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Description of key information

FAT 92368/A was concluded to be a skin sensitiser based on the results of GPMT and Buehler test.

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 10 May, 1993 to 10 June, 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Principles of method if other than guideline:
not applicable
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Data from a reliable in vivo test conducted before the enforcement of Commission Regulation (EU) 640/2012 of 06 July 2012 amending, for the purpose of its adaptation to technical progress, Regulation (EC) No 440/2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) are available.
Specific details on test material used for the study:
Test article: FAT 92368/A
Batch No.: PLN 13
Additional specification: Lanacron Gelb S-2G roh Lösung laboreingedampft
Contents/Purity: ca.80 %
Physical properties: solid; orange powder
Storage conditions: room temperature
Validity: March 1998
Test article received: April 6, 1993
Species:
guinea pig
Strain:
other: Pirbright White Strain (Tif: DHP)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production, 4332 Stein / Switzerland
- Weight at study initiation: 332 to 416 g
- Housing: The animals were housed individually in Macrolon cages (Type 3)
- Diet (e.g., ad libitum): Standard guinea pig pellets - NAFAG No. 845, Gossau SG, ad libitum
- Water: Fresh water, ad libitum
- Acclimation period: At least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30-70 %
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: To: 10 May 1993 to 10 June 1993
Route:
intradermal
Vehicle:
other: FCA/physiological saline
Concentration / amount:
5 %
Day(s)/duration:
Week 1
Adequacy of induction:
highest technically applicable concentration used
Route:
epicutaneous, occlusive
Vehicle:
other: Vaseline
Concentration / amount:
50 %
Day(s)/duration:
week 2
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: Vaseline
Concentration / amount:
20 %
Day(s)/duration:
Week 5
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Control group: 10 animals (5 male and 5 female)
Test group: 20 treated animals (10 male and 10 female)
Details on study design:
Induction procedure (weeks 1 and 2):
The induction was a two-stage operation. First, intradermal injections (into the neck region); second, closed patch exposure over the injection sites one week later.

First induction week, intradermal injection:
Three pairs of intradermal injections (0.1 mL/injection) were made simultaneously into the shaved neck of the guinea pigs as follows:
- adjuvant/saline mixture 1:1 (v/v)
- test substance in physiological saline (w/v)
- test substance in the adjuvant/saline mixture (w/v)

Second induction week, epidermal application:
In the second week of induction test substance was incorporated in vaseline (w/w) and applied on a filter paper patch to the neck of the animals (patch 2x4 cm approx. 0.4 g paste per patch: occluded administration for 48 h).

Rest period:
During weeks 3 and 4 no treatments were performed.

Challenge (week 5):
The animals were tested on the flank with test substance in Vaseline (w/w) and the vehicle alone (patch 2x2 cm; approx. 0.2 g paste per patch; occluded administration for 24 h).

Control group:
A control group of 10 animals (5 males/5 females) was treated with adjuvant and the vehicle during the induction period. During the challenge period the group was treated with the vehicle as well as with the test substance to check the maximum subirritant concentration of the test substance in adjuvant treated animals.
Challenge controls:
no data
Positive control substance(s):
yes
Remarks:
2-Mercaptobenzothiazole puriss. tested in another study
Positive control results:
Positive response was observed in 90% of the treated animals after the occlusive epidermal challenge application.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
20 %
No. with + reactions:
4
Total no. in group:
20
Clinical observations:
Very slight erythema
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
20 %
No. with + reactions:
9
Total no. in group:
20
Clinical observations:
Very slight erythema
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Vehicle control and test article
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Vehicle control and test article
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Intradermal induction: 0.2 %, epidermal induction: 5 % and epidermal challenge: 1 %
No. with + reactions:
9
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
Intradermal induction: 0.2 %, epidermal induction: 5 % and epidermal challenge: 1 %
No. with + reactions:
9
Total no. in group:
10
Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
The test substance was concluded to have induced delayed contact hypersensitivity in treated animals.
Executive summary:

A guinea pig maximization study was conducted to evaluate the skin sensitization potential of the test substance (of ca. 80 % purity) according to OECD Guideline 406 and EU Method B.6 in compliance with GLP.

Based on the results of a preliminary study, 5 and 50 % concentrations were selected as intradermal and topical induction doses. The highest non-irritating concentration used for challenge application was 20 %. After the challenge application, 20 % and 45 % of the animals of the test group showed skin reactions 24 and 48 h after removing the dressings, respectively. Hence, the test substance was concluded to have induced delayed contact hypersensitivity in treated animals.

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

Two sensitization studies were performed on the test substance including a Guinea Pig Maximization Test and a Buehler Test:


In the Guinea pig maximisation test conducted according to OECD Guideline 406 and EU Method B.6, 20 % and 45 % of the animals of the test group showed skin reactions 24 and 48 h after after challenge application. Hence, FAT 92368/A was concluded to have induced delayed contact hypersensitivity in treated animals.


Similarly in a Buehler test conducted according OECD Guideline 406, 50 and 35 % of the animals of the test group and 10 % of the animals of the control group showed skin reactions 24 and 48 h after challenge application. Further, after the rechallenge application, 40 % of the animals of the test group showed skin reactions 24 and 48 h after removing the dressings. Hence, FAT 92368/A was concluded to have induced delayed contact hypersensitivity in treated animals.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

- skin sensitisation:


Based on the above stated assessment of the skin sensitisation potential in the Guinea Pig Maximization Test and Buehler Test, the substance should be classified as a skin sensitizer according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and as a Catagory 1B according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU.


- respiratory sensitisation:


As no data on respiratory sensitization is available for the substance a classification is not possible according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU.