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Diss Factsheets

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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
19 September 1997 to 30 April 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted under GLP in accordance with an internationally recognised guideline
Justification for type of information:
Please refer to attached justification for read across.
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: reputable supplier of laboratory animals
- Age at study initiation: 4-7 weeks on arrival + 5 days acclimatisation
- Weight at study initiation: 338-411 g
- Housing: the guinea-pigs were housed in groups of five in suspended metal cages with wire mesh floors
- Diet: vitamin C enriched guinea-pig diet, ad libitum
- Water: drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 21°C
- Humidity (%): 26 to 58%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

IN-LIFE DATES: From: To: 21 October to 21 November 1997
Route:
intradermal and epicutaneous
Vehicle:
coconut oil
Concentration / amount:
Preliminary study: intradermal 0, 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 7.5, 10.0 % v/v
Preliminary study: topical: 30,50,70 % v/v
Preliminary study: challenge, 25 and 50% v/v
Main study, induction: intradermal 5% v/v
Main study, induction topical: as supplied
Main study, challenge: 25 and 50% v/v
Route:
epicutaneous, occlusive
Vehicle:
coconut oil
Concentration / amount:
Preliminary study: intradermal 0, 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 7.5, 10.0 % v/v
Preliminary study: topical: 30,50,70 % v/v
Preliminary study: challenge, 25 and 50% v/v
Main study, induction: intradermal 5% v/v
Main study, induction topical: as supplied
Main study, challenge: 25 and 50% v/v
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS:
The intradermal and topical irritancy of a range of dilutions of the test substance was investigated to identify where possible (a) concentrations of the test substance that would produce irritation suitable for the induction phase of the main study and (b) a maximum non-irritant concentration by the topical route of administration for the challenge phase.

Animals for these investigations were pre-treated with an intradermal injection of Freund's complete adjuvant, 50 : 50 with water for irrigation (Ph.Eur.), approximately two weeks prior to the start of the preliminary investigations. Based on the results of the preliminary investigations, the following concentrations of T-12 were selected:

Induction intradermal injection- 5% v/v in Alembicol D (the highest concentration that caused irritation but did not adversely affect the animals).
Induction topical application - as supplied (produced some irritation but did not adversely affect the animals).
Topical challenge- 50 and 25% v/v in Alembicol D

From preliminary investigations 50% v/v in Alembicol D was the highest concentration not giving rise to irritating effects.

MAIN STUDY
A. INDUCTION EXPOSURE - intradermal
- No. of exposures: 1
- Exposure period: one week intradermal
- Test groups: 5% v/v test substance in Alembicol D; 5% v/v test substance in a 50: 50 mixture of Freund's complete adjuvant and Alembicol D.
- Control group:50/50 Freund's complete adjuvant/water for irrigation
- Site: 40 x 60 mm area of dorsal skin on the scapular region, clipped free of hair with electric clippers. Three pairs of intradermal injections made into a 20 x 40 mm area within the clipped area.
- Frequency of applications: application in duplicate (two sites)

A. INDUCTION EXPOSURE - topical
- No. of exposures: 1
- Exposure period: 48 hours
- Test groups: 0.4ml test substance as supplied absorbed onto a 20 x 40 mm patch of Whatman No. 3 paper. The patch was placed on the skin of the test animals and covered by a length of impermeable plastic adhesive tape (50 mm width). This in turn was firmly secured by elastic adhesive
bandage (50 mm width plaster) wound round the torso of the animal and fixed with impervious plastic adhesive tape.
- Control group: the control animals were treated similarly to the test animals with the exception that the test substance was omitted from the intradermal injections and topical application.
- Site: the same 40 x 60 mm area of dorsal skin on the scapular region as used for the intradermal injections, clipped and shaved free of hair..
- Frequency of applications: application at one site


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: two weeks after topical induction
- Exposure period: 24 hours
- Test and control groups: test substance in Alembicol D
- Site: hair was removed by clipping and then shaving from an area on the left flank of each guinea-pig
- Concentrations: 50 and 25% v/v
- Evaluation (hr after challenge): 24 and 48 hours after removal of the patch
Positive control results:
Hexyl cinnamic aldehyde - 10/10 positive, 0/10 inconclusive or negative
Mercaptobenzothiazole - 9/10 positive, 1/10 inconclusive, 0/10 negative
Reading:
other: not reported
Hours after challenge:
168
Group:
positive control
Dose level:
Induction (intradermal): 10 % v/v
Induction (topical): 83.33 % v/v
Challenge: 83.33 % v/v and 40 % v/v
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
Not reported
Remarks on result:
positive indication of skin sensitisation
Remarks:
Mercaptobenzothiazole
Reading:
other: Not specified in report
Hours after challenge:
168
Group:
positive control
Dose level:
Induction (intradermal): 10 % v/v
Induction (topical): as supplied
Challenge: as supplied and 50 % v/v
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
none reported
Remarks on result:
positive indication of skin sensitisation
Remarks:
Hexyl cinnamic aldehyde
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25% and 50%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no signs of ill health or toxicity
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 25% and 50%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: no signs of ill health or toxicity.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25% and 50%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no signs of ill health or toxicity
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 25% and 50%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: no signs of ill health or toxicity.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25% and 50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no signs of ill health or toxicity
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25% and 50%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no signs of ill health or toxicity.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25 and 50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no signs of ill health or toxicity
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25 and 50%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no signs of ill health or toxicity.

Bodyweight increases were recorded for all guinea-pigs over the period of the study

Site

Intradermal injection

Topical application

Test animals

Control animals

Test animals

Control animals

1

Necrosis

Necrosis

Slight erythema

Slight erythema

2

Slight irritation

Slight irritation

3

Necrosis

Necrosis

Control animals:

(Site 1)   0.1 ml of Freund's complete adjuvant 50: 50 with water for irrigation (Ph.Eur.).

(Site 2)    0.1 ml of Alembicol D.

(Site 3)   0.1 ml of Freund's complete adjuvant 50: 50 with Alembicol D.

Test animals:

(Site 1)   0.1 ml of Freund's complete adjuvant 50: 50 with water for irrigation (Ph.Eur.).

(Site 2)   0.1 mi of T-12, 5% v/v in Alembicol D.

(Site 3)   0.1 ml of T-12, 5% v/v in a 50: 50 mixture of Alembicol D and Freund's complete adjuvant.

 

A volume of 0.1 ml was injected into both the left and right injection sites.

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
T-12 did not produce evidence of skin sensitisation (delayed contact hypersensitivity) in any of the ten test animals.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The skin sensitisation of T-12 was determined by HLS, 1998, Report No.: IDK 61. The study was conducted in accordance with EU method B6 and was considered reliable.


 


T-12 is an analogue of T-13h and is considered suitable for read across. A detailed justification for read across from T-12 to T-13h, considering the overall properties and composition of the two substances, is given in section 13 (Assessment reports) of this dossier. T-12 is a mixture of 6 diastereoisomer pairs (isomer B, C, D, E, F) and T-13h is a mixture comprising two of the diastereoiosmer pairs (D, F).


Migrated from Short description of key information:


The test substance, T-12, an analogue of the registered substance T-13h, was found not to be sensitising to skin in a guinea pig maximisation test.


 


Justification for selection of skin sensitisation endpoint:


A single study is available. It is considered to be adequate and reliable.

Justification for classification or non-classification