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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:
25 April 1984 to 9 May 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline-compliant, proprietary study. Read across for fumaric acid.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report date:
1984

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
Study was conducted in accordance with OECD Method 404
GLP compliance:
yes

Test material

Constituent 1
Reference substance name:
Fumaric acid/Fumaril
IUPAC Name:
Fumaric acid/Fumaril
Details on test material:
- Physical state: Solid
- Analytical purity: 99.5%
- odour: odourless

- Name of test material (as cited in study report): fumaric acid

- Impurities (identity and concentrations): benzoic, maleic and phthalic acid <0.05%
- Composition of test material, percentage of components:

- Stability under test conditions:
- Storage condition of test material:
- Other: pH 2.1 at 4.9 g/L density 1.63 g/cm3

Test animals

Species:
rabbit
Strain:
other: small white Russian
Details on test animals or test system and environmental conditions:
Male and female rabbits between 1.9 and 2.8 kg were housed in individual stainless steel cages and acclimated for 14 days. Rabbits received K4 single diet for rabbits (Ssniff Special Feed GmbH) and water ad libitum. Room temperature was 20C with 60% relative humidity. Air was exchanged 15 times per hour and a 12 hr light-dark cycle was employed.

Test system

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
other: paraffin oil
Controls:
not required
Amount / concentration applied:
0.5 g test material wetted with paraffin oil
Duration of treatment / exposure:
4 hrs
Observation period:
1, 24, 48 and 72 hours as well as 5, 7, 8, 12 and 14 days
Number of animals:
3 males and 3 females
Details on study design:
TEST SITE
- Area of exposure: 6 cm2 patch of skin
- Type of wrap if used: linen cloth (2.5 x 2.5 cm) covered with a polyethylene foil (6 x 6 cm). The application site was secured with an elastic band.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): distilled water

SCORING SYSTEM:

Erythema and Eschar Formation:
No erythema...0
Very slight erythema (barely perceptible)...1
Well-defined erythema...2
Moderate to severe erythema...3
Severe erythema to slight eschar formation...4

Oedema Formation:
No oedema...0
Very slight oedema...1
Slight oedema...2
Moderate oedema...3
Severe oedema...4

Reaction values for redness and swelling were calculated for 1, 24, 48 and 72 hours after patch removal. These absolute values were added together and divided by the number of assessment times (4) to determine irritation index:

0 - 0.5 Not irritating
0.6 - 3.0 Mildly irritating
3.1 -5.0 Moderately irritating
5.0 - 8.0 Highly irritating

Results and discussion

In vivo

Results
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72 hrs
Score:
0.63
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
The mean score over 24-72 hours for redness was calculated to be 0.72
The mean score over 24-72 hours for swelling was calculated to be 0.11
Neither scores warrant classification for skin irritation

Any other information on results incl. tables

Individual and average redness (R) and swelling (S) values

 Animal number  1 hr     24 hr    48 hr     72 hr   
 R  S  R  S  R  S  R  S
 1  0  0  0  0  0  0  0  0
 2  0  0  1  0  1  0  1  0
 3  0  0  *2  0  *1  1  *2  0
 4  0  0  0  0  1  0  1  0
 5  0  0  0  0  0  0  0  0
 6  0  0  0  0  1  0  2  1
 Total     0     0.5     0.83     1.17
 Average                       2.50 / 4 = 0.63
    *Redness directly on the application surface

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
This study supports the conclusion that fumaric acid is a mild skin irritant that does not require classification for dermal irritation according to EU and GHS systems. It is proposed to classify malic acid the same way.
Executive summary:

Read across to fumaric acid is considered valid and malic acid is concluded to have low toxicity and classification is not required

The rational for read across is that fumaric acid will metabolise in biological systems to malic acid.

It is not considered valid to perform further animal tests on malic acid.

Dermal application of 0.5 g fumaric acid was mildly irritating to the skin of male and female rabbits. Fumaric acid did not elicit dermal reactions that would exceed the threshold for classification in accordance with EU criteria.