Registration Dossier

Administrative data

Description of key information

Skin irritation (OECD 404), rabbit: not irritating
Eye irritation (OECD 405), rabbit: not irritating

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:
05 Feb - 28 June 1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
yes
Remarks:
no data on purity available
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products, Inc., Denver, PA, USA
- Age at study initiation: young adult
- Weight at study initiation: 2739 - 2903 g
- Fasting period before study: no
- Housing: individually housed in wire-mesh cages
- Diet: Purina Certified Rabbit Chow No. 5322, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.7-20.4
- Humidity (%): 34.7-60.2
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated sites of the same animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 ml
Duration of treatment / exposure:
4 h
Observation period:
8 days
Reading time points: 1, 24, 48 and 72 h and 4, 5, 6, 7 and 8 days
Number of animals:
6 (2 males, 4 females)
Details on study design:
TEST SITE
- Area of exposure: approximately 6 cm²
- Type of wrap if used: test substance was applied under a secured 2-ply gauze patch overwrapped with a gauze binder and secured with Dermiform tape

REMOVAL OF TEST SUBSTANCE
- Washing: at the end of the treatment period the sites were wiped with disposable paper towels moistened with deionized water
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
other: mean of all 6 animals
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
other: mean of all 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No oedema reactions were observed in any animal at any time point. After 0.5-1 h no erythema reactions were observed. After 24 h 2/6 animals showed erythema (grade 1), which were fully reversible within 7 days. In addition, in the 2 animals with erythema reactions desquamation was observed from Day 3 until Day 7.
Other effects:
No deaths, clinical signs of toxicity or body weight changes were observed throughout the study period.

Table 1: Individual scores from skin irritation study in rabbits.

Rabbit No.

1 (male)

2 (male)

3 (female)

4 (female)

5 (female)

6 (female)

Observation time

Ery.

Oed.

Ery.

Oed.

Ery.

Oed.

Ery.

Oed.

Ery.

Oed.

Ery.

Oed.

1 h

0

0

0

0

0

0

0

0

0

0

0

0

24 h

0

0

1

0

0

0

1

0

0

0

0

0

48 h

0

0

1

0

0

0

1

0

0

0

0

0

72 h

0

0

1d

0

0

0

1d

0

0

0

0

0

4 d

-

-

1d

0

-

-

1d

0

-

-

-

-

7 d

-

-

0

0

-

-

0d

0

-

-

-

-

8 d

-

-

-

-

-

-

0

0

-

-

-

-

Mean value

0

0

1

0

0

0

1

0

0

0

0

0

24 + 48 + 72 h

Ery.: Erythema

Oed.: Oedema

d: Desquamation

Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
In a skin irritation study according to OECD 404 the test item was found to be not irritating to skin. Treatment of 6 New Zealand White rabbits under semi-occlusive conditions with 0.5 ml undiluted test substance induced no edema in any animal at any time point. Slight erythema (grade 1) were observed in 2/6 animals but were fully reversible within 7 days. Furthermore no signs of systemic toxicity no effects on body weight were observed.
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:
05 Feb - 28 June 1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
no data on purity available
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products, Inc., Denver, PA, USA
- Age at study initiation: young adult
- Weight at study initiation: 2425 - 3073 g
- Fasting period before study: no
- Housing: individually housed in mesh-bottom cages
- Diet: Purina Certified Rabbit Chow No. 5322, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.8-20.2
- Humidity (%): 35.0-42.6
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated left eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 ml
Duration of treatment / exposure:
single instillation without washing
Observation period (in vivo):
4 days
Reading time points: 1, 24, 48 and 72 h and 4 days
Number of animals or in vitro replicates:
6 (3 males, 3 females)
Details on study design:
SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: hand-held penlight / fluorescein (UV light)
Irritation parameter:
cornea opacity score
Basis:
other: mean of all 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
other: mean of all 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
other: mean of all 6 animals
Time point:
24/48/72 h
Score:
0.61
Max. score:
3
Reversibility:
fully reversible within: 4 days
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
other: mean of all 6 animals
Time point:
24/48/72 h
Score:
0.06
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No effects on cornea or iris were observed in any animal at any time point. Slight conjuntivae redness (grade 1-2) was observed in every animal 1 h after instillation of test item and were fully reversible within 4 days. Chemosis (grade 1) was observed in every animal 1 h after instillation of test substance and was fully reversible within 48 h. Clear discharge was observed in 1 animal 1 h after instillation of test substance but was fully reversible within 24 h.
Other effects:
No signs of systemic toxicity or effects on body weight gain were observed.

