Registration Dossier

Administrative data

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
Study period:
August 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study performed equivalent or similar to OECD 406 guideline, but predating GLP.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
no
Remarks:
Study performed around/just before the time GLP was introduced in Europe, but internal QA statement.
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: bred in Environmental Safety Laboratory
- Age at study initiation: no data available
- Weight at study initiation: approx. 320 g
- Housing: no data available
- Diet: free access to RGP pellets and hay
- Water: free access to water
- Acclimation period: no data available

ENVIRONMENTAL CONDITIONS
- No data available.
Route:
intradermal and epicutaneous
Vehicle:
other: 6% acetone/0.01% dodecylbenzene sulphonate/0.9% physiological saline (Acetone/Dobs/saline) (intradermal induction); acetone/polyethylene glycol 400 (challenge)
Concentration / amount:
1% for the intradermal induction and undiluted for the epidermal induction.
50% for the challenge phase.
Route:
epicutaneous, occlusive
Vehicle:
other: 6% acetone/0.01% dodecylbenzene sulphonate/0.9% physiological saline (Acetone/Dobs/saline) (intradermal induction); acetone/polyethylene glycol 400 (challenge)
Concentration / amount:
1% for the intradermal induction and undiluted for the epidermal induction.
50% for the challenge phase.
No. of animals per dose:
Test animals: 20 (10 males, 10 females)
Control animals: 10 (males, females)
Details on study design:
RANGE FINDING TESTS:
Intradermal injections:
Four female guinea pigs weighing approximately 320g were each injected intradermally on the clipped flanks with 0.1mL aliquots of a range of concentrations 0.1%, 0.25%, 0.5%, 1% and 2% test substance in Acetone/Dobs/saline. Twenty-four hours later the reactions were examined for size in millimetres (length and breadth), erythema and oedema.
A concentration which produces a definite irritation reaction is selected as the intradermal injection induction concentration.
- Result: 1% caused definite irritation (elevation/oedema).

Epidermal application:
Eight millimetre diameter filter paper patches in 11mm aluminium patch test cups were saturated with a range of concentrations 5%, 10%, 25%, 50% and 100% test substance in acetone/polyethylene glycol 400 and the cups applied to the clipped flanks of 4 female guinea pigs weighing approximately 450g. The patches were held in place by adhesive plaster wound around the trunk. The patches were removed 24 hours after application and the treatment sites were examined 24 hours and 48 hours after removal of the patches.
The resulting reactions were scored for irritation on a scale from 0 to 3 as described below. For shoulder induction a concentration giving slight but definite irritation is selected. The highest concentration which causes no visible irritation is selected for challenge.
- Result: At 100% at the 24 hours observation time, one animal showed very faint erythema, used for induction in the main study. 50% was the highest non-irritant concentration, as no skin reactions were observed, used for challenge in the main study.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1

1) Intradermal injections on day1:
- Concentration: 1%
- Site: the dorsal shoulder region
Three pairs of intradermal injections:
1) Two 0.1mL injections of 50% Freund's complete adjuvant (FCA) in Acetone/Dobs/saline.
2) Two 0.1mL injections of 1% test substance in Acetone/Dobs/saline (control animals: 0.1mL Acetone/Dobs/saline)
3) Two 0.1mL injections of 1:1 mixture of 2% test substance with FCA (undiluted)

2) Topical application on day 8:
- Concentration: undiluted
- Amount: saturated patch (control animals: Acetone/Dobs/saline)
- Area: 8 cm^2
- Exposure period: 48 hours (occlusive)

B. CHALLENGE EXPOSURE (all animals, with 50% test substance in acetone/polyethylene glycol 400)
- Day(s) of challenge: day 20 (challenge) and 29 (second challenge)
- Exposure period: 24 hours (occlusive)
- Site: flank
- Amount: saturated patch
- Evaluation (hr after challenge): 24 and 48 hours after patch removal.
A reaction in a test animal is considered to be a sensitization response if it is significantly greater than the response in any control animal. Where there is no response in controls, a test reaction of 1 (see above scores epidermal application range finding) or more is considered to be sensitization.
Challenge controls:
At challenges subsequent to the second challenge previously untreated animals of the same sex and weighing approximately the same as the test animals at that challenge are treated in exactly the same way as the test animals.
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
One animal was humanely killed after it suffered a broken leg.
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 19.0. Clinical observations: One animal was humanely killed after it suffered a broken leg..
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
1
Total no. in group:
19
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 1.0. Total no. in groups: 19.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 19.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 19.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
vehicle
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: vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0.

- One guinea pig out of 19 tested showed signs of a slight reaction at challenge; this response was not confirmed as a sensitization reaction at the rechallenge.

- Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a guinea pig maximisation test according to OECD 406 guideline, the skin sentisation potential of the substance was tested, showing absence of skin sensitising properties.
Executive summary:

In a guinea pig maximisation test according to OECD 406 guideline, the skin sentisation potential of the substance was tested. One guinea pig out of 19 tested showed signs of a slight reaction at challenge; this response was not confirmed as a sensitisation reaction at the rechallenge. The substance was considered to be not skin sensitising.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:
Migrated from Short description of key information:
In a guinea pig maximisation test according to OECD 406 guideline, the skin sensitisation potential of the substance was tested. One guinea pig out of 19 tested showed signs of a slight reaction at challenge; this response was not confirmed as a sensitisation reaction at the rechallenge. The substance was considered to be not skin sensitising.

Justification for selection of skin sensitisation endpoint:
The one study available is sufficiently adequate to cover this endpoint.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the results of the available study, the substance does not need to be classified as a skin sensitiser in accordance with Regulation EC No. 1272/2008 and Directive 67/548/EEC.