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:
23 July 1985
Reliability:
1 (reliable without restriction)
Justification for type of information:
The LLNA was performed in 2005 and is submitted in the dossier.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
see below
Qualifier:
according to
Guideline:
other: 84/449/EC (annex V and VI)
Principles of method if other than guideline:
Due to the insolobility of the substance into water at more then 50% (W/W) it was not possible to determine for the induction phase the concentration of the substance that provoked a weat to moderate sensitization via occlusive topica application for 48h and to verify if such cincentration was the non-irritant Maximum concentration (N.I.M.C.) via occlusive topical application of the " challenge" exposure.
The irritant effect of the water was absent, such vehicle was not appled to the right flank of the animals during the "challenge" exposure
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The LLNA was performed in 2005 and is submitted in the dossier.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
Before the start of the experiment the animals are kept for at least 8 days to allow time for acclimatization and selected at random after elimination of animals showing possible cutaneous lesions.The animals are kept in a ventilated and air conditionned animal house in groups of 5 (males and females apart) in polystyrene cages measuring 540 x 360 x 315 nm, with a performed polystyrene floor. The lighting is artificial for 12 hours per day ( 7:30 a.m. - 7:30 p.m.). the weight of the animals at study initiation was from 300 to 500 g.
50g of food is provided per animal per day ( granules Cobaye Extra Labo - Ets Pitrement - Sainte Colombe - 77650 Longueville), drinking water is provided ad libitum in an automatic watering system (softened and filtered water: 15 microns).
Route:
other: intradermal, occlusive
Vehicle:
water
Concentration / amount:
Applications of the induction phase were carried out

By intradermal route: injection of 2 x 0.1 ml:
- of the test substance in a 25 % (W/W) solution in water for injection ;
- of 50/50 (V/V) mixture : test compound in a 50 % solution (W/W) in water for injection + 50 % (V/V) solution of Freund¿s complete adjuvant in water for injection, i.e. a final 25 % concentration of the test substance.

The injection of the test substance in a 25 % solution did not provoke any important irritation.

By topical occlusive route for 48 hours, with test substance in a 50 % (W/W) dilution with water for injection and at the dose of 0.50 ml per animal this application having provoked no irritation macroscopically noticeable, the skin was treated on D7, with 0.50 ml of 10 % Sodium Lauryl Sulfate in Codex Petrolatum.

For the challenge exposure, the occlusive topical application for 24 hours was carried out with the test substance in a 50 % (W/W) solution with water for injection arid at the dose of 0.50 ml per guinea pig.
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Applications of the induction phase were carried out

By intradermal route: injection of 2 x 0.1 ml:
- of the test substance in a 25 % (W/W) solution in water for injection ;
- of 50/50 (V/V) mixture : test compound in a 50 % solution (W/W) in water for injection + 50 % (V/V) solution of Freund¿s complete adjuvant in water for injection, i.e. a final 25 % concentration of the test substance.

The injection of the test substance in a 25 % solution did not provoke any important irritation.

By topical occlusive route for 48 hours, with test substance in a 50 % (W/W) dilution with water for injection and at the dose of 0.50 ml per animal this application having provoked no irritation macroscopically noticeable, the skin was treated on D7, with 0.50 ml of 10 % Sodium Lauryl Sulfate in Codex Petrolatum.

For the challenge exposure, the occlusive topical application for 24 hours was carried out with the test substance in a 50 % (W/W) solution with water for injection arid at the dose of 0.50 ml per guinea pig.
No. of animals per dose:
30 adult ( from 5 to 7 weeks old) Albino Dunking-Hartley guinea-pigs ( 15 males and 15 female not pregnant) were put on study + 2 additional for possible mortality in the treated group:
- 10 ( 5 male and 5 female) were assigned to the control group ( the test substance was not administrated to the animals)
- 20 (10 male and 10 female) were assigned to the treated group
Details on study design:
Definitive Study:
A. Induction Exposure
Exposure period: 10 days
Test groups: 20 animals
Control groups: 10 animals
Site of the treatment: the injections and the occlusive application were on scapular reagion

B. Rest period: Treatment was suspended from day 10 to day 20 inclusive for a period of 11 days.

C. Challenge Exposure
Duration of the exposure: 1 day
Test group: 20 animals
Control group: 10 animals
Site of the treatment: the test substance at 50%(W/W) in water ( at the non irritant maximum concentration) was appliend on the left flank, the vehicle alone was applied on the right flank.


