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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:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Published NTP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: NTP protocol
Principles of method if other than guideline:
The induction of peripheral blood erythrocyte micronuclei was investigated in mice follwoing the oral administration of sodium dichromate for 3 months.
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
See details presented in the other 90-day NTP studies. A coded aliquot of the test material was sent to the testing laboratory.

Test animals

Species:
mouse
Strain:
other: various: B6C3F1, BALB/c, and am3-C57BL/6
Sex:
male/female

Administration / exposure

Route of administration:
oral: drinking water
Duration of treatment / exposure:
90 days
Frequency of treatment:
Continuous (administration via drinking water)
Post exposure period:
None
Doses / concentrations
Remarks:
Doses / Concentrations:
62.5-100 mg/l
Basis:
nominal in water
sodium dichromate dihydrate
No. of animals per sex per dose:
Five
Control animals:
yes, concurrent no treatment

Examinations

Tissues and cell types examined:
Peripheral blood erythrocytes

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
ambiguous
Remarks:
Positive in one strain
Toxicity:
yes
Remarks:
Reduced PCE count in one assay
Vehicle controls valid:
not applicable
Negative controls valid:
yes
Positive controls valid:
not applicable

Any other information on results incl. tables

The results of the micronucleus tests conducted in three strains of mice were variable:

Study 1

Micronucleus frequencies were determined in peripheral blood erythrocytes of male and female B6C3F1 mice administered sodium dichromate dihydrate over an exposure concentration range of 62.5 to 1000 mg/L for 3 months. No significant increases were seen in micronucleated normochromatic erythrocytes in male or female mice over the exposure concentration range tested; there was a decrease in the percentage of polychromatic erythrocytes among total erythrocytes (an indication of bone marrow toxicity), but the changes were small and did not clearly correlate with exposure concentration.

Study 2

Micronucleus frequencies were evaluated in male B6C3F1, BALB/c, and am3 -C57BL/6 mice administered sodium dichromate dihydrate over an exposure concentration range of 62.5 to 250 mg/L in drinking water for 3 months. An increase in micronucleated erythrocytes that was judged to be equivocal was noted in male B6C3F1 mice, based on the trend test (P=0.031), which showed an increase in micronucleated normochromatic erythrocytes that did not reach statistical significance (required P value of 0.025); no exposed groups were significantly increased over the control group in this study. No increase in micronucleated normochromatic erythrocytes was observed in male BALB/c mice (Table B4). A significant exposure concentration-related increase (P<0.001) in micronucleated erythrocytes was noted in male am3-C57BL/6 mice (Table B5). In this study, two of three dose groups were significantly (P<0.008) elevated over the control group. No significant effect of chemical exposure on the percentage of polychromatic erythrocytes was observed in any of the three micronucleus tests conducted in study 2.

Study 1

B6C3F1

Male

Female

Male

Female

Micronucleated NCEs (/1000)

PCEs (%)

0

2.70

1.70

4.1

3.6

62.5

2.60

1.20

3.5

2.5

125

2.20

1.60

3.1

3.4

250

3.70

1.80

3.3

3.9

500

2.50

2.10

2.7

3.2

1000

2.00

1.90

3.3

2.7

Study 2

B6C3F1

0

2.20

-

3.3

-

62.5

3.20

-

3.6

-

125

3.00

-

3.2

-

250

3.80*

-

2.8

-

BALB/c

0

4.70

-

3.7

-

62.5

3.90

-

4.0

-

125

3.30

-

3.3

-

250

4.20

-

3.5

-

am3-C57BL/6

0

1.65

-

2.9

-

62.5

2.50

-

2.8

-

125

3.05

-

2.9

-

250

3.72*

-

2.6

-

*significant by the trend test

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): ambiguous
A significant increase in the frequency of peripheral blood erythrocyte micronuclei was seen in one (transgenic) mouse strain under the conditions of this study; similar findings were not apparent in the other strains.
Executive summary:

The potenital of sodium dichromate to induce micronuclei was investigated in the peripheral blood erythrocytes of three strains of mice following administration via drinking water for 3 months. A significant increase in the frequency of micronuclei was seen in the transgenic am3 -C57/BL6 strain, however similar findings were not apparent in B6C3F1 of BALB/c mice. The results of this study are therefore equivocal.