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Administrative data

Description of key information

Skin irritation: Minor irritation effects were noted which cleared and were not sufficient for classification.
Eye irritation: Minor effects were noted which cleared and were not sufficient for classification.

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:
other: Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.
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 (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Animals were received from Ace Animals, Boyertown, PA.
- Weight at study initiation: 2.2 - 2.5 kg
- Housing: 1 animap per cage in suspended wire cages. Bedding was placed beneath the cages and changed at least three times/week.
- Diet (e.g. ad libitum): Fresh Purina Rabbit Chow was provided daily.
- Water (e.g. ad libitum): Water was freely available at all times.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): The animal room was temperature controlled.
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle.

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: 0.9% sodium chloride solution.
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The test article was dosed by dry weight, 0.5 g/rabbit.
Duration of treatment / exposure:
4 hours.
Observation period:
72 hours.
Number of animals:
6 (3 males and 3 females).
Details on study design:
TEST SITE
- Area of exposure: The prepared site was approximately 10 x 10 cm and remained intact. The test article was placed under a 2.5 x 2.5 cm, moistened 4 ply, surgical gauze patch. The patch was moistened with approximately 1 ml of 0.9% sodium chloride solution to enhance contact of the test article with the dose site.
- Type of wrap if used: Gentle pressure was applied to the gauze to aid in the distribution of the test substance over the prepared site. The patch was
secured with non-irritating tape. The 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 (if done): Residual test article was removed from the test site by gentle washing with lukewarm tap water at the end of the exposure period.
- Time after start of exposure: 4 hours.

SCORING SYSTEM:
The test sites were scored for dennal irritation at 30 to 60 minutes and 24, 48 and 72 hours after removal of wrappings. Erythema and edema were scored according to the numerical Draize technique below.
The skin was also evaluated for ulceration and necrosis or any evidence of tissue destmction. Additional signs were described.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.11
Max. score:
4
Reversibility:
fully reversible within: 3 days
Remarks on result:
other: Calculated on the basis of the scores at 24, 48, and 72 hours for ALL animals.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.11
Max. score:
4
Reversibility:
fully reversible within: 3 days
Remarks on result:
other: Calculated on the basis of the scores at 24, 48, and 72 hours for ALL animals.
Irritant / corrosive response data:
Erythema and oedema, absent at 30 to 60 minutes after patch removal, were absent to very slight (in one male animal) at 24 and 48 hours and cleared by 72 hours.
There were no abnormal systemic signs noted during the observation period.
Body weight changes were normal.
Other effects:
There were no signs of ill health or toxicity in any animal.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance is not classified as a skin irritant.
Executive summary:

Objective:

To determine the potential of the test article to induce dermal imtation when administered demially to New Zealand White rabbits. The study is designed to comply with the standards set forth by:

-EPA - Primary Demnal Initation, 40 CFR 798.4470 (latest revision -1995)

-EC Official Joumal of the European Communities, L 383 A, Part B, Method B.4. Acute Toxicity (Skin Initation) 12/29/92

-OECD Guidelines for Testing of Chemicals, No. 404, Acute Dermal Irritation/Corrosion, adopted 7/17/92.

Method Synopsis:

Six healthy New Zealand White rabbits (3 males-3 females) were dosed dermaily with the test substance. The test article (0.5 g) was applied 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 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.

Summary:

Erythema and edema, absent at 30 to 60 minutes after patch removal, were absent to very slight at 24 and 48 hours and cleared by 72 hours.

There were no abnormal systemic signs noted during the observation period. Body weight changes were normal.

Conclusion:

The test substance is not classified as a skin 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:
other: Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.
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 (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: New Zealand White rabbits were received from Ace Animals, Boyertown, PA.
- Age at study initiation: Approx 3 months.
- Weight at study initiation: The pretest bodyweight range was 2.0-2.1 kg.
- Housing: The animals were housed 1 per cage in suspended cages. Bedding was placed beneath the cages and changed at least three times/week.
- Diet (e.g. ad libitum): Fresh Purina Rabbit Chow (Diet #5321) was provided daily.
- Water (e.g. ad libitum): Water was available ad libitum.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): The animal room was temperature controlled.
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle.

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The test article (0.1 ml equivalent (88 mg)) was placed by syringe-type applicator into the conjunctival sac which was formed by gently pulling the lower eyelid away from the eye. After instillation, the lids were held together for approximately one second to insure adequate distribution of the test article.

One eye of each rabbit was dosed. The contralateral eye served as a control.
Duration of treatment / exposure:
A single application of the test material.
Observation period (in vivo):
72 hours.
Number of animals or in vitro replicates:
6 females.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not performed.


