Registration Dossier

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: Comparable to guideline study under GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
: other positive control as recommended, only 3 animals per dose group
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): Ro 81-1789
- Substance type: organic
- Physical state: solid
- Purity test date: 03.11.1982
- Lot/batch No.: 549 317

Test animals

Species:
mouse
Strain:
other: Füllinsdorf Albino SPF
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Institute of Biological and Medical Research, CH-4414 Füllinsdorf, Switzerland
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 27.8-32.1g
- Housing: maximum 6 animals per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2°C
- Humidity (%): 55±10%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
rape oil
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: the test compound was dissolved in rape oil and then administered at 0.1 mL/kg bw
Duration of treatment / exposure:
The substances were administered 30, respectively 6 h before animals were killed.
Frequency of treatment:
The substances were administered 30, respectively 6 h before animals were killed.
Post exposure period:
No post-observation was performed.
Doses / concentrations
Remarks:
Doses / Concentrations:
100, 2500, and 5000 mg/kg bw
Basis:
nominal in diet
No. of animals per sex per dose:
3 male and 3 female animals were treated per dose group.
Control animals:
yes, concurrent vehicle
Positive control(s):
Procarbazine hydrochloride in PBS
- Route of administration: oral
- Doses / concentrations: 50 mg/kg bw at 0.1 mL/kg bw

Examinations

Tissues and cell types examined:
bone marrow derived polychromaticerythrocytes
Details of tissue and slide preparation:
DETAILS OF SLIDE PREPARATION:
Four bone-marrow smears per animal were prepared according to the method of Schmid (Mutat. Res. 1975, 31:9)

METHOD OF ANALYSIS:
For each animal 2000 polychromatic erythrocytes were examined in a double blind fashion. Only cells with clearly identifiable anomalies were recorded as cells containing micronuclei. Micronuclei contained in mature erythrocytes were recorded separately, but not taken into the statistical evaluation.
Evaluation criteria:
For each animal 2000 polychromatic erythrocytes were examined in a double blind fashion. Only cells with clearly identifiable anomalies were recorded as cells containing micronuclei. Micronuclei contained in mature erythrocytes were recorded separately, but not taken into the statistical evaluation.
Statistics:
The results were evaluated by means of the Jonckheere-test and the U-test.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid

Any other information on results incl. tables

Table 1: Micronucleus Test with Fuellinsdorf Albino Mice (SPF) given twofold oral application of BMDBM

Single dose [mg/kg bw]

Animal No.

A: Number of PCE with one or more micronuclei

Median of A

B: Percentage of PCE with one or more micronuclei

Median of B + significance levels

0

1

2

3

5

6

7

6

5

4

12

3

4

4.5

0.30

0.30

0.20

0.60

0.15

0.20

0.23

1000

1

2

3

5

6

7

8

9

7

1

4

3

5.5

0.40

0.45

0.35

0.05

0.20

0.15

0.28

2500

1

3

4

5

6

7

13

4

2

3

10

6

5.0

0.65

0.20

0.10

0.15

0.50

0.30

0.25

5000

3

5

6

7

9

11

3

5

74

4

6

4.5

0.65

0.20

0.10

0.15

0.50

0.30

0.23

Number of PCE scored per animal: 2000

Footnote for significance levels

* Jonckheere <5%

** Jonckheere <1%

 

Table 2: Micronucleus Test with Fuellinsdorf Albino Mice (SPF) given twofold oral application of positive control substance Procarbazine HCl

Single dose [mg/kg bw]

Animal No.

A: Number of PCE with one or more micronuclei

Median of A

B: Percentage of PCE with one or more micronuclei

Median of B + significance levels

0

1

2

3

5

6

7

6

5

4

12

3

4

4.5

0.30

0.30

0.20

0.60

0.15

0.20

0.23

50

1

2

3

98

68

89

89

4.90

3.40

4.45

4.45

Number of PCE scored per animal: 2000

Footnote for significance levels

* Jonckheere <5%

** Jonckheere <1%

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
After twofold oral application of 1000, 2500 and 5000 mg/kg bw, butyl methoxydibenzoylmethane induces neither chromosome breaks nor mitotic non-disjunctions in bone marrow cells of mice.
Executive summary:

Butyl methoxydibenzoylmethane (BMDBM), an UVA sunscreen, was evaluated for a potential induction of chromosome breaks and/or mitotic non-disjunctions in vivo by means of the micronucleus test.

After twofold oral application of 1000, 2500 and 5000 mg BMDBM per kg body-weight 30 and 6 hours prior to sacrifice of the mice, no compound related increase of micronuclei could be observed. The dose of 5000 mg/kg is the highest applicable one as determined by preliminary experiments.

It is therefore concluded that under the experimental conditions described in this report, BMDBM induces neither chromosome breaks nor mitotic non-disjunctions in mouse bone marrow cells.