1H-1,2,4-triazole, sodium salt

Endpoint summary

Description of key information

A GLP study performed according to OECD 406

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)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD 406). No GLP study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

see below

Qualifier:

according to guideline

Guideline:

other: 84/449/EC (annex V and VI)

Principles of method if other than guideline:

Due to the insolubility 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 induced a weat to moderate sensitization via occlusive topic a application for 48h and to verify if such concentration 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 applied 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:

This study was performed before implementation of the LLNA guideline.

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Iffa-Credo (F69210-L'Arbresle), Charles River (F76410 St Aubin) or David Hall (DE 13BRJ Burton England)
- Age at study initiation: 5-7 semaines
- Weight at study initiation: 300-500 g.
- Housing: in groups of 5 (males and females apart) in polystyrene cages
- Diet (e.g. ad libitum): 50g of food is provided per animal per day (granules Cobaye Extra Labo, Ets Pitrement, Ste Colombe - 77650 Longueville)
- Water (e.g. ad libitum): drinking water is provided ad libitum in an automatic watering system (softened and filtered water: 15 microns)
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+/-3°C
- Humidity (%): 30-70%
- Air changes (per hr): yes, but not precised
- Photoperiod (hrs dark / hrs light): The lighting is artificial for 12 hours per day ( 7:30 a.m. - 7:30 p.m.)

Route:

other: intradermal and 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 applied 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 chemical

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 chemical

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 chemical

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 chemical

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:

GHS criteria not met

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:

This study was made according to the method of Magnusson and Kligman and the OECD Guideline N° 406.

Applications of the induction phase were carried out by intradermal route and by topical occlusive route. By intradermal route : injection of 2 x 0.1 ml of the test substance in a 25 % (W/W) solution in water for injection ; orof 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 induced 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 induced 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 and at the dose of 0.50 ml per guinea-pig.

Considering the macroscopic andhistologicalresults obtained under the conditions of the study, the test substance caused a reaction of cutaneous sensitization in one out of the 20 treated guinea-pigs (5 %), no topical cutaneous abnormality, and different from the preliminary study, was noted in the 10 control guinea-pigs.

According this study, 1,2,4 -triazole appears to be not sensitising.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

This study was made according to the method of Magnusson and Kligman and the OECD Guideline N° 406.

Applications of the induction phase were carried out by intradermal route and by topical occlusive route. By intradermal route : injection of 2 x 0.1 ml of the test substance in a 25 % (W/W) solution in water for injection ; orof 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 induced 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 induced 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 and at the dose of 0.50 ml per guinea-pig.

Considering the macroscopic and histological results obtained under the conditions of the study, 1,2,4 -triazole caused a reaction of cutaneous sensitization in one out of the 20 treated guinea-pigs (5 %), no topical cutaneous abnormality was noted in the 10 control guinea-pigs.

According this study, 1,2,4 -triazole appears to be not sensitising.

Migrated from Short description of key information:
A guideline (OECD 406) study was available for this endpoint, it's a maximization test on guinea pigs. According this study, 1,2,4 -triazole appears to be not sensitising.

Respiratory sensitisation

Endpoint conclusion

Additional information:

Migrated from Short description of key information:
No available study.

Justification for classification or non-classification

According to EU regulation (EC) No 1272/2008 (CLP) :

1,2,4 -triazole sodium salt was not a skin sensitizer.

Positive result was observed in 5% of the treated animals (<30%).