Azelaic acid

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

13 Nov - 13 Dec 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP - Guideline study, tested with the source substance CAS 68937-75-7. In accordance to the ECHA guidance document "Practical guide 6: How to report read-across and categories (March 2010)", the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

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:

Fatty acids, C8-10

EC Number:

273-086-2

EC Name:

Fatty acids, C8-10

Cas Number:

68937-75-7

IUPAC Name:

68937-75-7

Details on test material:

- Name of test material (as cited in study report): PRIFRAC 2911
- Physical state: liquid
- Analytical purity: >99.5%
- Storage condition of test material: In the original container at room temperature in the dark

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, West-Germany
- Age at study initiation: approx. 14 weeks
- Weight at study initiation: 2884 - 3069 g
- Housing: individually in cages with perforated floors equipped with an automatic drinking system (ITL, Bergen / The Netherlands)
- Diet: standard laboratory diet (LKK-20, pellet diameter 4 mm, Hope Farms, Woerden / The Netherlands) approx. 100 g per day.
- Water (ad libitum): free access to tap water diluted with decalcified water
- Acclimation period: at least five days under test conditions


ENVIRONMENTAL CONDITIONS
Standard Laboratory Conditions
- Temperature (°C): 21 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin sites of same animals

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

21 days

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: dorsal skin
- Site preparation: approximately 24 hours before treatment, the dorsal fur was shaved with an electric clipper, exposing an area of approximately 100 square centimetres (10 cm x 10 cm). Prior to test substance administration, the animals were physically examined and the skin. found to be intact and normal.
- Type of wrap if used: surgical gauze patch 2x3 cm mounted on Micropore tape (3M, U.S.A.). The dressing was wrapped around the abdomen and secured with an elastic bandage (Coban, 3M, U.S.A.)


REMOVAL OF TEST SUBSTANCE
- Washing (if done): tissue moistened with tap-water and subsequently a dry tissue
- Time after start of exposure: 4 h


SCORING SYSTEM:
In order to facilitate the scoring, the skin area concerned of all animals was shaved again before the observation on days 2, 3, 4, 8, 15 and 22.
Scoring acc. to Draize (1994):

Erythema:
0 - no erythema
1 - very slight erythema (barely perceptible)
2 - well-defined erythema
3 - moderate to severe erythema
4 - severe erythema (beet redness) to slight eschar formation (injuries in deep)

Edema:
0 - no edema
1- very slight edema (barely perceptible)
2 - slight edema (edges of area well defined by definite raising)
3 - moderate edema (raised appr. 1 mm)
4 - severe edema (raised >1 mm and extending beyond area of exposure)

Additionally, a primary dermal irritation index (PDII) was calculated by combining the average skin irritation scores for erythema and oedema after 24 and 72 hours:
0 - non-irritating
0.1 - 2.0 mildly irritating
2.1 - 5.0 moderately irritating
5.1 - 8.0 severely irritating

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: mean 24 - 48 - 72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 21 days

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: mean 24 - 48 - 72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: mean 24 - 48 - 72 h

Score:

3.7

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: mean 24 - 48 - 72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: mean value could not be calculated for animals #1 and #2 due to the omission of edema scores due to eschar formation

Irritant / corrosive response data:

PRIFRAC 2911 resulted in an estimated primary irritation index of 7 (severely irritating, when using grade 3 for missing edema scores) when applied to the intact rabbit skin.
The observed skin irritation consisted of eschar formation and slight to moderate edema.
The irritation was reversible within 14 days after exposure in animal #3, within 21 days after exposure in animal #1, but had not resolved by day 22 in animal #2. Animal #2 showed new skin formation with very slight erythema and slight edema on day 22. No corrosive effect was evident on the skin.

Other effects:

In the area of application brown staining of the treated skin by the test substance and adherence of the test article was observed. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Readings:

Time	Animal	Erythema	Edema	Additional findings
1 h	1	2	1
	2	1	2
	3	1	2
24 h	1	4	3	e
	2	2	4
	3	4	4	e
48 h	1	4	-	n
	2	2	4
	3	4	-	n
72 h	1	4	-	n
	2	2	4
	3	4	-	n
7 d	1	4	-	n
	2	4	-	n
	3	4	-	n
14 d	1	1	1	new skin formation on treated skin
	2	1	1	new skin formation with scaling.
	3	0	1	new skin formation on treated skin
21 d	1	1	0	± 50 % new skin formation
	2	1	0	± 50 % new skin formation
	3	1	2	-
mean 24 - 48 - 72 h	1	4	3
	2	2	4
	3	4	4
mean		3.3	3.7

n: edema could not be scored due to eschar formation

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU