Registration Dossier

Administrative data

Description of key information

-Skin irritation : 1,2,4-triazole is not irritant in rabbit (according to Thyssen(1976) and Procopio (1992) studies.
-Eye irritation : 1,2,4-triazole is irritant for eyes in rabbit (according toThyssen (1976) and Procopio (1992) studies.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study without detailed documentations
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
reliability scoring was based on 2002 guideline
Deviations:
yes
Remarks:
Chemical characteristics of test substance and temperature, light cycle, and humidity not provided; grading scale of irritation not included and an incorrect number of animals were used
GLP compliance:
no
Remarks:
study pre-dates GLP requirements
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: from the breeder Winkelmann (Borchen)
- Age at study initiation: no data
- Weight at study initiation: 3-4kg
- Fasting period before study: no data
- Housing: singly in standard rabbit cages
- Diet (e.g. ad libitum): Rabbit food 222 (Hoeing co.), ad libitum
- Water (e.g. ad libitum): not precised, ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS: no data
Type of coverage:
occlusive
Preparation of test site:
other: hairless skin on ears
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
Small cellulose patches (1.5 cm X 1.5 cm) with 500 mg of the test substance applied was attached to skin of the ears of rabbits with an adhesive dressing for 24 hours.
Duration of treatment / exposure:
24 hours of exposure
Observation period:
7 days
Number of animals:
2
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hour
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
A score of 0 for all time points, factors and animals.
Other effects:
No changes for up to 7 days after application.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: Regulation EC no.1272/2008 (CLP)
Conclusions:
In this study, mean erythema score and mean edema score are equal to 0 : 1,2,4-triazole is not a skin irritant.
Executive summary:

A non GLP Acute Dermal Irritation / Corrosion test comparable to OECD 404 guideline was carried out with 1,2,4 -triazole. The test substance was applied undiluted on a occlusive patch on hairless skin on ears. The test material induced no erythema and no edema on two animals.

Under the experimental conditions, the test substance is not irritant and is not classified according to regulation EC no.1272/2008 (CLP).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study without detailed documentation
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
reliability scoring based on 2002 guideline
Deviations:
yes
Remarks:
Source, purity, chemical characteristics of test substance, temperature, light cycle, and humidity not provided; grading scale for irritation not reported
GLP compliance:
no
Remarks:
study pre-dates GLP requirements
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: from the breeder Winkelmann (Borchen)
- Age at study initiation: no data
- Weight at study initiation: 3-4kg
- Fasting period before study: no data
- Housing: singly in standard rabbit cages
- Diet (e.g. ad libitum): Rabbit food 222 (Hoeing co.), ad libitum
- Water (e.g. ad libitum): not precised, ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS: no data
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
Test article was instilled into the conjuctival sac of the left eye of 2 rabbits at a dose of 50 mg/animal.
Duration of treatment / exposure:
Single administration
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
2
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
2 rabbits
Time point:
other: 24-48h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: (1 rabbit)
Irritation parameter:
iris score
Basis:
mean
Remarks:
2 rabbits
Time point:
other: 24-48 h
Score:
0.5
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other: (1 rabbit)
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
2 rabbits
Time point:
other: 24-48h
Score:
2.5
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
2 rabbits
Time point:
other: 24-48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: (1 rabbit)
Irritant / corrosive response data:
One hour after application intense reddening and a very intense swelling of the conjectivae of the treated eyes had developed. 24 hours after application intense reddening and moderate swelling of the conjuctivae was still present. In one animal, there was still slight redness and swelling of the conjuctivae 5 days after application, while it was normal in the other animal. The conjuctivae of both animals were normal after 7 days. During the first and second days after application, a slight, dispersed, diffuse opacity of the cornea was observed. The iris was slightly reddened and swollen.
Interpretation of results:
other: Category 2 : Causes serious eye irritation.
Remarks:
Criteria used for interpretation of results: other: CLP (EC1272/2008)
Conclusions:
The authors concluded that 1,2,4-triazole has a irritant effect on the mucous membrane.
Executive summary:

A non GLP comparable Guideline 405 (Acute Eyes Irritation / Corrosion) test was carried out with 1,2,4 -triazole.

Undiluted test article was instilled into the conjuctival sac of the left eye of 2 rabbits at a dose of 50 mg/animal.

One hour after application intense reddening and a very intense swelling of the conjectivae of the treated eyes had developed. 24 hours after application intense reddening and moderate swelling of the conjuctivae was still present. In one animal, there was still slight redness and swelling of the conjuctivae 5 days after application, while it was normal in the other animal. The conjuctivae of both animals were normal after 7 days. During the first and second days after application, a slight, dispersed, diffuse opacity of the cornea was observed. The iris was slightly reddened and swollen.

Under the experimental conditions, the test substance is irritant and is classified in category 2 according to regulation EC no.1272/2008 (CLP).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation :

A GLP OECD 404 key study (Procopio, 1992) was carried out with 1, 2, 4 triazole. No edema and no other erythema was observed during the study. In the abraded skins, very slight erythema was observed on two application sites at 24 hr and on one application site at 72 hr. No other erythema and no edema was observed during the study. The test item was shown to be slightly irritant but was not sufficient for classification.

A non GLP Acute Dermal Irritation / Corrosion test with restricted limitations was carried out with 1,2,4 -triazole (Thyssen, 1976) . The test substance was applied undiluted on a occlusive patch on hairless skin on ears. The test material induced no erythema and no edema on two animals (scores = 0).

Eye irritation :

In a GLP key OECD 405 study (Procopio, 1992). 1,2,4, Triazole is categorized as SUBSTANTIALLY IRRITATING to the eye (i.e. ocular effects reversible within 21 days but not 7 days after dosing in rabbits).

A supportive non GLP OECD Guideline 405 (Acute Eyes Irritation / Corrosion) test was carried out with 1,2,4 -triazole.

Undiluted test article was instilled into the conjuctival sac of the left eye of 2 rabbits at a dose of 50 mg/animal.

One hour after application intense reddening and a very intense swelling of the conjectivae of the treated eyes had developed. 24 hours after application intense reddening and moderate swelling of the conjuctivae was still present. In one animal, there was still slight redness and swelling of the conjuctivae 5 days after application, while it was normal in the other animal. The conjuctivae of both animals were normal after 7 days. During the first and second days after application, a slight, dispersed, diffuse opacity of the cornea was observed. The iris was slightly reddened and swollen.


Effects on eye irritation: irritating

Justification for classification or non-classification

Skin irritation :

1,2,4 -triazole is not a skin irritant and is not classified for this endpoint according to Regulation EC no.1272/2008 (CLP) and according to the EU Directive 67/548/EEC.

Eye irritation :

1,2,4 -triazole is a eye irritant and is classified for this endpoint in category 2 (H319: Causes serious eye irritation) according to Regulation EC no.1272/2008 (CLP) and "R36" according to the EU Directive 67/548/EEC.