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Diss Factsheets

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed in accordance with validated guidelines and in GLP compliance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report date:
2004

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
2-(4-bromophenyl)-2-methylpropionic acid methyl ester
EC Number:
450-630-9
EC Name:
2-(4-bromophenyl)-2-methylpropionic acid methyl ester
Cas Number:
154825-97-5
Molecular formula:
C11H13BrO2
IUPAC Name:
methyl 2-(4-bromophenyl)-2-methylpropanoate
Test material form:
other: liquid
Details on test material:
The test material was a colourless oil of FEXO-03 with a degree of purity >95%.

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: lbm: GOHI; SPF-quality guinea pigs (synonym: Himalayan spotted)
Sex:
male
Details on test animals and environmental conditions:
The test animals were guinea pigs (lbm GOHI; SPF-quality). The age of the animals at pretest start/beginning of acclimatization period was 4-6 weeks. The body weight of the animals at pretest start was 382-394 g and the body weight of the animals at beginning of acclimatization period was 329-412 g.
One week for the control and test group under test conditions after health examination. No acclimatization for the animals of the pretest. Only animals without any visible signs of illness were used for the study.
Air-conditioned with target ranges for room temperature 20 ± 3 °C, relative humidity 30-70 % and approximately 10-15 air changes per hour. Room temperature and humidity were monitored continuously and values outside of these ranges occasionally occurred, usually following room cleaning.
These transient variations are considered not to have any influence on the study and, therefore, these data are not reported but are retained at RCC. The animals were provided with an automatically controlled light cycle of 12 hours light and 12 hours dark. Music was played during the daytime light period.
The animals were accomodated individually in Makrolon type-4 cages with standard softwood bedding. The diet of the animals were based on pelleted standard Provimi Kliba 3418, batch no. 52103, guinea pig breeding/maintenance diet, containing Vitamin C, ad libitum and community tap water, ad libitum.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
polyethylene glycol
Remarks:
PEG 300
Concentration / amount:
Concentration of test material and vehicle used at induction:
100% for intradermal injection
100% for topical application
Concentration of test material and vehicle used for each challenge:
50% in PEG 300
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
polyethylene glycol
Remarks:
PEG 300
Concentration / amount:
Concentration of test material and vehicle used at induction:
100% for intradermal injection
100% for topical application
Concentration of test material and vehicle used for each challenge:
50% in PEG 300
No. of animals per dose:
Number of animals in test group: 10
Number of animals in negative control group: 5
Details on study design:
An area of dorsal skin from the scapular region (approximately 6 x 8 cm) was clipped free of hair. Three pairs of intradermal injections (0.1 mL/site) were made at the border of a 4 x 6 cm area in the clipped region as follows:

Test Group:
injection 1) 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiological saline.
injection 2) The test item at 100 %.
injection 3) The test item a t 100 %.

Control Group:
injection 1) 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiological
injection 2) PEG 300
injection 3) 1:1 (w/w) mixture of PEG 300 in a 1:1 (v/v) mixture of Freund's. Complete Adjuvant and physiological saline.

EPIDERMAL APPLICATIONS/PERFORMED ON TEST DAY 8
One week after the injections, the scapular area (approximately 6 x 8 cm) was again clipped and shaved free of hair prior to the application. A 2 x 4 cm patch of filter paper was saturated with the undiluted test item and placed over the injection sites of the test animals. The volume of test item preparation applied was approximately 0.3 mL. The patch was covered with aluminum foil and firmly secured by an elastic plaster wrapped around the trunk of the animal and secured with impervious adhesive tape. The occlusive dressings were lelt in place for 48 hours. The epidermal application procedure described ensured intensive contact of the test item.
The guinea pigs of the control group were treated as described above with PEG 300 only, also applied at a volume of approximately 0.3 mL.
The reaction sites were assessed approximately 24 and 48 hours after removal of the bandage for erythema and oedema according to the method of Magnusson and Kligman.
Challenge controls:
CHALLENGE/PERFORMED ON TEST DAY 22
The test and control guinea pigs were challenged two weeks after the epidermal induction application and were treated in the same way.
Hair was clipped and shaved from a 5 x 5 cm area on the left and right flank of each guinea pig just prior to the application. Two patches (3 x 3 cm) of filter paper were saturated with the test item at the highest tested non-irritating concentration of 50% (applied to the left flank) and the vehicle only (PEG 300 applied to the right flank) using the same method as for the epidermal application. The volume of test item preparation and vehicle applied was approximately 0.2 mL. The dressings were left in place for 24 hours.
Twenty-one hours alter removal of the dressing the test sites treated with the test item were depilated as described in the epidermal pretest.
Three hours later (48 hours from the start of the challenge application) the skin reaction was observed and recorded according to the numerical grading system.
Approximately 24 hours alter this observation a second observation (72 hours from the start of the challenge application) was made and once again recorded.
Positive control substance(s):
yes
Remarks:
ALPHA-HEXYLCINNAMALDEHYDE

