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Description of key information

Skin irritation


Skin irritation, guinea pig, 24 h occlusive, slightly irritating


 


Eye irritation


Eye irritation, rabbit, 8 days, slight eye irritant

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Remarks:
in vivo study that was performed prior to current requirement for in vitro alternative testing
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15 JUL 1985 - 20 DEC 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
5 guinea pigs were exposed to the test item under occlusive conditions for 24 h.
GLP compliance:
not specified
Species:
guinea pig
Strain:
Hartley
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Strain: CRL (HA)BR Hartley
- Weight at study initiation: 435 - 502g
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Remarks:
Undilute as received
Controls:
no
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
24 hours
Observation period:
2 weeks
Number of animals:
five (5)
Details on study design:
no details given
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
ca. 3
Max. score:
4
Reversibility:
not specified
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
ca. 2
Max. score:
4
Reversibility:
not specified
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24 h
Score:
ca. 3
Max. score:
4
Reversibility:
not specified
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24 h
Score:
ca. 3
Max. score:
4
Reversibility:
not specified
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24 h
Score:
ca. 2
Max. score:
4
Reversibility:
not specified
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Score:
ca. 3
Max. score:
4
Reversibility:
not specified
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Score:
ca. 2
Max. score:
4
Reversibility:
not specified
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
48 h
Score:
ca. 3
Max. score:
4
Reversibility:
not specified
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
48 h
Score:
ca. 3
Max. score:
4
Reversibility:
not specified
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
48 h
Score:
ca. 2
Max. score:
4
Reversibility:
not specified
Irritation parameter:
erythema score
Basis:
animal: 1-5
Time point:
72 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Score:
ca. 0
Max. score:
4
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24 h
Score:
ca. 1
Max. score:
4
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24 h
Score:
ca. 1
Max. score:
4
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24 h
Score:
ca. 2
Max. score:
4
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24 h
Score:
ca. 1
Max. score:
4
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
animal #1
Time point:
48 h
Score:
ca. 0
Max. score:
4
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
animal #2
Time point:
48 h
Score:
ca. 1
Max. score:
4
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
animal #3
Time point:
48 h
Score:
ca. 1
Max. score:
4
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
animal #4
Time point:
48 h
Score:
ca. 2
Max. score:
4
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
animal #5
Time point:
48 h
Score:
ca. 1
Max. score:
4
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
animal: 1-5
Time point:
72 h
Remarks on result:
not measured/tested
Irritant / corrosive response data:
Slight or very slight edema was observed in 1 of 5 and 3 of 5 guinea pigs, respectively, at 24-48 hours after exposure to m-diisopropylbenzene. Edema was accompanied by moderate to severe erythema in 2 of 5 guinea pigs, and well-defined erythema in 2 of 5 guinea pigs. Moderate to severe erythema without edema was observed in 1 of 5 guinea pigs at 24-48 hours after exposure. For all test animals, there were no signs of edema or erythema at 2 weeks after exposure.
animal no. finding skin (post-exposure)
24-48 hrs 2 weeks
1 erythema mod-severe normal
edema normal
2 erythema well-defined normal
edema very slight normal
3 erythema mod-severe normal
edema very slight normal
4 erythema mod-severe normal
edema slight normal
5 erythema well-defined normal
edema very slight normal
Interpretation of results:
GHS criteria not met
Conclusions:
The test article was determined to be slightly irritating. However, the exposure duration was 24 h and not 4 h as by the OECD Test Guideline 404. Thus, this is a clear worst-case result.
Executive summary:

A skin irritation test in guinea pigs was performed. Slight or very slight edema was observed in 1 of 5 and 3 of 5 guinea pigs, respectively, at 24-48 hours after exposure to the test item. Edema was accompanied by moderate to severe erythema in 2 of 5 guinea pigs, and well-defined erythema in 2 of 5 guinea pigs. Moderate to severe erythema without edema was observed in 1 of 5 guinea pigs at 24-48 hours after exposure. For all test animals, there were no signs of edema or erythema at 2 weeks after exposure. This compound was determined to be slightly irritating. However, the exposure duration was 24 h and not 4 h as by the OECD Test Guideline 404. Thus, this is a clear worst-case result.

