(2RS,3RS)-3-(2-chlorophenyl)-2-(4-fluorophenyl)-[(1H-1,2,4-triazol-1-yl)methyl]oxirane

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(2RS,3RS)-3-(2-chlorophenyl)-2-(4-fluorophenyl)-[(1H-1,2,4-triazol-1-yl)methyl]oxirane

EC Number:

406-850-2

EC Name:

(2RS,3RS)-3-(2-chlorophenyl)-2-(4-fluorophenyl)-[(1H-1,2,4-triazol-1-yl)methyl]oxirane

Cas Number:

133855-98-8

Molecular formula:

C17 H13 Cl F N3 O

IUPAC Name:

1-{[(2R,3R)-3-(2-chlorophenyl)-2-(4-fluorophenyl)oxiran-2-yl]methyl}-1H-1,2,4-triazole

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, Germany
- Weight at study initiation: males 273 +/- 8.6 g, females 193 +/- 6.2 g
- Age at study initiation: 8-9 weeks
- Housing: In groups of 5 in Type -D-III cages
- Diet ad libitum: Pelleted Kliba rat diet 343,
- Water ad libitum: Tap water
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20- 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose/head only

Vehicle:

air

Remarks:

supplied via a central air-conditioning system

Mass median aerodynamic diameter (MMAD):

3.9 µm

Geometric standard deviation (GSD):

2.3

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
The animals were placed in tubes of the head-nose inhalation system INA 20 (BASF AG, chamber volume: 55l) with their snouts in an inhalation chamber with excess pressure. The test substance was dosed unchanged.
The dust/air mixture was generated by means of a microgenerator and the concentration was adjusted by varying the rotation of the metering disc. The supply air was conditioned via a central air-conditioning system and the air flow was set at 1500 l/h. Temperatures in the exposure system were 19 - 25°C.
By means of an exhaust air system the pressure ratios in the inhalation system were adjusted in such a way that the amount of exhaust air was about 10% lower (excess pressure). This ensured that the mixture of the test substance and air was not diluted with laboraoty air in the breathing zones of the animals.
AIR SAMPLING FOR ANALYSIS OF TEST MATERIAL CONCENTRATIONS, METHOD FOR PARTICEL SIZE ANALYSIS
Samples of the test atmosphere (1l) were taken adjacent to the animals’ nose once an hour with an air flow of 1.25 m/s. The concentration was determined gravimetrically.
Particle size analysis was done 30 minutes after the beginning of the test. A sample of 9 l was analyzed using an impactor. The MMAD was 3.9 µM and the GSD was 2.3. The respirable dust fraction was determined as 77%.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gravimetric determination of the inhalation atmosphere concentration

Duration of exposure:

4 h

Concentrations:

The mean analytical concentration of 4 samples was 5.26 +/-0.07 mg/l. The nominal concentration was 63 mg/l.

No. of animals per sex per dose:

5 males per dose, 5 females per dose

Control animals:

no

Details on study design:

Duration of observation period following administration: 14 days
- Frequency of observations for clinical symptoms: Several times during exposure, afterwards at least once daily at workday.
- Frequency of observations for mortality: Daily
- Frequency of weighing: On first day (before exposure), day 7 and day 14.
- Necropsy of survivors performed: yes, all animals were sacrificed and subjected to gross pathology at study termination.

Statistics:

The statistical evaluation of the concentration/effect relationship was carried out on the basis of the binomial test (Wittig, H.: Mathematische Statistik 1974, pp. 32 35) in accordance with tables of the BASF Computer Center.
The calculation of the particle size distribution was carried out in the Department of Toxicology of BASF Aktiengesellschaft on the basis of mathematical methods for evaluating particle measurements (Silverman, L.: Particle Size Analysis in Industrial Hygiene, 1971, pp. 235 -259).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.3 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: No mortality occured.

Mortality:

No mortality occured.

Clinical signs:

other: During exposure accelerated breathing and a slight reddish discharge from noses were seen. The slight reddish discharge persisted after exposure but no abnormalities were detected from day one onward.

Body weight:

The body weight gain of male and female rats in the test group was comparable to the historical control (for details see Table 1).

Gross pathology:

Upon necropsy no pathological findings were observed.

Other findings:

Signs of airway irritation during and shortly after exposure; no symptoms thereafter.
MMAD = 3.9µm

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose via inhalation of the test item in rats is higher than 5.3 mg/L.

Executive summary:

The substance was tested for its acute inhalation toxicity. The test method was based on EPA (FIFRA) and OECD 403 guidelines. GLP requirements were fulfilled. 5 mal and 5 female Wistar rats were exposed to a concentration of 5.3 mg/L of the test substance for a period of 4 hours. During and up to one day after the exposure inhalation specific clinical symptoms were observed. No mortality occurred. Thus, the inhalation LC50 (4h) in rats is higher than 5.3 mg/L.