Registration Dossier

Administrative data

Description of key information

The substance is a skin sensitizer.

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:
June 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Test was carried out befeore the implmenetation of the new guidline and the LLNA methods
Test material information:
Composition 1
Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
Hartley guinea pigs, Crl:(HA)BR.
Supplier: Charles River Wiga GmbH, D-32791 Sulzfeld.
Female healthy young adult and non pregnant animals.
Number in the preliminary study: 3.
Number in the main study: 15.
Body weight at allocation to the groups: ca. 370 g.
Age at first application: ca. 6 weeks.

Animal maintenance
Hygiene: improved hygienic conditions.
Room number: EHl-23.
Room temperature: average of ca. 22.5 °C.
Relative humidity: average of ca 50 %.
Control of room temp. and rel. humidity: continuous control and recording.
Air exchange: ca. 12/h.
Light: only artificial light from 6.00 a.m. to 6.00 p.m.
Cages: Makrolon cages type Ill (23 cm x 39 cm x 18 cm) with wire mesh lids, single caging.
Feed: Altromin Standard Diet No. 3022, ad libitum, offered in stainless steel containers. Analysis of the feed for ingredients and contaminants are performed randomly by Altromin GmbH, D-32791 Lage.
Bedding material: wood chips (aspen) from FINN TAPVEI KY, SF-73600 Kaavi. Reduction of microorganisms by autoclaving.
Water: tap water, acidified with HCl to pH = 3, offered in Makrolon
Identification of the animals: bottles with stainless steel canules, ad libitum.
Acclimatisation: ca. 2 weeks.
Route:
intradermal
Vehicle:
other:
Remarks:
and phosphate buffer solution
Concentration / amount:
0.5 %
Adequacy of induction:
not specified
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
25%
Day(s)/duration:
1
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
40%
Day(s)/duration:
24h
No. of animals per dose:
10
Details on study design:
First induction exposure: intradennal injections of the test substance, of FCA (to enhance a possible sensitisation) and of the test substance diluted with FCA. Application site was an area of approx. 2 cm x 4 cm in the interscapular region. Second induction exposure: epicutaneous application of the test substance to the sites of the intradennal injections.

Positive skin reactions of the test substance treated sites after the challenge exposure indicate a sensitising effect of the test substance, if the scores are higher than those of the vehicle treated sites and if the rate of those - positively reacting - animals is higher than the corresponding percentage of animals in the negative control group.
Challenge controls:
Challenge exposure: epicutaneous application of the test substance to the left flanks and application of the vehicle to the right flanks of all animals.
Positive control substance(s):
yes
Remarks:
Positive control substance: 1,4-phenylenediamine.
Positive control substance(s):
other: 1,4-phenylendiammine
Positive control results:
As recommended by the OECD-Guideline, the sensitivity of the test strain used to detect a possible sensitising potential of a test substance is checked periodically. Results of the last check, performed in September/October 1994 (guinea pig maximisation test,same methods as in the actual study):
Positive control substance: 1,4-phenylenediamine.
Concentrations:
0.5 % in physiological saline for intradermal induction exposure
10 % in white petrolatum for epicutaneous induction exposure
5 % in white petrolatum for epicutaneous challenge exposure.
Number of animals: 5 female guinea pigs for 1,4-phenylenediamine and 5 female guinea pigs for a control group (same strain of animals, supplier, animal maintainance, feed etc. as in the actual study).
Results after challenge exposure: The control areas of all animals were normal. There were no positive skin reactions at the 1,4-phenylenediamine treated sites of the negative control group. In the positive control group 515 animals, i.e. 100 %, had positive reactions on the 1,4-phenylenediamine treated sites 24 and 48 hours after the end of the challenge exposure and were regarded as sensitised.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25%
No. with + reactions:
16
Total no. in group:
20
Clinical observations:
well defined to severe erythema and/or oedema
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25%
No. with + reactions:
15
Total no. in group:
20
Clinical observations:
well defined to severe erythema and/or oedema
Remarks on result:
positive indication of skin sensitisation

Cranial and caudal injection sites: Local irritations were observed in all animals beginning on the day after the injections. The irritations started with local erythema, which became more severe and led to ulcerations. Lesions did not heal until the end of the study. This local alterations are known effects of Freund's adjuvant. Middle injection sites: 24 hours after induction exposure, no irritative reactions were observed in the negative control group, whereas very slight to well defined erythema were noted in 14 /20 animals of the test substance group. After the epicutaneous induction exposure all animals had severe erythema and oedema in the interscapular region (score "3"), which were attributed to the effects of the adjuvant. After the challenge exposure there were reactions of major interest for the grading of an allergenic potency of the test substance.

Negative control group:

Vehicle site: no positive skin reaction in any animal at any reading time.

Test substance site: no positive skin reaction in any animal at any reading time.

No animal had a "positive skin reaction".

Test substance group:

Vehicle site: no positive skin reaction in any animal at any reading time.

Test substance site: well defined to severe erythema and/or oedema in 16/20 animals

24 and/or 48 hours after the end of the exposure.

16/20 animals had a "positive skin reaction".

Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
1-CFT is a skin sensitizer according to the criteria in 67/548/EEC and 1272/2008.
Executive summary:

The "maximisation test" of B. Magnusson and A. M. K.ligman was performed to reveal a possible sensitising potential of "1-CFT". 20 female guinea pigs were used as a test

substance group and another 5 females were used as a negative control group. There were two induction exposures (intradermally and epicutaneously) and one epicutaneous challenge exposure. Test substance concentrations were:

2.5 % in physiological saline for the intradermal induction

25 % in white petrolatum for the epicutaneous induction and

25 % in white petrolatum for the challenge exposure.

Investigations performed were in conformance with the OECD-guideline 406. Application of Freund's complete adjuvant was included in the intradermal exposure of both groups to

enhance a possible sensitisation.

All animals survived till the end of the study. Intradermal injections of Freund's adjuvant caused severe local reactions in all animals, a known effect of the adjuvant. Sensitisation

excluded, no other adverse effects were noted.

In the negative control group, the control sites of all animals were also normal. At the test substance treated sites, positive skin reactions were noted in 16/20 animals. These animals, i.e. 80% of the test substance group animals, were regarded as sensitised.

1 -CFT is a skin sensitizer according to the criteria in 67/548/EEC and 1272/2008.

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

1 -CFT was sensitizing in an in vivo GPMT-test.

Justification for classification or non-classification