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

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 Aug 1985 to 19 Sep 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

1981

GLP compliance:

yes

Test type:

traditional method

Limit test:

no

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:

Wistar

Remarks:

KFM-HAN

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 10 weeks, same age for male and female rats
- Weight at study initiation: Males: 247- 285 g, females: 203- 227 g
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: At least one week under laboratory conditions after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22± 2
- Humidity (%): 55± 10
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 21 Aug 1985 to 19 Sep 1985

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

not specified

Remark on MMAD/GSD:

From the particle size distribution observed it could be stated that a mean particle size of approximately 41% in the low dose and 68% in high dose was within a size range of 1 to 5 microns.

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 100 L
- Method of holding animals in test chamber: During the experiment, rats were placed around the exposure chamber in separate radial polyvinylchloride tubes with their snouts and nostrils exposed to the aerosol only.
- Rate of air (airflow): The air flow was 1000 L per hour and air pressure was 3 atmospheres.
- System of generating particulates/aerosols: The aerosol was generated by a nozzle. The test substance was supplied to the nozzle by a Grafix Exactomat Injector into a high velocity air stream. The nozzle discharged into the air of the chamber.
- Method of particle size determination: Gravimetric determination was performed using an 8-stage Andersen Ambient Particle Sizing Sampler with selectron filters, pore size 0.2 cm (micrometers) and 76 mm in diameter

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gravimetrical determinations on selectron filters, pore size 0,2 cm and 50 mm in diameter

Duration of exposure:

4 h

Concentrations:

2.61 and 5.65 mg/L air

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of weighing: At day 1 (day of exposure), 8 and 15 of the test.
- Frequency of obervations: Four times during the first day and daily thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: At the high dose, histopathological examination was performed on the nasal cavity, lungs with mainstream bronchi, liver, kidneys, adrenal glands and all gross lesions. Only gross lesions were examined at the low dose.

Statistics:

The LC50 was estimated without use of a statistical model.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.65 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality was observed.

Clinical signs:

other:

Remarks:

Slight sedation, dyspnoea and ruffled fur were observed in all animals 4 hours post dosing

Body weight:

Body weight development was not affected in males; however females showed a reduction in body weight gain from day 1 to 8. By study termination females had recovered and showed no treatment related effects on body weight. See table 1 in ''Any other information on results incl. tables''.

Gross pathology:

No treatment-related findings were observed.

Any other information on results incl. tables

Table 1. Body weight gain in male and female rat following inhalation of the test substance

Animal No.	Body weight males
	Conc. Test Substance 2606 mg/m3			Conc. Test Substance 5645 mg/m3
	Day 1	Day 8	Day 15	Day 1	Day 8	Day 15
1/ 11	261	289	309	260	272	300
2/ 12	254	287	310	248	252	283
3/ 13	284	320	340	282	300	328
4/ 14	272	302	319	272	272	310
5/ 15	247	269	285	260	280	330
	Body weight females
	Day 1	Day 8	Day 15	Day 1	Day 8	Day 15
6/ 16	217	217	227	227	233	248
7/ 17	225	222	231	217	220	234
8/ 18	217	220	230	227	223	241
9/ 19	223	220	221	203	207	232
10/ 20	219	224	231	213	216	235

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of this study, the acute inhalation LC50 of the test substance suspended in air for male and female rats was determined to be higher than 5.65mg/ L air. No classification is required.

Executive summary:

In this acute inhalation toxicity study performed in accordance with OECD TG 403 and in accordance with GLP principles, 5 male and 5 female Wistar rats per group were exposed to the test substance to determine the potential to produce toxicity from a single exposure. The rats were exposed to concentrations of 2.61 and 5.65 mg/L air of the test substance via the inhalation (nose-only exposure) route for 4 hours. The airflow was 1000 mL/ hour and air pressure was 3 atmospheres. The nozzle discharged into the air of the exposure chamber. The parameters of inhalation exposure including; oxygen content, relative humidity, temperature, particle size and airflow velocity were all monitored. The actual concentration of the test substance in the chamber was determined gravimetrically. The measurements were conducted at regular intervals throughout the exposure period. The study was terminated 15 days post dosing. The animals were observed for clinical signs of toxicity four times a day during the first day and daily thereafter. Individual bodyweights were recorded at day 1 (pre-test), day 8 and day 15 of the test. Necropsy was performed on all animals. At the high dose, histopathological examination was performed on the nasal cavity, lungs with mainstream bronchi, liver, kidneys, adrenal glands and all gross lesions. Only gross lesions were examined at the low dose.

Results showed that no animals died during the study. Slight sedation, dyspnoea and ruffled fur were observed in all animals 4 hours post dosing. All rats had recovered completely by 24 hours after initiation of exposure. Body weight development was not affected in males; however females showed a reduction in body weight gain from day 1 to 8. By study termination females had recovered and showed no treatment related effects on body weight.

Based on the results of this study, the acute inhalation LC50 of the test substance suspended in air for male and female rats was determined to be higher than 5.65 mg/ L air.