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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report date:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Methyl 2-ethylhexanoate
EC Number:
212-429-2
EC Name:
Methyl 2-ethylhexanoate
Cas Number:
816-19-3
Molecular formula:
C9H18O2
IUPAC Name:
methyl 2-ethylhexanoate
Test material form:
other: liquid
Details on test material:
- Physical state: Liquid
- Storage condition of test material: Room temperature.
- Other: Clear colourless

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Recognised supplier
- Age at study initiation: Young adult
- Weight at study initiation: Not reported.
- Housing: individually housed in labeled cages with mesh floors conform to the size recommendations in the most recent Guide for the Care
and Use of Laboratory Animals DHEW (NIH)
- Diet (e.g. ad libitum): Pelleted Purina Rabbit Chow #5326
- Water (e.g. ad libitum): filtered tap water ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 22
- Humidity (%): Not reported.
- Air changes (per hr):Not reported.
- Photoperiod (hrs dark / hrs light): 12 hour light/12 hour dark cycle

IN-LIFE DATES: From: 01/10/03 To: 15/10/03

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5ml test material
Duration of treatment / exposure:
4 hours ( test sites were gently cleaned of any residual test substance).
Observation period:
Individual dose sites were scored at approximately 1, 24, 48 and 72 hours and at 7, 10 and 14 days after patch removal.
Number of animals:
3; all females
Details on study design:
TEST SITE
- Area of exposure: applied to one 6 cm2 intact dose site on each animal
- % coverage: not reported
- Type of wrap if used: semi-occlusive 3 inch Micropore tape

SCORING SYSTEM: Draize scoring system; the classification of irritancy was obtained by adding the average erythema and edema scores for the
1, 24, 48, and 72-hour scoring intervals and dividing by the number of evaluation intervals and calculation of the resulting Primary Dermal Irritation Index (PDll).
1. Evaluation of Skin Reactions
Erythema and eschar formation:
No erythema - 0
Very slight erythema (barely perceptible) - 1
Well-defined erythema - 2
Moderate to severe erythema - 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) - 4
Edema formation:
No edema - 0
Very slight edema (barely perceptible) - 1
Slight edema (edges of area well defined by definite raising) - 2
Moderate edema (raised approximately 1 millimeter) - 3
Severe edema (raised more than 1 millimeter and extending beyond the area of exposure) - 4

Primary Dermal Irritation Index (PDll)
PDII / Classification
0 / Non-irritating
> 0-2.0 / Slightly irritating
2.1-5.0 / Moderately irritating
>5.0 / Severely irritating

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1 hour
Score:
1.3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hour
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 hour
Score:
3.3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hour
Score:
3.3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 7 days
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 10 days
Score:
2.3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 14 days
Score:
2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1 hour
Score:
1
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hour
Score:
1
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 hour
Score:
2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hour
Score:
2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 7 days
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 10 days
Score:
2.3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 14 days
Score:
2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Score:
4.5
Remarks on result:
other: 1, 24, 48, and 72 hour evaluation; 4 evaluation intervals
Irritant / corrosive response data:
Individual skin irritation scores are presented. A summary of primary skin irritation scores used for calculation of Primary Dermal Irritation Index is presented. Within 24 hours of patch removal, all three treated sites exhibited severe erythema and very slight edema. Desquamation was noted for two animals between Days 10 and 14. Although the overall severity of irritation decreased gradually by the end of the study, irritation persisted for all animals through Day 14 (study termination).
Other effects:
All animals appeared active and healthy. Apart from the dermal irritation, there were no other signs of gross toxicity, adverse pharmacologic effects or abnormal behavior.

Applicant's summary and conclusion

Interpretation of results:
moderately irritating
Remarks:
Migrated information Criteria used for interpretation of results: US EPA pesticides
Conclusions:
Under the conditions of the study the test substance is considered to be moderately irritating to skin.
Executive summary:

The study was performed to US EPA OPPTS 870.2500 and OECD 405 to assess the primary skin irritancy potential of the test substance in accordance with GLP. Five-tenths of a milliliter of the test substance was applied to one 6 cm2 intact dose site on each animal and covered with a 1 inch x 1 inch, 4-ply gauze pad. The pad and entire trunk of each animal were then wrapped with semi-occlusive 3 inch Micropore tape to avoid dislocation of the pad. After 4 hours of exposure to the test substance, the pads and collars were removed and the test sites were gently cleaned of any residual test substance. Individual dose sites were scored according to the Draize scoring system at approximately 1, 24, 48, and 72 hours and at 7, 10, and 14 days after patch removal. The classification of irritancy was obtained by adding the average erythema and edema scores for the 1, 24, 48, and 72-hour scoring intervals and dividing by the number of evaluation intervals. Within 24 hours of patch removal, all three treated sites exhibited severe erythema and very slight edema. Desquamation was noted for two animals between Days 10 and 14. Although the overall severity of irritation decreased gradually by the end of the study, irritation persisted for all animals through Day 14 (study termination). The Primary Dermal Irritation Index for the test substance is 4.5. Under the conditions of this study the substance is classified as moderately irritating to the skin.