Registration Dossier

Administrative data

Description of key information

The material was applied onto skin and into eyes of rabbits to examine irritating properties of the test item (according OECD guideline 404 and 405, GLP). Application onto skin did not induce any effects or clinical signs. Installation into eyes resulted in transient effects, i.e. opacity in one animals and conjunctival irritation in all animals. All symptoms resolved within 72h. The test material is therefore not considered to be irritating to skin or 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:
1998-02-05 - 1998-04-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted on 17 July 1992
Deviations:
no
Qualifier:
according to guideline
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 or test system and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Boyertown, PA (on 01/20/98)
- Age at study initiation: Animals were born the weeks 11/09 through 11/23/97, Experimental Start Date: 02/10/98
- Weight at study initiation: 2.0 – 2.5 kg (1 male/ 5 females)
- Housing: 1 animal/sex/cage in suspended wire cage, bedding was changed three times/week
- Diet: Fresh Purina Rabbit Chow, provided daily
- Water: ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Photoperiod: 12 hours dark / 12 hours light
- Animal room was temperature controlled, kept clean and vermin free

IN-LIFE DATES: From: 1998-02-10 To: 1993-02-13
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g, based on the dry weight
Duration of treatment / exposure:
4 hours
Observation period:
72 hours after patch removal
Number of animals:
6 rabbits (1 male, 5 females)
Details on study design:
TEST SITE
- 24 h before: Dorsal area of the trunk of each animal was clipped free of hair
- Area of exposure: approximately 10 x 15 cm
- Test item was placed under a 2.5 x 2.5 cm surgical gauze patch moistened with distilled water
- Gentle pressure was applied to the gauze to aid in the distribution of the test item
- Patch was secured with non-irritating tape
- Type of wrap: Torso was wrapped with plastic in a semi-occlusive manner and secured with non-irritating tape which completely covered the plastic.

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test item was gently washed with distilled water from the dose site prior to dermal observations.

OBSERVATIONS
- Duration of observation period following administration: 72 hours
- Test sites were scored for dermal irritation at 30 to 60 minutes post patch removal and again at 24, 48 and 72 hours post patch removal using the numerical Draize scoring code. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction. Additional signs were described.
- The general health status of the animals was monitored at each observation time.
- Frequency of weighing: recorded pretest
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Erythema and edema were absent at all observation intervals. The modified Primary Initation Index was 0.
Other effects:
There were no abnormal systemic signs noted during the observation period.
Interpretation of results:
GHS criteria not met
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:
1998-02-03 - 1998-04-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted on 24th Feb 1987
Deviations:
no
Qualifier:
according to guideline
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: Ace Animals, Boyertown, PA (on 01/20/98)
- Age at study initiation: Animals were born the weeks 11/09 through 11/23/97, Experimental Start Date: 02/09/98
- Weight at study initiation: 2.2 – 2.3 kg
- Housing: 1 animal/sex/cage in suspended wire cages, Bedding was changed three times/week
- Diet: Fresh Purina Rabbit Chow, provided daily
- Water: ad libitum
- Acclimation period: at least five days
- Approximately 24 hours prior to study start, both eyes of each animal were examined

ENVIRONMENTAL CONDITIONS
- Photoperiod: 12 hours dark / 12 hours light
- Animal room was temperature controlled, kept clean and vermin free

IN-LIFE DATES: From: 1998-02-09 To: 1998-02-12
Vehicle:
unchanged (no vehicle)
Controls:
other: The contralateral eye served as a control.
Amount / concentration applied:
33 mg test item
Duration of treatment / exposure:
Up to the end of the observation period, no removal after 24 hours.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
6 female rabbits
Details on study design:
APPLICATION
- Test article (0.1 mL equivalent [33 mg]) was placed by syringe-type applicator into the conjunctival sac. After instillation, the lids were held together for approximately one second. One eye of each rabbit was dosed.

REMOVAL OF TEST SUBSTANCE
- Washing: not performed

SCORING SYSTEM
- according to the numerical Draize technique

TOOL USED TO ASSESS SCORE
- Sodium fluorescein

OTHER OBSERVATIONS
- Body weights were recorded pretest
- General health status of the animals was monitored at each observation time
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.11
Max. score:
2
Reversibility:
fully reversible within: 48 h
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.06
Max. score:
1
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.44
Max. score:
2
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.17
Max. score:
1
Reversibility:
fully reversible within: 72 h
Irritant / corrosive response data:
Corneal opacity and iritis, noted in 1/6 eyes, cleared by 48 hours. Conjunctival irritation, noted in 6/6 eyes, cleared by 72 hours.
Other effects:
There were no abnormal systemic signs noted during the observation period.

Individual Results

Animal 1 Animal 2 Animal 3 Animal 4 Animal 5 Animal 6
Cornea 1h 0 0 0 0 0 0
24h 2 0 0 0 0 0
48h 0 0 0 0 0 0
72h 0 0 0 0 0 0
mean 24-72 h 0.67 0.00 0.00 0.00 0.00 0.00 0.11 total mean
Iris 1h 0 0 0 0 0 0
24h 1 0 0 0 0 0
48h 0 0 0 0 0 0
72h 0 0 0 0 0 0
mean 24-72 h 0.33 0.00 0.00 0.00 0.00 0.00 0.06 total mean
Redness 1h 2 2 2 2 2 2
24h 2 2 1 0 1 1
48h 1 0 0 0 0 0
72h 0 0 0 0 0 0
mean 24-72 h 1.00 0.67 0.33 0.00 0.33 0.33 0.44 total mean
Chemosis 1h 1 2 1 1 1 1
24h 0 0 0 0 1 1
48h 0 0 0 0 1 0
72h 0 0 0 0 0 0
mean 24-72 h 0.00 0.00 0.00 0.00 0.67 0.33 0.17 total mean
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Dermal irritation

Six healthy New Zealand White rabbits (5 males-1 female) were dosed dermally with the test item for 4h under semi-occlusive conditions (0.5g into intact skin). Dermal reactions were scored at 30 to 60 minutes and 24, 48 and 72 hours after removal of wrappings. Systemic signs were recorded at each observation period. Body weights were recorded pretest. Erythema and edema were absent at all observation intervals. There were no abnormal systemic signs noted during the observation period. In conclusion, the test substance is not considered to be irritating to skin.

Ocular Irritation

33 mg (0.1 ml) of the test material were installed into the conjunctival sac of one eye of one eye each of six healthy New Zealand White rabbits (females). The eyes were examined and scored by the Draize technique at 1, 24, 48 and 72 hours post dose. Sodium fluorescein was used to determine corneal effects following the 24 and 48 hour observation. Body weights were recorded pretest. Corneal opacity and iritis, noted in 1/6 eyes, cleared by 48 hours. Conjunctival irritation, noted in 6/6 eyes, cleared by 72 hours. There were no abnormal systemic signs noted during the observation period. In conclusion, the test substance is not considered to be irritating to skin or eyes.

Justification for classification or non-classification

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.