Results and discussion

Positive control results:
For validation of sensitivity of the Maximization-Test of B. Magnusson and A.M. Kligman (1969) as well as the sensitivity of the test system used, a known sensitizer ALPHA-HEXYLCINNAMALDEHYDE was selected as a positive control. This was performed in accordance with the recommendation of the OECD for testing of chemicals number 406 "Skin Sensitization Test", adopted by the Council on July 17, 1992 (reported Paris, April 29, 1993).
The test described was performed under GLP-conditions with a final QA-check. The study was performed with 15 (10 test and 5 control) male albino guinea pigs (GOHI). The intradermal induction of sensitization in the test group was performed in the nuchal region with a 10% dilution of the test item in PEG300 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 10% in PEG300 one week after the intradermal induction. The animals of the control group were intradermally induced with PEG 300 and FCA/physiological saline and epidermally induced with PEG 300 under occlusion. Two weeks after epidermal induction the control and test animals were challenged
by epidermal application of the test item at 3% in PEG300 and PEG300 alone under occlusive dressing.
Cutaneous reactions were evaluated at 24 and 48 hours after removal of the dressing.
Based on the above mentioned findings, ALPHA-HEXYLCINNAMALDEHYDE does have to be classified and labelled as a skin sensitizer and proved the sensitivity of the test system.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Discrete/patchy erythema was observed
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: Discrete/patchy erythema was observed.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100 %
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
Discrete/patchy erythema was observed
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100 %. No with. + reactions: 6.0. Total no. in groups: 10.0. Clinical observations: Discrete/patchy erythema was observed.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
50 %
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
Discrete/patchy erythema was observed
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 50 %. No with. + reactions: 8.0. Total no. in groups: 10.0. Clinical observations: Discrete/patchy erythema was observed.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
50 %
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
Discrete/patchy erythema was observed
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 50 %. No with. + reactions: 8.0. Total no. in groups: 10.0. Clinical observations: Discrete/patchy erythema was observed.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No erythematous or oedematous reaction was observed
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: No erythematous or oedematous reaction was observed.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No erythematous or oedematous reaction was observed
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: No erythematous or oedematous reaction was observed.
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No erythematous or oedematous reaction was observed
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: No erythematous or oedematous reaction was observed.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No erythematous or oedematous reaction was observed
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: No erythematous or oedematous reaction was observed.

Any other information on results incl. tables

Maximum concentration not causing irritating effects in preliminary test: 50 %

Signs of irritation during induction:
After intradermal induction : expected and common findings were observed in the control and in the test group after the different applications using FCA intradermally. These findings consisted of erythema, oedema, necrotizing dermatitis, encrustation and exfoliation of encrustation.


After topical application: discrete/patchy erythema was observed in all animals at the 24 hour reading and in six out of 10 animals at the 48 hour reading after treatment with the undiluted test item.

Evidence of sensitisation of each challenge concentration:
The substance showed evidence of skin sensitising potential at the final challenge concentration.

Other observations:
No clinical signs of systemic toxicity were observed in the animals.

No mortality was recorded during the study.

No body weight variations were noted in comparison with control.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance was sensitizer under the test conditions.