Registration Dossier

Administrative data

Description of key information

Skin irritation: Not irritating in rabbits (OECD 404)
Eye irritation: Not irritating in rabbits (OECD 405)

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Millbrook Breeding Labs, Amherst, MA
- Age at study initiation: 4 months
- Weight at study initiation: 3.0 to 3.8 kg
- Housing: housed 1/cage in suspended wire cages
- Diet (e.g. ad libitum): PMI rabbit chow provided daily
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): averaged 21 °C
- Humidity (%): 60 to 82 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle


IN-LIFE DATES: From: 06/20/2006 To: 06/23/2006
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL/site

VEHICLE no vehicle used
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: 10 x 10 cm
- Type of wrap if used: piece of fabric (semiocclusive) secured with adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with paper towels saturated with tap water and blotted dry with paper towels
- Time after start of exposure: 4 hours

SCORING SYSTEM: A modified Primary Irritation Index was calculated by adding the mean erythema and edema scores at the 60 minute after removal of wrappings, 24, 48 and 72 hour scoring intervals, and dividing by the number of evaluation intervals (4).
Erythema and Eschar
0: No erythema
1: Very slight erythema (barely perceptibe)
2: Well defined erythema
3: Moderate to severe erythema
4: Severe erythema (beet redness) to slight eschar formation (injuries in depth)

Oedema
0: No oedema
1: Very slight oedema (barely perceptible)
2: Slight oedema (edges of area well-defined by definite raising)
3: Moderate oedema (raised approximately 1.0 mm)
4: Severe oedema (raised more than 1.0 mm, extending beyond the area of exposure)
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 72 hours
Score:
0.25
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
Erythema was absent to very slight at 60 minutes and 24 hours after patch removal and absent at 48 and 72 hours. There was no oedema noted at any observation period.
Other effects:
There were no abnormal physical signs noted during the observation period.
All body weight changes were normal.
Interpretation of results:
other: Not classified in accordance with EU criteria
Conclusions:
A modified primary mean irritation score of 0.25 was determined in this study.
Executive summary:

To determine the irritant or corrosive effects, if any, of the test substance when applied dermally, a study following OECD Guideline Number 404 was performed.

Since the test article was not expected to produce severe irritation or corrosion, three healthy New Zealand White rabbits (females) were dosed dermally with the test substance. The test article (0.5 mL) was applied dermally to one intact site/rabbit. The test article was kept in contact with the skin for 4 hours at which time the wrappings were removed. Dermal reactions were scored at 60 minutes after removal of wrappings. Reactions were scored again at 24, 48 and 72 hours. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction at these time periods. Body weights were recorded pretest and at termination. A modified Primary Irritation Index was calculated using the 60 minute, 24, 48 and 72 hour scoring intervals.

Erythema was absent to very slight at 60 minutes and 24 hours after patch removal and absent at 48 and 72 hours. There was no oedema noted at any observation period.

There were no abnormal physical signs noted during the observation period. All body weight changes were normal.

The study authors concluded that the substance is not a dermal irritant.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
The control eye of animal #G8794/F was not scored at one hour. This did not appear to impact the study results since all scores for the animal were zero for the remainder of the study.
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Millbrook Breeding Labs, Amherst, MA
- Age at study initiation: 3 months old
- Weight at study initiation: 2.3 to 2.5 kg
- Housing: housed 1/cage in suspended cages
- Diet (e.g. ad libitum): PMI Rabbit Chow provided daily
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 14-21 °C
- Humidity (%): 72- 92 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle


IN-LIFE DATES: From: June 26, 2006 To: June 29, 2006
Vehicle:
unchanged (no vehicle)
Controls:
other: contralateral eye of dosed rabbit
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

VEHICLE no vehicle used
Duration of treatment / exposure:
24 hour
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated and control eye were washed with saline following the 24 hour observation interval for approximately one minute using a volume and velocity of flow which did not cause injury.
- Time after start of exposure: 24 hours


SCORING SYSTEM: graded according to the numerical Draize technique


TOOL USED TO ASSESS SCORE: Mini-Maglite(R) flashlight equipped with a high intensity bulb
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 hour
Score:
0
Max. score:
80
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hour
Score:
0
Max. score:
10
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48 and 72 hour
Score:
0.11
Max. score:
20
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hour
Score:
0
Irritant / corrosive response data:
There was no corneal opacity or iritis noted at any observation period. Conjunctival irritation, noted in 3/3 eyes, cleared by 48 hours.
All three control eyes appeared normal at each observation period.
Other effects:
There were no abnormal physical signs noted during the observation period.
Interpretation of results:
other: Not classified in accordance with EU criteria
Conclusions:
Ocular administration of the test substance produced conjunctival irritation which cleared by 48 hours.
Executive summary:

To determine the irritant and/or corrosive effects, the test substance was instilled into the rabbit eye. This study was designed to follow OECD Guideline 405.

Three healthy New Zealand White rabbits (2 males - 1 female), free from evidence of ocular irritation and corneal abnormalities, were dosed with the test substance. The test article (0.1 mL) was placed into the conjunctival sac of one eye of each rabbit. The contralateral eye served as control. The treated and untreated eye of each rabbit were examined and scored by the Draize technique at 1, 24, 48 and 72 hours postdose. Both eyes were washed with saline following the 24 hour observation interval for approximately one minute using a volume and velocity of flow which did not cause injury. The eye irritation score for each rabbit was calculated each day. Body weights were recorded pretest and at termination.

Treated Eyes: There was no corneal opacity or iritis noted at any observation period. Conjunctival irritation, noted in 3/3 eyes, cleared by 48 hours.

Control Eyes: All three control eyes appeared normal at each observation period.

There were no abnormal physical signs noted during the observation period.

Ocular administration of the test substance produced conjunctival irritation which cleared by 48 hours.

 

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

Additional information

To determine the irritation or corrosive potential of the test substance in eyes and skin of rabbits, studies were performed according to OECD 404 and 405. Dermal reactions were scored and a modified Primary Irritaion Index was calculated using the 60 minute, 24, 48 and 72 hour scoring intervals. The eyes were examined and scored by the Draize technique at 1, 24, 48 and 72 hours post dose.

Erythema was absent to very slight at 60 minutes and 24 hours after patch removal and absent at 48 hours and 72 hours in the dermal irritation study in rabbits. There were no abnormal physical signs noted during the observation period.

In treated rabbit eyes, there was no corneal opacity or iritis noted at any observation period. Conjunctival irritation, noted in 3/3 eyes, cleared by 48 hours. There were no abnormal physical signs noted during the observation period.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to skin and eye irrittaion/corrosion.