Challenge controls:
The challenge control used was the vehicle: water that was anyway not applied ( see the note of "Deviations")
Positive control substance(s):
no
Positive control results:
Not applicable
Reading:
1st reading
Hours after challenge:
1
Group:
test group
Dose level:
0.5 ml of a solution 50% (W/W)
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 1.0. Group: test group. Dose level: 0.5 ml of a solution 50% (W/W). No with. + reactions: 1.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
6
Group:
test group
Dose level:
0.5 ml of a solution 50% (W/W)
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 6.0. Group: test group. Dose level: 0.5 ml of a solution 50% (W/W). No with. + reactions: 1.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.5ml of a solution 50% (W/W)
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5ml of a solution 50% (W/W). No with. + reactions: 1.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
0.5 ml of a solution 50% (W/W)
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
1 animal was subjected to a biopsy in order to evaluate a weak skin irritation. The examen didn't highlighted anything to be noted.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5 ml of a solution 50% (W/W). No with. + reactions: 0.0. Total no. in groups: 19.0. Clinical observations: 1 animal was subjected to a biopsy in order to evaluate a weak skin irritation. The examen didn't highlighted anything to be noted..
Reading:
1st reading
Hours after challenge:
1
Group:
negative control
Dose level:
-
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 1.0. Group: negative control. Dose level: -. No with. + reactions: 1.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
6
Group:
negative control
Dose level:
-
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 6.0. Group: negative control. Dose level: -. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
-
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: -. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
-
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: -. No with. + reactions: 0.0. Total no. in groups: 10.0.
Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Considering the macroscopic and histological results obtained under the conditions of the study, the test substance caused a reaction of cutaneous sensitization in one out of the 20 treated guinea pig (5%).
Executive summary:

An in vivo skin sensitization test with guinea pigs was carried out with 1,2,4 -triazole.

The test substance was induced intradermal and occlusive (two stages).

5% of animals in the test group exhibited erythema at 24 hours (1 animal out of 20); 0% at 48 h.

The test substance showed no skin sensitizing potential in albino guinea pigs.

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

Skin sensitisation : Key study - OECD 406 (Gonnet 1985)

An in vivo skin sensitization test with guinea pigs was carried out with 1,2,4 -triazole.

The test substance was induced intradermal and occlusive (two stages).

5% of animals in the test group exhibited erythema at 24 hours (1 animal out of 20); 0% at 48 h.

The test substance showed no skin sensitizing potential in albino guinea pigs. Skin sensitization : Key study -OECD 406 (Frosh 1998) A second in vivo skin senstization test with guinea pig was carried out with 1,2,4 triazole. The animals showed a very homogeneous reaction to the application of the test article. The intradermal injection of the 10 % solution of the test article in combination with sensitisation potentiating FCA lead to slight erythema and oedema. The same pattern was seen at injection site 1 (FCA/water mixture) in all animals. Only two animals reacted after intradermal injection of the 10% solution alone with a slight erythema over 48 hours. Topical induction was attempted with (lie 75:25 mixture of the test article in vaseline on day 7. After removal of the occlusive dressing no skin reaction was recorded. After challenge with the 75:25 preparation in vaseline no skin reaction was observed. The skin-fold thickness was not significantly increased after the challenge procedure. 1,2,4-Triazole has no skin sensitisation effect. Skin sensitisation: Key study - OECD 429 (Weber 2005)

The test substance was applied in mouse (5 animals/dose) at the concentrations of 0, 10, 25 or 34.6% (equivalent to 0, 15, 37.5, or 51.9 mg, respectively) to the dorsal surface of the ears, on Days 1,2, and 3. Dimethylsulfoxide was used as vehicle. Stimulations indices (SI) are calculated for each concentration. The SI are : 1 for the negative control, 1.2 for the low dose (10%), 1.9 for the mid dose, 1.7 for the high dose and 7.8 for the positive control. Results of controls (negative and positive) are valided. The test substance is not classified as skin sensitizer because none SI is higher than 3.


Migrated from Short description of key information:
1,2,4-triazole is not a skin sensitiser. Two guideline study are available for this endpoints : a skin sensitisation test with guinea pigs (OECD 406) and a Skin Sensitisation: Local Lymph Node Assay (OECD 429). This two studies are flagged as "key study" because these studies have the same results and the same relevance.

Respiratory sensitisation

Endpoint conclusion
Additional information:
Migrated from Short description of key information:
no study is available.

Justification for classification or non-classification

Skin sensitisation :

1,2,4 -triazole is not classified for this endpoint, according to the Regulation EC no.1272/2008 ant the EU Directive 67/548/EEC.

Justification (CLP) : Redness in < 30% of the test animals (first study), and SI < 3 (second study).

Respiratory sensitisation :

1,2,4 -triazole is not classified for this endpoint, beacause there are no data.