Ethyl 2-methylvalerate

Endpoint summary

Description of key information

The result of the irritation / corrosion studies is that EMV was not found to be not irritating to skin or eyes.

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:

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)

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

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

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.

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

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

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

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

- 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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03 September to 05 September 1986.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: New Zealand White albino rabbits

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: obtained from ENKI-Konijnenfarm, Someren, the Netherlands
- Age at study initiation: young adult
- Weight at study initiation: body weight range 2500-3500 g
- Housing: The animals were identified by earmarking, and 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

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated eye

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 ml

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

3

Details on study design:

Experimental design:
- Both eyes of each rabbit provisionally selected were examined within 24 hours before testing. Three animals without observable eye effects were used.
- One tenth of a millilitre of the undiluted test substance was allowed to fall on the everted lower lid of one eye of each rabbit. After administration the upper and lower eye lid were carefully closed and subsequently held together for about one second before releasing, to prevent loss of material. The other eye remaining untreated, served as a control. The eyes were not washed out following administration and the animals were released immediately.
- Ocular reactions were judged using the scoring scale which is given in an appendix at the end of this report (see page 10 of attached report).
- Eye effects were examined after one hour, 24, 48 and 72 hours, or until the eye effects had cleared completely.

Irritation parameter:

cornea opacity score

Basis:

animal: 4020

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal: 4022

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal: 4023

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal: 4020

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal: 4022

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal: 4023

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal: 4020

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 48h

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal: 4022

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 48h

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal: 4023

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 48h

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal: 4020

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal: 4022

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal: 4023

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

- After one hour and after 24 hours, the eye effects observed in all (three) rabbits consisted of slight redness and slight swelling of the conjunctivae.

- After 48 hours, all eye effect had cleared completely.

Table 1. Individual Scores Awarded to the Ocular Lesions Elicited by Manzanate

Rabbit number	Cornea opacity	Iris	Conjunctivae
			Redness	Chemosis
			After one hour
4020	0	0	1	1
4022	0	0	1	1
4023	0	0	1	1
			After 24 hours
4020	0	0	1	1
4022	0	0	1	1
4023	0	0	1	1
			After 48 hours
4020	0	0	0	0
4022	0	0	0	0
4023	0	0	0	0

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 1984), the undiluted test substance Manzanate is not irritating or corrosive to eyes.

Executive summary:

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

2. The test substance caused slight eye effects in all (three) rabbits. After 48 hours, all eye 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 eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

- Skin irritation:

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.

- Eye irritation:

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

2. The test substance caused slight eye effects in all (three) rabbits. After 48 hours, all eye 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 eyes.

Justification for selection of skin irritation / corrosion endpoint:
Selected as key study.

Justification for selection of eye irritation endpoint:
Only study available

Justification for classification or non-classification

All studies returned a negative result. Therefore EMV will not be classified as irritating or corrosive.