Ethyl 2-methylvalerate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 August 26 to 09 September 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: - Study performed according to GLP - Study performed according to OECD Guideline 404 (Acute Dermal Irritation / Corrosion) and EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl 2-methylpentanoate

Cas Number:

39255-32-8

IUPAC Name:

Ethyl 2-methylpentanoate

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): Manzanate, DL 4979/F4-24
- Physical state: clear, colourless, slightly viscous liquid
- Other:
- A sample of the test substance was received from the sponsor on August 14, 1986

Test animals

Species:

rabbit

Strain:

other: New Zealand White albino rabbits

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: obtained from ENKI-Konijnenfarm, Someren, the Netherlands
- Weight at study initiation: 2500-3500 g
- Age at study initiation: Healthy male, young adult
- Housing: The animals were identified by earmarking, and subsequently housed individually in suspended, galvanized cages, fitted with wire-mesh floor and front
- Diet (e.g. ad libitum): A standard laboratory rabbit diet was provided ad libitum.
- Water (e.g. ad libitum): tap water was provided ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): at least 40% (relative humidity)
- Air changes (per hr): ventilation c. 10 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark cycle

Test system

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 ml

Duration of treatment / exposure:

Exposure period of 4 hours

Observation period:

- After an exposure period of 4 hours the patches and the test material applied were removed and the resulting skin reactions were evaluated by the method of Draize et al. (J. Pharmacol. Exp. Ther. 82 (1944) 377-390).
- Further readings were made after 28, 52 and 76 hours, and after 7 and 14 days.

Number of animals:

3

Details on study design:

Experimental design:
- The procedure was extended with treatment on the abraded skin. After an acclimatization period of six days, i.e. one day prior to the start of the experiment, the hair was removed from the back and flanks of the animals using electric clippers in a way as to avoid abrasions. Three rabbits were treated on the intact skin and on the abraded skin. The abrasions were minor incisions of the stratum corneum, but not sufficiently deep to disturb the derma or to produce bleeding.
- An amount of 0.5 ml of the undiluted test substance was brought on the intact and the abraded skin under a patch measuring 1 inch x 1 inch. The patches were fixed to the application sites by means of adhesive tape and the entire trunk of each rabbit was wrapped with an impervious material to maintain the test patches in position and to retard evaporation of volatile substances. After an exposure period of 4 hours the patches and the test material applied were removed and the resulting skin reactions were evaluated by the method of Draize et al. (J. Pharmacol. Exp. Ther. 82 (1944) 377-390). A transcript of the grading system by Draize et al. is given in an appendix to this report (see page 11 of attached report).
- Further readings were made after 28, 52 and 76 hours, and after 7 and 14 days.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

fully reversible within: 14d

Remarks on result:

other: Intact skin

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.6

Max. score:

1

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: Intact skin

Results 3

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

fully reversible within: 14d

Remarks on result:

other: abraded skin

Results 4

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.6

Max. score:

1

Reversibility:

fully reversible within: 14h

Remarks on result:

other: Abraded skin

Irritant / corrosive response data:

Skin reaction scoring used the Draize system

Any other information on results incl. tables

- After 4-76 hours, the skin effects observed in all (three) rabbits generally consisted of very slight or well-defined erythema, and very slight oedema (not after 4 hours). In addition, after 52 hours, all application sites showed very slight scaliness and after 76 hours, slight scaliness.

- After 7 days, well-defined erythema and very slight oedema were still observed in one rabbit (no. 4017), and slight scaliness was still observed in all (three) rabbits.

- After 14 days, all skin effects had cleared completely.

- There were no significant differences between the reactions of the intact skin and those of the abraded skin.

Table 1 - Individual and average irritation scores of Manzanate

Rabbit no.	Intact skin
	4 hr	28 hr	52 hr	76 hr
	A-B	A-B	A-B	A-B
4017	2-0	2-1	2-1	2-1
4018	1-0	1-1	1-1	1-1
4028	1-0	1-1	1-0	1-0
Average	1.3	2.3	2.0	2.0

Rabbit no.	Abraded skin
	4 hr	28 hr	52 hr	76 hr
	A-B	A-B	A-B	A-B
4017	2-0	2-1	2-1	2-1
4018	1-0	1-1	1-1	1-1
4028	1-0	1-1	1-1	1-0
Average	1.3	2.3	2.3	2.0

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

On the basis of the results obtained it is concluded that, according to the EEC-standards (as published in the Official Journal of the European Communities, L 257, Volume 26, 16 September 1983), the undiluted test substance Manzanate is not irritating or corrosive to skin.

Executive summary:

1. A sample of Manzanate was examined undiluted for acute denial irritating/corrosive properties in an experiment with three albino rabbits.

2. The test substance caused very slight or well-defined erythema, very slight or slight scaliness, and very slight oedema in all (three) rabbits.

After 14 days, all skin effects had cleared completely.

3. On the basis of the results obtained it was concluded that, according to the EEC-standards, the undiluted test substance Manzanate is not irritating or corrosive to skin.