SCORING SYSTEM: Ocular reactions were graded according to the numerical Draize technique (see below).

TOOL USED TO ASSESS SCORE: Using a Mini-Maglite flashlight equipped with a high intensity bulb, the treated eye of each rabbit was
examined for irritation of the comea, iris and conjunctiva at 1, 24, 48, and 72 hours post dose. The eyes were scored again on day 7. Sodium fluorescein was used to determine corneal effects following the 24 hour observation and at each subsequent reading until there was no stain retention.

The eyes were not scored on day 4 as specified in the protocol. This did not effect the outcome of the study.

Other:
Body weights were recorded pretest.
The general health of the animals was monitored at each observation time.
Irritation parameter:
conjunctivae score
Remarks:
: redness
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.72
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Calculated on the basis of the scores at 24, 48, and 72 hours for ALL animals.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.17
Max. score:
4
Reversibility:
fully reversible within: 2 days
Remarks on result:
other: Calculated on the basis of the scores at 24, 48, and 72 hours for ALL animals.
Irritation parameter:
conjunctivae score
Remarks:
: discharge
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 2 days
Remarks on result:
other: Calculated on the basis of the scores at 24, 48, and 72 hours for ALL animals.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.11
Max. score:
4
Reversibility:
fully reversible within: 2 days
Remarks on result:
other: Calculated on the basis of the scores at 24, 48, and 72 hours for ALL animals.
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 1 day
Remarks on result:
other: Calculated on the basis of the scores at 24, 48, and 72 hours for ALL animals.
Irritant / corrosive response data:
Corneal opacity, noted in 1/6 eyes, cleared by 48 hours. Iritis, noted in 2/6 eyes, cleared by 24 hours. Conjunctival irritation, noted in 6/6 eyes,
cleared by day 7.
There were no abnormal systemic observations.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance is not classified as an eye irritant.
Executive summary:

Objective:

To determine the potential of the test article to produce ocular irritation when instilled in the eyes of New Zealand White rabbits. The study was designed to comply with the standards set forth by:

-EPA - Primary Eye Imtation, 40 CFR 798.4500 (latest revision -1995

-EC Official Journal of the European Communities. L 383 A, Part B, Method B.5 Acute Toxicity (Eye Initation) 12/29/92.

-OECD Guidelines for Testing of Chemicals, No. 405, Acute Eye Initation/Corrosion, adopted 2/24/87.

Method Synopsis:

Six healthy New Zealand White rabbits (females), free from evidence of ocular irritation and corneal abnormalities, as determined by pretest fluorescein procedures, were dosed with the test substance. The test article (0.1 ml equivalent (88 mg)) was placed into the conjunctival sac of one eye of each rabbit. The eyes were examined and scored by the Draize technique at 1, 24, 48 and 72

hours post dose. The eyes were scored again on day 7. Sodium fluorescein was used to determine corneal effects following the 24 hour observation and at each subsequent reading until there was no stain retention. Body weights were recorded pretest.

Summary:

Corneal opacity, noted in 1/6 eyes, cleared by 48 hours. Iritis, noted in 2/6 eyes, cleared by 24 hours. Conjunctival irritation, noted in 6/6 eyes, cleared by day 7.

There were no abnormal systemic observations.

Conclusion:

The test substance is not classified as an eye irritant.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

Six healthy New Zealand White rabbits (3 males-3 females) were dosed dermaily with the test substance. The test article was kept in contact with the skin for 4 hours. 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, absent at 30 to 60 minutes after patch removal, were absent to very slight at 24 and 48 hours and cleared by 72 hours.

There were no abnormal systemic signs noted during the observation period. Body weight changes were normal.

The test substance is not classified as a skin irritant.

Eye irritation:

Six healthy New Zealand White rabbits (females) were dosed with the test substance. The test article (0.1 ml equivalent (88 mg)) was placed into the conjunctival sac of one eye of each rabbit. The eyes were examined and scored by the Draize technique at 1, 24, 48 and 72 hours post dose. The eyes were scored again on day 7. Sodium fluorescein was used to determine corneal effects following the 24 hour observation and at each subsequent reading until there was no stain retention. Body weights were recorded pretest.

Corneal opacity, noted in 1/6 eyes, cleared by 48 hours. Iritis, noted in 2/6 eyes, cleared by 24 hours. Conjunctival irritation, noted in 6/6 eyes, cleared by day 7.

There were no abnormal systemic observations.

The test substance is not classified as an eye irritant.

Justification for classification or non-classification

Although minor skin and eye irritation effects were seen in the skin and eye irritation studies, these effects cleared and were not sufficient to cause classification.

The substance does not meet the criteria to be classified as a skin or eye irritant.