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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:
1998-09-21 to 1999-02-03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD Guideline under GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
and 96/54/EEC,B6
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The in vitro LLNA test was not available at the time the study was conducted.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): acetic aldehyde
- Substance type: pure substance
- Physical state: liquid
- Analytical purity: 99.5%
- Lot/batch No.: not given
- Expiration date of the lot/batch: indefinitely under nitrogen and opaque container
- Storage condition of test material: In the original container in the refrigator away from direct sunlight, under nitrogen.

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Ibm:GOHI (Himalayan spotted)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Biotechnology and Animal Breeding Division
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 348-374
- Housing: Individually in Macrolon type 4 cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: one week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23 °C
- Humidity (%): 36-79%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: acetone
Concentration / amount:
see details on study design
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: acetone
Concentration / amount:
see details on study design
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS: YES, 2 animals


MAIN STUDY
A. INDUCTION EXPOSURE
Test group:
First stage - Intradermal three pairs of intradermal injections at the flanks of the animals: 0.1 mL of a 5% dillution of the test article in acetone and 0.1 mL of a 5% dillution of the test article in Freund's complete adjuvant/physiological saline (1:1) and 0.1 mL of a 50% dillution of Freund's complete adjuvant in pysiological saline
Second stage on day 8 - dermal application at the shoulder of the animals: 50 % in acetone over an area 4x2cm for 48 h
Control group:
First stage - Intradermal three pairs of intradermal injections: 0.1 mL of acetone and 0.1 mL of a 50% dillution of Freund's complete adjuvant in pysiological saline and 0.1 mL of a 50% dillution of Freund's complete adjuvant in pysiological saline.
Second stage on day 8 - dermal application: acetone over an area 4x2cm.
Positive control group:
First stage - Intradermal three pairs of intradermal injections at the flanks of the animals: 0.1 mL of a 5% dillution of alpha-Hexylcinnamaldehyde in PEG 400 and 0.1 mL of a 5% dillution of alpha-Hexylcinnamaldehyde in Freund's complete adjuvant/physiological saline (1:1) and 0.1 mL of a 50% dillution of Freund's complete adjuvant in pysiological saline
Second stage on day 8 - dermal application at the shoulder of the animals: 50 % of alpha-Hexylcinnamaldehyde in PEG 400 over an area 4x2cm for 48 h
- Evaluation (hr after challenge): Reaction sites were assessed for erythema and oedema 24 and 48 hours after removal of the dressing


B. CHALLENGE EXPOSURE
- Test group:
Two patches (2x2 cm) were saturated with acetic aldehyde at the highest non irritation concentration of 25% (left flank) and the vehicle only (right flank). The occlusive dressing was left for 24 hours.
- Control group:
Four patches of filter paper (2x2 cm) were used in the control group. One saturated with acetic aldehyde at the highest non irritation concentration of 25% (left cranial flank), one with alpha-Hexylcinnamaldehyde (5% in PEG 400 on the left caudal flank and 1% in PEG 400 on th right cranial flank) and one with with the vehicle only (right caudal flank). The occlusive dressing was left for 24 hours.
Positive Control group: Two patches were used with alpha-Hexylcinnamaldehyde (5% in PEG 400 on the left caudal flank and 1% in PEG 400 on th right cranial flank)
- Evaluation (hr after challenge): Reaction sites were assessed for erythema and oedema 24 and 48 hours after removal of the dressing accordin to DRAIZE
Challenge controls:
see details on test design
Positive control substance(s):
yes
Remarks:
alpha-Hexylcinnamaldehyde

Results and discussion

Positive control results:
Very slight to moderate/severe erythematous reactions were observed at the 24- and 48 hour reading in eight out of 10 animals when treated with alpha-Hexylcinnamaldehyde at 5% in PEG 400. Very slight oedema was also observed in two animal at the same reading time. With 1% in PEG 400 only slight edema in 5/10 animals were observed.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25% in acetone
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25% in acetone. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25% in acetone
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25% in acetone. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
adjuvant and saline 1:1
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
adjuvant and saline 1:1
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
5% alpha-hexylcinnamaldehyde in PEG 400
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
none
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
5% alpha-hexylcinnamaldehyde in PEG 400
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
none
Remarks on result:
positive indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Acetaldehyde has no sensitizing potential under the conditions described in this report.
Executive summary:

In order to assess the cutaneous allergenic potential of acetaldehyde, the Guinea Pig Maximization Test according to OECD 406 was carried out in 30 female guinea pigs. The intradermal induction of sensitisation was performed with 5% dilution of Acetaldehyde in acetone and in an emulsion of Freund's Complete Adjuvant/physiological saline . The epidermal induction of sensitization was conducted under occlusion with acetaldehyde at 50% in acetone. Two weeks after the epidermal induction application the callenge was completed by epidermal application of the test item at 25% in acetone under occlusive dressing. The animal of the control group were induced with acetone and Freund's Complete Adjuvant/physiological saline and callenged similarly to those of the test group. Cutaneous reactions, ie erythema and eschar, as well as oedema formation were evaluated at 24 and 48 hours after the removal of the dressing. Neither the test group nor the control group erythematous reactions were obsered. The positve control group that was treated with the known sensitizer alpha-Hexylcinnamaldehyde did show the expected reaction from slight to severe edemas. Therefore, acetaldehyde is considered not to be a sensitizer under the conditions of the test.