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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Performed as a guinea pig maximisation study in 1987 to GLP. Challenge concentrations appear to have been high, but otherwise considered reliable.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
OECD guideline 406 has been followed.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
Weight range 291 - 368 g (average 328 g)
Adaptation period 7 days
Room temperature 22 C +/- 2C
12 hour light - dark cycle
Air exchange 10 times / hour
Humidity approximate 50%
Route:
intradermal and epicutaneous
Vehicle:
propylene glycol
Concentration / amount:
Intradermal induction 0.1 ml at 2.5%
Topical induction at 50%
Challenge 1 at 50%
Challenge 2 at 10% (the lower concentration at the second challenge was due to strong reactions at 50%)
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
Intradermal induction 0.1 ml at 2.5%
Topical induction at 50%
Challenge 1 at 50%
Challenge 2 at 10% (the lower concentration at the second challenge was due to strong reactions at 50%)
No. of animals per dose:
20 treated animals
10 control
Details on study design:
Animals were shaved in the area of administration 24 hours before dosing
Challenge controls:
Periodic validation with formaldehyde
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50%
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: 50%. No with. + reactions: 15.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50%
No. with + reactions:
4
Total no. in group:
20
Clinical observations:
9 / 20 with flakey skin / scabbing
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 4.0. Total no. in groups: 20.0. Clinical observations: 9 / 20 with flakey skin / scabbing.
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
10%
No. with + reactions:
7
Total no. in group:
20
Clinical observations:
17/20 with flakey skin / scabbing
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 7.0. Total no. in groups: 20.0. Clinical observations: 17/20 with flakey skin / scabbing.
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
10%
No. with + reactions:
4
Total no. in group:
20
Clinical observations:
18/20 with flake skin / scabbing
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 4.0. Total no. in groups: 20.0. Clinical observations: 18/20 with flake skin / scabbing.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50%
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50%. No with. + reactions: 1.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50%
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
(note same animal with reaction)
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50%. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: (note same animal with reaction).
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
10%
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 10%. No with. + reactions: 1.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0.

The results of the range finder study with intradermal and topical applications resulted in flakey skin at all concentrations in two animals 2 days after treatment. This delayed response was mirrored in the main study at the first challenge, but at the re-challenge, this effect was noted in the first and second 24 hours after administration. Control animals showed little in the way of flakey skin or scabbing, even 48 hours after administration.

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Responses were seen in treated animals and the report differentiates between scabbing and flakey skin and the responses more often associated with positive sensitisers (eg swelling). If the scabbing and flakey skin is disregarded as being a positive effect and if it is accepted that the 50% challenge concentration was too high, then the number of positive responses at the 10% re-challenge are not sufficiently high to warrant classification.
However, the low level of reaction in the control animals receiving the same challenge concentration suggests that the flakey skin and scabbing is indeed a positive response.
Executive summary:

The clinical observations of flakey skin and scabbing were not necessarily considered to be 'positive' signs by the author of the report, but these would have masked any further observations. However, in view of the fact that these clinical signs were only observed in the test group, it is very likely that these are a result of sensitisation and not just irritation.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Four endpoints included;

Key : Guinea Pig maximised study with very high induction and challenge concentrations. Control animals showed lower levels of reaction to the test-substance treated animals

Supporting, Buehler: Non-maximised, with no adverse effects in treated or control animals

Supporting, human: Low number of reported cases, but not statistically possible in view of limited exposure. No primary data.

Supporting, FCA: non-standard method and some details not reported, but appears to give moderate to strong responses.

Migrated from Short description of key information:

Considered potential sensitiser with reactions seen in test animals stronger than those for the negative controls

Justification for selection of skin sensitisation endpoint:

This was a valid Guinea Pig study performed with a maximisation method

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Considered to be a potential sensitiser on the basis of a Guinea Pig Maximised study that provoked a higher level of skin reaction in the treated group than obvsered in control groups. However, a very high challenge concentration of 50% was used and many animals only showed flakey skin and scabbing consistent with local irritation and not raised skin or redness.

The substance provoked no signs of irritation in a rabbit skin irritation study and caused no effects in a non-maximised Buehler assay at concentrations up to 25%