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Remarks:
in vivo study that was performed prior to current requirement for in vitro alternative testing
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Justification for type of information:
in vivo study that was performed prior to current requirement for in vitro alternative testing
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
0.1 mL of undiluted material was applied to each of 2 eyes of 3 rabbits; material was immediately washed from one eye of each rabbit with distilled water.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Strain: New Zealand White
- Weight at study initiation: not determined
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.1 mL of undiluted material was applied to each of 2 eyes of 3 rabbits; material was immediately washed from one eye of each rabbit with distilled water
Duration of treatment / exposure:
one single application
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): distilled water
- Time after start of exposure: immediate washing was palliative
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
not specified
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
not specified
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
unwashed, washed
Time point:
other: 1 h
Score:
ca. 1
Max. score:
4
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
not specified
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Reversibility:
not specified
Remarks on result:
not measured/tested
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Reversibility:
not specified
Remarks on result:
not measured/tested
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Reversibility:
not specified
Remarks on result:
not measured/tested
Irritant / corrosive response data:
Slight irritation was observed in the conjunctiva and nicitating membrane of 3 of 3 rabbits at one hour after instillation of 0.1 mL of m-diisopropylbenzene. After 24 hours, irritation was not observed in the conjunctiva and nicitating membrane, but was observed in the eyelids in 3 of 3 rabbits. By 48 hours, there were no signs of ocular irritation in any treated animal. There were no signs of irritation observed in the cornea or iris at any time during the study. The test substance was considered to be a slight eye irritant.
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was considered to be a slight eye irritant, which does not meet the criteria for classification and labelling according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008.
Executive summary:

The eye irritation was tested in three rabbits. Slight irritation was observed in the conjunctiva and nicitating membrane of 3 of 3 rabbits at one hour after instillation of 0.1 mL of test item. After 24 hours, irritation was not observed in the conjunctiva and nicitating membrane, but was observed in the eyelids in 3 of 3 rabbits. By 48 hours, there were no signs of ocular irritation in any treated animal. There were no signs of irritation observed in the cornea or iris at any time during the study. The test substance was considered to be a slight eye irritant, which does not meet the criteria for classification and labelling according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) 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

Skin irritation / corrosion
A skin irritation test in guinea pigs was performed. Slight or very slight edema was observed in 1 of 5 and 3 of 5 guinea pigs, respectively, at 24-48 hours after exposure to test item. Edema was accompanied by moderate to severe erythema in 2 of 5 guinea pigs, and well-defined erythema in 2 of 5 guinea pigs. Moderate to severe erythema without edema was observed in 1 of 5 guinea pigs at 24-48 hours after exposure. For all test animals, there were no signs of edema or erythema at 2 weeks after exposure. This compound was determined to be slightly irritating. However, the exposure duration was 24 h and not 4 h as by the OECD Test Guideline 404. Thus, this is a clear worst-case result.


 


Eye irritation
Eye irritation was tested in three rabbits. Slight irritation was observed in the conjunctiva and nictitating membrane of 3 of 3 rabbits at one hour after instillation of 0.1 mL of test item. After 24 hours, irritation was not observed in the conjunctiva and nictitating membrane but was observed in the eyelids in 3 of 3 rabbits. By 48 hours, there were no signs of ocular irritation in any treated animal. There were no signs of irritation observed in the cornea or iris at any time during the study. The test substance was considered to be a slight eye irritant.

Justification for classification or non-classification

In two independent studies, the test item produced slight, transient irritation when applied to the skin of guinea pigs, and therefore does not satisfy the criteria for classification as a dermal irritant according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008 or UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS). 


 


When instilled into the eye, test item produced mild and transient irritation of the conjunctiva, but no evidence of corneal opacity in rabbits.  


Based upon these findings, test item does not satisfy the criteria for classification as an ocular irritant according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008 or UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS).