Reaction mass of aluminium fluoride and chromium trifluoride and nickel difluoride

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

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

Study period:

data not available

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study meets accepted scientific principles, acceptable for assessment.

Data source

Reference

Reference Type:

publication

Title:

Cytotoxic effect of nickel chloride on the somatic chromosomes of swiss albino mice mus musculus

Author:

Mohanty P.K.

Year:

1987

Bibliographic source:

Current Science, Vol. 56, No. 22

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

yes

Remarks:

No positive control, No determination of the mitotic index.

GLP compliance:

no

Type of assay:

chromosome aberration 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 chloride
- Physical state: no data
- Analytical purity: no data
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Storage condition of test material: no data

Test animals

Species:

mouse

Strain:

other: Swiss albino mice mus musculus

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: 10 - 12 weeks old
- Weight at study initiation: no data
- Assigned to test groups randomly: no data
- Fasting period before study: no data
- Housing: no data
- Diet: no data
- Water: no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: no data

Details on exposure:

The effect of different doses of nickel chloride with 3 different exposures was studied on the mice. In chronic treatment the highest dose was divided into 5 equal parts and the individual mouse was injected with each fraction 5 times at intervals of 24 hr and the animals sacrificed 24 hr after the last injection.

Duration of treatment / exposure:

Acute treatment: one injection
Chronic treatment: 5 times at intervals of 24 hr

Frequency of treatment:

Acute treatment: one injection
Chronic treatment: 5 times at intervals of 24 hr

Post exposure period:

6, 24 and 48 hr for each dose.

Doses / concentrations

Remarks:

Doses / Concentrations:
24, 12 and 6 mg/kg bw
Basis:
nominal conc.

No. of animals per sex per dose:

No data

Control animals:

yes

Positive control(s):

No data

Examinations

Tissues and cell types examined:

Cytological preparations of bone-marrow cells were carried out.

Details of tissue and slide preparation:

No data

Evaluation criteria:

No data

Statistics:

Statistical evaluation by 't-test' was performed.

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:

not examined

Additional information on results:

Qualitatively, the chemical induced general physiological effects like corrosion, chromatin and centromeric stretching. Quantitative scoring indicates chromatid gaps and breaks, exchange of chromatid and centromeric fission. Biometrical aspects show that all the doses induced the highest effect after 24 hr of exposure and irrespective of the dose and hour of acute exposures, the highest frequency of aberration (4.33 %) was induced by the dose of 12 mg/kg body weight after 24 hr exposure. considering the frequency of gps and breaks, it is evident that a greater number of gaps is induced rather than breaks.
The combined distribution of gap and break points obtained from all the treatments in bone-marrow cells was analysed to determine the localized effects produced by the chemical. Results indicate that the distal end of longsized chromosomes is comparatively more susceptible to nickel chloride. considering the initial action on the protein moety of the chromatids, the ditribution of gaps is greater than breaks irrespective of the dose and hour of treatment. Also, larger size chromosomes are more affected to gaps and breaks. Statistical evaluation by 't-test' show that aberrations induced by all the acute doses differ significantly from the control.

Any other information on results incl. tables

Table 1 : Frequency of chromosal aberration in bone-marrow cells of mice induced by Nickel chloride treated intraperitoneally

Dose mg/kg	Exposure time (hr)	No. Of cells studied	Chomatid		Fragment	Exchange	Centromeric fission	Total	% of Aberration +/- S.E.	t-value
			Gap	Break
6	6	300	3	2	1	1	-	7	2.33 +/- 0.32
	24	300	6	4	-	-	-	10	3.33 +/- 0.32	6.11*
									2.66 +/- 0.32
12	6	300	5	3	-	1	-	9	3.00 +/-0.57
	24	300	7	4	2	-	-	13	4.33 +/- 0.66	7.03*
	48	300	6	3	-	1	1	11	3.66 +/- 0.32
24	6	300	5	3	-	-	-	8	2.66 +/- 0.32
	24	300	7	4	-	-	1	12	4.00 +/- 0.99	6.25*
	48	300	5	4	1	-	-	10	3.33 +/- 0.57
Chronic 5 x 4.8	120	300	5	4	2	2	1	14	4.66 +/- 0.87
Control (pooled)		900	4	2	-	-	-	6	0.66 +/- 0.57

*P< 0.01 (significant at 0.01 % level); *P - calculated from t-table.

Table 2: Region-wise frequency distribution of gaps and breaks

Region of the chromosomes	Nature of aberration
	Gap	Break
Proximal	4	3
Middle	31	9
Distal	19	22

Table 3: Size-wise frequency distribution of gaps and breaks

Size of the chromosome according to length	No. Of chromosomes	Nature of aberration
		Gap	Break
Long size	6 pairs	4	3
Medium size	10 pairs	31	9
Short size	4 pairs	19	22

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): positive
Under the conditions of this test, the frequency of chromosomal aberration in bone-marrow cells of mice was induced by Nickel chloride.

Executive summary:

In a chromosome aberration test (Mohanty; 1987), Swiss albino mice were treated intraperitoneally with nickel chloride at doses of 6, 12 and 24 mg/kg bw. The effect of different doses of nickel chloride with 3 different exposures (6, 24 and 48 hr for each dose) was studied in the mice. In chronic treatment the highest dose of 24 mg/kg bw was divided into 5 equal parts and the individual mouse was injected with each fraction 5 times at intervals of 24 hr and animals sacrificed 24 hr after the last injection. Cytological preparations of bone-marrow cells were carried out following the conventional technique. For all treated experiments parallel controls were prepared by injecting equal volumes of distilled water. Qualitatively, the test chemical induced general physiological effects like corrosion, chromatin and centromeric stretching. Quantitative scoring showed chromatid gaps and breaks, exchange of chromatid and centromeric fission after a single administration or chronic treatments. Under the conditions of this test, the frequency of chromosomal aberrations in bone-marrow cells of mice was significantly increased by intraperitoneal administation of nickel chloride.