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Description of key information

The test material is not irritating to skin under test conditions. The test conditions were more stringent than required by OECD TG 404 (i.e. 24 h treatment, occlusive coverage, and scarified skin instead of 4 h treatment, semi-occlusive coverage, and intact skin).

The test material was not irritating to eyes in all animals under test conditions, which are basically in accordance with todays standard methods regarding dosing, exposure duration, scoring system and reading time points. Therefore, it is concluded that the submission substance is not irritating to eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 26 AUG 1976 to 16 SEP 1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: FDA guideline (minor deviations from OECD guideline)
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
other: FDA guideline (Federal Register 38, NO. 187, 27.9.1973, p 27019)
Deviations:
no
GLP compliance:
no
Remarks:
study was performed previous to GLP implementation
Species:
rabbit
Strain:
Himalayan
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- weight at study initiation: 1.5- 2.0 kg
- Housing: single
- Diet: ERKA 8300, Robert Koch oHG/ Hamm, Germany, ad libitum
- Water: tap water ad libitum
Type of coverage:
occlusive
Preparation of test site:
other: clipped intact and clipped scarified
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg
Duration of treatment / exposure:
24 h
Observation period:
48 h after removal of patch with observation time points immediately after removal, 24 and 48 h later.
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: erythema and edema scores ranging from 0-4.

Skin was evaluated immediately, 24 h and 48 h after after removal of the patch. Mean values of the readings 24 and 48 h after removal are reported in the results table.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 and 48 h
Score:
0
Max. score:
4
Reversibility:
other: not relevant since no effect
Remarks on result:
other: clipped intact and clipped scarified
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 and 48 h
Score:
0
Max. score:
4
Reversibility:
other: not relevant since no effect
Remarks on result:
other: clipped intact and clipped scarified
Irritant / corrosive response data:
Immediately after removal of patch no erythema score could be determined due to coloration of the skin, no edema was detectable at the end of the exposure duration (score 0). No erythema or edema were detectable at any later time point.
Results with scarified skin were the same.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material is not irritating to skin under these test conditions.
This conclusion is legitimate even though the applied testing regime differs from today's standard methods. Since the test conditions were more stringent than required by OECD TG 404 (i.e. 24 h treatment, occlusive coverage, and scarified skin instead of 4 h treatment, semi-occlusive coverage, and intact skin) the test results are considered adequate to fulfill the endpoint requirements.
Executive summary:

The test material was tested for skin irritancy according to FDA guidelines. Both intact and scarified skin sites of six rabbits were exposed to 0.5 g test substance for 24 h under occlusive conditions and the skin responses were watched for 48 hours after end of exposure. Immediately after removal of patch no erythema score could be determined due to pigment overlay. No erythema were seen at the later observation time points. No edema were seen at any time point (score 0). The test item is not irritating under these test conditions.

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From 26 AUG 1976 to 16 SEP 1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: FDA guideline (minor deviations from OECD guideline)
Justification for type of information:
See read acrodd justification document in chapter 13
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
other: FDA guideline (Federal Register 38, NO. 187, 27.9.1973, p 27019)
Deviations:
no
GLP compliance:
no
Remarks:
study was performed previous to GLP implementation
Species:
rabbit
Strain:
Himalayan
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- weight at study initiation: 1.5- 2.0 kg
- Housing: single
- Diet: ERKA 8300, Robert Koch oHG/ Hamm, Germany, ad libitum
- Water: tap water ad libitum
Type of coverage:
occlusive
Preparation of test site:
other: clipped intact and clipped scarified
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg
Duration of treatment / exposure:
24 h
Observation period:
48 h after removal of patch with observation time points immediately after removal, 24 and 48 h later.
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: erythema and edema scores ranging from 0-4.

