cyproconazole (ISO); (2RS,3RS;2RS,3SR)-2-(4-chlorophenyl)-3-cyclopropyl-1-(1H-1,2,4-triazol-1-yl)butan-2-ol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 Jul 2005 to 4 Aug 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

1998

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: JMAFF 59 NohSan No. 4200, January 28

Version / remarks:

1985

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-(4-chloro-phenyl)-3-cyclopropyl-1-[1,2,4]triazol-1-yl-butan-2-ol

Cas Number:

94361-06-5

Molecular formula:

C15H18ClN3O

IUPAC Name:

2-(4-chloro-phenyl)-3-cyclopropyl-1-[1,2,4]triazol-1-yl-butan-2-ol

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adults
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals DHEW (NIH). Litter paper was placed beneath the cage and was changed at least three times per week.
- Water: Ad libitum
- Acclimation period: 40 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 22
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 26 Jul 2005 to 4 Aug 2005

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.06 g

Duration of treatment / exposure:

Single treatment

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

2 females and 1 male

Details on study design:

SCORING SYSTEM: Draize scale for scoring eye lesions and Kay and Calandra scheme for classifying eye irritants. Observations were made at 1, 24, 48 and 72 hours.

TOOL USED TO ASSESS SCORE: Fluorescein

OTHER EXAMINATIONS:
- General health

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal: #1, #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72h

Results 4

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48h

Results 5

Irritation parameter:

chemosis score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Within one hour after test substance instillation, “positive” iritis and conjunctivitis were noted for all three treated eyes. The overall incidence and severity of irritation decreased with time. All animals were free of ocular irritation within 72 hours. Mean scores following grading at 24, 48 and 72 hours were below 1 in all animals.

Other effects:

- Other observations: There were no other signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour.

Any other information on results incl. tables

Table 1. Individual scores for ocular irritation

	Rabbit #1 (Female)				Rabbit #2 (Female)				Rabbit #3 (Male)
	Hours				Hours				Hours
	1	24	48	72	1	24	48	72	1	24	48	72
I. Cornea
A. Opacity	0	01	0	0	0	01	0	0	0	01	0	0
B. Area	4	4	4	4	4	4	4	4	4	4	4	4
(AxB)x5	0	0	0	0	0	0	0	0	0	0	0	0
II. Iris
A. Values	1	0	0	0	1	0	0	0	1	0	0	0
Ax5	5	0	0	0	5	0	0	0	5	0	0	0
III. Conjunctivae
A. Redness	2	1	1	0	2	1	1	0	2	1	0	0
B. Chemosis	1	0	0	0	1	0	0	0	1	0	0	0
C. Discharge	2	1	0	0	2	1	0	0	2	1	0	0
(A+B+C)x2	10	4	2	0	10	4	2	0	10	4	0	0
Total	15	4	2	0	15	4	2	0	15	4	0	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on these results, the test substance is mildly irritating to the eye, but not sufficient for classification under CLP.

Executive summary:

In accordance with OECD TG 405 and GLP principles, a primary eye irritation test was conducted with 1 male and 2 females New Zealand White rabbits to determine the potential for the test substance to produce irritation from a single instillation via the ocular route. One-tenth of a mL (0.06 grams) of the test substance was instilled into the right eye of three healthy rabbits. The left eye remained untreated and served as a control. Observations were made 1 hour, 24 hours, 48 hours and 72 hours after instillation of the test substance. Ocular irritation was evaluated by the Draize scale method.

Results showed that within one hour after test substance instillation, “positive” iritis and conjunctivitis were noted for all three treated eyes. The mean average score (24, 48, and 72h) for cornea opacity, chemosis and the iris was 0 for all the animals. The mean average score for conjunctivae redness (24, 48, and 72h) was 0.67 for animal #1, #2 and 0.33 for animal #3. The overall incidence and severity of irritation decreased with time. All animals were free of ocular irritation within 72 hours.

Based on these results, the test substance is mildly irritating to the eye, but not sufficient for classification under CLP.