5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1996-02-23 to 1996-04-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

421-300-1

EC Name:

-

Cas Number:

138564-59-7

Molecular formula:

C12H9N3O2S

IUPAC Name:

5-methyl-2-[(2-nitrophenyl)amino]thiophene-3-carbonitrile

Test material form:

solid: particulate/powder

Details on test material:

97.7%
Item code QA405K
Lilly lot no: 356MO1

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Sponsor and 356M01
- Purity test date: 1995-11-10

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: In the dark under ambient conditions

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Formulated as a suspension in CMC

FORM AS APPLIED IN THE TEST (if different from that of starting material)
Suspension in 0.5% conc. CMC.

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 Limited, Shaw's Farm, Blackthorn, Bicester, OX6 OTP
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 120-150 g
- Fasting period before study: Overnight
- Housing: The dose ranging animals were singly housed and the main study animals housed multiply by sex in polypropylene cages (dimensions 42 x 27 x 20 cm and 59 x 38.5 x 20 cm respectively), with stainless steel tops. A paper lined tray was suspended beneath each cage.
- Diet (e.g. ad libitum): Rat and Mouse No. I Maintenance Diet, supplied by Special Diets Services, I Stepfield, Witham, Essex, CMS 3AD was available ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: >5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 and 21 mean
- Humidity (%): 50 mean
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 99.5%
- Amount of vehicle (if gavage): 10 ml/kg bodyweight

MAXIMUM DOSE VOLUME APPLIED:
2.21 ml

Doses:

1

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Observation/weighing on Day 1, 2, 3, 4, 8, and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Statistics:

No statistical analysis were conducted

Results and discussion

Preliminary study:

No mortality or clinical signs were observed during the range-finding study.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

There were no premature decedents during the study.

Clinical signs:

other: Clinical signs in males and females on Days 2 and 3 of the study were limited to orange staining of the urine and the cage tray paper.

Gross pathology:

No abnormalities were detected at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

This study found that the test substance did not meet GHS criteria for an acute oral toxin. Under the conditions of the study, no mortality and no evidence of toxicity were noted following a single oral administration of 2000 mg/kg bodyweight of the test substance.

Executive summary:

This study was carried out in accordance with EU Method B1 and OECD guideline 420. The study investigate the acute oral toxicity of the test material after a single oral gavage administration to rats. Under the conditions of the study, no mortality and no evidence of toxicity were noted following a single oral administration of 2000mg/kg of the test substance.