4-(trifluoromethoxy)aniline

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June to October 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

first version adopted 1981

Deviations:

yes

Remarks:

No information on whether drinking water provided ad libitum or the number of animals/cage; for males, there were two trials at 75 mg/kg bw; for females, there weree two trials at 100 mg/kg bw. No explanation was provided.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-(trifluoromethoxy)aniline

EC Number:

207-317-5

EC Name:

4-(trifluoromethoxy)aniline

Cas Number:

461-82-5

Molecular formula:

C7H6F3NO

IUPAC Name:

4-(trifluoromethoxy)aniline

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann (Borchen), Germany
- Weight at study initiation: 160-220 g
- Fasting period before study: 16 hours
- Housing: Makrolon cages, type III
- Diet: Altromin-R-haltungsdiät

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 0.5 mL/100 g body weight

Doses:

1, 10, 75, 100, 150, or 250 mg/kg bw for males, 1, 10, 25, 50, 75, or 100 mg/kg bw for females

No. of animals per sex per dose:

15 animals/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: not specified
- Necropsy of survivors performed: yes
- Clinical signs of toxicity were observed and reported.

Statistics:

Calculation of the median lethal dose (LD50) was calculated according to Litchfield and Wilcoxon (J. Pharmac. Exper. Therap. 96, 99, 1949).

Results and discussion

Preliminary study:

Preliminary study not conducted

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

63 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

102 mg/kg bw

Based on:

test mat.

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

82.5 mg/kg bw

Based on:

test mat.

Mortality:

For males, mortality occurred at doses of greater than or equal to 75 mg/kg bw. At these dose levels, 5, 8, 13, and 15 animals died at 75, 100, 150, and 250 mg/kg bw, respectively. For males, the 75 mg/kg bw dose level was tested 2 times, with no mortality seen in the first, and 5/15 animals found dead in the second trial.

For females, mortality occurred at doses of greater than or equal to 50 mg/kg bw. Four and 9 females died at 50 and 75 mg/kg bw, respectively. For females, the 100 mg/kg bw dose level was tested 2 times, with 14/15 cases of mortality reported for the first, and 15/15 cases of mortality reported for the second trial.

Clinical signs:

other: The clinical signs of toxicity included apathy, labored breathing, cyanosis, and spastic gait. These signs of clinical toxicity were seen in all groups except for the lowest dose of 1 mg/kg bw and lasted for up to 7 days.

Gross pathology:

Necropsy of the animals that died prior to sacrifice revealed a clay to rusty-brown coloring of the internal organs, most strongly defined in the lung. There were isolated cases of emphysema of the lung or confluent ulceration of the mucous membrane of the glandular stomach. For those animals that survived until scheduled necropsy, dark swollen spleens with a clear follicle structure were observed.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

In a study conducted in a similar method to OECD 401, the mean LD50 for male and female rats was 82.5 mg/kg bw.