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

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 Jul 2005 to 1 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:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

1998

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: JMAFF 59 NohSan No. 4200, January 28, 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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adult
- 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: 9 days

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

IN-LIFE DATES: 26 Jul 2005 to 1 Aug 2005

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

Distilled

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.71 g of the test mixture

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48, and 72 hour

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: The test substance was applied by placing it on a 1 inch x 1 inch, 4-ply gauze pad .
- % coverage: 6 cm^2 intact dose site
- Type of wrap if used: The pad and entire trunk of each animal were wrapped with semi-occlusive 3 inch Micropore tape to avoid dislocation of the pad.

REMOVAL OF TEST SUBSTANCE
- Washing: After 4 hours of exposure to the test substance, the pads and collars were removed and the test sites were gently cleansed of any residual test substance.

OBSERVATION TIME POINTS
1, 24, 48, and 72 hours after patch removal

SCORING SYSTEM:
- Method of calculation: The classification of irritancy was obtained by adding the average erythema and edema scores for the 1, 24, 48, and 72-hour scoring intervals and dividing by the number of evaluation intervals

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 1, 24, 48 and 72h

Score:

0.3

Reversibility:

fully reversible within: 24h

Results 2

Irritation parameter:

erythema score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

edema score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

One hour after patch removal, very slight erythema was noted for all three treated dose sites. All animals were free from dermal irritation within 24 hours.

Other effects:

All animals appeared active and healthy during the study. Apart from the skin irritation noted below, there were no other signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour

Any other information on results incl. tables

Table 1. Individual skin irritation scores, erythema/oedema

Animal No.	Sex	Hours After Patch Removal
		1	24	48	72
#1	M	1/0	0/0	0/0	0/0
#2	F	1/0	0/0	0/0	0/0
#3	M	1/0	0/0	0/0	0/0
Total		3/0	0/0	0/0	0/0
Mean		1.0/0.0	0.0/0.0	0.0/0.0	0.0/0.0

Table 2. Summary of primary skin irritation scores

	Hours
	1	24	48	72
Erythema	1.0	0.0	0.0	0.0
Oedema	0.0	0.0	0.0	0.0
TOTAL (PDI)^2	1.0	0.0	0.0	0.0

Primary Dermal Irritation Index (PDII) : (PDI for 1, 24, 48 and 72 hours) /4=0.3

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the test substance is slightly irritating to the skin, but not sufficient for classification under CLP.

Executive summary:

In a primary skin irritation test that was performed in accordance with OECD TG 404 and GLP principles, 2 males and 1 female New Zealand White rabbit were used to determine the potential for the test substance to produce irritation after a single topical application. Five-tenths of a gram of the test substance was moistened with distilled water and then applied to the skin for 4 hours using a semi-occlusive dressing. Following exposure, dermal irritation was evaluated by the method of Draize et al. Observations were done at 1, 24, 48, and 72 hour after patch removal.

Results showed that one hour after patch removal, very slight erythema was noted for all three treated dose sites. All animals were free from dermal irritation within 24h. The Primary Dermal Irritation Index (PDII) calculated for this substance was 0.3. The mean average scores for oedema and erythema was 0 for all the animals for 24, 48, and 72h.

Under the conditions of this study, the test substance is slightly irritating to the skin, but not sufficient for classification under CLP.