Registration Dossier

Administrative data

Description of key information

Skin irritation was tested in a guideline study according to OECD guideline 404 in 3 New Zealand White rabbits. With reference the reported scores and the full reversibility of effects within 48 h the test item does not have to be classified as irritant to the skin according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).
N,N’-Bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide was tested for its eye irritant properties in 3 New Zealand White rabbits. The study was performed according to OECD Guideline 405. Effects on conjunctivae (redness and swelling), as well as iris congestion and cornea opacity were observed in all animals one hour after application. These signs were fully reversible within 14 days.

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:
1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline conform GLP study.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: E.S.D. (Chatillon-sur-Chalaronne, France)
- Age at study initiation: 3 months
- Weight at study initiation: 2 - 3 kg
- Housing: individually in stainless steel cages
- Diet (e.g. ad libitum): 150 g/animal/d of pelleted complete rabbit diet (diet reference 112 C-10 Usine d'Alimentation Rationnelle, Epinay-sur-Orge, France)
- Water (e.g. ad libitum): softened and filtered mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 +/- 3 °C
- Humidity (%): >/= 45%
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
not required
Amount / concentration applied:
500 mg
Duration of treatment / exposure:
4 h
Observation period:
72 h
Number of animals:
3
Details on study design:
- Preparation of exposure area
at least the day before application of the test item, the back and the flanks of the rabbits were carefully clipped. At the time of application, only the animals showing a healthy intact skin, with no evidence of macroscopic irritation were used in the study.

-Method of administration
The test item was applied under a semi-occlusive dressing composed of a gauze pad approx. 2.5 cm x 2.5 cm, maintained in contsct with the skin with a perforated tape. This tape was applied on a crimped gauze bandage which fully covered the clipped area to avoid possible irritation reactions and was wrapped around the animal without blocking the respiratory and abdominal movements.
The powder was moistened with water for injection to obtain a homogeneous paste.

SCORING SYSTEM:

Erythema and eschar formation
No erythema.......................................................................................................................0
very slight erythema (barely perceptible)......................................................................1
well-defined erythema......................................................................................................2
moderate to severe erythema..........................................................................................3
severe erythema (beet redness) to slight eschar formation (lesion in depth).........4

Oedema
No oedema...................................................................................................................................0
very slight oedema (barely perceptible)..................................................................................1
slight oedema (edges of area well defined by definite raising)............................................2
moderate oedema (raised approximately 1mm)....................................................................3
severe oedema (raised more than 1mm and extending beyond area of exposure.........4
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: overall at 24, 48 and 72 h
Score:
0.33
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 anf 72 h
Score:
0.1
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Mean erythema score (all animals; 24, 48 and 72 h): 0.1; fully reversible within 48 h
Mean edema score (all animals; 24, 48 and 72 h): 0
Other effects:
No effects observed
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
With reference the reported scores and the full reversibility of effects within 48 h the test item does not have to be classified as irritant to the skin according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).
Executive summary:

N,N’-Bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide was tested for its skin irritant properties in 3 New Zealand White rabbits. The study was performed according to OECD Guideline 404.

With reference the reported scores and the full reversibility of effects within 48 h the test item does not have to be classified as irritant to the skin according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

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:
1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline conform GLP study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: E.S.D. (Chatillon-sur-Chalaronne, France)
- Age at study initiation: 3 months
- Weight at study initiation: 2 -3 kg
- Housing: individually in stainless steel cages
- Diet (e.g. ad libitum): 150 g/animal/day of pelleted complete rabbit diet (Diet reference 11 C-10-Usine d'Alimentation Rationelle, Epiny-sur-Orge, France)
- Water (e.g. ad libitum): softened and filtered amins drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19+/-3°C
- Humidity (%): >/= 45%
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
64 mg (quantity corresponding to a vloume of 0.1 mL)
Duration of treatment / exposure:
24 h
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
3
Details on study design:
- Method of administration
Each animal was immobilised in a restraining box. The test article was administered into the inferior conjunctival sac of the right eye of each of the rabbits, the left eye serving as control. The lower and upper eyelids were held in contact for a few seconds to prevent loss of the test item. To prevent rubbing of the eye, the animals were kept in restraining boxes for about 1 h after treatment. They were then returned to their individual cages.

