4-chloroaniline

Genetic toxicity: in vivo

Administrative data

Endpoint:

genetic toxicity in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study Report from 1986/1987, but main requirements of the test guideline are fulfilled.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1987

Reference 2

Reference Type:

review article or handbook

Title:

p-Chloranilin, BUA-Stoffbericht 151

Author:

BUA

Year:

1995

Bibliographic source:

Beratergremium für umweltrelevante Altstoffe (BUA) der Gesellschaft Deutscher Chemiker, 1995

Materials and methods

Principles of method if other than guideline:

Micronucleus test

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-chloroaniline

EC Number:

203-401-0

EC Name:

4-chloroaniline

Cas Number:

106-47-8

Molecular formula:

C6H6ClN

IUPAC Name:

4-chloroaniline

Test animals

Species:

mouse

Strain:

other: CFLP

Sex:

male/female

Details on test animals or test system and environmental conditions:

Softwood sawdust bedding material, 24 hour cycle of 12 hours light/12 hours dark; room temperature 21 +/- 2 °C, tap water and Heygate´s rat and mouse diet 41B.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: suspended in 0.25% Gum Tragacanth

Duration of treatment / exposure:

24, 48, and 72 hours

Frequency of treatment:

single exposure

Doses / concentrations

Remarks:

Doses / Concentrations:
180 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

cyclophosphamide
- Doses / concentrations: 40 mg/kg bw

Examinations

Tissues and cell types examined:

Femur bone marrow

Results and discussion

Test results

Test results 1

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 2

Sex:

female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

Mean Frequency of micronucleus formation %
Treatment        24 hours				48 hours			72 hours
M		F	Total	M	F	Total	M	F	Total
Negative control	0.29	0.20	0.24	0.14	0.08	0.11	0.27	0.00	0.14
Positive control	0.91	1.06	0.99
180 mg/kg 4 -chloraniline	0.40	0.18	0.29	0.29	0.18	0.23	0.23	0.06	0.15

p-chloroaniline is negative in the micronucleus test in the mouse at the maximum tolerated oral dose (180 mg/kg body weight). There was one female outlier after 48 hours, therefore that dose group was repeated and revealed a negative response. Overall there was a slight decrease of the mean ratio PCE/NCE not enough to show a toxic effect on erythropoiesis, but indicating that the bone marrow was reached by the test substance.

- The dose was selected based on a range-finding study using 4, 20, 100 and 500 mg/kg (3 male and 3 female mice/group). All the females and one male dosed with 500 mg/kg died, but non dosed with 100 mg/kg. A LD50 of 225 mg/kg bw was derived from these data, with a maximum tolerated dose of 180 mg/kg,

The positive control group showed the expected positive response.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative