Registration Dossier

Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: scientifically acceptable and sufficient documented

Data source

Reference
Reference Type:
publication
Title:
The detection of carcinogen-induced sperm head abnormalities in mice
Author:
Topham JC
Year:
1980
Bibliographic source:
Mutat Res 69, 149-155 (1980)

Materials and methods

Principles of method if other than guideline:
Groups of 5 (male CBA x female BALB/c) F1 male mice; 10-12 weeks old; received 5 daily i.p. injections of the test substance (25, 50, 100 or 200 mg/kg bw) or vehicle alone (5 ml/kg bw/day). Positive controls (20 mg/kg/day cyclophosphamide monohydrate) are included in the study. 5 weeks after the last dose the mice are killed and sprem from the cauda epididymidis are suspended in saline. Smears of sperm from each animal are dried and stained with Eosin Y. Sperm heads are classified as of normal or abnormal morphology. differences in the incidence of abnormal sprem between the groups are compared using the Wilcoxson Rank Sum Test.
GLP compliance:
no
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
m-chloroaniline was obtained from Aldrich Chemical Co. (Gillingham, England)

Test animals

Species:
mouse
Strain:
other: (male CBA x female BALB/c) F1 male mice
Sex:
male

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
5 days
Frequency of treatment:
daily
Duration of test:
5 days treatment and 5 weeks post exposure period
Doses / concentrations
Remarks:
Doses / Concentrations:
25, 50, 100 or 200 mg/kg bw
Basis:

No. of animals per sex per dose:
5 animals per dose
Control animals:
yes, concurrent vehicle

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
200 mg/kg bw/day
Based on:
test mat.
Sex:
male
Basis for effect level:
other: sperm head abnormalities

Any other information on results incl. tables

m-chloroaniline did not significantly increase the incidence of abnormal sperm heads.

Applicant's summary and conclusion

Executive summary:

Groups of 5 (male CBA x female BALB/c) F1 male mice; 10-12 weeks old; received 5 daily i.p. injections of the test substance (25, 50, 100 or 200 mg/kg bw) or vehicle alone (5 ml/kg bw/day). Positive controls (20 mg/kg/day cyclophosphamide monohydrate) are included in the study. 5 weeks after the last dose the mice are killed and sprem from the cauda epididymidis are suspended in saline. Smears of sperm from each animal are dried and stained with Eosin Y. Sperm heads are classified as of normal or abnormal morphology. Differences in the incidence of abnormal sprem between the groups are compared using the Wilcoxson Rank Sum Test.

As a result, m-chloroaniline did not significantly increase the incidence of abnormal sperm heads in the highest applied dose of 200 mg/kg bw (1/2 LD50).