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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
Study period:
From February 16, 1987 to March 16, 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was performed according to OECD recommendation with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
(only 1000 erythrocytes per animal were scored for the incidence of micronuclei instead of at least 2000 as recommended in the guideline)
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Dimethylbenzylamine.
- Analytical purity: 99.34 %
- Purity test date: Dec. 04, 1986
- Lot/batch No.: 173.


Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Zentralinstitut fur Versuchstiere D-3000 Hannover, F.R.G.
- Age at study initiation: 2,5 - 4 months.
- Weight at study initiation: Weighing of the animals was done directly before the administration of the test substance.
- Assigned to test groups randomly: yes, under following basis: random selection within the sexes.
- Fasting period before study: 18 h before administration of the test substance, positive and negative controls.
- Housing: Each animal was housed in an own cage. Macrolon, type I (EBECO, D-4620 Castrop-Rauxel,F.R.G.). The cages were numbered. The animals were identified by the cage number.
- Diet (e.g. ad libitum): ad libitum. ALTROMIN - Standard diet.
- Water (e.g. ad libitum): ad libitum. Tap water from the water supply of the Southern Hessian Gas and Water Board, Darmstadt (Siidhessische Gas- und Wasser AG, D-6100 Darmstadt)
- Acclimation period: The animals underwent quarantine in the animal house of LMP for two weeks after their arrival. During this period the animals did not show signs of illness or altered behaviour.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3 ºC.
- Humidity (%): 40 - 60 %.
- Air changes (per hr): 10 changes of air per hour.
- Photoperiod (hrs dark / hrs light): artificial light 6.00 a.m. - 6.00 p.m.

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
other: per os (stomach tube)
Vehicle:
- Vehicle(s)/solvent(s) used: DMSO.
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
Dissolved in: Dimethylsulfoxide (DMSO).
Solution prepared on day of administration. The test substance was administered singly amounting to 15, 50 or 150 mg/kg b.w.
Duration of treatment / exposure:
24, 48 and 72 hours.
Frequency of treatment:
Single application
Post exposure period:
24, 48 and 72 hours.
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
15 mg/kg b.w.
Basis:
actual ingested
Remarks:
Doses / Concentrations:
50 mg/kg b.w.
Basis:
actual ingested
Remarks:
Doses / Concentrations:
150 mg/kg b.w.
Basis:
actual ingested
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Positive control(s):
Cyclophosphamide (CPA)
- Route of administration: per os (stomach tube); singly.
- Doses / concentrations: 30 mg/kg b.w. Dissolved in 0.9 % NaCl-solution. Volume administered: 10 mL/kg b.w.

Examinations

Tissues and cell types examined:
Polychromatic erythrocytes (PE) in the bone marrow cells of the mouse.
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION:
Dosing was chosen with regard to the results of a pre-experiment. 150 mg/kg b.w. of the test substance was the highest non-lethal dose. With this dose the animals expressed slight toxic reactions: reduction of spontaneous activity, no food and water uptake for 1 hour after administration. With higher doses of the test substance animals died:
200 mg/kg b.w. dosing: 1 out of 6 treated animals died.
250 mg/kg b.w. dosing: 1 out of 6 treated animals died.
300 mg/kg b.w. dosing: 3 out of 6 treated animals died.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
(At 150 mg/kg b.w. the animals expressed slight toxic reactions: reduction of spontaneous activity, no food and water uptake for 1 hour after administration)
Negative controls valid:
yes
Positive controls valid:
yes

Any other information on results incl. tables

Table 1. Summary of results.

 

Group

Substance

Dose

(mg/Kg b.w.)

Preparation hours

p. admin.

Poly-chromatic erythrocytes with micronuclei

Range

PE/NE

1

Solvent

0

24

0.14 %

0 - 5

1000/455

2

Solvent

0

48

0.06 %

0 – 3

1000/885

3

Solvent

0

72

0.09 %

0 – 2

1000/435

4

CPA

30

24

1.22 %

4 – 24

1000/644

5

Test Substance

15

24

0.15 %

0 – 4

1000/498

6

Test Substance

50

24

0.18 %

0 – 4

1000/516

7

Test Substance

150

24

0.13 %

0 – 2

1000/441

8

Test Substance

150

48

0.10 %

0 – 2

1000/702

9

Test Substance

150

72

0.10 %

0 - 3

1000/442

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
The test substance did not show any mutagenic activity as determined by the micronucleus test with mouse bone marrow cells.
Executive summary:

The test substance was assessed for mutagenic properties in the micronucleus test with bone marrow cells of the mouse according to OECD recommendations and GLP regulations.

 

The preparation of the cells was done 24, 48 and 72 h after the treatment with the high dose and 24 h after the treatment with the medium and low dose. The doses of the test substance administered orally were 15; 50; 150 mg/kg b.w. In each experimental group 1,000 cells from each of 10 animals (5 males; 5 females) were scored.

There was no enhancement of the number of cells with micronuclei in the groups treated with the test substance as compared with the negative controls treated with the solvent.

On the other hand, the sensitivity of the test system was demonstrated by significantly enhanced micronuclei rates after treatment with 30 mg/kg b.w. of the positive control.

 

The results allow to draw the conclusion that the test substance did not induce micronuclei in mouse bone marrow cells under the experimental conditions described in the report mentioned above.