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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: guideline study with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
Comparison of the Skin Sensitizing Potential of Unsaturated Compounds as Assessed by the Murine Local Lymph Node Assay (LLNA) and the Guinea Pig Maximization Test (GPMT)
Author:
Kreiling R, Hollnagel HM, Hareng L, Eigler D, Lee MS, Griem P, Dreeßen B, Kleber M, Albrecht A, Garcia C, Wendel A
Year:
2008
Bibliographic source:
Food and Chemical Toxicology, doi: 10.1016/j.fct.2008.01.019 (epub ahead of print)

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
not specified
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Maleic acid
- Analytical purity: 99%

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann
- Weight at study initiation: 300 -500 g
- Housing: group housed in Terluran cages on Altromin saw fiber bedding or Lignocel bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 3 °C
- Humidity (%): 55 +- 10%
- Air changes (per hr): at least 10/hour
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: isotonic saline (NaCl 0.9%) or vaseline
Concentration / amount:
intradermal induction: 0.5%; topical induction: 25%; challenge: 25%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: isotonic saline (NaCl 0.9%) or vaseline
Concentration / amount:
intradermal induction: 0.5%; topical induction: 25%; challenge: 25%
No. of animals per dose:
10 test animals and 5 control animals
Details on study design:
RANGE FINDING TESTS: A range finding for the test concentration was performed in a preliminary experiment assessing the irritant effects of the test
compound after intradermal and topical application.

MAIN STUDY
see: any other information on material and methods

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. No with. + reactions: 1.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. No with. + reactions: 1.0. Total no. in groups: 10.0.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test group
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading:
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading:
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. No with. + reactions: 1.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
72
Group:
test group
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 72.0. Group: test group. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
rechallenge
Hours after challenge:
72
Group:
negative control
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 72.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 5.0.

Any other information on results incl. tables

No signs of systemic toxicity were observed in any of the animals. Maleic acid caused a grade 1 skin reaction in one animal of the treatment group. The skin reaction was observed 24 and 48 hours after patch removal. As from the visible inspection of the treated skin site, a sensitizing reaction cannot be differentiated from a skin irritation reaction, a re-challenge was performed in order to clarify this question. A sensitized animal is expected to react again upon re-challenge, i.e., when it is exposed to the test substance another time. After re-challenge with maleic acid, the animal that had reacted after the fist challenge failed to react. Since the skin reaction observed after the fist challenge was not reproducible upon re-challenge the animal was not considered sensitized against the test substances.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
The skin reaction observed after the fist challenge in one animal was not reproducible upon re-challenge in the same animal, however a second anima showed a weak skin reaction. The skin reaction in both animals was attributed to skin irritation and as less then 30% of the animals showed a skin reaction, the substance is not sensitising under the conditions of this test.