Sodium zirconium lactate

Genetic toxicity: in vivo

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

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

Test material information

Constituent 1

Reference substance name:

Dichloro(oxo)zirconium

Cas Number:

7699-43-6

Molecular formula:

Cl2OZr

IUPAC Name:

Dichloro(oxo)zirconium

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 or test system 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 / concentrations

Doses / concentrations 1

Dose / conc.:

225 mg/kg bw/day

Remarks:

males

Doses / concentrations 2

Dose / conc.:

750 mg/kg bw/day

Remarks:

males

Doses / concentrations 3

Dose / conc.:

2 250 mg/kg bw/day

Remarks:

males

Doses / concentrations 4

Dose / conc.:

220 mg/kg bw/day

Remarks:

females

Doses / concentrations 5

Dose / conc.:

734 mg/kg bw/day

Remarks:

females

Doses / concentrations 6

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.