Methyl 2-ethylhexanoate

Endpoint summary

Description of key information

Skin irritation: moderately irritating, EPA OPPTS 870.2500, Product Safety Laboratories 2003
Eye irritation: not-irritating, EPA OPPTS 870.2400, Product Safety Laboratories 2003

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

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

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

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

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

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

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.

 

Eye irritation:

The study was performed according to US EPA OPPTS 870.2400 and OECD 405 acute eye irritation in vivo and in accordance with GLP. A volume of 0.1 ml of the test material was placed into the conjunctival sac of one eye of 3 animals. The other eye remained untreated and was used for control purposes. Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment. There was no corneal opacity or iritis observed during this study. One hour after test substance instillation, all three treated eyes exhibited conjunctivitis. The overall incidence and severity of irritation decreased with time. All animals were free of ocular irritation by 72 hours. All animals appeared active and healthy. There were no other signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour. Under the conditions of this study the test material is mildly irritating.

 

The applicant’s re-calculation of the mean scores following grading at 24, 48 and 72h and the individual scores which were fully reversible within 72 hours, the test material is not considered to be irritating to the eye under Regulation (EC) 1272/2008 criteria.

Justification for selection of skin irritation / corrosion endpoint:
one in vivo GLP compliant Klimisch 1 study.

Justification for selection of eye irritation endpoint:
one in vivo non-GLP study Klimisch 1 study

Effects on skin irritation/corrosion: moderately irritating

Justification for classification or non-classification

The substance meets classification criteria under EU Directive 67/548/EEC for dermal irritation; R38

The substance meets classification criteria under Regulation (EC) No 1272/2008 for dermal irritation category 2; H315

 

The substance does not meet classification criteria under EU Directive 67/548/EEC for eye irritation.

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for eye irritation.