sodium 2-{N-[(3,5-difluorophenyl)carbamoyl]ethanehydrazonoyl}nicotinate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995-05-10 until 1995-06-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Scientifically valid study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Version / remarks:

November 1984

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

sodium 2-{N-[(3,5-difluorophenyl)carbamoyl]ethanehydrazonoyl}nicotinate

EC Number:

635-156-4

Cas Number:

109293-98-3

Molecular formula:

C15 H12 F2 N4 O3 .Na

IUPAC Name:

sodium 2-{N-[(3,5-difluorophenyl)carbamoyl]ethanehydrazonoyl}nicotinate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Olac Ltd, Bicester, Oxon, England
- Age at study initiation: 7 - 10 weeks
- Weight at study initiation: 192 - 260 g
- Housing: metal cages with wire mesh floors
- Diet: a standard laboratory rodent diet (SDS LAD 1), ad libitum
- Water: ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3°C
- Humidity: 30 - 70 %
- Air changes: 10 - 15 air changes per hour
- Photoperiod: 12 hours of artificial light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 1 % w/v aqueous methylcellulose

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/ kg

Doses:

5000, 3200, 1600 mg/kg bw

No. of animals per sex per dose:

10 rats per dose: 5 males, 5 females

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily - clinical signs - daily and weighing 3 times during the observation period (once a week)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights

Statistics:

The acute median lethal oral dose (LD50) to male and female rats was calculated using the method of Finney [FINNEY, D.J. (1971) Probit Analysis, 3rd Cambridge University Press, Cambridge].

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

4 800 mg/kg bw

Based on:

test mat.

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

3 300 mg/kg bw

Based on:

test mat.

Mortality:

Two females at 3200 mg/kg bw and 3 males and all females at 5000 mg/kg died during the study. Deaths occurred between 24 to 48 hours of dosing.

Clinical signs:

Clinical signs of reaction to treatment included piloerection and soft to liquid faeces, seen among rats at all three dosages. In addition, abnormal body carriage, abnormal gait, lethargy, decreased respiratory rate, partially closed eyelids, pallor of the extremities, increased urine production, increased salivation, gasping, walking on toes, unsteadiness, increased lacrimation, bluish colour to skin/extremities, cold body surfaces, prostration, brown staining around nose and mouth and red stained urine were seen among rats at one or more dose levels. Recovery of surviving rats was complete in all instances by day 7.

Body weight:

Slight bodyweight losses were recorded for all decedents. A slightly low bodyweight gain was recorded on day 8 for one male at 5000 mg/kg and two females at both 1600 and 3200 mg/kg. A similar trend was noted on day 15 for two males and one female at 1600 m g/kg, with one further female at 1600 mg/kg showing a slight bodyweight loss at this time. All other surviving animals achieved satisfactory bodyweight gains throughout the study.

Gross pathology:

Macroscopic examination revealed changes to all major organs and tissues of animals who died during the observation period. No abnormalities were recorded at the macroscopic examination on day 15.