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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
GPMT test
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 17 September and 12 October 1991.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Justification for type of information:
The information is used for read across to Rosmarel. The GPMT test with Prismantol was performed before LLNA or in vitro tests became the first test of selection.
Cross-reference
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
GPMT test
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read across information
Justification for type of information:
The full read-across document can be found in the Endpoint Summary in text and in the attached file.
Reason / purpose:
read-across source
Justification for non-LLNA method:
The GPMT test was performed before LLNA or in vitro tests became the first test of selection.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
Localized dermal reactions, dryness and sloughing of the epidermis
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25%
No. with + reactions:
19
Total no. in group:
20
Clinical observations:
Localized dermal reactions, dryness and sloughing of the epidermis
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
5% and 1% formalin
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
other: Skin sensitizer Category 1B
Remarks:
According to EU CLP (EC/1272/2008 and its amendments).
Conclusions:
Skin sensitisation: sensitising (sensitizer 1B), based on read-across from Prismantol, which was tested in OECD TG 406.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(1981)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The GPMT test was performed before LLNA or in vitro tests became the first test of selection.

Test material

Reference
Name:
Unnamed
Specific details on test material used for the study:
The test substance was gently melted in a water bath at 60°C and prepared prior to each application in Alembicol D.

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D. Hall, Newchurch, Staffordshire, England
- Sex: females, nulliparous and non-pregnant
- Age at Acclimatization Start: ap. 6 to 7 weeks of age
- Weight at Acclimatization Start: 304 to 353 g
- Housing: in groups of ten in suspended metal cages with wire mesh floors.
- Diet: a vitamin C-enriched guinea-pig Diet F.D.1. and drinking water were provided ad libitum. Hay was given weekly to provide dietary supplement. The routine analyses of diet and water was done.
- Water: free access to tap water
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: Alembicol D
Remarks:
Supplied by Alembic Products, Saltney, Chester, England
Concentration / amount:
7.5%
Route:
epicutaneous, occlusive
Vehicle:
other: Alembicol D
Remarks:
Supplied by Alembic Products, Saltney, Chester, England
Concentration / amount:
60%
Day(s)/duration:
48 h
Challenge
Route:
epicutaneous, occlusive
Vehicle:
other: Alembicol D
Remarks:
Supplied by Alembic Products, Saltney, Chester, England
Concentration / amount:
25 and 50%
Day(s)/duration:
24 h
No. of animals per dose:
Test animals: 20
Control animals: 10
Details on study design:
RANGE FINDING TESTS
- Intradermal injections:
Intradermal injections were made into the clipped flank of animals at concentrations of 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 7.5 and 10.0% of the test substance in Alembicol D. The reactions were examined after 24 and 72 hours for size, erythema and oedema.
As well-defined erythema (grade 2) was observed with 7.5% in both animals, this concentration was selected as the intradermal induction concentration.

- Epidermal application:
Patches of filter paper (2x4 cm) were saturated with 0.4 ml of the undiluted test substance at the concentration of 60% in Alembicol D. These were applied to the clipped and shaved flanks of each of 2 males and 2 females and were covered by a length of impermeable plastic adhesive tape. This was firmly secured by elastic adhesive bandage wrapped around the trunk and fixed with "Sleek" impervious plastic adhesive tape. The patches were removed 48 hours after application and the treatment sites were examined immediately and 24 hours and 48 hours after removal of the patches.
At 60% in three animals only very slight erythema (grade 1) was observed immediately after patch removal and in three animals after 24 and 48 hours, in one animal a well-defined erythema (grade 2) was observed after 24 and 48 hours, and in one animal a necrotic patch was observed. Therefore, this concentration was used for the topical induction concentration.
As at 50% no erythema was observed at any time of observation, this concentration was used for the highest challenge exposure.

MAIN STUDY
A. INDUCTION EXPOSURE
1) Intradermal injections (0.1 ml)
- Concentration: 7.5%
- Site: the dorsal scapular region
Three pairs of intradermal injections:
1) Freund's complete adjuvant (FCA) 50:50 with water for irrigation
2) Test substance at 7.5% in Alembicol D
3) Test substance at 7.5% in Alembicol D in a 50:50 mixture of FCA with Alembicol D
Control group:
1) Freund's complete adjuvant (FCA) 50:50 with water for irrigation
2) Alembicol D
3) 50:50 mixture of FCA with water for irrigation
- Readings: daily
- Results: Erythema and edema was observed in both groups

2) Topical applications one week after the injections:
- Concentration: 60%
- Amount: saturated patch (control animals: water for irrigation only)
- Area: 8 cm2
- Exposure period: 48 hours (occlusive)
- Readings: immediately after patch removal and 24 and 48 hours after patch removal

B. CHALLENGE EXPOSURE (control and test group)
- Day of challenge: 2 weeks after the epidermal induction application
- Concentrations: 25 and 50%
- Exposure period: 24 hours (occlusive)
- Sites: left flank, anterior and posterior sites
- Amount: saturated patch
- Readings: at 24, 48 and 72 hours after patch removal
Positive control substance(s):
yes
Remarks:
Formalin

Results and discussion

Positive control results:
The results of the latest sensitivity check of August-September 1991 showed that the system was responsive (10 of 10 animals reacted positive).

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
Localized dermal reactions, dryness and sloughing of the epidermis
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25%
No. with + reactions:
19
Total no. in group:
20
Clinical observations:
Localized dermal reactions, dryness and sloughing of the epidermis
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
5% and 1% formalin
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation

Any other information on results incl. tables

Preliminary study:

- At topical application of 60% no edema was observed at any time point and in three animals a very slight erythema (grade 1) was observed immediately after patch removal and in all four exposed animals after 24 and 48 hours, of which in one animal a well-defined erythema (grade 2) was observed after 24 and 48 hours, and in one animal a necrotic patch was observed. Therefore, this concentration was used for the topical induction concentration. As at 50% no erythema was observed at any time of observation, this concentration was used for the highest challenge exposure.

Main study:

- The body weight gain of the animals was normal, no signs of ill health, no systemic toxicity and no mortality was seen.

- The ten animals exposed to negative control did not show any signs of irritation.

- Intradermal injections: Application area around the injection sites (at 7.5%) was found to show a slight irritation.

Applicant's summary and conclusion

Interpretation of results:
other: Skin sensitizer Category 1B
Remarks:
According to EU CLP (EC/1272/2008 and its amendments).
Conclusions:
In a guinea pig maximisation test performed similar to OECD 406 (1981) and according to GLP principles, the substance is considered a 1B skin sensitiser.
Executive summary:

The skin sensitisation potential of Prismantol was tested in a guinea pig maximisation test performed similar to OECD 406 (1981) and according to GLP principles. A concentration of 7.5% was used for the intradermal induction, 60% for the epidermal induction and 25 and 50% for the topical challenge. The substance produced evidence of skin sensitization in all tested twenty animals and therefore was considered a skin sensitiser. Because ≥ 30% (100%) of animals responded at a dose of > 1% (7.5%), Prismantol is 1B sensitizer.