Reaction mass of 3-[3-(9-butyl-1,1,3,3,5,5,7,7,9,9-decamethylpentasiloxanyl)propoxy]-2-hydroxypropyl 2methylprop-2-enoate and 1-[3-(9-butyl-1,1,3,3,5,5,7,7,9,9-decamethylpentasiloxanyl)propoxy]-3-hydroxypropan-2-yl 2-methylprop-2-enoate

Endpoint summary

Description of key information

The test substance is not an skin or eye irritant.

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:

September 8 2006 to October 23 2006

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of relevant results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

not specified

Species:

rabbit

Strain:

other: Kbs:JW

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kitayama Labes Co., Ltd
- Age at study initiation: 11 weeks
- Weight at study initiation: Average 2.20 kg
- Housing:Rabbit cage 690 x 490 x 380 (mm). Floor space 3380 cm2
- Diet: Solid feed for rabbits and guinea pigs. Approximately 120-130g of feed was fed with limit using a suspending feeder made of aluminium attached to the cage.
- Water : ad libitum, from the automatic water supply system.
- Acclimation period: 7 days after receipt.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.0-22.7
- Humidity (%): 52.0-60.1
- Air changes (per hr): Over 7 times/hour
- Photoperiod (hrs dark / hrs light): 12 hours (lighted hours: 8:00am-8:00pm

Type of coverage:

semiocclusive

Preparation of test site:

other: Clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): A half mL of the test article was evenly applied to lint cloth.

Duration of treatment / exposure:

4 hours.

Observation period:

72 hours after the removal of the test article.

Number of animals:

3.

Details on study design:

TEST SITE
Area of exposure: Approx 6 cm2 (1-inch-square, approx 2.5 cm x 2.5 cm).

Type of wrap if used: Test article applied to a lint cloth. The lint cloth was wrapped with plastic membrane and then with adhesive-elastic dressing.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the application period, the adhesive-elastic dressing was immediately removed and the applied site of the test article was washed clean with distilled water.
- Time after start of exposure: 4 hours.

Observation of general condition

Animals were observed before the application, 1, 24, 48, and 72 hours after the
removal of the test article.
Body weight

Animals were weighed using the electronic scale before the application and 72 hours
after the removal of the test article.
Skin observation

Skin was scored based on the criteria described below for erythema and incrustation
and development of edema at 1, 24, 48, and 72 hours after the removal of the test
article. The applied site was assessed not to have any problem before the application
of the test article.

Evaluation

The test article was evaluated for corrosivity and irritability based on the average
scores for erythema and incrustation and development of edema at 24, 48, and 72
hours after the removal of the test article according to the Globally Harmonized
System of Classification and Labeling of Chemicals.

SCORING SYSTEM:
The rating criteria for skin reactions
Rating criteria Scores
1) Erythema and incrustation
No erythema ·················································································································0 points
Very mild erythema (barely visible) ·············································································1 point
Clear erythema ··············································································································2 points
Moderate to severe erythema ························································································3 points
Dark red erythema to slight incrustation (damage to deeper area) ·······························4 points
2) Development of edema
No edema ······················································································································0 points
Very mild edema (barely visible)··················································································1 point
Mild edema (clear edge recognized by obvious swelling) ············································2 points
Moderate edema (swelling to approximately 1 mm)·····················································3 points
Severe edema (swelling of 1 mm and spreading beyond the exposed area) ···············4 points

Irritation parameter:

erythema score

Basis:

animal: 00101

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No effects seen at any time point

Irritation parameter:

erythema score

Basis:

animal: 00102

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No effects seen at any time point

Irritation parameter:

erythema score

Basis:

animal: 00103

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No effects seen at any time point

Irritation parameter:

edema score

Basis:

animal: 00101

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No effects seen at any time point

Irritation parameter:

edema score

Basis:

animal: 00102

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No effects seen at any time point

Irritation parameter:

edema score

Basis:

animal: 00103

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No effects seen at any time point

Irritant / corrosive response data:

There was no erythema and incrustation and development of edema observed in skin at 1, 24, 48, and 72 hours after the removal of the test article. Therefore, the average score for erythema and incrustation and development of edema in each animal was 0.0.

Other effects:

None.

No histopathological examination was performed since there was no skin reaction.

There was no abnormality found in general condition in animals before the application, 1, 24, 48, and 72 hours after the removal of the test article.

There was no weight loss observed in weight changes between the application and 72 hours after the removal of the test article.

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Compound A was applied for 4 hours on the skin of rabbits in order to evaluate the skin irritability. No erythema and incrustation and development of edema were observed at any time at skin evaluation 1, 24, 48, and 72 hours after the removal of the test article.
As a result of skin evaluation based on the Globally Harmonized System of Classification and Labeling of Chemicals, Compound A was considered to be classified as non-corrosive and non-irritant.

Executive summary:

In a primary dermal irritation conducted to OECD Guideline 404, three rabbits were dermally exposed to 0.5ml of the undiluted test material for four hours.

After 4 hours of skin application, no erythema, incrustation, or developments of edema were observed on the skin at 1, 24, 48, and 72 hours after the removal of the test article. In addition, there was no abnormality seen in general condition or weight change. Based on the above results, Compound A was considered to be classified as non-corrosive and non-irritant.

