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Description of key information

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:
July 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: done under GLP condition and acc. to OECD guideline no. 404
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River France, L'Arbresle Cedex, France
- Age at study initiation: 6 weeks
- Weight at study initiation: 1.0 kg
- Housing: individually housed in labeled cages with perforated floors and shelters.
- Diet: pelleted diet approx 100 g per day
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0
- Humidity (%): 40-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped with electric clippers
Vehicle:
water
Controls:
no
Amount / concentration applied:
0.5 g of test substance moistened with 0.2 mL of the vehicle and applied to the skin
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure:150 square centimeters (10x15 cm)
- Type of wrap if used: Micropore Tape

REMOVAL OF TEST SUBSTANCE
- Washing: tap water
- Time after start of exposure: 4 hours

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) * 4
*. Where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the
maximum grade for erythema (= 4) is given.

Oedema formation:
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 millimeter) 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure) 4
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1,24,48 and 72 hours
Score:
0
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
none
Other effects:
none
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on these results Nadide does not have to be classified and has no obligatory labelling requirements for skin irritation acc to the : GHS and EU CLP regulations
Executive summary:

Primary skin irritation/corrosion study with nadide in the rabbit (4-hour semi-occlusive application).

The study was carried out based on the guidelines described in:

OECD No.404, "Acute Dermal Irritation/Corrosion" (2002)

Three rabbits were exposed to 0.5 grams of nadide, moistened with water by application onto clipped skin for 4 hours using a semi-occlusive dressing. Skin reactions were assessed 1, 24, 48 and 72 hours after exposure.

 

 No skin irritation was caused by 4 hours exposure to nadide.

Based on these results nadide does not have to be classified and has no obligatory labelling requirement for skin irritation according to the EU CLP

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:
July-August 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted under GLP and acc. to OECD guideline no. 405
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
The study integrity was not adversely affected by the deviations.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River France, L'arbresle Cedex, France
- Age at study initiation: 6 weeks
- Weight at study initiation: 1.0 kg
- Housing: individually housed
- Diet: pelleted diet at 100 g per day
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 40-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12

Vehicle:
unchanged (no vehicle)
Controls:
other: the second eye remained untreated and served as the reference control
Amount / concentration applied:
approx 42 mg of the tgest substance (volume approx. 0.1 mL)
Duration of treatment / exposure:
3 days
Observation period (in vivo):
3 days
Number of animals or in vitro replicates:
3 males
Details on study design:
CORNEAL IRRITATION
Opacity: degree of density (area most dense taken for reading)
No ulceration or opacity (may include slight dulling of normal luster) 0
Scattered or diffuse areas of opacity, details of iris clearly visible 1
Easily discernible translucent area, details of iris slightly obscured 2
Nacreous area, no details of iris visible, size of pupil barely discernible 3
Opaque cornea, iris not discernible through the opacity 4

Area of cornea involved:
No ulceration or opacity 0
One quarter or less but not zero 1
Greater than one quarter, but less than half 2
Greater than half, but less than three quarters 3
Greater than three quarters, up to whole area 4

IRIS
Normal 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia,
or injection, any of these or combination thereof, iris still reacting to light
(sluggish reaction is positive) 1
No reaction to light, hemorrhage, gross destruction (any or all of these) 2

CONJUNCTIVAL IRRITATION
Redness (refers to palpebrae and sclera, excluding cornea and iris):
Blood vessels normal 0
Some blood vessels definitely hyperaemic (injected) 1
Diffuse, crimson color, individual vessels not easily discernible 2
Diffuse beefy red 3

Chemosis (refers to lids and/or nictitating membranes):
No swelling ………………………………………… 0
Any swelling above normal (includes nictitating membranes) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids more than half closed 4

Discharge:
No discharge (may include small amounts observed in inner canthus of normal animals) 0
Any amount different from normal and/or lacrimation 1
Discharge with moistening of the lids and hairs just adjacent to lids 2
Discharge with moistening of the lids and hairs (considerable area around the eye) 3


Where standard lighting was considered inadequate for observing minor effects, eye examinations were performed using an ophthalmic examination lamp.
In cases of equivocal results when comparing the treated and untreated eyes, the illustrated guide from the Consumer Product Safety Commission, Washington, D.C. 20207 was used for additional control purposes.
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 h
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
Instillation of approximately 42 mg of b-Nicotinamide-adenine Dinucleotide II (nadide) (a volume of approximately 0.1 mL) into one eye of each of three rabbits resulted in irritation of the conjunctivae, which consisted of redness and chemosis. The irritation had completely resolved within 48 hours.

No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.


Other effects:
none
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on these results nadide does not have to be classified and has no obligatory labelling requirement for eye irritation according to the: GHS and EU CLP.

Executive summary:

Acute eye irritation/corrosion study with nadide in the rabbit.

 

The study was carried out based on the guidelines described in: OECD No.405 (2002) "Acute Eye Irritation / Corrosion"

Single samples of approximately 42mg of Nadide (a volume of approximately 0.1 mL) were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours after instillation.

 

Instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness and chemosis. The irritation had completely resolved within 48 hours.

 

 Based on these results nadide does not have to be classified and has no obligatory labelling requirement for eye irritation according to the EU CLP

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:
both in vivo and in vitro skin irritation studies are valid and performed according to the respective OECD guideline and under GLP.

Justification for selection of eye irritation endpoint:
based on the equivocal results from the in vitro BCOP assay it was concluded that there was a need to perform the in vivo eye irritation study in rabbit to establish the possible eye irritating properties of the test substance.

Justification for classification or non-classification

both in vitro and in vivo skin irritation studies showed no irritiating effect of the substance. The mean in vitro irritancy score in the BCOP assay was above 55.1 and based on that result alone Nadide would have been considered as a severe irritant or corrosive. However, as no skin effects were noted in the previous studies and the effect in the BCOP seemed to be only on one endpoint (opacity) an in vivo eye irritation study was then conducted in the rabbit. based on these results Nadide was not found to be an eye irritant and hence based on the CLP and GHS criteria has no obligatory labelling for eye irritation.