Skin was evaluated immediately, 24 h and 48 h after after removal of the patch. Mean values of the readings 24 and 48 h after removal are reported in the results table.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 and 48 h
Score:
0
Max. score:
4
Reversibility:
other: not relevant since no effect
Remarks on result:
other: clipped intact and clipped scarified
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 and 48 h
Score:
0
Max. score:
4
Reversibility:
other: not relevant since no effect
Remarks on result:
other: clipped intact and clipped scarified
Irritant / corrosive response data:
Immediately after removal of patch no erythema score could be determined due to coloration of the skin, no edema was detectable at the end of the exposure duration (score 0). No erythema or edema were detectable at any later time point.
Results with scarified skin were the same.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material is not irritating to skin under these test conditions.
This conclusion is legitimate even though the applied testing regime differs from today's standard methods. Since the test conditions were more stringent than required by OECD TG 404 (i.e. 24 h treatment, occlusive coverage, and scarified skin instead of 4 h treatment, semi-occlusive coverage, and intact skin) the test results are considered adequate to fulfill the endpoint requirements.
Executive summary:

The test material was tested for skin irritancy according to FDA guidelines. Both intact and scarified skin sites of six rabbits were exposed to 0.5 g test substance for 24 h under occlusive conditions and the skin responses were watched for 48 hours after end of exposure. Immediately after removal of patch no erythema score could be determined due to pigment overlay. No erythema were seen at the later observation time points. No edema were seen at any time point (score 0). The test item is not irritating under these test conditions.

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

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 26 AUG 1976 to 16 SEP 1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: FDA guideline, similar to OECD 405.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
other: FDA guideline (Federal Register Vol. 38, nr. 187, p. 27019, 1973)
Deviations:
no
GLP compliance:
no
Remarks:
study was performed previous to GLP implementation
Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Housing: single
- Diet: ERKA 8300, Robert Koch oHG/ Hamm, Germany, ad libitum
- Water: tap water ad libitum
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 100 mg
Duration of treatment / exposure:
24 h after exposure eyes were washed with physiological saline.
Observation period (in vivo):
72 h with observation time points at 1, 7, 24, 48 and 72 h after application.
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 h

SCORING SYSTEM: according to Draize

TOOL USED TO ASSESS SCORE: loupe / fluorescein (for 24 and 48 h reading)
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #3 and #4 each
Time point:
other: mean of 24, 48 and 72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
cornea opacity score
Basis:
animal: #2 and #5 each
Time point:
other: mean of 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not relevant since no effect
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
other: mean of 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: the shortened observation period of 72 h
Remarks on result:
other: considered to be reversible within a prolonged observation period of 7 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: not relevant since no effect
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: #1, #2, #3, #4 and #5 each
Time point:
other: mean of 24, 48 and 72 h
Score:
0
Max. score:
3
Reversibility:
other: not relevant since no effect
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #6
Time point:
other: mean of 24, 48 and 72 h
Score:
1
Max. score:
3
Reversibility:
not fully reversible within: the shortened observation period of 72 h
Remarks on result:
other: considered to be reversible within a prolonged observation period of 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not relevant since no effect
Irritant / corrosive response data:
individual data for animal #1, #2, #3, #4, #5 and #6 after 1h / 7h / 24h / 48h / and 72h

cornea score: 1/1/1/0/0, 1/1/0/0/0, 2/1/1/0/0, 1/1/1/0/0, 0/0/0/0/0, 1/1/1/1/1
iris score: 0/0/0/0/0, 0/0/0/0/0, 0/0/0/0/0, 0/0/0/0/0, 0/0/0/0/0, 0/0/0/0/0
conjunctivae redness: 1/1/0/0/0, 0/0/0/0/0, 1/0/0/0/0, 1/1/0/0/0, 1/0/0/0/0, 0/1/1/1/1
conjunctivae chemosis: 0/0/0/0/0, 0/0/0/0/0, 0/0/0/0/0, 0/0/0/0/0, 0/0/0/0/0, 0/1/0/0/0
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material was not irritating to eyes in all animals under test conditions which are basically in accordance with todays standard methods regarding dosing, exposure duration, scoring system and reading time points. Therefore, it is concluded that the submission substance is not irritating to eyes.
Executive summary:

