 1
Time after Patch Removal	Systemic Findings	Specific Local Findings (apart from erythema/oedema)	Comments
1 hour	nsf	nsf	-
24 hours	nsf	nsf	-
48 hours	nsf	nsf	-
72 hours	nsf	nsf	-
Individual Systemic and Local Findings - Animal No. 2
Time after Patch Removal	Systemic Findings	Specific Local Findings (apart from erythema/oedema)	Comments
1 hour	nsf	nsf	-
24 hours	nsf	nsf	-
48 hours	nsf	nsf	-
72 hours	nsf	nsf	-
Individual Systemic and Local Findings - Animal No. 3
Time after Patch Removal	Systemic Findings	Specific Local Findings (apart from erythema/oedema)	Comments
1 hour	nsf	nsf	-
24 hours	nsf	nsf	-
48 hours	nsf	nsf	-
72 hours	nsf	nsf	-

nsf = no specific findings

Table: Absolute Body Weights in kg

	Animal No. 1	Animal No. 2	Animal No. 3
Start of Study (weight in kg)	4.4	4.2	3.1
End of Study (weight in kg)	4.4	4.2	3.2

Interpretation of results:

GHS criteria not met

Conclusions:

No irritant effects to rabbit skin were observed in a study conducted according to current OECD guideline and under 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:

2012-10-29 to 2012-11-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Germany
- Age at study initiation: ca. 14 weeks old
- Weight at study initiation: >2kg
- Housing: plastic rabbit cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +/- 3
- Humidity (%): 55 +/- 10
- Air changes (per hr): minimum 10
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml


The test item was gently warmed in a water bath at 32 °C for liquid application.

Duration of treatment / exposure:

single instillation,

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
The test item was applied at a single dose in the conjunctival sac of one eye of each test animal after pulling the lower lid away from the eyeball. The lids were then gently held together for about 1 second in order to prevent loss of the material. The untreated contralateral eye served as control.
The treated eye was not rinsed 24 hours after the application.

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

After the application into the eyes of three female NZW rabbits the test item produced slightly irritant but no corrosive effects.
Upon fluorescein examinations at the end of the observation period of 72 hours no corneal lesions were found in any animal.
Conjunctival redness and discharge were observed in all animals.

Other effects:

Neither mortalities nor significant clinical signs of toxicity were observed.

Table:  Eye Irritation Scores – Animal No. 1

Animal No. 1	Single Data
		Time Post-Application				Average Score (24, 48 and 72 hours)
		1 hour	24 hours	48 hours	72 hours
		T/C	T/C	T/C	T/C
	Conjunctival Redness	1/0	1/0	1/0	0/0	0.67
	Conjunctival Chemosis	0/0	0/0	0/0	0/0	0
	Iris	0/0	0/0	0/0	0/0	0
	Cornea	0/0	0/0	0/0	0/0	0

T =test item,     C = control

Table:  Eye Irritation Scores – Animal No. 2

Animal No. 2	Single Data
		Time Post-Application				Average Score (24, 48 and 72 hours)
		1 hour	24 hours	48 hours	72 hours
		T/C	T/C	T/C	T/C
	Conjunctival Redness	1/0	1/0	1/0	0/0	0.67
	Conjunctival Chemosis	0/0	0/0	0/0	0/0	0
	Iris	0/0	0/0	0/0	0/0	0
	Cornea	0/0	0/0	0/0	0/0	0

T =test item,     C = control

 

Table:  Eye Irritation Scores – Animal No. 3

Animal No. 3	Single Data
		Time Post-Application				Average Score (24, 48 and 72 hours)
		1 hour	24 hours	48 hours	72 hours
		T/C	T/C	T/C	T/C
	Conjunctival Redness	1/0	1/0	1/0	0/0	0.67
	Conjunctival Chemosis	0/0	0/0	0/0	0/0	0
	Iris	0/0	0/0	0/0	0/0	0
	Cornea	0/0	0/0	0/0	0/0	0

T =test item,     C = control

Table:  Clinical Signs of Toxicity

Animal No. 1	Time after Test Item Application	Systemic Findings	Local Findings (apart from findings in Table 3)
	1 hour	nsf	discharge grade 1
	24 hours	nsf	nsf
	48 hours	nsf	nsf
	72 hours	nsf	nsf
Animal No. 2	Time after Test Item Application	Systemic Findings	Local Findings (apart from findings in Table 4)
	1 hour	nsf	discharge grade 2
	24 hours	nsf	discharge grade 1
	48 hours	nsf	nsf
	72 hours	nsf	nsf
Animal No. 3	Time after Test Item Application	Systemic Findings	Local Findings (apart from findings in Table 5)
	1 hour	nsf	discharge grade 2
	24 hours	nsf	nsf
	48 hours	nsf	nsf
	72 hours	nsf	nsf

nsf: no specific findings

Table:  Absolute Body Weights in kg

	Animal No. 1	Animal No. 2	Animal No. 3
Start of Study (weight in kg)	3.1	3.1	3.0
End of Study (weight in kg)	3.2	3.2	3.1

Interpretation of results:

GHS criteria not met

Conclusions:

No irritant effects to rabbit eyes were observed in a study conducted according to current OECD guideline and under 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 skin irritation study for 2,4,6-trimethyl-2,4,6-tris(3,3,3-trifluoropropyl)cyclotrisiloxane, conducted according to OECD Test Guideline 404 and in compliance with GLP, the registered substance was concluded to be not irritating to rabbit skin (BSL Bioservice, 2013a). Following a 4-hour semioccluded application of 0.5 ml of the undiluted test material onto the skin of 3 rabbits, mild irritant effects were present in one animal, which were fully reversible within 24 hours. Neither mortalities nor significant clinical signs of toxicity were observed.

In the key eye irritation study for 2,4,6-trimethyl-2,4,6-tris(3,3,3-trifluoropropyl)cyclotrisiloxane, conducted according to OECD Test Guideline 405 and in compliance with GLP, the registered substance was concluded to be not irritating to eyes (BSL Bioservice, 2013b). Following a single ocular instillation of 0.1 ml of the undiluted test material into the eyes of 3 rabbits, no ocular symptoms were noted.

Justification for classification or non-classification

Based on the available information, no classification for skin or eye irritation is required for 2,4,6-trimethyl-2,4,6-tris(3,3,3-trifluoropropyl)cyclotrisiloxane according to Regulation (EC) No 1272/2008.