α-n-butyl-α-(4-chlorophenyl)-1H-1,2,4-triazole-1-propanenitrile

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

29-May-1984 to 19-June-1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

0.1 g of the ground amber solid test substance was applied to the corneal surface of 6 rabbits. Another 3 rabbits were treated, the eyes of these rabbits were irrigated with water for approximately 60 seconds starting 20-20 seconds after dosing. The eyelids were held open momentarily after dosing and then released gently to allow the animal to blink freely. The treated eyes were scored according to Draize's Procedure at 24, 48 and 72 hours after instillation, and at day 7, 14 and 21.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

α-n-butyl-α-(4-chlorophenyl)-1H-1,2,4-triazole-1-propanenitrile

EC Number:

410-400-0

EC Name:

α-n-butyl-α-(4-chlorophenyl)-1H-1,2,4-triazole-1-propanenitrile

Cas Number:

88671-89-0

Molecular formula:

C15H17ClN4

IUPAC Name:

2-(4-chlorophenyl)-2-[(1H-1,2,4-triazol-1-yl)methyl]hexanenitrile

Test material form:

liquid: viscous

Remarks:

solid

Specific details on test material used for the study:

Crude myclobutanil; 95.7% purity

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Remarks:

Albino

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hazleton Dutchland. Denver. PA.
- Age at study initiation: Young adult
- Weight at study initiation: approximately 2.0 - 3.5 kg
- Housing: Rabbits were housed individually in stainless steel cages
- Diet: Purina Laboratory Rabbit Chow
- Water: Drinking quality water was available ad libitum either by an automatic watering system or by water bottles.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not specified
- Humidity (%): not specified
- Photoperiod (hrs dark / hrs light): 12-hr light/dark

Test system

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.1g of the ground amber solid test substance was applied to the corneal surface

Observation period (in vivo):

The treated eyes were scored for signs of eye irritation at 24, 48 and 72 hours and at 7, 14 and 21 days after dose application.

Number of animals or in vitro replicates:

6 males (no washing after instillation);
3 males (eyes were rinsed with water 20-30 seconds after instillation)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: For 3 of these rabbits, the treated eyes were irrigated with water for approximately 60 seconds. The treated eyes of the rest of the rabbits were remained unwashed.
- Time after start of exposure: 20-30 seconds after dosing

SCORING SYSTEM: The severity of the ocular effects were scored according to the system of Draize (J. Pharmacol, Exp. Therap. 82, 377-390, 1944).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

not measured/tested

Results 2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

5

Max. score:

20

Reversibility:

fully reversible within: 14 days

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.6

Max. score:

10

Reversibility:

fully reversible within: 48 hours

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

7.8

Max. score:

80

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Remarks:

after 21 days: 1 animal with 1-2mm long blood vessel extended onto cornea; another animal: a 3 mm distinct hazy yellow area stain on the cornea

Irritant / corrosive response data:

For rabbits with unwashed eyes, slight to moderate irritation was observed in the cornea (6/6), iris (3/6) and conjunctiva (6/6) at 24 hours post-dosing. An uneven, pitted area was observed at the centre of the cornea of one rabbit with corneal and conjunctival effects. Test substance was noted to be present in the eyes of 3/6 rabbits, and around the eyes of the remaining 3 rabbits.
Irritation of reducing severity was present at 48 and 72 hours in the cornea (4/6 and 3/6, respectively) and conjunctiva (6/6 at both timepoints). Test substance was noted to be present around the eyes of the same 3 rabbits as before at 48 hours and in 1 rabbit at 72 hours.
At 7 days, irritation of the conjunctiva was still present in 2 rabbits. No irritation was observed at 14 and 21 days. However, a few blood vessels had extended into the cornea of one rabbit from Day 7 (one of the 3 rabbits with test material observed in the treated eye at 24 hrs) and, after dosing, a 3mm distinct hazy yellow stained area was seen on the cornea of another rabbit (one of the 3 rabbits with test material observed around the treated eye at 24, 48 and 72 hrs).

For rabbits with washed eyes, irritation was observed in all 3 animals in the conjunctiva at 24 hours, and only in 1 animal at 72 hours, respectively.

Any other information on results incl. tables

The results are included in Table 1 below.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

The results of an in vivo eye irritancy test performed in rabbits indicated long-lasting effects on the eye for crude myclobutanil. Based on the duration of the ocular effects, the test substance was considered severely irritating to the eyes of rabbits (i.e., vascularization of the cornea was present at 21 days). Irrigating the exposed eyes with water for 60 seconds beginning 20 to 30 seconds after exposure prevented the corneal effects, decreased the conjunctival effects and shortened the recovery period.