Registration Dossier

Administrative data

Description of key information

The test material was subject to a skin irritation test in the rabbit as described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO). Shaved and both intact and scarified skin sites of six rabbits were exposed to 0.5 g test substance in a 50% polyethylene glycol 400 trituration for 24 hours under occlusive conditions. None of the animals showed any skin reactions immediately and 48 hours after the end of exposure. Therefore, the test item has not to be classified for skin irritation according to Regulation (EC) No 1272/2008.

The test material was tested for eye irritancy according to FDA guideline (Fed. Reg., Vol. 37, No. 38, 1972). 0.1 ml test substance was applied to the conjunctival sac of one eye each of eight rabbits (washing after 24 h in 5 animals, group 1, or after 5 minutes in 3 animals, group 2) and eye responses were observed for seven days. Only slight eye responses were noted, fully reversible within 72 h. The test item is not irritating to eyes according to the classification criteria of Regulation (EC) No 1272/2008.

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:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report which meets basic scientific principles.
Qualifier:
according to guideline
Guideline:
other: described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO).
Deviations:
not specified
GLP compliance:
not specified
Species:
rabbit
Strain:
other: Russian breed
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1.5-2 kg
- Housing: individually
- Diet: rabbit food (NAFAG, Gossau SG) ad libitum
- Water: ad libitum
Type of coverage:
occlusive
Preparation of test site:
other: shaved and one flank intact, one flank scarified
Vehicle:
other: polyethylene glycol 400
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 g
- Concentration: 50% polyethylene glycol (PEG 400) trituration.
Duration of treatment / exposure:
24 h
Observation period:
48 h
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5x2.5 cm² gauze patch.
- Type of wrap if used: plastic film 5x5 cm, fixed with adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h.

SCORING SYSTEM: in accordance with OECD TG 404.
Scores were read 24 and 72 h after start of exposure, which lasted for 24 h. For classification, the readings are stated here as immediately and 48 h after end of exposure.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Erythema score 0 and edema score 0 were noted in every animal immediately and 48 h after exposure.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP regulation
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, as no skin reactions were observed in 6/6 animals immediately and 48 h after the end of exposure, which lasted 20 h longer than required by OECD TG 404.
Executive summary:

The test material was subject to a skin irritation test in the rabbit as described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO). Shaved and both intact and scarified skin sites of six rabbits were exposed to 0.5 g test substance in a 50% polyethylene glycol 400 trituration for 24 hours under occlusive conditions. None of the animals showed any skin reactions immediately and 48 hours after the end of exposure. Therefore, the test item has not to be classified for skin irritation according to Regulation (EC) No 1272/2008.

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report which meets basic scientific principles.
Justification for type of information:
Please see read across document in chapter 13
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
other: described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO).
Deviations:
not specified
GLP compliance:
not specified
Species:
rabbit
Strain:
other: Russian breed
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1.5-2 kg
- Housing: individually
- Diet: rabbit food (NAFAG, Gossau SG) ad libitum
- Water: ad libitum
Type of coverage:
occlusive
Preparation of test site:
other: shaved and one flank intact, one flank scarified
Vehicle:
other: polyethylene glycol 400
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 g
- Concentration: 50% polyethylene glycol (PEG 400) trituration.
Duration of treatment / exposure:
24 h
Observation period:
48 h
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5x2.5 cm² gauze patch.
- Type of wrap if used: plastic film 5x5 cm, fixed with adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h.

SCORING SYSTEM: in accordance with OECD TG 404.
Scores were read 24 and 72 h after start of exposure, which lasted for 24 h. For classification, the readings are stated here as immediately and 48 h after end of exposure.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Erythema score 0 and edema score 0 were noted in every animal immediately and 48 h after exposure.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP regulation
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, as no skin reactions were observed in 6/6 animals immediately and 48 h after the end of exposure, which lasted 20 h longer than required by OECD TG 404.
Executive summary:

The test material was subject to a skin irritation test in the rabbit as described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO). Shaved and both intact and scarified skin sites of six rabbits were exposed to 0.5 g test substance in a 50% polyethylene glycol 400 trituration for 24 hours under occlusive conditions. None of the animals showed any skin reactions immediately and 48 hours after the end of exposure. Therefore, the test item has not to be classified for skin irritation according to Regulation (EC) No 1272/2008.

