Registration Dossier

Administrative data

Description of key information

Valid irritation/corrosion studies with the test substance are available. In a study conducted according to OECD guideline 404 no skin reactions were observed after treatment (rabbit, RCC743490, 1999). In a study conducted according to OECD guideline 405 only minor eye reactions were observed after treatment which was fully reversible within 72 h (rabbit, RCC743501, 1999). Thus, the test substance was not irritating to skin and eyes.

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:
1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD-guideline and GLP-compliant
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
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: Elevage Scientifique des Dombes, F-01400 Chatillon sur Chalaronne / France
- Age at study initiation: 14 weeks (males), 15 weeks (females)
- Mean weight at study initiation: 2804 g
- Housing: Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with wood and haysticks for gnawing
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet
- Water (e.g. ad libitum): Community tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-24 °C
- Humidity (%): 48-88 %
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
other: untreated skin of the same animals
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mg

VEHICLE
- Amount(s) applied (volume or weight with unit): moistened with water
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours
Number of animals:
1 male,
2 females
Details on study design:
TEST SITE
- Area of exposure: flank
- % coverage: 10 cm x 10 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): flushed with lukewarm tap water
- Time after start of exposure: 4h

SCORING SYSTEM: numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992
Irritation parameter:
erythema score
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
edema score
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritant / corrosive response data:
- Application of the test article to healthy intact rabbit skin resulted in a primary irritation score of 0.00.
- Local signs (mean values from 24 to 72 hours) consisted of grade 0.00 erythema and grade 0.00 edema. No signs of irritation were observed.
- No staining by the test article of the treated skin was observed.
Other effects:
- No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred.
- Animals gained normal body weight.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
After dermal application of 0.5 mg test substance according to OECD guideline 404 for 4 h skin was flushed with water and the skin was scored for erythema and edema after 24, 48 and 72 h. Since neither erythema nor edema were seen the test substance is considered to be "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:
1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD-guideline and GLP-compliant
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: Elevage Scientifique des Dombes, F-01400 Chatillon sur Chalaronne / France
- Age at study initiation: 14 weeks (males), 15 weeks (females)
- Housing: Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with wood and haysticks for gnawing
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet
- Water (e.g. ad libitum): Community tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22-24 °C
- Humidity (%):48-88 %
- Air changes (per hr):10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of the same animal
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volue or weight with unit): 0.1 g
Duration of treatment / exposure:
unrinsed
Observation period (in vivo):
1, 24, 48 and 72 hours
Number of animals or in vitro replicates:
1 male,
2 females
Details on study design:
SCORING SYSTEM: numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992 at approximately 1, 24, 48 and 72 hours after administration

Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
iris score
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72 h
Score:
0.44
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72 h
Score:
0.22
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritant / corrosive response data:
Application of the test article to healthy rabbit conjunctivae resulted in a primary irritation score of 0.67. Slightly reddened and/or slight swelling of the conjunctivae, white solid remnants in eye or conjunctival sac were observed in all animals 1 and 24 hours after application as well as in one female at the 48-hour reading. Slight watery discharge was observed in the male and one female animal at the 1-hour reading. Slightly reddened sclera were observed in all animals at the 1-hour reading and in one female at the 24-hour reading.
Other effects:
- No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occuned.
- No staining of the treated eyes by the test article was observed.
- All animals gained normal body weight

Eye irritation scores: individual values

Animal No.

Sex

Evaluation interval

Corneal opacity

Iris

Conjunctivae

Redness

Chemosis

1

M

 

1 h

0

0

1

1

2

F

0

0

1

1

3

F

0

0

1

1

1

M

 

24 h

0

0

1

0

2

F

0

0

1

0

3

F

0

0

1

1

1

M

 

48 h

0

0

0

0

2

F

0

0

0

0

3

F

0

0

1

1

1

M

 

72 h

0

0

0

0

2

F

0

0

0

0

3

F

0

0

0

0

1

M

 

24-72 h

0

0

0.33

0.00

2

F

0

0

0.33

0.00

3

F

0

0

0.67

0.67

Mean (1-2-3)

24-72 h

0.00

0.00

0.44

0.22

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based upon the referred classification criteria, the test substance is considered to be "not irritating" to the rabbit eye.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

After application of the test substance to rabbits skin according to OECD guideline 404 (1992) under semi-occlusive conditions for 4 hours, skin reactions were scored 1, 24, 48 and 72 hours after removal of test substance (RCC743490, 1999). Local signs (mean values from 24 to 72 hours) consisted of grade 0.00 erythema and grade 0.00 edema. The test article caused no staining of the treated skin. No signs of systemic toxicity were observed and no mortality occurred. Thus, the test substance was considered to be not irritating to skin.

 After application of 0.1 g test substance to rabbits eye according to OECD guideline 405 (1993) without rinsing, eye reactions were scored 1, 24, 48 and 72 hours after application of test substance (RCC743501, 1999). Chemosis (graded 1) was seen in 1/3 animals after 24 and 48 h which recovered after 72 h. Redness (graded 1) was seen in 3/3, 1/3 and 0/3 animals after 24, 48 and 72 h. No further eye reactions, no staining of the treated eyes and no signs of systemic toxicity were observed. Thus, the test substance was considered to be not irritating to eyes.

No valid data for respiratory irritation are available.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified as irritating for skin or eyes under Directive 67/548/EEC.

                                             

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for irritation under Regulation (EC) No. 1272/2008.