1,2,4-triazole

Endpoint summary

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

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 or test system 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:

24 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

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

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:

guideline study without detailed documentation

Qualifier:

equivalent or similar to guideline

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:

24/48 h

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:

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:

24/48 h

Score:

2.5

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

2 rabbits

Time point:

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:

Category 2 (irritating to eyes) based on GHS criteria

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.