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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Review and collection of existing data. Though secondary literature, the reliability is regarded as being high (RL=2) because guideline studies according to OECD 405 and conducted under GLP were assessed and referenced (deviations of the actual tests from test guideline: observation period only 7 days).

Data source

Reference
Reference Type:
review article or handbook
Title:
Unnamed
Report Date:
1999

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
: observation period only 7 days
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 3-methylbutyraldehyde
- Analytical purity: >98.5%
- Impurities (identity and concentrations): no data
- Stability under test conditions: yes

Test animals

Species:
rabbit
Strain:
other: albino
Details on test animals and environmental conditions:
according to OECD test guideline 404

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
7
Number of animals:
4
Details on study design:
according to OECD test guideline 404

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24, 48, and 72 h
Score:
2.83
Max. score:
8
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: at day 7, erythema and edema scores had subsided, but skin irritation had not disappeared completely.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 48, and 72 h
Score:
1.42
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: Grading scores for day 7 are displayed below under Remarks on results
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48, and 72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48, and 72 h
Score:
2
Max. score:
4
Reversibility:
other: almost fully reversible within 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48, and 72 h
Score:
1.83
Max. score:
4
Reversibility:
other: almost fully reversible within 7 d
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48, and 72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48, and 72 h
Score:
1.17
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48, and 72 h
Score:
0.33
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: 24, 48, and 72 h
Score:
1.33
Max. score:
4
Reversibility:
other: almost fully reversible within 7 days
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: 24, 48, and 72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Other effects:
At day 7, markde desquamation from the skin was observed for animal 3 and 4.

Any other information on results incl. tables

Grading Scores of Skin Reactions

 

 

Animal 1

Animal 2

Animal 3

Animal 4

Observation time

(day after patch removal)

Erythema

Edema

Erythema

Edema

Erythema

Edema

Erythema

Edema

1 (hour)

2

2

1

2

1

1

1

1

1

2

2.5

2

1.5

2

1

1

1

2

2

2

2

1.5

1

0

1

1.5

3

2

1.5

1.5

1

0.5

0

2

1.5

7

1

0.5

0.5

0

1 *

1

0.5 *

0

Mean (day 1 to 3)

2

2

1.83

1.33

1.17

0.33

1.33

1.33

* marked desquamation from the skin

 

In this study, skin reactions were only observed for 7 days after removal of the patch. No data are reported for day 14.

 

At day 7, scores of skin reactions had decreased after passing peaks between day 1 and 3. But the effects of skin irritation had not completely disappeared. Based on the low level of irritation scores at day 7 (maximum score 1), it is estimated that skin reaction is fully reversible within 14 days.

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Isovaleraldehyde caused slight irritation after application of 0.5 mL on the rabbit's skin after a 4-h contact period. Overall irritation score for time periods 24, 48, and 72 h was 1.42 with highest individual scores of 2 and 2.5 (erythema and edema respectively). After 7 days, skin reactions had almost completely subsided. Based on the 7 day scores, It is estimated that skin reactions are reversible within 14 days.
Executive summary:

In a primary dermal irritation study according to OECD test guideline 404 and conducted under GLP conditions, four albino rabbits were dermally exposed to 0.5 mL of isovaleraldehyde (3-methylbutyraldehyde) (purity 98.5 %) for 4 hours. Animals were then observed for 7 days but not for 14 days. Irritation was scored by the method of Draize/OECD test guideline 404.

 

Skin reactions could be observed in all animals starting 1 h after removal of the patch with a maximum erythema and edema score of 2 and 2.5 respectively (day 1). Scores had subsided at day 7 but irritation effects had not completely disappeared. Considering the day 7 scores, it is estimated that irritation effects are reversible within 15 days.

 

Isovaleraldehyde is slightly irritating to the skin but it does not require classification according to EU regulations based on irritation scores and reversibility of irritating effects (ECETOC, 1995).