Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline-conform study under GLP without deviations. Read-across justification is given in the read-across document attached in IUCLID Section 13.

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Physical state: liquid
- Stability under test conditions: stable at room temperature
- Storage condition of test material: At room temperature (range of 20 ± 5 °C), light protected.

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH
- Age at study initiation: 5-6 weeks
- Weight at study initiation: 282 – 388 g
- Housing: Individually in Makrolon type-4 cages with standard softwood bedding
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 guinea pig breeding / maintenance diet, ad libidum
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: 2008-09-18 to 2008-10-13


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30-70 %
- 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:
water
Concentration / amount:
MAIN STUDY
A: INDUCTION EXPOSURE (IN TEST GROUP)
Intradermal induction:
Day 1: three intradermal injections/animal (0.1 mL/site)
- Freund's Complete Adjuvant/physiological saline, 1:1
- 5% test item in purified water
- 5% test item in a 1:1 mixture of Freund's Complete Adjuvant/physiological saline

Epidermal induction:
Day 7: application of 50% test item in purified water
Days 8 and 9: cutaneous reactions assessment


B.
CHALLENGE EXPOSURE
Day 22: 0.2 mL of test item (0%) on 3 cm x 3 cm area on the left flank; 0.2 mL vehicle (purified water) on 3 cm x 3 cm area on the right flank
Day 23: dressing removal and skin reaction assessment
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
MAIN STUDY
A: INDUCTION EXPOSURE (IN TEST GROUP)
Intradermal induction:
Day 1: three intradermal injections/animal (0.1 mL/site)
- Freund's Complete Adjuvant/physiological saline, 1:1
- 5% test item in purified water
- 5% test item in a 1:1 mixture of Freund's Complete Adjuvant/physiological saline

Epidermal induction:
Day 7: application of 50% test item in purified water
Days 8 and 9: cutaneous reactions assessment


B.
CHALLENGE EXPOSURE
Day 22: 0.2 mL of test item (0%) on 3 cm x 3 cm area on the left flank; 0.2 mL vehicle (purified water) on 3 cm x 3 cm area on the right flank
Day 23: dressing removal and skin reaction assessment
No. of animals per dose:
5 control animals (males)
10 treated animals (males)
Details on study design:
RANGE FINDING TESTS:
A: Intradermal injections:
Four intradermal injections (0.1 mL/site) of a 1:1 (v/v) mixture of Freund's Complete Adjuvant/physiological saline (day 1) (shaved neck of one guinea pig)
Five days later: Four intradermal injections (0.1 mL/site) at concentrations of H = 15 %, I = 10 % and J = 5 % of the test item in purified water (clipped flank of the same guinea pig)
Dermal reactions assessed 24 hrs later.

B: Epidermal applications:
Four intradermal injections (0.1 mL/site) of a 1:1 (v/v) mixture of Freund's Complete Adjuvant/physiological saline (day 1) (shaved necks of two guinea pigs)
Five days later: Epidermal application with the test item at K = 15 %, L = 10 %, M = 5 % and N = 3 % in purified water (shaved flanks of the same two guinea pigs)
Dermal reactions assessed 24 and 48 hrs after removal of the bandage.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal / epicutaneously)
- Exposure period: injected / 48 h occlusive
- Site: scapular region (clipped free of hair)
- Frequency of applications: 1 / 1
- Duration: 0 - 8 days
- Concentrations:
1st application: 5% intradermal; 2nd application: 50% epicutaneous

B.
CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 22
-Exposure period: 24 hrs
- Site: left flank (test item); right flank: vehicle (clipped free of hair)
- Concentrations: 5% occlusive epicutaneous
- Evaluation (hr after challenge): 24 and 48 hrs
Positive control substance(s):
yes
Remarks:
ALPHA-HEXYLCINNAMALDEHYDE

Results and discussion

Positive control results:
Discrete/patchy to moderate/confluent erythema with or without scaling was observed in nine out of ten test animals at the 24- and 48-hour reading after the challenge treatment with ALPHA-HEXYLCINNAMALDEHYDE at 1 % in PEG 300 (left shoulder). Five test animals showed discrete/patchy erythema at the 24-hour reading after treatment with ALPHAHEXYLCINNAMALDEHYDE at 0.1 % in PEG 300 (left flank). No skin effect was observed in the control group.
Based on the above mentioned findings in an adjuvant sensitization test (M&K-test) in guinea pigs and in accordance to Commission Directive 2001/59/EC, ALPHAHEXYLCINNAMALDEHYDE has to be classified and labelled as a skin sensitizer.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
5% i.d., 50% epic.
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: 5% i.d., 50% epic.. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
5% i.d., 50% epic.
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: 5% i.d., 50% epic.. 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:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Based on the above mentioned findings in an adjuvant sensitization test (M&K-test) in guinea pigs and in accordance to Commission Directive 2001/59/EC, SCG 3028 does not have to be classified and labelled as a skin sensitizer.
Executive summary:

The sensitization potential of SCG 3028 was evaluated in guinea-pig according to the Maximization Test by Magnusson and Kligman.

The intradermal induction of sensitization in the test group was performed in the nuchal region with a 5 % dilution of the test item in purified water and in an emulsion of Freund's Complete Adjuvant (FCA)/physiological saline. The epidermal induction of sensitization was conducted for 48 hours under occlusion with the test item at 50 % one week after the intradermal induction

Two weeks after epidermal induction the control and test animals were challenged by epidermal application of the test item at 5 % in purified water under occlusive dressing. Cutaneous reactions were evaluated at 24 and 48 hours after removal of the dressing.

No toxic signs were evident in the guinea pigs of the control or test group. No deaths occurred. No skin reactions were observed in the control and test group after the challenge treatment with SCG 3028 at 5 % in purified water.