Benzenamine, 4-fluoro-N-(1-methylethyl)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 Jun - 22 Jul 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

448-100-7

EC Name:

-

Cas Number:

70441-63-3

Molecular formula:

C9H12FN

IUPAC Name:

4-fluoro-N-(propan-2-yl)aniline

Test material form:

liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SPF-bred Wistar rats (Wsd/Win:WU strain, formerly named: Bor: WISW (SPF Cpb)) from Harlan-Winkelmann GmbH, Borchen, Germany
- Females nulliparous and non-pregnant: yes
- Age at delivery on 25 Jun and 02 Jul 1993: males were 7 - 8 weeks of age, females were 9 - 10 weeks of age
- Mean body weight at study initiation: males: 169 g; females 156 g
- Fasting period before study: approximately 16 hours before and 4 hours after test substance administration feed was withdrawn from animals
- Housing: Animals were conventionally housed in Makrolon cages type III on low-dust wooden granulate (Source: Ssniff, Soest/Westfalen, Germany). Animals were group housed; 5 animals per cage.
- Diet: "fixed-formula" standard diet, Altromin® 1324 pellets (Source: Altromin GmbH und Co KG, Lage, Germany), ad libitum. Composition and potential contamination of diet was analysed on a routine basis.
- Water: tap water of drinking water quality, ad libitum.
- Acclimation period: at least 5 days
- Microbiological status: SPF-bred rats were used
- Method of randomisation in assigning animals to test and control groups: Animals were assigned to study groups based on random numbers from a randomlist.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 5
- Air changes (per hr): 15 - 20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 30 Jun To: 22 Jul 1993

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

physiological saline

Remarks:

plus 2 % Cremophor EL (v/v)

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg bw

DOSAGE PREPARATION
Test substance was formulated in physiological saline with 2 % Cremophor EL under continuous stirring. Detailed analyses of test substance identity, stability and homogeneity were conducted.

Doses:

200, 633, and 2000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: On the day of test substance administration animals were repeatedly observed for clinical signs of toxicity. During the 14-day observation period animals were observed twice daily. On weekends and public holidays animals were observed once daily. Animals were weighed directly before, one week after and two weeks after (end of observation period) test substance administration.
- Clinical signs including body weight : type, start, duration, and intensity of clinical signs was recorded.

Statistics:

Calculation of the median lethal dose.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

356 mg/kg bw

Based on:

test mat.

Mortality:

All animals of the lowest dose group (200 mg/kg bw) survived until scheduled sacrifice.
All animals of both, the mid and the high dose group (633 and 2000 mg/kg bw) died within 8 hours following single administration of the test substance by gavage.

Clinical signs:

other: Clinical signs of toxicity were reported for the mid and high dose groups (663 and 2000 mg/kg bw) whereas no such signs were seen at the lowest tested dose of 200 mg/kg bw. The clinical signs observed included sedation, paleness and ruffled fur. Signs of

Gross pathology:

Findings at necropsy:
2000 mg/kg bw: stomac filled with white liquid
633 mg/kg bw: inflated stomac filled with liquid, reddened lungs. Additionally, the liver of the females of this dose group was pale and spotted.
200 mg/ kg bw: No gross pathological abnormalities were found in the animals sacrificed at study termination.

Any other information on results incl. tables

Table 1. Mortality and incidence of clinical signs

Dose [mg/kg bw]	Mortality	Clinical signs
	N*	N*
Males
200	0/5	0/5
633	5/5	5/5
2000	5/5	5/5
Females
200	0/5	0/5
633	5/5	5/5
2000	5/5	5/5

*N= Number of animals/ number of animals used

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Examining the test substance for acute oral toxicity in male and female Wistar rats resulted in a LD50 value of 356 mg/kg bw.