Methyl valerate

Endpoint summary

Description of key information

Skin irritation (rat):  not irritating [Kurth 2006]
Eye irritation (rabbit): not irritating [Amir 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:

from August 2002 to February 2003

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

- exposure time 24 hrs instead of 4 hrs, 6 animals instead of 3, few details in test description and reporting

GLP compliance:

not specified

Specific details on test material used for the study:

- Solubility and stability of the test substance in the solvent/vehicle: The liquid original compound was used

Species:

rat

Strain:

other: Shoe: WIST (SPF)

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated skin served as control

Amount / concentration applied:

2000 mg/kg bw

Duration of treatment / exposure:

24 hours

Observation period:

14 days

Number of animals:

3 males and 3 females

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0.78

Max. score:

4

Reversibility:

fully reversible within: 6 days

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Test compound ZK 56406 (2000 gm/kg)		Animal number and sex
Location (finding)	Time-point after end of exposure	20M	21M	22M	4F	5F	6F
Reddening and scab formation	1 hour*	0	0	0	0	0	0
	24 or 25 hours	2	2	0	0	0	0
	48 hours	2	2	0	0	1	1
	72 hours	2	2	0	0	0	0
Individual mean values:		2	2	0	0	0.33	0.33
Mean value of all animals:							0.78
Swellings	1 hour*	0	0	0	0	0	0
	24 or hours	0	0	0	0	0	0
	48 hours	0	0	0	0	0	0
	72 hours	0	0	0	0	0	0
Individual mean values:		0	0	0	0	0	0
Mean values of all animals:							0

*         = not included in calculations of mean values

Interpretation of results:

other: very slight local intolerance reactions up to day 6.

Executive summary:

After a single dermal administration of the test substance for 24 hours to male and female rats at a dose of 2000 mg/kg very slight local intolerance reactions at the administration area and above were observed up to day 6. The mean values of findings relevant for classification (reddening, scab formation and swelling of the skin) at the time-points 24, 48 and 72 hours after the end of administration were 0.

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:

August to September 2002

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

4 animals (2M, 2F)

GLP compliance:

not specified

Specific details on test material used for the study:

- Solubility and stability of the test substance in the solvent/vehicle: The liquid original compound was used

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

other: the left eye, which remained untreated, served as control.

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

test substance remained in the eye (eye was not rinsed)

Observation period (in vivo):

4 days

Number of animals or in vitro replicates:

2 females, 2 males

Details on study design:

0.1 mL corresponded to ca. 91 mg

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

reddening

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.5

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

swelling

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.25

Max. score:

4

Reversibility:

fully reversible within: 3 days

Table 1: Results of the study

		Irritant effects (score)
Animal no. (sex)	Irritation parameter	24 h	48 h	72 h	Mean scores
1 (M)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	0	0	0	0.0
	Conjunctiva (swelling)	0	0	0	0.0
2 (M)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	0	0	0	0.0
	Conjunctiva (swelling)	0	0	0	0.0
3 (F)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	1	1	1	1.00
	Conjunctiva (swelling)	1	0	0	0.33
4 (F)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	1	1	1	1
	Conjunctiva (swelling)	1	1	0	0.67

The control eyes were without findings.

A single application of 0.1 ml ZK 28520 into the conjunctival sac of the rabbit eye led to slight to moderate secretion, reddening and swelling of the outer eyelids and eyelid closure mainly on days 1-2. Additionally, reddening and swelling of the conjunctivae were observed which were slight to moderate up to day 2, while slight conjunctival reddening and/or vascular injection were observed up to day 7. One animal was without findings on day 2, while the other animals were without findings on days 7 or 8.

Interpretation of results:

other: slight to moderate irritation which is fully reversible on day 7

Executive summary:

In a local tolerance test on the rabbit eye similar to OECD TG 405 a single application of the test substance into the conjunctival sac provoked on the whole slight irritation which lasted up to day 7. The mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after application were 0 for the parameters cornea and iris, 0.25 for conjunctival swelling and 0.50 for conjunctival reddening. According to EU classification criteria the test substance need not be labelled as an eye irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

After a single dermal administration of the test substance for 24 hours to male and female rats at a dose of 2000 mg/kg very slight local intolerance reactions at the administration area and above were observed up to day 6. The mean values of findings relevant for classification (reddening, scab formation and swelling of the skin) at the time-points 24, 48 and 72 hours after the end of administration were 0.

In a local tolerance test on the rabbit eye similar to OECD TG 405 a single application of the test substance into the conjunctival sac provoked on the whole slight irritation which lasted up to day 7. The mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after application were 0 for the parameters cornea and iris, 0.25 for conjunctival swelling and 0.50 for conjunctival reddening. According to EU classification criteria the test substance need not be labelled as an eye irritant.

Justification for classification or non-classification

Based on the study results a classification according to Directive 67/548/EEC or Regulation (EC) No. 1272/2008 (CLP) is not required.