Test material was subject to a test of eye irritancy according to FDA guidelines (Fed. Reg. Vol. 38, No. 187, p. 27019, 1973). 100 mg of substance were applied to one eye of six animals. The eyes were washed 24 h after application and eye responses were noted for 72 h after start of the exposure. No iridial effects were observed in any animal, and only 1/6 animals had a chemosis score of 1 in the 7 h reading which was completely reversible within 24 h. Slight to moderate corneal effects were visible in 5/6 animals. Apart from 1 animal these effects were completely reversible within the observation time. Conjunctivae redness was observed in 4/6 animals, the effect was also reversible within 72 h for all animals apart from one. It can be concluded that a longer observation period would have resulted in a complete reversibility.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From 26 AUG 1976 to 16 SEP 1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: FDA guideline, similar to OECD 405.
Justification for type of information:
See read across justification document in chapter 13
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
other: FDA guideline (Federal Register Vol. 38, nr. 187, p. 27019, 1973)
Deviations:
no
GLP compliance:
no
Remarks:
study was performed previous to GLP implementation
Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Housing: single
- Diet: ERKA 8300, Robert Koch oHG/ Hamm, Germany, ad libitum
- Water: tap water ad libitum
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 100 mg
Duration of treatment / exposure:
24 h after exposure eyes were washed with physiological saline.
Observation period (in vivo):
72 h with observation time points at 1, 7, 24, 48 and 72 h after application.
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 h

SCORING SYSTEM: according to Draize

TOOL USED TO ASSESS SCORE: loupe / fluorescein (for 24 and 48 h reading)
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #3 and #4 each
Time point:
other: mean of 24, 48 and 72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
cornea opacity score
Basis:
animal: #2 and #5 each
Time point:
other: mean of 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not relevant since no effect
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
other: mean of 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: the shortened observation period of 72 h
Remarks on result:
other: considered to be reversible within a prolonged observation period of 7 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: not relevant since no effect
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: #1, #2, #3, #4 and #5 each
Time point:
other: mean of 24, 48 and 72 h
Score:
0
Max. score:
3
Reversibility:
other: not relevant since no effect
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #6
Time point:
other: mean of 24, 48 and 72 h
Score:
1
Max. score:
3
Reversibility:
not fully reversible within: the shortened observation period of 72 h
Remarks on result:
other: considered to be reversible within a prolonged observation period of 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not relevant since no effect
Irritant / corrosive response data:
individual data for animal #1, #2, #3, #4, #5 and #6 after 1h / 7h / 24h / 48h / and 72h

cornea score: 1/1/1/0/0, 1/1/0/0/0, 2/1/1/0/0, 1/1/1/0/0, 0/0/0/0/0, 1/1/1/1/1
iris score: 0/0/0/0/0, 0/0/0/0/0, 0/0/0/0/0, 0/0/0/0/0, 0/0/0/0/0, 0/0/0/0/0
conjunctivae redness: 1/1/0/0/0, 0/0/0/0/0, 1/0/0/0/0, 1/1/0/0/0, 1/0/0/0/0, 0/1/1/1/1
conjunctivae chemosis: 0/0/0/0/0, 0/0/0/0/0, 0/0/0/0/0, 0/0/0/0/0, 0/0/0/0/0, 0/1/0/0/0
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material was not irritating to eyes in all animals under test conditions which are basically in accordance with todays standard methods regarding dosing, exposure duration, scoring system and reading time points. Therefore, it is concluded that the submission substance is not irritating to eyes.
Executive summary:

Test material was subject to a test of eye irritancy according to FDA guidelines (Fed. Reg. Vol. 38, No. 187, p. 27019, 1973). 100 mg of substance were applied to one eye of six animals. The eyes were washed 24 h after application and eye responses were noted for 72 h after start of the exposure. No iridial effects were observed in any animal, and only 1/6 animals had a chemosis score of 1 in the 7 h reading which was completely reversible within 24 h. Slight to moderate corneal effects were visible in 5/6 animals. Apart from 1 animal these effects were completely reversible within the observation time. Conjunctivae redness was observed in 4/6 animals, the effect was also reversible within 72 h for all animals apart from one. It can be concluded that a longer observation period would have resulted in a complete reversibility.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

No classification

No irritant effects were detected in vivo on skin and eyes of rabbits.