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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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No OECD Guideline defined.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987
Reference Type:
secondary source
Title:
Dimethylbenzylamine - Micronucleus test in bone marrow cells of the mouse
Author:
Völkner W.
Year:
1987
Bibliographic source:
LMP 262 (1987)||cited in:|Heiman H-G, Huber W|Mutagenitätsprüfungen von Arbeitsstoffen mit wesentlicher Bedeutung und Verbreitung|GUM, 4/89: 2-6 (1989)
Reference Type:
publication
Title:
Mutagenitätsprüfungen von Arbeitsstoffen mit wesentlicher Bedeutung und Verbreitung
Author:
Heimann K.-G- et al.
Year:
1998
Bibliographic source:
GUM 4/89

Materials and methods

Principles of method if other than guideline:
The test substance was assessed for mutagenic properties in the micronucleus test with bone marrow cells of the mouse. The dosing was 15, 50, 150 mg/kg bw. (24 h); 150 mg/kg bw (48h); 150 mg/kg bw (72 h). The administration was per os (stomach tube); singly. Preparation of the bone marrow cells was done 24, 48 and 72 h after the administration of the test substance.
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
TS-Freetext:
Purity: 99.34 %

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 2.5-4 months
- Housing: individually
- Diet ad libitum
- Water ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 40-60
- Air changes (per hr):10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
DMSO
Details on exposure:
Single oral administration of the test substance diluted in DMSO by gavage
Duration of treatment / exposure:
single administration
Frequency of treatment:
single administration
Post exposure period:
24, 48, 72 hours, respectively
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 15, 50, 150 mg/kg bw
Basis:

No. of animals per sex per dose:
10
Control animals:
yes
Positive control(s):
cyclophosphamide

Examinations

Tissues and cell types examined:
mouse bone marrow cells
Details of tissue and slide preparation:
The animals were killed by cervical dislocation. The femora were removed and freed from muscles and tissue. The epiphyses were cut off with scissors and the marrow was fluxhed out with fetal calf serum. The cell suspension was centrifuged and the pellet spread on a slide . The smear was air-dryed and then stained with May-Grünwald/Giemsa. Cover slips were mounted with Eukitt. 3 Slides were made from each animal.
Evaluation criteria:
no data

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
150 mg/kg bw: reduction of spontaneous activity and reduced food and water consumption in a pre-test.
Vehicle controls validity:
not specified
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Toxicity:
150 mg/kg produced reduction of spontaneous activity and reduced food and water
consumption in a pre-test.

Any other information on results incl. tables

RS-Freetext:
Toxicity:
150 mg/kg produced reduction of spontaneous activity and reduced food and water consumption in a pre-test.

Micronuclei:
The incidence of micronuclei was not altered by treatment with DMBA (control: 0.06 - 0.14%; treated: 0.10 - 0.18 %, non dose dependent).
The positive control, cyclophophamide, increased the incidence of micronuclei to 1.22 %.

Applicant's summary and conclusion

Executive summary:

The test substance was assessed for mutagenic activity in the micronucleus test in vivo with bone marrow cells of the mouse.

Male and female mice were given single oral doses by gavage 0, 15, 50, 150 mg/kg bw. (24 h); 150 mg/kg bw (48h); 150 mg/kg bw (72 h).diluted in DMSO. Toxicity was examined in a pre-experiment. 150 mg/kg bw was the highest non-lethal dose but animals showed reduction of spontaneous activity and no food and water uptake was observed for up to 1 hour post application in that test..

Preparation of mice bone marrow cells was done 24, 48 and 72 h after the administration of the test substance.

With no dose at no preparation time any enhanced micronucleus rates were found. The sensitivity of the test system was shown by administration of cyclophosphamide (positive control) which induced a significantly higher micronucleus rate as compared to the negative controls.

The test substance did not show any mutagenic activity as determined by the micronucleus test with bone marrow cells.