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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study according OECD 474

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Principles of method if other than guideline:
The micronucleus test was employed to investigate P-Chlorotoluene in male and female mice for a possible clastogenic effect on the chromosomes of bone-marrow erythroblasts. The known clastogen and cytostatic agent, cylophosphamide,served as positive control.
The treated animals received a single intraperitoneal administration of either p-chlorotoluene or cyclophosphamide. The femoral marrow of groups treated with p-chlorotoluene was prepared 16, 24 and 48 hours after administration. All negative and positive control animals were sacrificed
after 24 hours. The doses of p-chlorotoluene and the positive control, cyclophosphamide, were 1000 and 20 mg/kg body weight, respectively.
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Constituent 1
Chemical structure
Reference substance name:
4-chlorotoluene
EC Number:
203-397-0
EC Name:
4-chlorotoluene
Cas Number:
106-43-4
Molecular formula:
C7H7Cl
IUPAC Name:
4-chlorotoluene
Details on test material:
p-chlorotoluene - content: 99.81 %

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female

Administration / exposure

Route of administration:
intraperitoneal
Duration of treatment / exposure:
single administration
Frequency of treatment:
single administration
Post exposure period:
16, 24, or 48 hours after administration
Doses / concentrations
Remarks:
Doses / Concentrations:
1000 mg/kg bw disssolved in corn oil, dosage based on a pilot test
Basis:
nominal conc.
No. of animals per sex per dose:
5 males and 5 females per group
Control animals:
yes

Examinations

Tissues and cell types examined:
bone-marrow erythroblasts

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

general toxicity:
compound-related signs of toxicity observable until sa-
crifice 16, 24 and 48 hours after the administration:
apathy, roughened fur, staggering gait, spasms, twitch-
ing, shivering and difficulty in breathing;
death of 2/40 treated animals during the test period; autopsy findings:
slightly inflated lungs, spotted livers

no indications of a clastogenic effect of p-chlorotoluene were found; the ratio of polychromatic to normochromatic erythrocytes was not altered.
The positive contol was functional.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Executive summary:

method: the micronucleus test was employed to investigate p-chlorotoluene in male and female mice for a possible clastogenic effect on the chromosomes of bone-marrow erythroblasts. The treated animals received a single intraperitoneal administration of either p-chlorotoluene or cyclophosphamide. The femoral marrow of groups treated with p-chlorotoluene was prepared 16, 24 and 48 hours after administration. All negative and positive control animals were sacrificed after 24 hours. The doses of p-chlorotoluene and the positive control, cyclophosphamide, were 1000 and 20 mg/kg body weight, respectively.

result: negative; no indications of a clastogenic effect of p-chlorotoluene were found after a single intraperitoneal treatment with 1000 mg/kg.