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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The paper provides a comparison of GPMT and LLNA designs for assessment of sensitising potential rather than a method for assessing the sensitisation potential of succinic acid. Succinic acid is included as one of the range of test materials under consideration but the results are used to compare the relative merits of the two study designs.
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
Succinic acid
EC Number:
203-740-4
EC Name:
Succinic acid
Cas Number:
110-15-6
Molecular formula:
C4H6O4
IUPAC Name:
succinic acid
Details on test material:
- Name of test material (as cited in study report): succinic acid
- Substance type: endogenous substance
- 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: SPF-Hsd Poc: DH guinea pigs
- Source: Harlan Winkelmann,Borchen Germany.
- Age at study initiation: not stated
- Weight at study initiation: 300-500g
- Housing:Group housed in Terlauronmakrolon type cages with saw fibre bedding
- Diet (e.g. ad libitum): Altromin 3122 maintenance diet or Ssniff Ms-H, 4mm V2233-000
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least five days


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

IN-LIFE DATES: From: not stated To: not stated

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
cotton seed oil
Concentration / amount:
intradermal induction: 0.5%
topical induction: 25 %
Challenge application: 10%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
cotton seed oil
Concentration / amount:
intradermal induction: 0.5%
topical induction: 25 %
Challenge application: 10%
No. of animals per dose:
10 test and 5 controls
Details on study design:
RANGE FINDING TESTS: various tests performed to determine suitable dose concentrations for each phase of the main study

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 - intradermal and topical
- Exposure period:
- Test groups: 10 guinea pigs exposed to FCA and test material in vehicle on day 1, treated with SLS (sodium lauryl sulphate) prior to topical application after one week, topical induction applied over injection sites and occluded for 48 hours
- Control group: as test group but with test material. only 5 guinea pigs used
- Frequency of applications: once on day 1 and 8
- Duration: intradermal injections unlimited, topical induction exposure for 48 hours
- Concentrations: 0.5 and 25%

B. CHALLENGE EXPOSURE
- No. of exposures: two
- Day(s) of challenge: day 20 and 28
- Exposure period: 24 hours
- Test groups: ten animals
- Control group: five animals
- Site: dorsum
- Concentrations: 10 %
- Evaluation (hr after challenge): 24 and 48 and 72 hours post patch removal

Positive control substance(s):
not required

Study design: in vivo (LLNA)

Statistics:
Not required.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10%
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 1.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10%
No. with + reactions:
1
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 10%. No with. + reactions: 1.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
10%
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 10%. No with. + reactions: 1.0. Total no. in groups: 10.0.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
rechallenge
Hours after challenge:
72
Group:
test chemical
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 72.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
72
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 72.0. Group: negative control. Dose level: 10%. 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. Succinic acid caused skin reactions in two animals of the treatment group, one showing a reaction only at 24 h after patch removal and another only at 72 h. One animal of the control group showed a skin reaction of the same grade and time course, i.e., a grade 1 reaction at 24 h, but not at 48 and 72 h.

Neither of the two animals of the treatment group displayed a skin reaction upon re-challenge, supporting the conclusion that the reactions in these animals (as that of the control group) were non-specific, i.e., not caused by a specific immune reaction.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Succinic acid was non-sensitising in the guinea pig maximisation test.
Executive summary:

The skin sensitisation potential of one saturated and eight unsaturated lipid biochemicals was tested in a LLNA and guinea pig Maximisation test for comparative purposes to test the hypothesis that chemicals with unsaturated carbon-carbon double bonds may give a higher false positive rate in LLNA results than in the GPMT.

Succinic acid was non-sensitising in the GPMT.

The relative merits of the two assays are further discussed in the paper but are not directly relevant to the assessment of succinic acid sensitising potential.