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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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restricitions.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1993
Reference Type:
publication
Title:
Evaluation of a Three-Exposure Mouse Bone Marrow Micronucleus Protocol: Results With 49 Chemicals
Author:
Shelby M.D. et al.
Year:
1993
Bibliographic source:
Environ. Mol. Mutagen., 21, 160-179

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
only 5-7 males per dose used, differing staining agent
Principles of method if other than guideline:
NTP Standard protocol
GLP compliance:
not specified
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
All test chemicals were received from the NTP chemical repository (Radian Corporation, Austin, TX).

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male
Details on test animals and environmental conditions:
Male B6C3F1 mice (obtained from the National Toxicology Program production facility at Taconic Farms) of a common age between 9 and 14 weeks and weighing within a 2 g range of a mean weight between 25 and 33 g were used. Additional information on animal husbandry can be found in Tice et al. [1990a].

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: corn oil
Details on exposure:
Injection volume was 0.4 ml.

Duration of treatment / exposure:
one injection/day on 3 consecutive days
Frequency of treatment:
one injection/day on 3 consecutive days
Post exposure period:
1st study: For evaluation of bone marrow smears animals were sacrificed 24 hours after the 3rd exposure; for evaluation of peripheral blood smears
animals were sacrificed 48 hours after the 3rd exposure
2nd study: animals were sacrificed 24 hours after the 3rd exposure for both evaluation of bone marrow smears and evaluation of peripheral blood smears.
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0; 500; 1000; 2000 mg/kg (1st study)
Basis:

Remarks:
Doses / Concentrations:
1000 and 2000 mg/kg (2nd study)
Basis:

No. of animals per sex per dose:
5 (exemption: only 3 animals were scored at the concentration of 2000 mg/kg bw in the first study)
Control animals:
yes, concurrent vehicle
Positive control(s):
7,12-dimethylbenzanthracene (12.5 mg/kg)

Examinations

Tissues and cell types examined:
bone marrow and peripheral blood
Details of tissue and slide preparation:

DETAILS OF SLIDE PREPARATION:
Staining with acridine orange

METHOD OF ANALYSIS:
Bone marrow:
Slides were evaluated for the number of MN-PCE among 2000 PCE and for the percentage of PCE among 200 erythrocytes.
Peripheral blood:
According to the NTP-Standard protocol 2000 PCEs are evaluated for the number of MN-PCE and 1000 erythrocytes are evaluated for teh percentage of PCE among erythrocytes.
Evaluation criteria:
Statistically significant increase in micronuclei.
Statistics:
When corn oil solvent control data were compared (two-tailed t-test) between laboratories, there was no statistically significant differences. But for PBS, the mean of ILS was significantly higher than that for EHRT (P = 0.009). For the positive control data, there were no significant differences between laboratories.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
No signs of toxicity were observed

Any other information on results incl. tables

Table 1: MN data analysis

Dose (mg/kg)

MN-PCE/1000

(No. of animals scored)

P value (a)

Survival

%PCEs (b)

1st study, bone marrow

(Sample collection time: 24 hours)

0.003

0

2.10 +/- 0.62 (5)

5/5

57.3

500

1.80 +/-0.34 (5)

0.685

5/5

56.6

1000

2.20 +/- 0.25 (5)

0.439

5/5

57.1

2000

3.80 +/- 0.70 (5)

0.013

6/6

56.1

Positive control

6.90 +/-

0.87 (5)

0.0001

-

-

2nd study, bone marrow

(Sample collection time: 24 hours)

0.340

0

4.60 +/- 0.64 (5)

5/5

60.9

1000

4.20 +/- 1.21 (5)

0.596

5/5

51.7

2000

5.30 +/- 1.59 (5)

0.344

5/6

56.3

Positive control

8.40 +/-

0.56 (5)

-

-

1st study, peripheral blood (c)

(Sample collection time: 48 hours)

0.964

0

2.70 +/- 0.26 (5)

5/5

1.2

500

3.50 +/- 0.91 (5)

0.154

5/5

1.5

1000

2.40 +/- 0.56 (5)

0.663

5/5

1.1

2000

1.50 +/- 0.76 (3)

0.940

3/5

1.2

2nd study, peripheral blood

(Sample collection time: 24 hours)

0.411

0

4.10 +/-

0.73 (5)

 no data available

  no data available

1000

3.60 +/-

0.93 (5)

0.716

no data available

no data available

2000

4.30 +/-

0.56 (5)

0.413

no data available

no data available

Positive control

8.40 +/-

0.40 (5)

0.0001

no data available

no data available

(a) omitting the high dose value

 (b) ((No. of PCEs)/(No. of PCEs + No. of NCEs)) x 100

(c) no data on positive control available

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative