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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:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Published study of non-standard design, however results are valid and the study is well reported.

Data source

Reference
Reference Type:
publication
Title:
Oral chromium(VI) does not affect the frequency of micronuclei in hematopoietic cells of adult mice and of transplacentally exposed fetuses
Author:
De Flora S, Iltcheva M, Balansky RM
Year:
2006
Bibliographic source:
Mutation Research 610(1-2): 38-47

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The study investigated the effects of oral Cr (VI) on micronucleus frequency in bone marrow or peripheral blood erythrocytes of mice.
GLP compliance:
not specified
Remarks:
published study
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Potassium dichromate, purchased from Sigma Chemical Co.

Test animals

Species:
mouse
Strain:
other: BDF1
Sex:
male
Details on test animals and environmental conditions:
BDF1 mice were 8 months old and weighed an average of 34.9 g. Mice were obtained from the Animal Laboratory National Centre of Oncology, Bulgaria. They were housed in plastic cages on sawdust bedding, and maintained on standard rodent chow and tap water ad libitum. The temperature of the room was maintained at 23±2°C, relative humidity was 50-55%, and a 12 hour light/dark cycle. Mice were acclimatised for 10-15 days.

Administration / exposure

Route of administration:
other: oral drinking water, gavage and i.p.
Vehicle:
None for drinking water groups. Sterile distilled water for gavage and intraperitoneal groups.
Details on exposure:
Male mice received potassium dichromate in the drinking water for 20 days at 0, 10 and 20 mg Cr(VI)/L (n=10). Additional groups of 10 mice each received a single oral gavage dose or a single intrapertioneal dose of 50 mg/kg bw on day 19 (equivalent to 17.7 mg Cr(VI)/kg bw).
Duration of treatment / exposure:
20 days
Frequency of treatment:
Continuous in drinking water or single dose
Post exposure period:
None.
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 10 and 20 mg Cr(VI)/L
Basis:
nominal in water
Remarks:
Doses / Concentrations:
17.7 mg Cr(VI)/kg bw
Basis:
nominal conc.
single gavage/i.p dose
No. of animals per sex per dose:
10
Control animals:
yes, concurrent no treatment
Positive control(s):
Not required.

Examinations

Tissues and cell types examined:
Peripheral blood and bone marrow
Details of tissue and slide preparation:
Peripheral blood samples were collected from the lateral tail vein of the controls and the mice exposed via the drinking water on days 0, 5, 12 and 20. On day 20 all mice were killed and the left femurs removed and dissected for collection of bone marrow cells.
Immediately after collection, duplicate smears of peripheral blood were preprared, air-dried and stained with May-Grunwald-Giemsa. From each mouse, 40000 normochromatic erythrocytes (NCE) were scored for the presence of micronucleated cells.
Immediately after collection duplicate smears of bone marrow cells were prepared, air-dried, and stained with May-Grunwald-Giemsa. 2000 polychromatic erythrocytes (PCE) per mouse were scored for the presence of micronucleated cells. 200 NCE and the corresponding PCE were scored for determining the PCE/NCE ratio.
Statistics:
Student's t-test and ANOVA for repeated measures.

Results and discussion

Test resultsopen allclose all
Sex:
male
Genotoxicity:
negative
Remarks:
oral exposure
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Sex:
male
Genotoxicity:
positive
Remarks:
intraperitoneal exposure
Toxicity:
yes
Additional information on results:
Administration of potassium dichromate in the drinking water for 20 days had no effect on the frequency of micronucleated PCE or the PCE/NCE ratio in bone marrow. There was also no effect on the frequency of micronucleated NCE in peripheral blood. Similarly, a single gavage dose of 17.7 mg Cr(VI)/kg bw had no effect on the frequency of micronucleated PCE or the PCE/NCE ratio in bone marrow.
When administered i.p., potassium dichromate caused an increase in the frequency of micronucleated PCE in bone marrow, but did not affect the PCE/NCE ratio.

Any other information on results incl. tables

There were no effects on body weight change in mice exposed via the drinking water. The daily intakes of chromium were calculated to be approximately 3 and 6 mg/kg bw in the mice drinking water containing 10 and 20 mg Cr (VI)/L, respectively.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: genotoxicity is dependent on route of exposure
Orally adminstered Cr (VI) is adequately detoxified in the gastrointestinal tract before it exerts genotoxic effects, however bypassing the detoxification mechanisms (intraperitoneal route of exposure) results in positive mutagenic responses.
Executive summary:

Potassium dichromate did not affect the frequency of micronucleated polychromatic erythrocytes when administered orally to male mice. However potassium dichromate significantly increased the frequency micronucleated polychromatic erythrocytes when administered intraperitoneally. The authors concluded that orally administered Cr (VI) is adequately detoxified in the gastrointestinal tract before it exerts genotoxic effects, however bypassing the detoxification mechanisms (intraperitoneal route of exposure) results in positive mutagenic responses.