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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:
Study initiated: end fo March 1981 and reporting 30th April
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Currently no LLNA study is available for assessment. The Guinea Pig Maximization Test (GPMT) has been carried out as an animal test to predict human sensitization for over a decade and is recommended by international test guidelines such as OECD.

Test material

Reference
Name:
Unnamed

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
Animals were housed in suspended cages with wire mesh floors, with free access to tap water and Vitamin C-enriched Guiney-pig Diet Standard F.D.I. No 803189W. Hay was given once a week.
Animal room temperature was 21oC and the air exchange was maintained at 15 air changes/hour
Lighting was controlled using a 12 hour light/dark cycle.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
paraffin oil
Concentration / amount:
Intradermal injection were in 1% v/v liquid paraffin
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
Intradermal injection were in 1% v/v liquid paraffin
No. of animals per dose:
15 test animals and 15 control animals
Details on study design:
A 4x6 cm area of dorsal skin on the scapular region of the guiney-pig was clipped free of hair with electric clippers. Three pairs of intradermal injections were made simulataneously into this area. Injections were as follows: 1) Freund's complete adjuvant was diluted with an equal volume of water for injection; 2) Cyclocitronellene acetate 10% v/v in liquid paraffin and; 3) Cyclocitronellene 10% in a 50:50 mixture of Freund's adjuvant and liquid paraffin.
Topical application One week after the injections, the same 4x6 cm interscapular area was clipped and shaved free of hair. A 2x4 cm patch of Whatmen No 3 mm paper was saturated with cyclocitronellene acetate as supplied (100%). The patch was placed on the skin and covered by a length of impermeable plastic adhesive tape (5 cm width 'Blenderm'). This in turn was firmly secured by elastic adhesive bandage ('Elastoplast' of 5 cm width) wound around the torso of the animal and fixed with 'Sleek" impervious plastic adhesive tape. The dressing was left in place for 4h hours.
The control animals were treated similarly but with the exception that the test compound was omitted from the intradermal injection and the topical application.
Challenge controls:
Challenge applications were applied 2 weeks after last exposure using 20 and 10% in liquid paraffin. The challenge sites were evaluated 24, 48 and 72 hours after removal of the patches
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.2 mL and 20%
No. with + reactions:
3
Total no. in group:
14
Clinical observations:
Localised dermal reaction (restricted to a small area)
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.2 mL and 20%. No with. + reactions: 3.0. Total no. in groups: 14.0. Clinical observations: Localised dermal reaction (restricted to a small area).
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.2 mL and 20%
No. with + reactions:
4
Total no. in group:
14
Clinical observations:
Localised dermal reaction (restricted to a small area)
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.2 mL and 20%. No with. + reactions: 4.0. Total no. in groups: 14.0. Clinical observations: Localised dermal reaction (restricted to a small area).
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test group
Dose level:
0. 2 ml and 20%
No. with + reactions:
2
Total no. in group:
14
Clinical observations:
dryness and sloughing of the epidermis
Remarks on result:
other: Reading:
Key result
Reading:
other: Overall result of the test
Hours after challenge:
24
Group:
test group
Dose level:
20%
No. with + reactions:
0
Total no. in group:
0
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.2 ml and 20%
No. with + reactions:
4
Total no. in group:
14
Clinical observations:
Localised dermal reaction (restricted to a small area)
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.2 ml and 20%. No with. + reactions: 4.0. Total no. in groups: 14.0. Clinical observations: Localised dermal reaction (restricted to a small area).
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.2 ml and 20%
No. with + reactions:
3
Total no. in group:
14
Clinical observations:
Localised dermal reaction (restricted to a small area)
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.2 ml and 20%. No with. + reactions: 3.0. Total no. in groups: 14.0. Clinical observations: Localised dermal reaction (restricted to a small area).
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
Dose level:
0.2 ml and 20%
No. with + reactions:
3
Total no. in group:
14
Clinical observations:
Localised dermal reaction (restricted to a small area) and one animal showed dryness and sloughing of the epidermis
Remarks on result:
other: see Remark
Remarks:
Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 0.2 ml and 20%. No with. + reactions: 3.0. Total no. in groups: 14.0. Clinical observations: Localised dermal reaction (restricted to a small area) and one animal showed dryness and sloughing of the epidermis.

Any other information on results incl. tables

Animals

Skin reaction

Scores

 

 

 

 

 

Result

Scoring after (hours

Challenge concentrations

 

24

10%

24h

20%

48

10

48

20

72

10

72

20

 

Controls

 

7/14

4/14

6/14

3/14

5/14

3/14

-

Test animals

Reaction*

4/14

3/14

5/14

3/14

5/14

0/14

-

*Skin reaction mainly consisted of localised dermal reactions (restriction to small area of the challenge site) and are therefore not considered skin sensitisation reactions.

Applicant's summary and conclusion

Interpretation of results:
other: not sensitising
Remarks:
according to CLP and its amendments (EC 1272/2008)
Conclusions:
Under the results of this study the test substance is not sensitising
Executive summary:

In a Maximisation test (OECD TG 406), with intradermal concentrations of 10% and challenge concentrations of 10 and 20% the skin sensitisation of the substance was investigated. In the test animals and controls localised dermal reactions were seen, which were thought to be related to skin irritation rather than sensitisation because the number and frequency of the findings were similar in the treated groups and the test animals. Therefore the substance is not considered skin sensitising.