4-(trifluoromethoxy)aniline

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Experimental procedures are only briefly described

GLP compliance:

no

Test type:

standard acute method

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

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 6 x 8 cm, based on the method of Noakes and Sanderson (Brit. J. Ind. Med. 26, 59, 1969)
- % coverage: not reported
- Type of wrap if used: occlusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Treated skin was cleaned with soap and water
- Time after start of exposure: Skin was cleaned 24 hours after exposure

TEST MATERIAL
- Amount(s) applied: not specified

Duration of exposure:

24 hours

Doses:

Males:
- 33 mg/kg bw
- 66 mg/kg bw
- 99 mg/kg bw
- 132 mg/kg bw
- 330 mg/kg bw

Females
- 3 mg/kg bw
- 66 mg/kg bw
- 99 mg/kg bw
- 132 mg/kg bw

No. of animals per sex per dose:

10 animals/sex/dose except for females in the 132 mg/kg bw dose group, which had 5 animals

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 done 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:

>= 33 - <= 66 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

84.5 mg/kg bw

Based on:

test mat.

Mortality:

For males, mortality occurred at doses of greater than or equal to 66 mg/kg bw. At these dose levels, 2, 7, 9, and 10 animals died at 66, 99, 132, and 330 mg/kg bw, respectively. For females, mortality occurred at doses of greater than or equal to 66 mg/kg bw. At these dose levels, 8, 10, 5 females died at 66, 99, and 132 mg/kg bw, respectively.

Clinical signs:

other: The clinical signs of toxicity included apathy, shallow and faster breathing, cyanosis, lying on side/prostration.

Gross pathology:

Necropsy of the animals that died prior to sacrifice revealed a clay to rusty-brown coloring of the lungs. There were isolated cases of emphysema of the lung and slightly enlarged thymus glands. For those animals that survived until scheduled necropsy, there were no gross findings.

Applicant's summary and conclusion

Interpretation of results:

Category 1 based on GHS criteria

Conclusions:

In a study conducted in a similar method to OECD 402, the LD50 for male rats was 84.5 mg/kg bw and the LD50 for female rats was within the range of 33 - 66 mg/kg bw. Based on the most sensitive gender, classification as Cat 1 in warranted with respect to acute dermal toxicity.