Nickel(2+) propionate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference 1

Reference Type:

other: ECHA disseminated Dossier

Title:

ECHA disseminated Dossier of Nickel sulfate (CAS 7786-81-4)

Year:

2007

Bibliographic source:

ECHA disseminated Dossier of Nickel sulfate (CAS 7786-81-4), query date 2020-11-25

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

mammalian erythrocyte micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

nickel(2+);sulfate;hexahydrate

EC Number:

600-152-3

Cas Number:

10101-97-0

Molecular formula:

H12NiO10S

IUPAC Name:

nickel(2+);sulfate;hexahydrate

Specific details on test material used for the study:

nickel sulfate hexahydrate

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Raleigh, NC, USA.
- Age at study initiation: 8 weeks
- Weight at study initiation: 239-267 g
- Fasting period before study: not reported
- Housing: 2 per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 64 - 79 deg F
- Humidity: humidity 30-70%
- Air changes (per hr): 10 per hr
- Photoperiod (hrs dark / hrs light): 12 hr light/dark cycle.

IN-LIFE DATES: From: April 21, 2003 To: Aug. 2003

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle/solvent used: Cell culture control water
- Lot No: 017156 and 01100526

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: each day the test article was prepared freshly by adding to the vehicle. Formulations were held at room temperature.
Animals were dosed by oral gavage once daily for three consecutive days, six males per dose level. The dose levels were 125, 250, or 500 mg/kg bw/day.

Duration of treatment / exposure:

3 days

Frequency of treatment:

Once daily

Post exposure period:

24 hours after 3rd dose

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

500 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

250 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

125 mg/kg bw/day (nominal)

No. of animals per sex per dose:

6 males

Control animals:

yes, concurrent vehicle

Positive control(s):

Cyclophosphamide was used as the positive control administered by oral gavage dissolved in deionized water at a dose of 60 mg/kg bw.

Examinations

Tissues and cell types examined:

Animals were euthanized approximately 24 hours after the third dose for extraction of bone marrow.
Blood was also collected prior to euthanization.
Nickel in bone marrow and blood was analyzed by AAS.

Details of tissue and slide preparation:

Following centrifugation to pellet the marrow, the supernatant was spread on slides, fixed with methanol and stained in acridine orange, dried, and analyzed under fluorescent microscopy.

Evaluation criteria:

Slides were scored for micronuclei and to determine the PCE to NCE cell ratio. The percent micronucleated cells was determined by analyzing micronuclei from at least 2000 PCEs per animal. The criteria were those of Schmid 1976.

Statistics:

Data analysis was conducted using ANOVA

Results and discussion

Test results

Key result

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Remarks:

no cytotoxicity effects on bone marrow even at maximum tolerated dose established based on mortality and clinical observations

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

RESULTS OF RANGE-FINDING STUDY
- Dose range: 125-1750 mg/kg bw/day
- No cytotoxicity observed at 750 or 1000 mg/kg bw/day. Mean PCE:NCE ratios were 0.32 and 0.64 compared to 0.81 (control)
The maximum tolerated dose was estimated at 500 mg/kg bw/day

RESULTS OF DEFINITIVE STUDY
Clinical signs of toxicity were noted in all treatment animals including hypoactivity, salivation, black feces, irregular respiration, squinted/closed eyes.
No mortality occurred.
Nickel did not significantly increase micronucleated PCEs at any dose level. Nickel was not significantly cytotoxic to bone marrow at any dose level.
Dose-dependent nickel concentrations were detected in plasma and bone marrow samples.
The author's suggest the results support the non-genotoxic mode of action for soluble nickel.

Applicant's summary and conclusion

Conclusions:

The test substance nickel sulfate hexahydrate was evaluated as negative in the rat bone marrow micronucleaus assay under the conditions of this assay.