Table 1: Individual scores from eye irritation study in male rabbits.

Rabbit #

(males) 

Time [h]

 

conjunctivae

 

iris

 

cornea

 

redness

swelling

1

 

 

 

 

1

2

1

0

0

24

1

0

0

0

48

0

0

0

0

72

0

0

0

0

average

(over 24, 48, 72 h)

0.33

0

0

0

2

 

 

 

 

1

2

1

0

0

24

1

0

0

0

48

1

0

0

0

72

1

0

0

0

96

0

0

0

0

average

(over 24, 48, 72 h)

1.00

0

0

0

3

 

 

 

 

1

1

1

0

0

24

1

0

0

0

48

1

0

0

0

72

1

0

0

0

96

0

0

0

0

average

(over 24, 48, 72 h)

1.00

0

0

0

 

 

Table 2: Individual scores from eye irritation study in female rabbits.

Rabbit #

(females) 

Time [h]

 

conjunctivae

 

iris

 

cornea

 

redness

swelling

1

 

 

 

 

1

1

1

0

0

24

1

0

0

0

48

0

0

0

0

72

0

0

0

0

average

(over 24, 48, 72 h)

0.33

0

0

0

2

 

 

 

 

1

2

1

0

0

24

1

0

0

0

48

0

0

0

0

72

0

0

0

0

96

0

0

0

0

average

(over 24, 48, 72 h)

0.33

0

0

0

3

 

 

 

 

1

2

1

0

0

24

1

1

0

0

48

1

0

0

0

72

0

0

0

0

96

0

0

0

0

average

(over 24, 48, 72 h)

0.66

0.33

0

0

 

 

Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
In an eye irritation study according to OECD 405 the substance was found to be not irritating to eyes. Treatment of 3 female and 3 male New Zealand White rabbits with 0.1 ml undiluted test substance resulted in no effects on cornea and iris in any animal at any time point. Slight conjuntivae redness (grade 1-2) was observed in every animal 1 h after instillation of test item and were fully reversible within 4 days. Chemosis (grade 1) was observed in every animal 1 h after instillation of test substance and was fully reversible within 48 h. Clear discharge was observed in 1 animal 1 h after instillation of test substance but was fully reversible within 24 h.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

A skin irritation study with [3-(trimethoxysilyl)propyl]urea (CAS 23843-64-3) is available and was performed according to OECD 404 and in compliance with GLP (WIL, 1996c). In the study four female and two male New Zealand White rabbits were exposed to 0.5 ml of the neat test material applied onto the clipped skin via semi-occlusive dressing for 4 hours. Skin reactions were evaluated 1, 24, 48 and 72 hours as well as 4, 7 and 8 days after removal of the test substance. No edema reactions were observed in any animal at any time point. After 0.5 - 1 h no erythema reactions were observed. After 24 h 2/6 animals showed erythema (grade 1), which were fully reversible within 7 days. In addition, in the 2 animals with erythema reactions desquamation was observed from day 3 until day 7. Mean values for erythema and edema were 0.33 and 0, respectively. No mortalities occurred and no remarkable body weight changes as well as clinical signs of toxicity were observed during the study period. Based on the study results and according to CLP classification criteria, the test substance is not considered to be irritating to skin.

 

Eye irritation

An eye irritation study with [3-(trimethoxysilyl)propyl]urea (CAS 23843-64-3) is available and was performed according to OECD 405 and in compliance with GLP (WIL, 1996d). For the assessment of the eye irritation properties 0.1 ml of the test substance was instilled in the eye of three New Zealand White rabbits of each sex. The eyes were examined and the changes were graded according to the Draize scoring system 1, 24, 48 and 72 hours and on Day 4 post-application. No effects on cornea or iris were observed in any animal at any time point. Slight conjunctivae redness (grade 1-2) was observed in all animals 1 h after instillation of test substance but were fully reversible within 4 days. Chemosis (grade 1) was observed in all animals 1 h after instillation of the test substance but was fully reversible within 48 h. Clear discharge was observed in one animal 1 h after instillation of test substance but was also fully reversible within 24 h. Mean values for conjunctivae and chemosis over all 6 animals were 0.61 and 0.06, respectively. No signs of systemic toxicity or effects on body weight gain were observed. Based on the study results and according to CLP classification criteria, the test substance is not considered to be irritating to eyes.

Justification for classification or non-classification

The available data on skin and eye irritation of the registered substance do not meet the criteria for classification according to Regulation (EC) No 1272/2008 and are therefore conclusive but not sufficient for classification.