Isovaleric acid

Endpoint summary

Description of key information

No other symptoms than respiratory irritation were noted in rats exposed for 7 hours at saturation concentration (approx. 2060 mg/m³, calculated).

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline studies

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

no data

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

not required

Duration of treatment / exposure:

3 minutes and 1 hour

Observation period:

8 days

Number of animals:

2 (1hr) and 4 (3 min exposure)

Details on study design:

TEST SITE
- Area of exposure:
- % coverage:
- Type of wrap if used:

REMOVAL OF TEST SUBSTANCE
- Washing (if done):
- Time after start of exposure:

SCORING SYSTEM: BASF; similar to the table of Draize contained in the OECD test guideline

Irritation parameter:

erythema score

Remarks:

skin contact: 1hr

Basis:

mean

Time point:

other: 1 hr

Score:

2

Max. score:

4

Remarks on result:

other: Contact period 1 hour in this and following lines.See also section "Any other information on results incl. tables" below.

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: day 1

Score:

3

Max. score:

4

Remarks on result:

other: necrosis in one animal

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: day 2

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: necrosis in both animals

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: day 8

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: necrosis in both animals; scoring of skin reaction not possible

Table 1: skin reactions following a 1-hour exposure. Findings were confirmed by pathologist.

animal	1 hour		Day 1		Day 2		Day 8
	erythema	edema	erythema	edema	erythema	edema	erythema	edema
1	2ext	2ext	4 N	2ext	4 N	2ext	N d	2ext
2	2ext	2ext	2ext N	2ext	4 N	2ext	N d	2ext

 

Table 2: skin reactions following a 3-minute exposure. Findings were confirmed by pathologist.

animal	1 hour		Day 1		Day 2		Day 8
	erythema	edema	erythema	edema	erythema	edema	erythema	edema
1	2ext	2ext	4 N	2ext	4 N	2ext	4 N	2ext
2	2	sup	2ext N	2	2ext N	2ext	Sup N	1
3	1ext	sup	4 N	2ext	4 N	2ext	4 N	2
4	2ext	sup	2ext	2ext	2ext	3ext	2	2

Legend:
grading 1, 2, 3, 4: according to table in OECD 404 (1992)
ext = exteing beyond area of exposure
N = necrosis; N d = deep, entire skin (= full thickness)

Sup = superficial

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Following a 1- hour exposure period isovaleric acid caused full thickness necrosis of the rabbit's skin. Classification (skin corrosion, Cat 1B) is required.

Executive summary:

Isovaleric acid caused irreversible skin reactions and necrosis of the rabbit's skin following a 1-hour skin contact period. Skin contact for 3 minutes caused also necroses, but these were seen one day after the treatment. The study was equivalent to OECD 404 (adopted 1992); (BASF, 1980).

The study is considered to be valid for assessment. According to the regulation EC/1272/2008 isovaleric acid was corrosive to the skin and requires Cat 1B classification.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Isovaleric acid caused irreversible skin reactions and necrosis of the rabbit's skin following a 1-hour skin contact period. Skin contact for 3 minutes caused also necroses, but these were seen only one day after the treatment. The study was equivalent to OECD 404 (adopted 1992); (BASF, 1980).

No study was located for eye irritation. The substance is corrosive to the skin, therefore sufficient information is available for the classification of the substance, and no study is required.

Regarding respiratory irritation, symptoms were noted in the acute inhalation study where rats were exposed for 7 hours at saturation concentraton (approx. 2060 mg/m³, calculated) (BASF, 1980).

Justification for selection of skin irritation / corrosion endpoint:
Isovaleric acid caused irreversible skin reactions and necrosis of the rabbit's skin following a 1-hour skin contact period. Skin contact for 3 minutes caused also necroses, but these were seen one day after the treatment. The study was equivalent to OECD 404 (adopted 1992); (BASF, 1980).

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Effects on respiratory irritation: irritating

Justification for classification or non-classification

According to the regulation EC/1272/2008 isovaleric acid was corrosive to the skin and requires Cat 1B classification (irreversible changes) following 1 hour of exposure. A 3 -minute exposure did also cause necrosis, but not within 1 hour. Classification into Cat 1A does therefore not apply.

According to regulation EC/1272/2008, section 3.3.2.3 skin corrosive substances shall be considered as leading to serious damage to the eyes as well (Category 1). This does apply to isovaleric acid and accordingly classification is proposed.