Trinickel dicitrate

Genetic toxicity: in vivo

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 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 restrictions (limited documentation)

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Modifying role of Phyllanthus emblica and ascorbic acid against nickel clastogenicity in mice.

Author:

Dhir, H. et al.

Year:

1991

Bibliographic source:

Cancer Letters 59, 9-18

Reference 2

Reference Type:

secondary source

Title:

Nickel Chloride, CAS-No.: 7718-54-9, EINECS-No.: 231-743-0, RISK ASSESSMENT, Final version March 2008, Chapters 0, 1, 2, 4, 5, 6 & 7 –human health only

Author:

Danish Environmental Protection Agency

Year:

2008

Bibliographic source:

European Union Risk Assessment Report

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

yes

Remarks:

1000 NCEs und PCEs were counted per animal

GLP compliance:

not specified

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Nickel chloride

EC Number:

253-399-0

EC Name:

Nickel chloride

Cas Number:

37211-05-5

IUPAC Name:

nickel(2+) dichloride

Details on test material:

- Name of test material (as cited in study report): nickel chloridex6H20; Sarabhai M. Chemicals, India
- Molecular weight (if other than submission substance): 237.71
- Analytical purity: no data

Test animals

Species:

mouse

Strain:

Swiss

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 22 ± 5 g
- Diet (e.g. ad libitum): commercial pellet diet (Lipton, India)
- Water (e.g. ad libitum): deionised water


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 50 ± 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

saline

Details on exposure:

The animals were injected with the metal salt solution twice. The two injections were 24 h apart.

Duration of treatment / exposure:

two i. p. injections

Frequency of treatment:

twice

Post exposure period:

24 and 48 h after the second dose

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
10, 20 and 40 mg/kg bw
Basis:
nominal conc.
nickel chloride

Doses / concentrations 2

Remarks:

Doses / Concentrations:
10.6, 21.1 and 42.2 mg/kg bw
Basis:
nominal conc.
nickel citrate calculated from nickel chloride

No. of animals per sex per dose:

6

Control animals:

yes, concurrent vehicle

Positive control(s):

mitomycin C
- Route of administration: intraperitoneal
- Doses / concentrations: 1.5 mg/kg bw

Examinations

Tissues and cell types examined:

bone marrow from the femurs

Details of tissue and slide preparation:

DETAILS OF SLIDE PREPARATION:
The femur bones were flushed out in 1% sodium citrate solution, centrifuged after 5 min and the slides were prepared by smear drawing. After air drying, the slides were stained in Giemsa-May Gruenwald solution and coded.

METHOD OF ANALYSIS:
500 polychromatic erythrocytes (PCEs) were scored per animal. To obtain the ration of normochromatic erythrocytes (NCEs) to PCEs, a total of approx. 1000 NCEs and PCEs were counted per animal.

Statistics:

two-way ANOVA test and Duncan's multiple range test

Results and discussion

Test results

Sex:

not specified

Genotoxicity:

positive

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Any other information on results incl. tables

	Sampling time [h]	% of MN in PCE± SEM	NCE/PCE ratio± SE
0	24	0.233± 0.061	0.985± 0.009
	48	0.167± 0.061	1.010± 0.024
10	24	0.933± 0.191	1.003± 0.007
	48	0.966± 0.033	1.002± 0.006
20	24	1.566± 0.174	1.000± 0.004
	48	1.033± 0.061	0.998± 0.005
40	24	2.400± 0.163	1.078± 0.017
	48	1.867± 0.217	1.016± 0.008
Mitomycin C	24	2.633± 0.280	1.067± 0.011
	48	2.567± 0.245	1.053± 0.024

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): positive