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:
From 11 FEB 1975 to 18 FEB 1975.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report which meets basic scientific principles.
Qualifier:
according to guideline
Guideline:
other: FDA guideline (Fed. Reg., Vol. 37, No. 38, 1972)
Deviations:
not specified
GLP compliance:
not specified
Species:
rabbit
Strain:
Himalayan
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 ml
Duration of treatment / exposure:
24 h (5 animals, group 1)
5 min (3 animals, group 2)
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
8
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: with 300 ml water for 2 min
- Time after start of exposure: 24 h (5 animals, group 1) or 5 min (3 animals, group 2)

SCORING SYSTEM: in accordance with OECD TG 405

TOOL USED TO ASSESS SCORE: fluorescein, UV light
Irritation parameter:
cornea opacity score
Basis:
animal: #1 (group 1)
Time point:
other: 24, 48, 72 h.
Score:
0.67
Max. score:
4
Reversibility:
fully reversible
Remarks:
72 h after application.
Irritation parameter:
cornea opacity score
Basis:
animal: #2 - #8
Time point:
other: 24, 48, 72 h.
Score:
0
Max. score:
4
Remarks on result:
other: group 1 + group 2
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 h.
Score:
0
Max. score:
2
Remarks on result:
other: group 1 + group 2
Irritation parameter:
conjunctivae score
Basis:
animal: #2 (group 1)
Time point:
other: 24, 48, 72 h.
Score:
1
Max. score:
3
Reversibility:
fully reversible
Remarks:
72 h after appl.
Remarks on result:
other: redness
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #3 (group 1)
Time point:
other: 24, 48, 72 h.
Score:
0.67
Max. score:
3
Reversibility:
fully reversible
Remarks:
72 h after appl.
Remarks on result:
other: redness
Irritation parameter:
conjunctivae score
Basis:
animal: #4, #5 (group 1)
Time point:
other: 24, 48, 72 h.
Score:
0.33
Max. score:
3
Reversibility:
fully reversible
Remarks:
48 h after appl.
Remarks on result:
other: redness
Irritation parameter:
conjunctivae score
Basis:
animal: #6 - #8 (group 2)
Time point:
other: 24, 48, 72 h.
Score:
0
Max. score:
3
Remarks on result:
other: redness
Irritation parameter:
chemosis score
Basis:
animal: #2 (group 1)
Time point:
other: 24, 48, 72 h.
Score:
0.33
Max. score:
4
Reversibility:
fully reversible
Remarks:
48 h after appl.
Irritation parameter:
chemosis score
Basis:
animal: #1, #3 - #5 (group 1), #6-#8 (group 2)
Time point:
other: 24, 48, 72 h.
Score:
0
Max. score:
4
Remarks on result:
other: group 1 + group 2
Irritant / corrosive response data:
Application of test substance resulted in conjunctival redness score 1 for all animals of group 1 for up to 48 hours. Additionally, animal #1 (group 1) showed corneal opacity score 1. The animals of group 2 showed one hour after application conjunctival redness score 1. No other responses were noted. 72 h after application no effects were observed.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP regulation
Conclusions:
According to the classification criteria of Regulation (EC) No 1272/2008 the test material is not irritating to eyes under these test conditions. This conclusion is legitimate as five animals (group 1) were tested basically in accordance with today's standard methods regarding dosing, exposure duration, scoring system, reading time points and the observed eye responses were fully reversible 72 hours after application.
Executive summary:

The test material was tested for eye irritancy according to FDA guideline (Fed. Reg., Vol. 37, No. 38, 1972). 0.1 ml test substance was applied to the conjunctival sac of one eye each of eight rabbits (washing after 24 h in 5 animals, group 1, or after 5 minutes in 3 animals, group 2) and eye responses were observed for seven days. Only slight eye responses were noted, fully reversible within 72 h. The test item is not irritating to eyes according to the classification criteria of Regulation (EC) No 1272/2008.

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

The test item was irritatnt neither to skin nor eyes in vivo