N-(4-aminophenyl)aniline

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:

other: GLP and guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: EPA Toxic substances control act test guidelines, 40 CFR part 789.1175, September 1985; and the EEC No. L 251/96: Methods for the determination of toxicity, part B.1, September 1984

Deviations:

no

GLP compliance:

yes

Test type:

other: acute oral toxicity study

Test material

Test material information

Constituent 1

Reference substance name:

N-(4-aminophenyl)aniline

EC Number:

202-951-9

EC Name:

N-(4-aminophenyl)aniline

Cas Number:

101-54-2

Molecular formula:

C12H12N2

IUPAC Name:

N1-phenylbenzene-1,4-diamine

Constituent 2

Reference substance name:

1-N-phenylbenzene-1,4-diamine

IUPAC Name:

1-N-phenylbenzene-1,4-diamine

Details on test material:

4-ADPA, Lot no.: KK11-527

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Doses:

250, 350, 500 mg/kg bw

No. of animals per sex per dose:

5 per dose and sex

Control animals:

no

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

370 mg/kg bw

Based on:

test mat.

Remarks on result:

other: clinical signs

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

300 mg/kg bw

Based on:

test mat.

Remarks on result:

other: clinical signs

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

336 mg/kg bw

Based on:

test mat.

Remarks on result:

other: clinical signs

Any other information on results incl. tables

Mortality occured as followed

Treatment	Level (mg/kg)	Males	Females	Combined
4 -ADPA	250	0/5	1/5	1/10
	350	1/5	4/5	5/10
	500	5/5	5/5	10/10

Mortality: All deaths for 4 -ADPA occured by study day 4.

Clinical observations: A variety of adverse clinical signs was observed in the LD50 study animals. The majority of the clinical signs occured during study 1 -5. The most notable clinical signs included piloerection, decreased activity, urine/faecal strains, decreased defecation, reddish/orange coloured urine, breathing abnormalities and dark material around the facial area.

Body weights: Body weight loss was noted in one female at 350 mg/kg dosage level during day 1 -8 weight period. Body weight gains were noted in all other surviving animals during test period.

Gross necropsy: In the animals surviving until necropsy on study day 15, one animal from 250 mg/kg level exhibited adhesions involoving the stomach and surrounding tissues. In animals which dies, the most notable findings consisted of colored fluid/mucoid/paste-like contents in the digestive tract, black foci and linear striations on the stomach mucosa, colored fluid contents of the urinary bladder, congested meningeal vessels of the brain, dark red adrenals, dark red thymus and dark red cervical/thymic lymph nodes. Adhesions involving spleen and stomach were also observed in one animal from the 350 mg/kg dose level.

Applicant's summary and conclusion

Executive summary:

The acute oral LD50 for 2 -ADPA for male rats was calculated to be 370 mg/kg bw. In female rats, the acute oral LD50 of ADPA was calculated to be 300 mg/kg bw. In the sexes combined, the acute oral LD50 of 4 -ADPA was calculated to be 336 mg/kg bw (Springorn Laboratories, Inc. 1991).