- Duration of treatment
After 24 h, the possible presence of corneal erosion was demonstrated uding flourescein which was eliminated with lukewarm tap water.

SCORING SYSTEM:

A. CORNEA
Degree of opacity (most dense area used)
No opacity ...................................................................................................................0
Scattered or diffuse areas, details of iris clearly visible........................................1
Easily discernible translucent areas, details of iris slightly obscured................2
Opalescent areas, no details of iris visible , size of pupil barely discernible ....3
Opaque, iris invisible, ulzeration ..............................................................................4

IRIS
Normal ......................................................................................................................... 0
Folds above normal , congestion, swelling, circumcorneal injection (any of all of these or combination of any thereof); iris still reacting to light
(sluggish reaction is positive) ......................... .........................................................1
No reaction to light, haemorrhage, gross destruction (any or all of these) ......2

CONJUNCTIVAE

A. Redness
Blood vessels normal...............................................................................................................0
Blood vessels definitely injected above normal ................................................................. 1
More diffuse, deeper crimson red, individual blood vessels not easily discernible .....2
Diffuse beefy red......................................................................................................................3

B. Chemosi s (refers to palpebral and bulbar conjunctivae)
No swelling .........................................................................................0
Any swelling above normal (includes nictitating membran) ..... 1
Obvious swelling with partial eversion of l i d s ...........................2
Swelling with lids about half closed ................................................3
Swelling with lids half closed to completely closed.......................4
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Time point:
other: overall at 24, 48 and 72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Time point:
other: overall at 24, 48 and 72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Time point:
other: overall at 24, 48 and 72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
1.6
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: overall at 24, 48 and 72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: overall at 24, 48 and 72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: overall at 24, 48 and 72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
1.4
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: overall at 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: overall at 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: overall at 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
Reversibility of the observed effects (chemosis mean grade 1.4, redness mean grade 1.6, cornea mean score grade 2 and iris mean score grade 1): Changes fully reversible within 14 days
Other effects:
none
Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
With reference the reported scores andreversibility of effects within 14 days N,N’-Bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide has to be classified as irritant to the eyes (H 319) according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).
Executive summary:

N,N’-Bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide was tested for its eye irritant properties in 3 New Zealand White rabbits. The study was performed according to OECD Guideline 405.

Effects on conjunctivae (redness and swelling), as well as iris congestion and cornea opacity were observed in all animals one hour after application. These signs were fully reversible within 14 days.

With reference the reported scores andreversibility of effects within 14 days N,N’-Bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide has to be classified as irritant to the eyes (H 319) according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation: 1 key study available: not irritating

Eye irritation: 1 key study available: irritating

 

There is one reliable study on the skin irritancy potential. Skin irritation was tested in a guideline study according to OECD guideline 404 in 3 New Zealand White rabbits.

With reference the reported scores and the full reversibility of effects within 48 h the test item does not have to be classified as irritant to the skin according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

There is one reliable study available on the eye irritancy potential. N,N’-Bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide was tested for its eye irritant properties in 3 New Zealand White rabbits. The study was performed according to OECD Guideline 405.Effects on conjunctivae (redness and swelling), as well as iris congestion and cornea opacity were observed in all animals one hour after application. These signs were fully reversible within 14 days.

With reference the reported scores and reversibility of effects within 14 days N,N’-Bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide has to be classified as irritant to the eyes (H 319) according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

Justification for selection of skin irritation / corrosion endpoint:
Guideline conform GLP study

Justification for selection of eye irritation endpoint:
Guideline conform GLP study

Effects on eye irritation: irritating

Justification for classification or non-classification

With reference the reported scores and the full reversibility of effects within 48 h the test item does not have to be classified as irritant to the skin according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

With reference the reported scores and reversibility of effects within 14 days N,N’-Bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide has to be classified as irritant to the eyes (H 319) according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).