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Diss Factsheets

Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 April to 9 May 1984
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

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)
Version / remarks:
12 May 1981
GLP compliance:
no
Remarks:
GLP was not yet legally implemented when the study was conducted.

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 20 °C 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 × 2.5 cm) covered with a polyethylene foil (6 × 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 the 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

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72 hrs
Score:
0.63
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 1.67
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
ca. 0.67
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
4
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 score warrants 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:
GHS criteria not met
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.
Executive summary:

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.