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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

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
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
LLNA study was not performed since in vivo guinea pig data were already available for the test substance.

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
429-220-9
EC Name:
-
Cas Number:
132584-17-9
Molecular formula:
C17 H18 O4
IUPAC Name:
ethyl 2-hydroxy-2-(4-phenoxyphenyl)propanoate
Test material form:
liquid
Specific details on test material used for the study:
Purity: not reported
Batch: Composite 15-35

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D Hall Ltd, Burton
- Age at study initiation: 4-6 weeks old
- Weight at study initiation: 261 - 353 g
- Housing: suspended polypropylene cages (six per battery) with open tops, solid floors and stainless steel mesh front panels (providing minimum internal dimensions of 61 x 81 x 25 cm).
- Diet (e.g. ad libitum): SQC FD1 (pelleted) diet from Special Diets Services Ltd., Witham was freely available
- Water (e.g. ad libitum): Mains water was provided, ad libitum, via cage mounted water bottles.
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 deg C
- Humidity (%): 40-80%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hrs light/dark

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.1 mL
Day(s)/duration:
3 injection sites on a single day; topical application stayed on for 48 hours
Challenge
Route:
epicutaneous, occlusive
Vehicle:
other: Alembicol D
Concentration / amount:
Concentration of test material and vehicle used at induction:
Intradermal injection: 15% in Alembicol D and/or adjuvant

Topical induction: 60% in Alembicol D

Concentration of test material and vehicle used for each challenge:
20% and 10% in Alembicol D


(25% provoked some irritation in the preliminary study)
Day(s)/duration:
1 day
No. of animals per dose:
Number of animals in test group: 20
Number of animals in negative control group: 10
Details on study design:
Induction phase - intradermal injection
The dorsum overlaying the scapulae of each guinea pig was clipped on the day before treatment commenced. The area was confirmed to be free from injury or irritation. On Day 1 three paired intradermal injections (0.1 mL per site) were placed in single rows parallel to and on either side of the dorsal mid-line of each guinea pig such that the anterior and posterior injection sites marked the corners of an approximate 20 x 40 mm area. The middle injection sites were positioned close to the anterior sites.

Induction phase - topical application
On Day 7 the areas of dorsum denuded for the first phase of induction were clipped. On Day 8 each dorsum was shaved. Approximately two hours later the area of skin including
the intradermal injection sites was subject to application of a 25 x 45 mm patch of Whatman No 4 filter paper loaded with approximately 0.5 mL of 60% m/m JG303 in Alembicol D (test animals) or Alembicol D alone (control group). Occlusion of the treated skin was effected by successive layers of Blenderm and Steroban. The patches and dressings remained in place for approximately 48 hours. The treated areas of skin were washed with arachis oil. Irritation or other dermal changes at the sites of occluded topical application were recorded by group on Day 11.

Challenge phase
Both flanks of all guinea pigs were clipped on Day 21 and shaved to remove hair stubble on Day 22. Approximately two hours later the left flank of each animal was subject to application of a 12 mm Finn chamber loaded with approximately 0.1 mL vehicle. Finn chambers containing the formulations selected for challenge, 20 and 10% mlm JG303 in Alembicol D were applied to the right flank. The chambers were kept in place by successive layers of Blenderm and Steroban. The chambers and dressings were removed approximately 24 hours after application and the treated areas of skin were washed with arachis oil. Challenge site locations were marked with indelible ink immediately after the washing procedure. The challenge sites were reshaved approximately 20 hours after removal of the chambers. Dermal responses to challenge were assessed approximately 24 and 48 hours after removal of the chambers. Responses to challenge were recorded individually.
Positive control substance(s):
yes
Remarks:
2-Mercaptobenzothiazole (MBTZ)

Results and discussion

Positive control results:
Induction 2.5% m/v Intradermal and 60% m/m topical and challenge of 30 and 15 % m/m:
positive results 6/9, inconclusive 2/9, negative 1/9

Induction 2.5% m/v Intradermal and 60% m/m topical and challenge of 30 and 15 % m/m:
positive results 6/10, inconclusive 2/10, negative 2/10

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
20 %
No. with + reactions:
15
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 20 %. No with. + reactions: 15.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10 %
No. with + reactions:
8
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: 8.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
20 %
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 20 %. No with. + reactions: 20.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10 %
No. with + reactions:
20
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: 20.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
20 %
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 20 %. No with. + reactions: 2.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10 %
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 10 %. No with. + reactions: 2.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
20 %
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 20 %. No with. + reactions: 2.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10 %
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 10 %. No with. + reactions: 2.0. Total no. in groups: 10.0.
Reading:
1st reading
Group:
positive control
Dose level:
30 and 15%
No. with + reactions:
6
Total no. in group:
9
Reading:
2nd reading
Group:
positive control
Dose level:
30 and 15%
No. with + reactions:
6
Total no. in group:
10

Any other information on results incl. tables

Maximum concentration not causing irritating effects in preliminary test: 25 %

Signs of irritation during induction:
Irritation was noted with all induction treatments, except
when the vehicle was injected alone.  Topical application in
the control animals provoked slight erythema.

Evidence of sensitisation of each challenge concentration:
Dermal reactions were apparent in all treated animals and
two control animals.  Reactions in the treated animals was
slightly more severe with the higher concentration, but
serevity at both concentrations increased over 48 hours.


The was a clear indication of a sensitising reaction.

Other observations:
There were no adverse clinical signs during the study.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
Ten animals gave a positive response indicative of delayed contact hypersensitivity, teh response for the remaining guindea pigs was negative. The test substance is considered a skin sensitizer.