α,α,α-trifluoro-o-toluidine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well performed GLP and OECD guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

84/449/EEC

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

α,α,α-trifluoro-o-toluidine

EC Number:

201-806-7

EC Name:

α,α,α-trifluoro-o-toluidine

Cas Number:

88-17-5

Molecular formula:

C7H6F3N

IUPAC Name:

2-(trifluoromethyl)aniline

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain specifics: Hoe: WISKf (SPF71)
- Source: Hoechst AG breeding colony
- Weight at study initiation: male 180 g - 217 g (mean 193,5 g), female 176 g - 227 g (mean 202,5 g) on day 1 (treatment)
- Fasting period before study: approximately 16 hours before treatment, access to water permitted
- Housing: in groups of five in Makrolon type 4 cages with standard softwood bedding
- Diet (e.g. ad libitum): standard rat diet (Albtromin 1324)
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 50 ± 20 %
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on oral exposure:

VEHICLE
- Purity: Ph. Eur. III
- Concentration in vehicle: 25 % (w/v)
- Amount of vehicle (if gavage): 5.0 - 12.6 mL/kg body weight (test item in vehicle administered)

Doses:

As a result of preliminary studies the following doses were tested:
1250, 1600, 2000 and 3150 mg/kg body weight

No. of animals per sex per dose:

5 males
5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days starting with treatment day 0
- Frequency of observations and weighing:
mortality/viability: during the first 30 minutes and approximately 1, 2, 4 and 6 h after administration on day 0 and daily on days 1-14
clinical signs: during the first 30 minutes and approximately 1, 2, 3 and 6 h after administration on day 0 and daily on days 1-14
body weights: on days 1 (prior to administration), 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examination

Statistics:

Probit analysis was applied to calculate LD50 of males, which was not possible for females due to the mortality ratio. LD50 values for males and females was within the same range, therefore LD50 for both sexes was calculated.

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

> 1 600 - < 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

1 890 mg/kg bw

Based on:

test mat.

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 870 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed in the low dose groups. All animals (male and female) of the high dose group died. Details see table below.

Clinical signs:

other: The following symptoms were observed after application of the test substance: reduction of spontaneous activity, stupor, narcosis, flankes pinched in, squatting posture, prone position, ataxic gait, forward crawling, palpebr. fissure wide and narrow, coat

Gross pathology:

There were no macroscopic findings at scheduled necropsy of surviving animals.
Macroscopic findings of died males and females: transparent stomach lining, small intestine filled with brown-black mass, intestinal vessels injected, pancreas reddened, adrenal glands dark discoloured, liver partly light discoloured, lung grey-rose and filled with blood

Any other information on results incl. tables

Dose	Mortality
[mg/kg bw]	male	male [%]	female	female [%]
1 250	0 / 5	0	0 / 5	0
1 600	1 / 5	20	0 / 5	0
2 000	3 / 5	60	4 / 5	80
3 150	5 / 5	100	5 / 5	100

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

LD50, rat (male/female): 1870 mg/kg bw

Regulation (EC) No. 1272/2008: Acute toxicity category IV, H302
Directive 67/548/EEC: Harmful, R 22

Executive summary:

In a OECD guideline and GLP compliant study the LD₅₀ of the test item for male and female rats was determined. Doses of 1250, 1600, 2000 and 3150 mg/kg body weight were administered to groups of 5 males and 5 females respectively. Probit analysis was applied to calculate LD₅₀ for males, which was not possible for females due to the mortality ratio. LD₅₀ values of males and females was within the same range, therefore LD₅₀ for both sexes was calculated.

Numerous clinical signs were observed after application of the test substance: reduction of spontaneous activity, stupor, narcosis, flankes pinched in, squatting posture, prone position, ataxic gait, forward crawling, palpebr. fissure wide and narrow, coat bristling, increased lacrimation, twitching, no paw-reflex to pinching, no placing reflex, irregular respirate, panting, cyanosis. In surviving animals symptoms were fully reversible after 1 day (males) and after 4 days (females) respectively.

There were no macroscopic findings at scheduled necropsy of surviving animals. Macroscopic findings of died males and females: transparent stomach lining, small intestine filled with brown-black mass, intestinal vessels injected, pancreas reddened, adrenal glands dark discoloured, liver partly light discoloured, lung grey-rose and filled with blood.

LD₅₀ (female): > 1600 - < 2000 mg/kg bw

The following LD₅₀ values were calculated:

LD₅₀ (male): 1890 mg/kg bw

LD₅₀ (male/female): 1870 mg/kg bw

Based upon these findings the test substance has to be classified:

Regulation (EC) No. 1272/2008: Acute toxicity category IV, H302

Directive 67/548/EEC: Harmful, R 22