Registration Dossier

Diss Factsheets

Administrative data

Description of key information

The key study for skin irritation found the test material a non-irritant to rabbit skin in a reliable study conducted according to OECD Test Guideline 404 and in compliance with GLP (Dow Corning Corporation, 1997).

The key study for eye irritation performed in accordance with OECD Test Guideline 405 and in compliance with GLP, found the test material non-irritating to the eyes of rabbits (Dow Corning Corporation, 1997).

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:
21 August 1995 to 30 September 1997
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
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kuiper Rabbit Ranch, Gary, IN
- Age at study initiation: 2.5 months
- Weight at study initiation: 1.74-2.23 kg
- Housing: stainless steel cages with mesh floors, 61.0 x 45.5 x 41.0 cm
- Diet (e.g. ad libitum): 150 g/day, Purina Lab Rabbit Chow HF #5326
- Water (e.g. ad libitum): ad libitum, reverse osmosis-purified water
- Acclimation period: 9 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23-34
- Humidity (%): 41-55
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12:12

IN-LIFE DATES: From: 29 August 1995 to 1 September 1995
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): undiluted
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: not stated, but test site covered with 6.25 cm2 patch (shaved area was 240 cm2)
- % coverage: no data
- Type of wrap if used: 2.5 x 2.5 cm 12-ply cotton gauze patch secured with porous tape; mid-section of each rabbit wrapped in lint-free cloth secured by an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not done (no residual test material visible) - area wiped with gauze
- Time after start of exposure: 4 hours

SCORING SYSTEM: Primary Dermal Irritation Score:
Erythema and eschar formation:
no erythema 0
very slight erythema 1
well-defined erythema 2
moderate-severe erythema 3
severe erythema (beet redness) to slight eschar formation (injuries in depth) 4

Oedema formation:
no oedema 0
very slight oedema 1
slight oedema 2
moderate oedema 3
severe oedema 4

Descriptive rating:
0 non-irritating (grade 0)
0.1-1.5 minimally irritating (grade 1)
1.6-3.0 mildly irritating (grade 2)
3.1-5.0 moderately irritating (grade 3)
5.1-8.0 severely irritating (grade 4)
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 30-60min, 24 h, 48 h, 72 h
Score:
0
Max. score:
8
Remarks on result:
other: All animals, all endpoints, all timepoints - score 0
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:
Non-irritant - see table 1
Other effects:
No deaths

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

One male and 2 female rabbits:

Score at time point / Reversibility

Erythema

Edema

Max. score: 0

Max. score: 0

30-60 min

0/0/0

0/0/0 

24 h

0/0/0

0/0/0 

48 h

0/0/0

0/0/0 

72 h

0/0/0

0/0/0 

Average 24h, 48h, 72h

0/0/0

0/0/0 

 

Erythema: 0=none, 1=very slight, 2=well defined, 3=moderate to severe 4=severe erythema to slight eschar formation

Edema; 0=none, 1=very slight, 2=slight, 3=moderate, 4 =severe 

Interpretation of results:
GHS criteria not met
Conclusions:
In the skin irritation study, which was conducted according to OECD Test Guideline 404 and in compliance with GLP, the undiluted test material was not irritating to the skin of rabbits, following 4 hours semi-occlusive contact.
Executive summary:

In a study performed according to OECD Test Guideline 404 (Acute dermal irritancy/corrosivity) and in compliance with GLP, the test material was tested for its potential to induce skin irritation in rabbits.

A 0.5 ml volume of the test material was applied undiluted for 4 hours to the shaved backs of three (two male and one female) New Zealand White rabbits, semi-occluded. All test sites were examined for signs of dermal irritation (i.e. oedema, erythema and/or eschar formation) and corrosivity (i.e. ulceration and/or necrosis) 30-60 minutes and 24, 48 and 72 hours following removal of the patch. The primary Dermal Irritation Index (PDII) was calculated according to Draize criteria.

 

No signs of dermal irritation or corrosivity were observed in the three rabbits at any timepoint. The PDII for the test material was 0.

Under the conditions of the test, the test material was not irritating to rabbit skin.

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:
21 August 1995 to 30 September 1997
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:
yes
Remarks:
temperature slightly higher than recommended (23-24 °C, temperature of 17-23 °C recommended)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kuiper Rabbit Ranch
- Age at study initiation: ~ 4.5 months
- Weight at study initiation: 3.21 to 3.46 kg
- Housing: individually in suspended stainless steel cages
- Diet (e.g. ad libitum): approximately 150 g daily
- Water (e.g. ad libitum): reverse osmosis-purified water ad libitum
- Acclimation period: ~ 9 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 to 24
- Humidity (%): 41 to 55
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 28 June 1995 To: 1 September 1995
Vehicle:
unchanged (no vehicle)
Controls:
other: left eyes of each rabbit served as untreated control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
up to 72 hours after administration (observed at 1, 24, 48 and 72 hours)
Number of animals or in vitro replicates:
Three females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, rinsed with lukewarm water
- Time after start of exposure: 24 h

