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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes (incl. QA statement)
Type of assay:
other: Micronucleus assay

Test material

Constituent 1
Reference substance name:
Reference substance 003
EC Number:
611-563-2
Cas Number:
57635-48-0
Test material form:
liquid

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
sesame oil, at volume of 10mg/kg bw
Duration of treatment / exposure:
2
Frequency of treatment:
one application per day
Post exposure period:
The animals were sacrificed 24hours after second application.
Doses / concentrations
Dose / conc.:
2 000 mg/kg bw/day
No. of animals per sex per dose:
5 males and 5 females as controls
5 males and 5 females for treatment with test material
5 males and 5 females for positive control (Endoxan, cyclophosphamide)
Control animals:
yes, concurrent vehicle
Positive control(s):
5 males and 5 females were treated with Endoxan once orally by gavage at a dose of 50 mg/kg bw

Examinations

Tissues and cell types examined:
2000 polychromatic erythrocytes

Results and discussion

Test results
Key result
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
decreased motor activity and squatting posture
Vehicle controls validity:
valid
Remarks:
sesame oil, 10 mg/mL
Positive controls validity:
valid
Remarks:
Endoxan, cyclophosphamide

Any other information on results incl. tables

Mice were treated twice with 2000 mg Emulsogen COL 020 per kg body weight to study the induction of micronuclei in bone marrow cells. All animals survived after treatment. The following signs of toxicity were observed: motor activity decreased and squatting posture. 24 hours after application all animals were free of clinical signs of toxicity. The dissection of the animals revealed no test substance related macroscopic findings. The bone marrow smears were examined for the occurrence of micronuclei in red blood cells. The results are summarized on page 19. Individual data of all animals in all treatment groups are presented on page 20. The incidence of micronucleated polychromatic erythrocytes in the dose group of Emulsogen COL 020 was within the normal range of the negative control groups. No statistically significant increase of micronucleated polychromatic erythrocytes was observed. The ratio of polychromatic erythrocytes to total erythrocytes remained essentially unaffected by the test compound and was not less than 20% of the control values in the pooled data. Cyclophosphamide (Endoxan®) induced a marked and statistically significant increase in the number of polychromatic erythrocytes with micronuclei, thus indicating the sensitivity of the test system.

Applicant's summary and conclusion

Conclusions:
No effect in in-vivo micronucleus assay in mouse
Executive summary:

The genotoxicity of the registration substance was investigated according to the OECD Guideline 474. Mice were treated at dose of 2000 mg/kg bw once per day for two days. 24hours after the seconed application the animals were sacrificed and the bone marros cells were collected. The incidence of mucronucleated polychromatic erythrocytes was comparable for treated and control mice. The ratio of polychromatic erythrocytes to total erhythrocytes remained unaffected. No clastogenic effect was found.