N-(4-aminophenyl)aniline

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian cell study: DNA damage and/or repair

Remarks:

Type of genotoxicity: DNA damage and/or repair

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: comparable to guideline study with acceptable restrictions (e.g. no documentation of systemic toxicity)

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Reference 2

Reference Type:

secondary source

Title:

In Vivo - In Vitro Hepatocyte DNA Repair (UDS) and DNA Replication Assay with 4-NDPA, 4-ADPA, DADPE & DNDPE. Study SR-86-175

Author:

Monsanto Co.

Year:

1988

Bibliographic source:

Short report with cover letter dated 10/18/88; NTIS/OTS 516609, Doc I.D. 89-890000009 (1988)

Materials and methods

Principles of method if other than guideline:

Method: other: in vivo-in vitor UDS comparable to current guidelines

GLP compliance:

yes

Type of assay:

unscheduled DNA synthesis

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

Details on test material:

IUCLID4 Test substance: other TS: purity: 95-97%

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Administration / exposure

Route of administration:

oral: gavage

Duration of treatment / exposure:

single dose

Frequency of treatment:

once

Post exposure period:

16 hrs (UDS), 48 hrs (DNA replication)

Doses / concentrations

Remarks:

Doses / Concentrations:
50, 100, 250 mg/kg bw
Basis:

No. of animals per sex per dose:

3

Control animals:

yes, concurrent vehicle

Examinations

Tissues and cell types examined:

liver tissue

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

RS-Freetext:
UDS study:
All doses of 4-ADPA and the vehicle control yielded mean values ranging  

from -4 to -4,1 and 4 net grain/nucleus (NG) whereas the positive control  

yielded 14.6 (NG). All animals receiving doses of 4-ADPA or vehicle  

control had less than 2% of cells undergoing repair compared with 70% for  

the positive control.
Induction of DNA replication:
4-ADPA yielded a mean value of 2,68% in S-phase at 250 mg/kg compared to  

the vehicle control with 0.06% in S-phase. On the basis of the criteria  

for a positive response it is concluded that 4-ADPA induces DNA  

replication in male rat liver.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative

Executive summary:

The test substance 4-ADPA induced no significant increase of unscheduled DNA synthesis in hepatocytes of Fischer-344 rats that had received single dosage of 50, 100 and 250 mg/kg bw by gavage. It induced DNA replication at 250 mg/kg bw (2.68 % compared to vehicle control 0.06%). The study was performed according to current international standard methods but no information is available on systemic toxicity in the high dose animals except the information that the highest dose had to be reduced to 250 mg/kg bw because at 400 mg/kg bw one of the two rats died prior to the 16-hour sacrifice and another yielded unscorable slides (Monsanto Co. 1986).