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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26-April-1994 to 10-May-1994.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Japan 59 NohSan Notification No. 4200

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

406-140-2

EC Name:

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

Cas Number:

114369-43-6

Molecular formula:

C19H17ClN4

IUPAC Name:

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

Test material form:

solid

Remarks:

White solid.

Test animals

Species:

rat

Strain:

other: Crl:CD.BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

Adult male and female Crl:CD rats were examined for physical abnormalities, identified by uniquely numbered ear tags, and quarantined for approximately one week. The animals were individually housed in suspended stainless steel cages (18x34x20 cm) with wire mesh fronts and bottoms. Cages were suspended above absorbent-paper pan liners which were changed 3 times a week. All animal rooms were environmentally controlled. The temperature and relative humidity were monitored 24 hr a day. During the study, the temperature ranged from 71°F to 73°F (22 to 23°C), and the relative humidity ranged from 39% to 49%. Although minor variations from these ranges occurred, they were of short duration and had no effect on the outcome of the study. The light cycle was automatically controlled, 12 hr on and 12 hr off. Throughout the test period, all rats had free access to filtered tap water (via automatic watering) and were fed PMI Purina Certified Rodent Diet.

On the day prior to treatment, male and female rats were selected from a healthy stock population, assigned to the study groups using a computer-generated sequence of random numbers, and fasted overnight. At the time they were dosed, the males were approximately 50 days old and the females were approximately 60 days old. The fasted body weights ranged from 187 to 237 g for males and from 185 to 210 g for females.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Details on oral exposure:

The solid test substance was ground in a mortar with a pestle and mixed with 0.5% methylcellulose. The suspensions were created by weighing Fenbuconazole into a graduated tri-pour beaker and adding the appropriate amount of 0.5% methylcellulose. All dosing suspensions were mixed with a glass stir rod and kept stirring using a magnetic stir plate. It was necessary to use a Brinkman homogenizer for the 5000 mg/kg group, since at this concentration the suspensions would not pass through the gavage needle.

Doses:

1000, 2000, 3000, 4000, and 5000 mg/kg bodyweight.

No. of animals per sex per dose:

6 rats in each dose group.

Details on study design:

Observations and Determinations:
All animals were observed for signs of ill health, or reaction to treatment at 1, 2 and 4 hr after dosing and once daily thereafter for 14 days. Body weights were recorded on day 0 (prior to dosing) and on days 7 and 14. Body weights were determined for found-dead animals when they survived beyond the day of treatment.

Decedents were necropsied as death occurred. Surviving rats were killed on day 14 and necropsied. Necropsy consisted of a gross examination of organs in situ.

Dose was calculated on an "as is" basis; no adjustment was made for percent active ingredient. All animals were dosed at a constant volume of 10 ml/kg body weight, and were dosed within 1 hr of preparation of the suspensions. After dose administration, samples were collected and submitted for subsequent analytical verification of the target concentration. The results of analysis of the dosing suspensions showed a proximity to target concentration range of 90 to 125%.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

Dose-related mortality was observed. Mortality in the 5000 mg/kg bw dose group was 1 male rat, and 1 female each in the 4000 mg/kg and 5000 mg/kg dose groups.

Clinical signs:

other: Clinical signs were observed in all dose groups among females and in all but the 1000 mg/kg dose group among males. Clinical signs related to the test substance included (but were not limited to): white material in feces, scant, soft or no feces, ataxia,

Gross pathology:

Necropsy of the survivors revealed no gross changes. Necropsy of the
decedents revealed the following gross changes: yellow material/fluid In the stomach, reddening of the stomach mucosa, reddening and/or enlargement of the adrenals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

According to an acute oral toxicity study performed according to EPA guideline 870.110, Fenbuconazole was found to be of limited toxicity by a single oral administration (i.e., the acute oral LD50 exceeds 5000 mg/kg in male and female rats).