1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 Nov 1987 to 9 Dec 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)

Version / remarks:

1981

GLP compliance:

yes

Test type:

traditional method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole

EC Number:

262-104-4

EC Name:

1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole

Cas Number:

60207-90-1

Molecular formula:

C15H17Cl2N3O2

IUPAC Name:

1-{[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl}-1H-1,2,4-triazole

Test animals

Species:

rat

Strain:

other: Tif:RAI f (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Sex: male and female
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 194-232 g
- Housing: 5/sex in Macrolon type 4 cages
- Diet: Rat food ad libitum (except during exposure)
- Water: Water ad libitum (except during exposure)
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22±2 °C
- Humidity: 55 ± 10 %
- Air changes (per hr): Not reported
- Photoperiod: 12 hours light/12 hours dark

IN-LIFE DATES: 10 Nov 1987 to 9 Dec 1987

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: ethanol

Mass median aerodynamic diameter (MMAD):

> 2.3 - < 2.6 µm

Geometric standard deviation (GSD):

> 2 - < 2.2

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
All exposures were conducted in a stainless steel, nose-only exposure system. The chamber was designed to ensure a rapid equilibration and a uniform exposure of all animals in the system. The flow in any individual aerosol delivery tube was standardized to 2 L/min (velocity 1.25 m/s).
For the inhalation period, the rats were placed in Macrolon animal holders positioned radially around the exposure chamber, so that only the snouts and nostrils of the animals were exposed to the aerosol. The chamber was maintained at an exactly balanced pressure to prevent leakage of the test atmosphere from the system, as well as dilution with outside air. The exhaust air was decontaminated by subsequent passage through a Pall HDC absolute filter.
The aerosol was generated in two pneumatic nebulizers arranged in parallel. Both units had a small aspirating reservoir (1-2 mL) and an attached bulk fluid container (to keep solvent evaporation to a minimum). The nebulizers were operated at 6 and 6 L/min (input pressure 76 and 58 kPa), and the aerosol was diluted with filtered humidified air to yield a total flow of 32 L/min. Coarse particles were removed from the aerosol by means of a glass cyclone. The throughput of the test material/vehicle mixture was determined by weighing the nebulizer, reservoir, and cyclone, before and after aerosol generation.

TEST ATMOSPHERE
Brief description of analytical method and equipment used: The aerosol concentration in the chamber (in the breathing zone of the animals), was determined gravimetrically 5 times during the exposure period. Particle size analysis was conducted with an APS-33 Aerodynamic Particle sizer, equipped with appropriate dilution systems to avoid coincidence counts. The number distribution in the 48 size classes was converted to a mass distribution, based on the bulk density of the test substance, which was determined separately.
Samples taken from breathing zone: yes

VEHICLE
Composition of vehicle: absolute ethanol
Concentration of test material in vehicle: 30% w/w solution

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5836 ± 186 mg/m3

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: During exposure they were observed at 1, 2 and 4 hours, as well as 2 hours after exposure and then daily throughout the study. Body weights were measured on Day 1 (prior to exposure), 7 and 14.
- Necropsy of survivors performed: yes, particular attention was given to the respiratory tract.
- Clinical signs: yes

Statistics:

Inhalation LC50 values (including their 95 % confidence limits) for a 4-hour treatment and a subsequent 14-day observation period could not be calculated, because no mortalities were elicited by the test substance at concentrations up to 5836 +/- 186 mg/m3, and thus only a limit test and not a full study was considered necessary.
The body weights of the treated animals and the controls were compared by analysis of variance.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 836 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

There were no deaths during the exposure or observation periods.

Clinical signs:

other: Signs of systemic toxicity (ruffled fur, dyspnea, abnormal body positions and reduced activity) were seen in control and, to a greater severity, in test animals. All animals had fully recovered by day 9 of the study.

Body weight:

All animals gained body weight during the study. The males exposed to the test article experienced a significantly lower body weight gain compared to controls.

Gross pathology:

There were no macroscopic abnormalities at the examination post mortem.

Any other information on results incl. tables

Table 1. Mortality / animals treated

Exposure concentration mg/m^3.	Mortality (Number dead / total)
	Males	Females	Combined
5836±186	0/5	0/5	0/10

Table 2. Intergroup comparison of mean body weight (g)

Exposure group	Males			Females
	Day 0 #	Day 7	Day 14	Day 0 #	Day 7	Day 14
Control	223	258	301	206	218	236
Test substance	219	242*	284	206	212	233

# Pre-exposure

*statistically significant difference from control

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute inhalation toxicity study performed in compliance with GLP and following a OECD 403 guideline the LC50 of the test substance after a 4 hour nose-only exposure was greater than 5836 mg/m3 in male and female rats.

Executive summary:

In an acute inhalation toxicity study performed in compliance with GLP and following a OECD 403 guideline, a group of five male and five female young adult Tif:RAI f (SPF) rats were exposed by nose-only inhalation route to an aerosol of test substance in absolute ethanol (as a 30% w/w solution) for 4 hours to a concentration of 5836 ± 186 mg/m³. Animals were observed for 14 days. Body weights were measured on days 1 (prior to exposure), 7 and 14. Clinical signs were recorded during the exposure at 1, 2 and 4 hours, 2 hours after exposure and then daily throughout the study. All animals were examined macroscopically at the end of the study. A control group of equal size was exposed to an inhalation of absolute ethanol GR (as a 30% w/w solution) under the same conditions as the test substance animals, within one week of the test substance study exposure. Test atmospheres were analyzed for aerosol concentration and particle size distribution.

There were no deaths. Signs of systemic toxicity (ruffled fur, dyspnea, abnormal body positions and reduced activity) were seen in control and, to a greater severity, in test animals. All animals had fully recovered by day 9 of the study. All animals gained body weight during the study. The males exposed to the test article experienced a significantly lower body weight gain compared to controls. There were no macroscopic abnormalities at the examination post-mortem.

The acute inhalation LC₅₀ of test substance after a 4-hour nose-only exposure was greater than 5836 mg/m³ in male and female rats.