4-nitro-3-(trifluoromethyl)aniline

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experimental phase: 1.3.2012 - 13.4.2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

One protocol deviation which does't have impact on the study. Cage materials were different.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-nitro-3-(trifluoromethyl)aniline

EC Number:

206-884-6

EC Name:

4-nitro-3-(trifluoromethyl)aniline

Cas Number:

393-11-3

Molecular formula:

C7H5F3N2O2

IUPAC Name:

4-nitro-3-(trifluoromethyl)aniline

Specific details on test material used for the study:

Name: FAMI-III, 2-Nitro-5-amino bentsotrifluoride
Alternative name: 4-Nitro-3-(trifluoromethyl)aniline
Batch number: 1332571
Expiry date: 31.12.2012
Description: tan-brownish yellow powder
Storage conditions: room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Italy S.r.l., San Pietro al Natisone (UD), Italy
- Age range: 6-7 weeks
- Weight range: 159-175 g
- Housing: group, 3/cage
- Water: Ad libitum
- Diet: Ad libitum exept fasting procedure
- Acclimation period: at least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 55 ± 15
- Air changes (per hr): 15-20
- Room lighting: Artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5 % aqueous solution

Details on oral exposure:

By gavage, using a plastic feeding tube attached to a graded syringe.

Doses:

2000 mg/kg, 200 mg/mL
300 mg/kg, 30 mg/mL
50 mg/kg, 5 mg/mL

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

The animals were fasted overnight before dosing up to 4 hours after dosing but had free access to water. The animals were observed on dosing and approximately 0,5; 2 and 4 hours after administration of the test item and daily thereafter. The observation period was 14 days. The animals were weighed individually on day before administration of the test item, on day 1 and thereafter on days 2, 8 and 15. Mortality and morbidity obsevations twice daily. Termination on day 15. Euthanasian method: Carbon dioxide narcosis.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 50 - < 300 mg/kg bw

Mortality:

All animals dosed at 2000 mg/kg died on Day 1-2. Mortality also occurred 3/6 animals dosed at 300 mg/kg on Day 2 to 4. No mortality occurred dosing at 50 mg/kg.

Clinical signs:

Dose 2000 mg/kg: reduced activity, ataxia, moribund status and yellow staining in the cage tray were observed.
Dose 300 mg/kg: Clinical signs were piloerection, reduced activity, lethargy, prone posture, yellow staining of the cage tray and moribund status.
Dose 50 mg/kg: Clinical signs were piloerection and yellow stainig in the cage tray.

Body weight:

Dose 300 mg/kg: Body weight losses or no body weight growth were recorded.
Dose 50 mg/kg: very slight body weight losses (few grams) were recorded.

Gross pathology:

2000 mg/kg
Gastrointestinal track: abnormal colous and/or contents in the stomach, jejunum and ileum. Peyer's patches resulted prominent in two animals.
Abdominal cavity: Abnormal red areas in the stomach. Abnormal colour of liver and mesenteric lymph nodes. Abnormal colour of ovaries associated with enlarged size. Abnormal colour of the adrenals.
Cranial cavity: abnormal colour of brain and pituitary.
Thoracic cavity: abnormal colour of thymus associated with abnormal areas and dark red colour of the lungs.
300 mg/kg
Decedent animals: yellow staining of the urogenital region.
50 mg/kg
Abnormal size (enlarged) of ovaries and abnormal areas of thymus.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Oral LD50 > 50 - < 300 mg/kg bw

Executive summary:

The acute oral toxicity of the test item 2-Nitro-5-amino bentsotrifluoride ( 4-Nitro-3-(trifluoromethyl)aniline) was evaluated in female Sprague Dawley rats according to OECD 423, EC 2008/440/EC B.1 tris, US EPA OPPTS 870.1100 guidelines and in compliance with GLP. The test substance induced mortality in the rat following oral administration of a single dose at levels of 2000 and 300 mg/kg. Main clinical sings after 2000 mg/kg were reduced activity, ataxia and moribund status and after 300 mg/kg reduced activity, lethargy, prone posture and moribund status. Gross pathology examination showed abnormal colour and/or abnormal contents in the parts of Gastrointestinal track, Abdominal cavity, Cranial cavity and Thoracic cavity at dose 2000 mg/kg. At 300 mg/kg dose decedent animals showed yellow stainign of the urogenital region. No mortality or other relevant signs of toxicity were observed following dosing at 50 mg/kg. The results suggest the LD50 to be greater than 50 mg/kg but lower than 300 mg/kg bw and indicate the classification of Acute Oral Toxicity Category 3.