Diphenylamine

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:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 486 (Unscheduled DNA Synthesis (UDS) Test with Mammalian Liver Cells in vivo)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

self certified

Type of assay:

unscheduled DNA synthesis

Test material

Test material information

Constituent 1

Reference substance name:

Diphenylamine

EC Number:

204-539-4

EC Name:

Diphenylamine

Cas Number:

122-39-4

Molecular formula:

C12H11N

IUPAC Name:

diphenylamine

Details on test material:

- Name of test material (as cited in study report): Diphenylamine
- Analytical purity: 99.9 %
- Lot/batch No.: OF-28001

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Administration / exposure

Route of administration:

oral: unspecified

Duration of treatment / exposure:

2-4 hour and 15-16 hour after dosing

Frequency of treatment:

Single dose

Post exposure period:

None

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
200, 500, 800, 1500 & 2000 mg/kg bw
Basis:
no data
(range finding test)

Doses / concentrations 2

Remarks:

Doses / Concentrations:
0, 750, 1500 & 2000 mg/kg bw
Basis:
no data
(UDS test)

No. of animals per sex per dose:

4 rats/sex/dose/timepoint

Control animals:

yes, concurrent vehicle

Positive control(s):

N-dimethylnitrosamine
- Route of administration: IP injection
- Doses / concentrations: 10 & 15 mg/kg bw, for the 2-to 4- hour and 15- to 16- hour timepoints, respectively

Examinations

Tissues and cell types examined:

Liver: hepatocytes

Details of tissue and slide preparation:

DETAILS OF SLIDE PREPARATION:
Hepatocytes were obtained by mechanicle dispersion of excised liver tissue, centrifuged and re-suspended to perform a viable cell count
Isolated cells were re-suspended and replicate cultures prepared, then incubated and radiolabelled with high specific activity thymidine for 4 hrs
Cells were washed, fixed and allowed to dry, then mounted on glass slides and dipped in an autoradiogaphic emulsion

METHOD OF ANALYSIS:
Autoradiography

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Remarks:

slight effects at the highest doses tested

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Diphenylamine was found inactive under the conditions of the study

Executive summary:

Fisher 344 rats were orally administered diphenylamine at : 0, 750, 1500 & 2000 mg/kg bw for the 2 -4 hr and the 15 -16 hr timepoints. All animals were observed throughout the duration of the assay for toxic symptoms and mortality. Moreover, hepatocytes were examined by autoradiography and the mean net nuclear grain count was determined from triplicates coverslips for each treated animal. The results were negative.