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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
Study period:
1981-08-26 to 1981-10-09
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Source: T04005 Control group consists of 8 instead of 10 animals; no GLP
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
Only 8 animals instead of 10 are used as control group.
Qualifier:
equivalent or similar to
Guideline:
other: method described by E.V Buehler in"Delayed Contact Hypersensitivity in teh Guinea Pig", Arch. Dermatol 91: 171-175 (1965)
Principles of method if other than guideline:
Not relevant
GLP compliance:
no
Type of study:
Buehler test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): C-243
- Molecular formula (if other than submission substance): Not documented
- Molecular weight (if other than submission substance): Not documented
- Smiles notation (if other than submission substance): Not documented
- InChl (if other than submission substance): Not documented
- Structural formula attached as image file (if other than submission substance): see Fig. Not documented
- Substance type: Not documented
- Physical state: Thin, clear liquid
- Analytical purity: Not documented
- Impurities (identity and concentrations): Not documented
- Composition of test material, percentage of components: Not documented
- Isomers composition: Not documented
- Purity test date: Not documented
- Lot/batch No.: Not documented
- Expiration date of the lot/batch: Not documented
- Radiochemical purity (if radiolabelling): Not documented
- Specific activity (if radiolabelling): Not documented
- Locations of the label (if radiolabelling): Not documented
- Expiration date of radiochemical substance (if radiolabelling): Not documented
- Stability under test conditions: Not documented
- Storage condition of test material: Room temperature
- Other: Received from Celanese Corporation

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dutchland Laboratories, Denver
- Age at study initiation: no data
- Weight at study initiation: 310 - 396 g (m); 303 - 354g (f)
- Housing: Individually in suspended stainless steel cages
- Diet: Charles River Vitamin-C fortified Guinea Pig diet ad libitum
- Water: Automatic watering system ad libitum
- Acclimation period: 16 d


ENVIRONMENTAL CONDITIONS
- Temperature: 18.3 - 23.9°C (monitored twice daily)
- Humidity (%): not specified but monitored twice daily
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: acetone
Concentration / amount:
- Induction: 75% (first) and 50% (2nd -9th induction); concentration was decreased because of severe irritations after the first induction (6 h/day; 3 days/week)
- Challenge: 10%
- Re-Challenge: 25%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: acetone
Concentration / amount:
- Induction: 75% (first) and 50% (2nd -9th induction); concentration was decreased because of severe irritations after the first induction (6 h/day; 3 days/week)
- Challenge: 10%
- Re-Challenge: 25%
No. of animals per dose:
20
Details on study design:
RANGE FINDING TESTS:
In the range-finding test, the highest concentration which produced mild irritation and highest concentration which did not produce irritation were determined. 16 animals were used and the concentration applied were 5, 10, 25, 50, 72 and 100%. The animals were closely clipped over the dorsal and lateral surfaces and each animal was dosed with 2 to 4 different concentrations at different sites (one concentration/site), one or two on either side of the spinal column.

0.2ml of the test substance was applied beneath a surgical gauze square and placed directly on the test site and secured with Dermicel tape. The animals were then wrapped with plastic sheeting and an adhesive elastic bandage. After 6 hours, the sheeting and gauze were removed.

Observations doe signs of dermal irritation were made approximately 24 and 48 hours after dosing. Based on the range-finding study, the following concentrations were used for the definitive sensitization study:
Induction: 75%
Challenge: 10%
Re-challenge: 25%

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 9 induction exposures
- Exposure period: 6 hours after which the test site was wiped free of excess material.
- Test groups: Not docuemnted
- Control group: Not docuemnted
- Site: Dorsal and lateral surfaces. The test site was to the right of the midline, as close to the midline as possible. Due to developing irritation, the test site was rotated over three different sites.
- Frequency of applications: Not documented
- Duration: Not documented
- Concentrations: 0.2ml of 75% test material.

B. CHALLENGE EXPOSURE
- No. of exposures: Not documented
- Day(s) of challenge: Not documented
- Exposure period: 6 hours
- Test groups: Not documented
- Control group: Not documented
- Site: A second site to the left side of the midline.
- Concentrations: 0.2ml of 10% test material
- Evaluation (hr after challenge): Not documented

OTHER: Irritation Control Challenge: In order to differentiate dermal reactions produced by irritation form those produced by sensitization, 8 previously untreated animals were subjected to the same challenge procedures as the animas which received the nine sensitizing exposures.

Re-challenge: Seven days after the initial challenge, a 2nd challenge was performed using a previously untreated site.
Challenge controls:
No information provided
Positive control substance(s):
yes
Remarks:
2,4-dinitrochlorobenzene (DNCB)

Study design: in vivo (LLNA)

Concentration:
Not relevant
No. of animals per dose:
Not relevant
Details on study design:
Not relevant
Positive control substance(s):
not specified
Statistics:
Not relevant

Results and discussion

Positive control results:
Nine of the 12 animals treated with the control substance had scores of 1 or greater at challenge, confirming the susceptibility of this group to sensitization.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
other: Irritation control DNCB
Dose level:
0.1%
No. with + reactions:
0
Total no. in group:
8
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group:
Reading:
2nd reading
Hours after challenge:
48
Group:
other: Irritation control DNCB
Dose level:
0.1%
No. with + reactions:
0
Total no. in group:
8
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group:
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1%
No. with + reactions:
10
Total no. in group:
12
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.1%. No with. + reactions: 10.0. Total no. in groups: 12.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.1%
No. with + reactions:
10
Total no. in group:
12
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.1%. No with. + reactions: 10.0. Total no. in groups: 12.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
8
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 8.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
8
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: 8.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10%
No. with + reactions:
0
Total no. in group:
20
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: 20.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
8
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 8.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
8
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 8.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
25%
No. with + reactions:
2
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 25%. No with. + reactions: 2.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
25%
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 25%. No with. + reactions: 1.0. Total no. in groups: 20.0.

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: Not relevant
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: Not relevant

Any other information on results incl. tables

No additional information

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
The test material does not meet the 15% sensitization criterion for classification as a sensitizer based on a non-adjuvant test according to Directive 2001/59/EC.
Executive summary:

In a valid standard skin sensitisation study on using the method of Buehler (similar to OECD 406), the skin of 20 guinea pigs was topically treated with 50% butyraldehyde in acetone 6 h /d, 3 d/wk for 3 weeks. 16 days later the animals were challenged with 10% butyraldehyde (also epicutaneously) and again 1 week later with 25% test substance in acetone. There were no reactions at the 10% challenge, while 2/20 animals exhibited some reactions with minimal erythema. There was no irritation observed in the 10 and 25% initiation controls. The results suggest that butyraldehyde has only low potential for induction of dermal sensitisation.