SCORING SYSTEM: according to the criteria of the Organisation for Economic Co-operation and Development, and Draize (see "Any other information on materials and methods incl. tables"

TOOL USED TO ASSESS SCORE: slit pen light. Fluorescein and ultraviolet light used to aid in the examination for corneal lesions after the 1-hour scoring (i.e. for the 24, 48 and 72-hour readings) and/or as long as corneal opacity persisted in individual rabbits.
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:
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:
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 #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
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:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
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:
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:
chemosis 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:
There was no irritation to the cornea or iris seen over the course of the experiment. At the 1-hour reading, conjunctival redness was observed in all animals (grade 2 in two, grade 1 in one), as was grade 1 chemosis. At the 24-hour reading, two animals exhibited grade 1 redness. There were no other irritant effects observed over the course of the study.
Other effects:
There were no deaths throughout the study.

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Cornea

Iris

Conjunctivae erythema

Conjunctivae chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

0/0/0

0/0/0 

1/2/2

1/1/1

24 h

0/0/0

0/0/0

1/1/0

0/0/0

48 h

0/0/0

0/0/0

0/0/0

0/0/0

72 h

0/0/0

0/0/0

0/0/0

0/0/0

Average 24h, 48h, 72h

0/0/0

0/0/0

0/0/0

0/0/0

Reversibility*

n/a

n/a

c

c

Average time (unit) for reversion

n/a

n/a

~ 48 h

24 h

 *Reversibility: c. = completely reversible;n.c.= not completely reversible; n. = not reversible

 

Interpretation of results:
GHS criteria not met
Conclusions:
In the eye irritation study, conducted according to OECD Test Guideline 405 and in compliance with GLP, the tes material was concluded to be not irritating to the eyes of three female rabbits when applied for 24 hours.
Executive summary:

In a GLP-compliant study performed in accordance with OECD Test Guideline 405, the test material was tested for its potential to irritate the eyes of rabbits.

 

0.1 ml of the test material was applied to the right eyes of three female rabbits for 24 hours, with the left eyes of each animal serving as an untreated control. Animals were observed at 1, 24, 48 and 72 hours after test substance administration using a slit pen light. Fluorescein and UV light were used to aid in the examination of corneal lesions after the 1-hour scoring and/or as long as corneal opacity persisted in individual rabbits.

 

Following treatment, no adverse effects were seen on the cornea or iris. Conjunctival redness and slight swelling was seen in all animals at the 1-hour reading, with redness persisting in two animals at the 24-hour reading. There were no other significant effects seen over the course of the study, and no mortality was observed.

 

An overall irritation score of 5.3 was calculated according to the Draize system of scoring (maximum possible Draize score = 110). Under the conditions of this study, the test material was not considered to be an eye irritant in rabbits.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The key study for skin irritation was performed according to OECD Test Guideline 404 and in compliance with GLP. The study found the test material was not irritating to skin in rabbits. A 0.5 ml volume of the test material was applied undiluted under semi-occlusive dressing for 4 hours onto the shaved backs of three (two male and one female) New Zealand White rabbits (Dow Corning Corporation, 2000). All test sites were examined for signs of dermal irritation (i.e. oedema, erythema and/or eschar formation) and corrosivity (i.e. ulceration and/or necrosis) 30-60 minutes and 24, 48 and 72 hours following removal of the patch. The primary Dermal Irritation Index (PDII) was calculated according to Draize criteria. No signs of dermal irritation or corrosivity were observed in the three rabbits at any timepoint. The PDII for test material was 0.

The key study for eye irritation, conducted in compliance with GLP and in accordance with OECD Test Guideline 405, found that the test material was not irritating to eyes of rabbit (Dow Corning Corporation, 1997).  Single instillation of 0.1 ml of the test material was applied to the right eyes of three female rabbits for 24 hours, with the left eye of each animal serving as an untreated control. Animals were observed at 1, 24, 48 and 72 hours after test substance administration using a slit pen light. Fluorescein and UV light were used to aid in the examination of corneal lesions after the 1-hour scoring and/or as long as corneal opacity persisted in individual rabbits. Following treatment, no adverse effects were seen on the cornea or iris. Conjunctival redness and slight swelling were seen in all animals at the 1-hour reading, with redness persisting in two animals at the 24-hour reading. There were no other significant effects seen over the course of the study, and no mortality was observed. An overall irritation score of 5.3 was calculated according to the Draize system of scoring (maximum possible Draize score = 110). Under the conditions of this study, the test material was therefore not considered to be an eye irritant in rabbits.


Justification for classification or non-classification

Based on the available information phenyl silsesquioxanes does not require classification for irritation according to Regulation (EC) No 1272/2008.