                                                      

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:

The study was performed between 30 June 2009 and 10 July 2009.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do no effect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories U.K. Ltd, Hillcrest, Belton, Loughborough, UK.
- Age at study initiation: Twelve to twenty weeks old.
- Weight at study initiation: 2.59 or 2.78 kg
- Housing: The animals were individually housed in suspended cages.
- Diet (e.g. ad libitum): Free access to food (2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed throughout the study
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study
- Acclimation period: At least five days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): The temperature wasset to achieve limits of 17 to 23°C.
- Humidity (%): The relative humidity was set to achieve limits of 30 to 70% respectively.
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): Lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Vehicle:

unchanged (no vehicle)

Controls:

other: The left eye remained untreated and was used for control purposes.

Amount / concentration applied:

TEST MATERIAL
The test material was used as supplied.

- Amount(s) applied (volume or weight with unit):
A volume of 0.1 ml of the test material was placed into the conjunctival sac of the right eye.


VEHICLE
Not applicable.

Duration of treatment / exposure:

72 hours.

Observation period (in vivo):

Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment.

Number of animals or in vitro replicates:

2.

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not applicable.
- Time after start of exposure: Not applicable.


SCORING SYSTEM: Assessment of ocular damage/irritation was made according to the Draize Scale for Scoring Ocular Irritation.
Any other ocular effects were also noted.

TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Irritation parameter:

conjunctivae score

Remarks:

: Redness

Basis:

mean

Remarks:

: Animal 1

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Max score of 2 at 1 hour reading.

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

: Animal 1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Max score of 2 at 1 hour reading.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

: Animal 1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No corneal effects noted.

Irritation parameter:

iris score

Basis:

mean

Remarks:

: Animal 1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: No iridial effects noted.

Irritation parameter:

conjunctivae score

Remarks:

: Redness

Basis:

mean

Remarks:

: Animal 2

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Max score of 2 at 1 hour reading.

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

: Animal 2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Max score of 2 at 1 hour reading.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

: Animal 2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No corneal effects noted.

Irritation parameter:

iris score

Basis:

mean

Remarks:

: Animal 2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: No iridial effects noted.

Irritant / corrosive response data:

Individual and group mean scores for ocular irritation are given in Table 1 and Table 2.
No corneal or iridial effects were noted.
Moderate conjunctival irritation was noted in treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24-hour observation.
Both treated eyes appeared normal at the 48-hour observation

Other effects:

Individual bodyweights and bodyweight changes are given in Table 3.
All animals showed expected gain in bodyweight during the study.

Table1              IndividualScores and Individual Total Scoresfor Ocular Irritation

Rabbit Number and Sex	68438Male				68441Male
	IPR= 2				IPR = 2
Time After Treatment	1 Hour	24 Hours	48 Hours	72 Hours	1 Hour	24 Hours	48 Hours	72 Hours
CORNEA
E = Degree of Opacity	0	0	0	0	0	0	0	0
F = Area of Cornea Involved	0	0	0	0	0	0	0	0
Score (E x F) x 5	0	0	0	0	0	0	0	0
IRIS
D	0	0	0	0	0	0	0	0
Score (D x 5)	0	0	0	0	0	0	0	0
CONJUNCTIVAE
A = Redness	2	1	0	0	2	1	0	0
B = Chemosis	2	1	0	0	2	1	0	0
C = Discharge	1	0	0	0	1	0	0	0
Score (A + B + C) x 2	10	4	0	0	10	4	0	0
Total Score	10	4	0	0	10	4	0	0

IPR= Initial pain reaction

Table2              Individual Total Scores and Group Mean Scoresfor Ocular Irritation

Rabbit Number and Sex	Individual Total Scores At:
	1 Hour	24 Hours	48 Hours	72 Hours
68438Male	10	4	0	0
68441Male	10	4	0	0
Group Total	20	8	0	0
Group Mean Score	10.0	4.0	0.0	0.0

Table3              Individual Bodyweights and Bodyweight Changes

Rabbit Number and Sex	Individual Bodyweight (kg)		Bodyweight Change (kg)
	Day 0	Day 3
68438Male	2.78	2.84	0.06
68441Male	2.59	2.64	0.05

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The test material produced a maximum group mean score of 10.0 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

Executive summary:

Introduction. 

The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

• OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted)
• Method B5 Acute Toxicity (Eye Irritation) of CommissionRegulation (EC) No. 440/2008

Result. 

A single application of the test material to the non-irrigated eye of two rabbits produced moderate conjunctival irritation. Both treated eyes appeared normal at the 48‑hour observation.

Conclusion.

The test material produced a maximum group mean score of 10.0and was classified as aminimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion:

In a primary dermal irritation conducted to OECD Guideline 404, three rabbits were dermally exposed to 0.5ml of the undiluted test material for four hours.

After 4 hours of skin application, no erythema, incrustation, or developments of edema were observed on the skin at 1, 24, 48, and 72 hours after the removal of the test article. In addition, there was no abnormality seen in general condition or weight change. Based on the above results, Compound A was considered to be classified as non-corrosive and non-irritant.

Eye irritation:

Introduction. 

The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

• OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted)
• Method B5 Acute Toxicity (Eye Irritation) of Commission Regulation (EC) No. 440/2008

Result. 

A single application of the test material to the non-irrigated eye of two rabbits produced moderate conjunctival irritation. Both treated eyes appeared normal at the 48‑hour observation.

Conclusion. 

The test material produced a maximum group mean score of 10.0and was classified as aminimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

                                                      

Justification for classification or non-classification

The results of the skin and eye irritation studies do not meet the criteria for classification according to CLP (Regulation (EC) No 1272/2008) or according to DSD (Directive 67/548/EEC).