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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 Jul 2005 to 16 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 870.1200 (Acute Dermal Toxicity)

Version / remarks:

1998

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: JMAFF 59 NohSan No. 4200, January 28

Version / remarks:

1985

GLP compliance:

yes

Test type:

standard acute method

Limit test:

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:

rat

Strain:

Sprague-Dawley

Remarks:

Albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: Young adult (9-10 weeks)
- Weight at study initiation: Males 282-330 g and females 194-217 g at experimental start.
- 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: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 26 Jul 2005 to 16 Aug 2005

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: Distilled water

Details on dermal exposure:

TEST SITE
- Area of exposure: 2 inch x 3 inch, 4-ply gauze pad was placed on a dose area of approximately 2 inches x 3 inches
- % coverage: 10% of the body surface
- Type of wrap if used: The gauze pad and entire trunk of each animal were wrapped with 3-inch Durapore tape to avoid dislocation of the pad and to minimize loss of the test substance.

REMOVAL OF TEST SUBSTANCE
- Washing: After 24 hours of exposure to the test substance, the pads were removed and the test sites were gently cleansed of any residual test substance.

TEST MATERIAL
- Constant volume or concentration used: yes
- For solids, paste formed: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: Individual body weights of the animals were recorded prior to test substance application (initial) and again on Days 7 and 14 (termination).
- Frequency of observations: The first several hours after application and at least once daily thereafter for 14 days
- Necropsy of survivors performed: yes, gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.
- Clinical signs: Gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea and coma.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: No signs of gross toxicity, dermal irritation, adverse pharmacologic effects or abnormal behaviour.

Gross pathology:

There were no signs of gross abnormalities.

Any other information on results incl. tables

Table 1. Individual body weights/weight gains and doses

Animal No.	Sex	Body Weight (g)					Dose^1
		Day 0 Weight	Day 7 Weight	Gain*	Day 14 Weight	Gain*	g
4106	M	330	356	26	407	77	0.94
4107	M	282	316	34	390	108	0.81
4108	M	290	329	39	389	99	0.83
4109	M	316	347	31	403	87	0.90
4110	M	307	340	33	388	81	0.88
4111	F	194	212	18	236	42	0.55
4112	F	200	219	19	241	41	0.57
4113	F	212	224	12	241	29	0.61
4114	F	206	221	15	253	47	0.59
4115	F	217	230	13	254	47	0.62

* - Body weight gain from Day 0.

¹ The test substance was applied as a 70% w/w mixture in distilled water.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The single dose acute dermal LD50 of the test substance is greater than 2000 mg/kg of body weight in male and female rats.

Executive summary:

An acute dermal toxicity study was performed in accordance with OECD TG 402 and according to GLP prinicples. The test was conducted with 5 male and 5 female Sprague-Dawley rats to determine the potential for the test substance to produce toxicity from a single topical application. 2000 mg/kg bw of the test substance was applied to the skin for 24 hours by using an occlusive dressing. The animals were observed for mortality, signs of gross toxicity, and behavioural changes at least once daily for 14 days. Body weights were recorded prior to application and again on days 7 and 14 (termination). Necropsies were performed on all animals at terminal sacrifice.

Results showed that all animals survived, gained body weight and appeared active and healthy during the study. There were no signs of gross toxicity, dermal irritation, adverse pharmacologic effects or abnormal behaviour. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Under the conditions of this study, the single dose acute dermal LD50 of the test substance is greater than 2000 mg/kg bw in male and female rats.