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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Cytotoxic effects of zirconium oxychloride on bone marrow cells of mice.
Author:
Ghosh, S; Sharma, A; Talukder, G.
Year:
1990
Bibliographic source:
Mutat Res 243:29−33.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
GLP compliance:
not specified
Type of assay:
mammalian bone marrow chromosome aberration test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Specific details on test material used for the study:
Zirconium oxychloride:

Test animals

Species:
mouse
Strain:
other: Swiss Albino
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8-9 Weeks
- Weight at study initiation: 28-30 g
- Diet: Gold Mohur mice feed; manufactured by Lipton India Limited
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Temperature controlled (temperature not specified)

Administration / exposure

Route of administration:
oral: unspecified
Duration of treatment / exposure:
24 h
Frequency of treatment:
Single dose
Post exposure period:
Mice were injected i.p. with 4 mg colchicine 2 hrs before sacrifice
Doses / concentrationsopen allclose all
Dose / conc.:
225 mg/kg bw/day
Remarks:
males
Dose / conc.:
750 mg/kg bw/day
Remarks:
males
Dose / conc.:
2 250 mg/kg bw/day
Remarks:
males
Dose / conc.:
220 mg/kg bw/day
Remarks:
females
Dose / conc.:
734 mg/kg bw/day
Remarks:
females
Dose / conc.:
2 200 mg/kg bw/day
Remarks:
females
No. of animals per sex per dose:
5 males / 5 females per dose
Control animals:
yes, concurrent vehicle

Examinations

Tissues and cell types examined:
After sacrifice, bone marrow was flushed out and prepared for analysis of chromosomal aberrations, following the usual hypotonic acetic acid-ethanol fixation and Giemsa staining schedule
Evaluation criteria:
Slides were coded and scored blind for total chromosomal abnormalities. 50 well-scattered metaphase plates per animal and a total of 250 metaphase plates per sex per treatment group were observed for chromosomal aberrations. 5000 cells per sex per treatment group (1000 cells/animal) were scored to estimate divisional frequency.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
positive
Toxicity:
not specified
Negative controls validity:
valid

Any other information on results incl. tables

Percentages Of Mitotic Division In Bone Marrow Of Mice Treated With Zirconium Oxychloride

Group

Chemical used

Dose (mg/kg b.w.)

Mitotic cells (%)

male

female

male

female

C

Distilled water

-

-

2.74

2.90

I

Zirconium

oxychloride

225

220

3.10

3.96

II

750

734

5.50

5.60

III

2250

2200

4.90

5.80

 

Percentages Of Total Chromosomal Abnormalities In Bone Marrow Of Mice Treated With Zirconium Oxychloride

Group

Chemical used

Dose (mg/kg b.w.)

Mitotic cells (%)

male

female

male

female

C

Distilled water

-

-

5.6

5.2

I

Zirconium

oxychloride

225

220

10.8

10.8

II

750

734

18.0

19.0

III

2250

2200

22.5

24.8

a Number of cells scored per group = 250.

 

Statistical Analysis Of In Vivo Cytogenetic Assay Of Mice Treated With Zirconium Oxychloride

Dose administered

Trend test (z value)

male

female

male

female

mg/kg

log dose

mg/kg

log dose

 

 

0

1.852

0

1.842

 

 

225

2.352

220

2.342

5.508***

6.12***

750

2.875

734

2.865

 

 

2250

3.352

2200

3.342

 

 

Level of significance p < 0.001.

Applicant's summary and conclusion

Conclusions:
A single exposure to zirconium oxychloride at 1/20th, 1/6th and 1/2 of the LD50 in mice significantly enhanced the frequency of aberrant metaphases as compared with the control. The percentages of total abnormalities were increased considerably in both sexes in a dose dependent manner at all concentrations used.
Executive summary:

A single oral administration of an aqueous solution of zirconium oxychloride to mice of both sexes in concentrations 1/20, 1/6, 1/2 of LDs0 induced chromosomal abnormalities in bone marrow cells. The frequencies of aberration were directly proportionate to the concentrations used. Female mice were found to be more

susceptible than male mice, though not to a significantly higher level.