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:
From 1994-12-06 to 1995-01-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to OECD test guideline No. 406 and in compliance with GLP
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP Compliance Program (inspection date: 1994-01-21)
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Limited, Burton-on-Trent, Staffordshire, UK
- Age at study initiation: 8 to 12 weeks old
- Weight at study initiation: 422-535 g
- Housing: singly or in pairs in solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): Guinea Pig FD1 Diet ad libitum (Special Diets Services Limited, Witham, Essex, UK)
- Water (e.g. ad libitum): mains tap water ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22 °C
- Humidity (%): 51-65 %
- Air changes (per hr): approximately 15 per hr
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
other: arachis oil BP for intradermal injection; unchanged for topical induction; 1:1 ethanol / diethylphtalate for topical challenge
Concentration / amount:
Intradermal induction: 5 % w/v; Topical induction: undiluted; Topical challenge 50 and 25 % w/v
Route:
epicutaneous, occlusive
Vehicle:
other: arachis oil BP for intradermal injection; unchanged for topical induction; 1:1 ethanol / diethylphtalate for topical challenge
Concentration / amount:
Intradermal induction: 5 % w/v; Topical induction: undiluted; Topical challenge 50 and 25 % w/v
No. of animals per dose:
20 test and 10 control animals
Details on study design:
RANGE FINDING TESTS:
- Intradermal induction: 2 females, 5 or 1 % w/v in arachis oil B.P. 5 % w/v was selected for the main study as the highest concentration that caused only mild to moderate skin irritation and was well tolerated systemically.
- Topical induction: 2 males; 100, 75, 50 and 25 % v/v in 1:1 ethanol diethylphtalate. The highest concentration producing only mild to moderate dermal irritation after a 48-h occlusive exposure was 100 %.
- Topical challenge: 2 males; 100, 75, 50 and 25 % v/v in 1:1 ethanol diethylphtalate. The highest non-irritant concentrations selected for the main study challenge were 50 and 25 % v/v.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 injections (Day 0) + 1 topical application (Day 7)
- Test groups: 1/ 1:1 FCA plus distilled water
2/ 5 % w/v dilution of test material in arachis oil B.P.
3/ 5 % w/v dilution of test material in a 1:1 preparation of FCA plus distilled water
- Control group: 1/ 1:1 FCA plus distilled water
2/ Arachis oil B.P.
3/ 50 % w/v dilution of Arachis oil B.P. in a 1:1 preparation of FCA plus distilled water
- Site: shoulder region
- Concentrations: 5 % w/v for injection; undiluted as supplied for topical application
- Duration: 48 h for topical application
- Evaluation: 24 and 48 h after injections; 1 and 24 h after patch removal

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21
- Site: right shorn flank
- Concentrations: 50 and 25 % v/v
- Duration: 24 h
- Evaluation (hr after challenge): approximately 24 and 48 h after challenge dressing removal
Challenge controls:
None
Positive control substance(s):
yes
Remarks:
Historical control data on 2,4-Dichlorobenzene are included
Statistics:
none
Positive control results:
Summary of positive control data from the lab are available. The latest study was conducted between 1994-10-31 and 1994-11-24 with 2,4-Dichlorobenzene. It was administered as a 0.1% concentration in arachis oil BP for the intradermal injections and a 1% concentration in arachis oil BP for the topical induction. Challenge was conducted at concentrations of 0.1% and 0.05% in arachis oil BP. The incidence of sensitisation was 100% (10/10 animals).
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50 % and 25 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50 % and 25 %. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50 % and 25 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50 % and 25 %. No with. + reactions: 0.0. Total no. in groups: 20.0.
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:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0 %
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: 0 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Skin reactions observed after intradermal induction

Very slight or well-defined erythema was noted at the intradermal induction sites of all test and control group animals at the 24 and 48-h observations.

Skin reactions observed after topical induction

Very slight erythema was noted at the induction sites of three test group animals and well-defined erythema at the induction sites of seventeen test group animals at the one hour observation. Very slight erythema was noted at the induction sites of eighteen test group animals and well-defined erythema persisted at the induction sites of two test group animals at the 24-h observation.

No skin reactions were noted at the treatment sites of the control group animals at the 1- and 24-h observations.

Skin reactions observed after topical challenge

No skin reactions were noted at the challenge sites of the test or control group animals at the 24- and 48-h observations.

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
HR 94/130966 did not produce evidence of skin sensitisation during the study.
Executive summary:

In a dermal sensitisation study performed according to the OECD guideline No. 406 and in compliance with GLP, HR 94/130966 was tested in Hartley guinea-pigs using the Guinea-Pig Maximisation Test method (20 treated animals + 10 controls).

The preliminary study determined the concentration which produced mild to moderate irritation to be used for the intradermal induction (5%) and for the topical induction (100%). 50 and 25 % were selected as the highest non-irritant test substance concentration for the challenge.

 

HR 94/130966 diluted in Arachis oil B.P. at 5 % (w/w) was administered by injection for intradermal induction. Topical induction was performed with the test material as supplied, 7 days after intradermal injections. For the challenge, HR 94/130966 was tested at 50 and 25 % v/v in a mixture of 1:1 ethanol/diethylphtalate.

 

The sensitivity of the guinea-pig is checked periodically at Safepharm with known sensitizers, like HCA and Mercaptobenzothiazole.

 

HR 94/130966 did not produce evidence of skin sensitization during the study.

Under the test conditions, HR 94/130966 is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and of the Directive 67/548/EEC.

This study is considered as acceptable and satisfies the requirement for skin sensitisation endpoint.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The study of Driscoll (1995, rel.1) was considered as the key study. In this dermal sensitisation study performed according to the OECD guideline No. 406 and in compliance with GLP, HR 94/130966 was tested in Hartley guinea-pigs using the Guinea-Pig Maximisation Test method (20 treated animals + 10 controls). Concentrations used in the main study were determined from information gained in a preliminary study. HR 94/130966 diluted in Arachis oil B.P. at 5 % (w/w) was administered by injection for intradermal induction. Topical induction was performed with HR 94/130966 as supplied, 7 days after intradermal injections. For the challenge, HR 94/130966 was tested at 50 and 25 % v/v in a mixture of 1:1 ethanol/diethylphtalate. The sensitivity of the guinea-pig is checked periodically at Safepharm with known sensitizers, like HCA and Mercaptobenzothiazole. HR 94/130966 did not produce evidence of skin sensitization during the study.

Two other studies showed no evidence of skin sensitisation but were only used as supporting studies due to the lack of details. The LLNA study conducted by Lees (1997) did not include justification for dose selection and the GPMT study conducted by Tanaka (2005) did not describe sufficiently methods and results.


Migrated from Short description of key information:
Not sensitising (OECD 406, GLP, K, rel.1)

Justification for selection of skin sensitisation endpoint:
The key study is GLP-compliant and of high quality (Klimisch score = 1).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008 including ATP3.

Self-classification:

Based on the available information no additional self-classification is proposed regarding the skin sensitisation according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and of the Directive 67/548/EEC. No data was available for respiratory sensitisation.