Registration Dossier

Administrative data

Description of key information

in vivo skin irritation, OECD 404, not classified

in vivo eye irritation, OECD 405, H319, Eye irritation 2

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:
march 2000
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Not GLP compliant but good described study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: REAL DECRETO 363/1995, 10 march
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: authorized supplier.
- Weight at study initiation: 2033-2113 g
- Housing: Stainless steel single cage
- Diet: daily dose of 150 g experimental diet for rabbits, provided by an authorized vendor
- Water: filtered tap water (5 µm) , ad libitum
- Acclimation period: 7 days
- Health check: during observation period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21± 2°C
- Humidity (%): 55 ± 25%
- Air changes (per hr): 15 air change per hour with filtered air (with 5 µm filter)
- Photoperiod : 12 hour cycle dark/light

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied:0.5 g
Duration of treatment / exposure:
4 hours of treatment
Observation period:
1, 24, 48 ,72 hours and 7+14 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure:dorsal-column area near the spine, forming a rectangle 20 cm x 13 cm .
- % coverage: 6 cm^2
- Type of wrap if used: simple bandage and covered in turn with a light hypoallergenic adhesive bandage .

REMOVAL OF TEST SUBSTANCE
- Washing : yes

SCORING SYSTEM: erithema and edema (similar to OECD 404)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 1.67
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0.67
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0.67
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible
Other effects:
no data
Interpretation of results:
other: not classified under Regulation 1272/2008
Conclusions:
The substance was tested for skin irritation following OECD 404.Under the experimental conditions the substance did not show any irritation properties.
Executive summary:

The substance was tested for skin irritation following OECD 404 . Three New Zealand white rabbits were tested with an occlusive method. After 14 days of observation no rabbit shows signs of erythema or edema. The substance is classified as non-irritating to the 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:
April 2000
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Not GLP compliant but good described study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: REAL DECRETO 363/1995, 10 march
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: authorized supplier.
- Weight at study initiation: 2099-2191 g
- Housing: Stainless steel single cage
- Diet: daily dose of 150 g experimental diet for rabbits, provided by an authorized vendor
- Water: filtered tap water (5 µm , ad libitum
- Acclimation period: 7 days
- Health check: during observation period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21± 2°C
- Humidity(%) :55 ± 25%
- Air changes (per hr): 15 air change per hour with filtered air (with 5 µm filter)
- Photoperiod: 12 hour cycle dark/light
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 g
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3
Details on study design:
OBSERVATIONS:
after 1, 24, 48, 72 hours and 7,14, and 21 days

SCORING SYSTEM:cornea, iris, conjunctiva (similar to OECD 405)

TOOL USED TO ASSESS SCORE: fluorescein

To facilitate consideration of the reactions, the operator had used a manual lamp and after 24 hours of application have used fiuorescein to evaluate any lesions.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 2.33
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 2.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 2.33
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 3.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 2.67
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Interpretation of results:
other: classified under Regulation 1272/2008 as H319 Cat 2
Conclusions:
The substance was tested for eye irritation following OECD 405. Under the experiemental conditions the substance show eye irritative properties.
Executive summary:

The substance was tested for eye irritation following OECD 405. Three NZW rabbits were tested for 24 hours and showed for 3/3 animals a score for conjuncitvae > 2.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

According to the CLP Regulation (EC n. 1272/2008) the following classifications apply:

 

Skin irritant cat2:

1) Mean value of ≥ 2,3 - ≤ 4,0 for erythema/ eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions; or

2)Inflammation that persists to the end of the observation period normally 14 days in at least 2 animals, particularly taking into account alopecia (limited area), hyperkeratosis, hyperplasia, and scaling; o

3) In some cases where there is pronounced variability of response among animals, with very definite positive effects related to chemical exposure in a single animal but less than the criteria above.

 

 

Eye irritant Cat 2:

at least in 2 of 3 tested animals, a positive response of:

1)     corneal opacity ≥ 1 and/or

2)     iritis ≥ 1, and/or

3)      conjunctival redness ≥ 2 and/or

4)      conjunctival oedema (chemosis) ≥ 2

5)     calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, and which fully reverses within an observation period of 21 days

Based on the results for the tests for skin and eye the substance is classified as H319, Eye irritation 2 and not classified as skin irritant.