Registration Dossier

Administrative data

Endpoint:
skin irritation / corrosion, other
Remarks:
Old in-vivo study from 1979 so no new amnimals have been used.
Type of information:
experimental study
Adequacy of study:
key study
Study period:
December 7, 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study performed similarly to US-FHSA guideline. Deviations from standard method : no data on test animals, 24 h exposure instead of 4h, occlusive dressing instead of semi-occlusive, observation at 24 and 72 h only (no 48h scoring), no reversibility period although effects have been observed until the end of the study. Even if full reversibility was not achieved for lesions, the observation period was only 3 days and effects were very slight and decreasing.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Section 1500.41 - Hazardous Substances and articles, Administration and Enforcement Regulations, Federal Register, Vol. 38, No. 187, P. 27019, 27 September 1973.
Deviations:
yes
Remarks:
purity of test item not reported; environmental conditions of experimental room not reported; occlusive patch 24 h instead of semi-occlusive patch 4 h; no details on removal of substance after patch removal; no observation for 14 days but only 72 h
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): MT-102.Methylpentenol isobutyrate
- Physical state: Clear colorless liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: approved USDA supplier
- Weight at study initiation: 3.27-3.60 kg
- Housing: Animals were housed individually in wire-meshed cages.
- Diet: Charles River Rabbit Formula, ad libitum
- Water, ad libitum

Test system

Type of coverage:
occlusive
Preparation of test site:
other: one side intact and clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): Undiluted
Duration of treatment / exposure:
24 h
Observation period:
24 and 72 h
Number of animals:
6
Details on study design:
PRETREATMENT
- 24 h prior to the dermal applications the backs and flanks of each rabbit were clipped free of hair with a commercial electric clipper with a No. 40 blade. The animals were then returned to their cages.

TEST SITE (intact skin)
- Area of exposure: Left side of the animal's back
- Type of wrap if used: The test sites were then immediately occluded with a one-inch by one-inch square gauze patch, two single layers thick. The patches were secured in place with masking tape. The trunk of each animal was wrapped with impervious plastic sheeting which helped hold the patches in position and retard evaporation of the test material during the 24 h exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize method

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
(6 animals)
Time point:
other: mean 24 and 72 h
Score:
1
Max. score:
4
Reversibility:
other: erythema cleared in the intact skin of 2/6 animals & no reversibility in 4/6 animals at 72h
Remarks on result:
other: Intact skin
Irritation parameter:
edema score
Basis:
mean
Remarks:
(6 animals)
Time point:
other: mean 24 and 72 h
Score:
0.58
Max. score:
4
Reversibility:
other: edema cleared in the intact skin of 5/6 animals & no reversibility in 1/6 animals at 72h
Remarks on result:
other: Intact skin
Irritant / corrosive response data:
Slight erythema and edema were observed in the intact skin of all six animals. Erythema cleared in the intact skin of two animals during the 72 h observation period and edema cleared in the intact skin of five animals during the 72 h observation period.
Other effects:
None

Any other information on results incl. tables

Table 7.3.1/1: Primary Skin Irritation Scores of Rabbits

Findings

Exposure Time (h)

Exposure unit (value)

 

Rabbit No.

1

2

3

4

5

6

Erythema and eschar formation:

Intact Skin

24

1

1

1

2

1

2

Intact Skin

72

1

1

1

1

0

0

Mean (24 and 72 h)

 

1

1

1

1.5

0.5

1.0

Edema formation:

Intact Skin

24

1

1

1

1

1

1

Intact Skin

72

0

0

0

1

0

0

Mean (24 and 72 h)

 

0.5

0.5

 

0.5

1.0

0.5

0.5

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the test material induced slight irritation to the skin of rabbits. Even if full reversibility was not achieved, the observation period was only 3 days and effects were slight and decreased between 48-hour and 72-hour observation periods.
Executive summary:

In a dermal irritation study, 0.5 mL of undiluted test material was dermally applied on the intact or abraded side surface of 6 New Zealand White rabbits. Test sites were covered with an occlusive dressing for 24 h. Animals were then observed for 72 h for edema and erythema.  Skin irritation was assessed and scored according to the Draize scale at 24 and 72 h after the removal of the patch.

Slight to mild erythema and slight edema were observed in the intact skin of all six animals at 24h and 72h observation periods. All the individual mean scores for erythema/eschar or oedema, from gradings at 24 and 72h after patch removal, were below the limit of classification (2.3). At 72h observation period, 4/6 animals were scored for erythema/eschar with a very low score (1). Erythema cleared in the intact skin of two animals during the 72 h observation period and edema cleared in the intact skin of five animals during the 72 h observation period.

Based on the weakness of the observed effects, that remain stable or cleared at 72h time point, and since this study was performed under worst case conditions (24h under occlusive conditions instead of 4h under semi-occlusive conditions), it is highly likely that the slight effects observed at 72h will clear in at least 4/6 animals within a 14 -day observation period.

Based on this expert judgement, the test material is not classified as irritant to the skin according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP).

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.