4-bromo-α,α,α-trifluoro-m-toluidine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-bromo-α,α,α-trifluoro-m-toluidine

EC Number:

206-885-1

EC Name:

4-bromo-α,α,α-trifluoro-m-toluidine

Cas Number:

393-36-2

Molecular formula:

C7H5BrF3N

IUPAC Name:

4-bromo-α,α,α-trifluoro-m-toluidine

Test material form:

solid: crystalline

Specific details on test material used for the study:

Manufacturer: Fuxin Jintelai FluorineBatch No.: 0026DB4 (D150701CC14001)Physical state: solid, crystalline substanceStorage: in a cool, dry

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Species and strain: Crl:(WI)Br ratsSource: TOXI COOP ZRT. Budapest, HungaryHygienic level during the study: good conventionalNumber of animals: 3 animals/groupSex: Female, nulliparous and non pregnant animalsAge of animals: Young adult rat, 8 weeks old in first, second, third and fourth stepBody weight range at starting (first step): 152 - 156 gBody weight range at starting (second step): 157 - 164 gBody weight range at starting (third step): 160 - 164 gBody weight range at starting (fourth step): 170 - 174 gAcclimatization time: 5 days in first step, 6 days in second step, 7 days in third step and 8 days in fourth stepAnimal health: Only healthy animals were used for the study. Health status was certified by the study director.Housing: Group caging (3 animals/cage)Light: Artificial light, from 6 a.m. to 6 p.m.Temperature: 22 ± 3 °CRelative humidity: 30 - 70 %Ventilation: 10-15 air exchanges/hour by central air-condition system.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Helianthi annui oleum raffinatum

Details on oral exposure:

A single oral administration - followed by a fourteen-day observation period - was performed by gavage. The day before treatment the animals were fasted. The food but not water was withheld overnight. Animals were weighed before the application and the food was given back 3 hours after the treatment.

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 animals/group

Control animals:

no

Details on study design:

Starting dose was selected on the basis of the available information about the test item.The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. Since all female animals died the test was continued at 300 mg/kg bw dose level on further three female rats. Two animals were sacrificed as moribund in the second step at 300 mg/kg bw dose level, the test was continued at 50 mg/kg bw dose level on further three female rats. There was no death in third step, so three further female rats were treated with the same (50 mg/kg bw) dose. No animal died in the fourth step, too, so the test was finished, the stopping criteria of Annex 2d of OECD Guideline No. 423. (presented in Appendix VII) was met.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 50 - <= 300 mg/kg bw

Based on:

test mat.

Mortality:

Three animals died in group 1 treated with 2000 mg/kg bw dose of the test item and two out of three animals were sacrificed as moribund in group 2 treated with 300 mg/kg bw dose of the test item. No death occurred after the single 50 mg/kg bw oral dose of the test item.

Clinical signs:

The observed clinical signs were related to the effect of the test item.There was no any effects related to the test item in body weight and body weight gain in the survived animal of group 2 (300 mg/kg bw) and in the animals of group 3 and 4 (50 mg/kg bw) during the study.Autopsy revealed treatment related pathological change as piloerection in group 2 treated with 300 mg/kg bw dose.

Body weight:

The body weight and body weight gain data of group 1 (2000 mg/kg bw) could not be evaluated, because of mortalities. In group 2 (300 mg/kg bw) the body weight of the survivor animal corresponded to its species and age throughout the study.In group 3 and 4 (50 mg/kg bw) the mean body weight of the animals corresponded to their species and age throughout the study.

Gross pathology:

All rats treated with 2000 mg/kg bw dose (group 1) of the test item spontaneously died during the study. An internal necropsy finding as autolysis was observed in these animals. It is normal physiological process after death.Two rats treated with 300 mg/kg bw dose (group 2) of the test item were sacrificed as moribund. External finding as piloerection and internal necropsy finding as pale kidneys was observed in these animals. External alterations could be related to the test item toxic effect. Pale kidneys could not be related to the test item toxic effect, but was regarded an individual variation. Most likely the observation is a congenital anomaly.The third animal of this dose group survived until the scheduled necropsy on Day 15. No pathological changes were found related to the effect of the test item in this animal.All animals treated with 50 mg/kg bw dose survived until the scheduled necropsy on Day 15. Slight hydrometra was observed in one animal of group 3 and moderate hydrometra was recorded in other animal of group 4. The hydrometra is physiological finding and connected to the cycle of the animal. No pathological changes were found related to the effect of the test item during the macroscopic examination of these animals.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The test item 4-BROMO-3-(TRIFLUOROMETHYL)ANILINE (CAS 393-36-2) was ranked into classes of Globally Harmonized Classification System (GHS) Category 3.