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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 Aug 2010 to 23 Sep 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Version / remarks:

2008

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

no

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: RjHan:WI

Sex:

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 rats, 8-11 weeks old
- Weight at study initiation: 189 - 230 g
- Housing: Individual caging in type II polypropylene/polycarbonate cage; lignocel bedding for laboratory animals was available to animals during the study to allow digging and other normal rodent activities
- Diet: Autoclavable complete feed for rats and mice – breeding and maintenance; ad libitum
- Water: tap water, ad libitum
- Acclimation period: At least 5 days under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study
- Method of randomisation in assigning animals to test and control groups: Selected by hand at time of delivery

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30 - 70 %
- Air changes: 15-20 air exchanges/hour
- Photoperiod: 12 hours daily, from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES: 24 Aug 2010 to 23 Sep 2010

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

2%

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2 %
- Batch no.: 1414646
- Amount of vehicle: 10 mL/kg bw

DOSAGE PREPARATION: test substance was formulated for treatment doses at 175, 550 and 2000 mg/kg (dose volume of 10 mL/kg). The test substance was formulated in 2% CMC.

Doses:

175, 550 and 2000 mg/kg

No. of animals per sex per dose:

175 mg/kg: 1 animal;
550 mg/kg: 3 animals;
2000 mg/kg: 2 animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: surviving animals were observed individually after dosing at 30 minutes, 1, 2, 3, 4, and 6
hours after dosing and once each day for 14 days thereafter; body weights were recorded on Day -1 and Days 0 (beginning of the experiment) 7 and 14 (surviving animals)
- Necropsy of survivors performed: yes
- Clinical signs including body weight : individual observations were performed on the skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern; particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Other examinations performed: All animals were subjected to macroscopic examination. Surviving animals were exsanguinated under pentobarbital anaesthesia. After examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs were observed. All gross pathological changes were recorded for each animal on the post mortem record sheets.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

550 mg/kg bw

Based on:

test mat.

Mortality:

The test substance caused mortalities at 2000 mg/kg bw (2/2) and at 550 mg/kg bw (1/3). No deaths occurred in any animals treated at 175 mg/kg bw.

Clinical signs:

other: Clinical signs including decreased activity, prone position, incoordination, lateral position and hunched back were observed in both animals treated at 2000 mg/kg bw. Additionally one animal dosed at 2000 mg/kg showed decreased body temperature and noisy

Other findings:

No treatment related macroscopic findings were observed. Macroscopic findings were seen in animals dosed at 2000 mg/kg and 550 mg/kg. These findings included dark/red discoloration and/or non-collapsing of the lungs. Additionally, dark grey foci in the lungs was observed in one animal dosed at 550 mg/kg. No findings were observed either the other animal dosed at 550 mg/kg bw or in the animal dosed at 175 mg/kg bw.

Any other information on results incl. tables

Table 2. Acute oral toxicity of the test substance in the rat, application scheme and mortality data

Dose (mg/kg body weight)	Volume given (mL/kg body weight)	Survival
2000	10	Killed on day 1
550	10	Survived
2000	10	Found dead (day 2)
550	10	Found dead (day 2)
175	10	Survived
550	10	Survived

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the conditions of this study performed in compliance with GLP and following the OECD 425 guideline, the acute oral median lethal dose (LD50) of the test subtance was calculated to be 550 mg/kg bw in female RjHan:WI rats.

Executive summary:

In the study performed in compliance with GLP and following the OECD 425 guideline a single oral (gavage) dose was administered followed by a 14 day observation period. The animals were fasted overnight prior to treatment. Animals were weighed before dosing and food was returned 3 hours after dosing. Single animals were dosed sequentially at no less than 24 hour intervals. The time intervals between dosing were determined by the onset, duration and severity of toxic signs. Limit test was not performed. The starting dose of the main test was 2000 mg/kg. Surviving animals were observed individually after dosing at 30 minutes, 1, 2, 3, 4 and 6 hours post treatment and once each day for 14 days thereafter. Body weight was measured on Day -1 and just before treatment and weekly after. All surviving animals were examined macroscopically at the end of the study.

Test substance caused mortalities at 2000 mg/kg bw (2/2) and at 550 mg/kg bw (1/3). No deaths occurred in any animals treated at 175 mg/kg bw. Clinical signs including decreased activity, prone position, incoordination, lateral position and hunched back were observed in both animals treated at 2000 mg/kg bw. Additionally, one animal dosed at 2000 mg/kg showed decreased body temperature and noisy respiration. Clinical signs were also observed in animals treated at 550 mg/kg bw. These included decreased activity (3/3), incoordination (3/3), hunched back (2/3), piloerection (2/3), lateral position (2/3) and decreased body temperature (2/3). No clinical signs were observed in the animal dosed at 175 mg/kg. Body weight and body weight changes of the surviving animals during the study showed no indication of a treatment-related effect. No treatment related macroscopic findings were observed in this study.

Under the conditions of this study, the acute oral median lethal dose (LD50) of the test substance was calculated to be 550 mg/kg bw in female RjHan:WI rats.