α-n-butyl-α-(4-chlorophenyl)-1H-1,2,4-triazole-1-propanenitrile

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24-June-2005 to 29-September-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 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

α-n-butyl-α-(4-chlorophenyl)-1H-1,2,4-triazole-1-propanenitrile

EC Number:

410-400-0

EC Name:

α-n-butyl-α-(4-chlorophenyl)-1H-1,2,4-triazole-1-propanenitrile

Cas Number:

88671-89-0

Molecular formula:

C15H17ClN4

IUPAC Name:

2-(4-chlorophenyl)-2-[(1H-1,2,4-triazol-1-yl)methyl]hexanenitrile

Test material form:

solid: crystalline

Remarks:

Light orange

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Raleigh, NC
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Young adult (9-10 weeks)
- Weight at study initiation: 112-127 grams
- Fasting period before study: yes, Overnight
- 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.
- Diet: Purina Certified Rodent Diet, ad libitum (except o/n before dosing)
- Water: Filtered tap water was supplied ad libitum by an automatic water dispensing system
- Acclimation period: 6-16 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22ºC
- Humidity (%): 66-70%
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

1.5% w/w solution in distilled water

Details on oral exposure:

An initial limit dose of 5,000 mg/kg was administered to one healthy female rat by oral gavage. Due to mortality in this animal, the study proceeded to the Main Test. Using the default starting level of 175 mg/kg bw and following the Up and Down procedure, eight additional females were dosed at levels of 550, 1,750, or 5,000 mg/kg bw.

Doses:

175 mg/kg bw, 550 mg/kg bw, 1,750 mg/kg bw and 5,000 mg/kg bw.

No. of animals per sex per dose:

175 mg/kg bw (1 animal), 550 mg/kg bw (1 animal), 1,750 mg/kg bw (3 animals) and 5,000 mg/kg bw (4 animals)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for mortality, signs of gross toxicity, and behavioral changes for the first several hours post-dosing and at least once daily thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: The external surface of the body and all orifices, tissues, and organs of the thoracic and abdominal cavities were examined.

Statistics:

The Acute Oral Toxicity (Guideline 425) Statistical Program (Weststat, version 1.0, May 2001) was
used for all data analyses including: dose progression selections, stopping criteria determinations
and/or LD50 and confidence limit calculations.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 1 750 - < 5 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals that were administered 5,000 mg/kg bw dose level of the test substance died within one day. No mortality occurred in the other dose groups.

Clinical signs:

other: 175 mg/kg (1 animal) and 550 mg/kg (1 animal) Dose Levels: There were no signs of adverse clinical signs. 1,750 mg/kg Dose Level (3 animals): Clinical signs observed for two animals included ano-genital staining and/or hypoactivity. However, the animals r

Gross pathology:

No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period, except the four rats that were administered the highest dose level (5,000 mg/kg). Gross necropsy of these four rats revealed discoloration of the intestines.

Any other information on results incl. tables

Results are provided in Table 1 below.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the conditions of this study, the acute oral LD50 of Myclobutanil was found to exceed 1750
mg/kg of body weight in female rats, and was lower than 5000 mg/kg bw/day.

Executive summary:

An acute oral toxicity test (Up and Down Procedure) was conducted with female Fischer 344 rats. Prior to use, the test substance was ground to a powder then mixed with a 1.5% w/w solution of carboxymethylcellulose (CMC) in distilled water to form a 25% w/w suspension. An initial limit dose of 5,000 mg/kg was administered to one healthy female rat by oral gavage. Due to mortality in this animal, the study proceeded to the Main Test. Using the default starting level of 175 mg/kg and following the Up and Down procedure, eight additional females were dosed at levels of 550, 1,750, or 5,000 mg/kg bw. All animals dosed at 5,000 mg/kg bw/day died within one day, no further mortality occurred. No effects on body weight gain were observed in the surviving rats. No clinical signs, abnormal behaviour and gross necropsy findings were noted for rats dosed at 175 and 550 mg/kg bw/day. At 1,750 mg/kg bw clinical signs were observed for two animals including ano-genital staining and/or hypoactivity. The animals recovered by Day 3. No necropsy findings were noted. 

Under the conditions of this study, the acute oral LD50 of the test substance was found to exceed 1750 mg/kg of body weight in female rats, and was lower than 5000 mg/kg bw/day.