Nickel dichloride

Specific investigations: other studies

Administrative data

Endpoint:

behavioural effects

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific methods

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Dietary administration of nickel: Effects on behavior and metallothionein levels.

Author:

Nation, J.R., Hare, M. F., Baker, D. M., Clark, D. E. and Bourgeois, A. E.

Year:

1985

Bibliographic source:

Physiol. Behav. 34(3):349-353.

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

No standard guideline followed. Methods described in the following sections.

GLP compliance:

not specified

Type of method:

in vivo

Endpoint addressed:

not applicable

Test material

Test material information

Constituent 1

Reference substance name:

Nickel dichloride

EC Number:

231-743-0

EC Name:

Nickel dichloride

Cas Number:

7718-54-9

Molecular formula:

Cl2Ni

IUPAC Name:

nickel(2+) dichloride

Details on test material:

- Name of test material (as cited in study report): NiCl2
- Molecular formula (if other than submission substance): not different than submission substance
- Molecular weight (if other than submission substance): not different than submission substance
- Smiles notation (if other than submission substance): not different than submission substance
- InChl (if other than submission substance): not different than submission substance
- Structural formula attached as image file (if other than submission substance): not different than submission substance
- Other details on test material not reported or not applicable

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Holtzman Co., Masison WI.
- Age at study initiation: 80 days old
- Weight at study initiation: weighing 180-200 g
- Fasting period before study: no data
- Housing: no data
- Diet (e.g. ad libitum): 10 g food deprivation diet throughout the experiment
- Water (e.g. ad libitum): Drinking water was provided ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS: not reported
IN-LIFE DATES: not reported

Administration / exposure

Route of administration:

oral: feed

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: NiCl3 added to feed, other details not reported

DIET PREPARATION
- Rate of preparation of diet (frequency): not reported
- Mixing appropriate amounts with (Type of food): Ni contaminated feed mixed with pellets of Purina laboratory chow in 10 kg batches
- Storage temperature of food: 0 deg C

VEHICLE: distilled water

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

not reported

Duration of treatment / exposure:

14 days

Frequency of treatment:

Daily

Post exposure period:

61 days for behavioral testing

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 10, or 20 mg Ni/kg body weight (as NiCl2)
Basis:
nominal in diet

No. of animals per sex per dose:

6 per dose

Control animals:

yes, plain diet

Details on study design:

Clinical observations conducted throughout the experiment. Body weights were measured on a daily basis. Animals were trained over a period of
61 days to lever press for food on a VI-2 operant training schedule while continuing to experience the indicated daily doses.

Examinations

Examinations:

Nickel in tissues measured. Concentrations of hepatic and renal metallothionein were measured.

Positive control:

none reported

Results and discussion

Details on results:

Those rats treated with 20 mg/kg Ni lever pressed at a significantly lower rate than controls. Behavior of the animals from the 10 mg/kg group was 
not significantly different than control subjects. Atomic absorption spectrophotometric analysis revealed a dose/response accumulation of Ni in the kidney, but analyses of blood, bone, brain, hair, small intestine, liver, and testes did not show differential agent accumulations. Neither hepatic nor 
renal metallothionein levels were increased above control levels.

Applicant's summary and conclusion

Conclusions:

There were no group differences in body weight, and overt signs of toxicity were not observed. The NOAEL was 10 mg Ni/kg bw/day and the LOAEL 20 mg/kg bw/day for reduced rate of lever pressing.

Executive summary:

ROBUST SUMMARY DEVELOPED BY AN INDEPENDENT REVIEWER.

Robust Summary for Nation et al. 1985:

Adult male Sprague-Dawley rats were fed either 0, 10, or 20 mg Ni/kg body weight (as NiCl2) via a 10 g daily food ration. Following 14 days of  

exposure, animals were trained over a period of 61 days to lever press for food on a VI-2 operant training schedule while continuing to  

experience the indicated daily doses. Those rats treated with 20 mg/kg Ni lever pressed at a significantly lower rate than controls. Behavior of  

the animals from the 10 mg/kg group was not significantly different than control subjects. Atomic absorption spectrophotometric analysis revealed  

a dose/response accumulation of Ni in the kidney, but analyses of blood, bone, brain, hair, small intestine, liver, and testes did not show  

differential agent accumulations. Neither hepatic nor renal metallothionein levels were increased above control levels.

STUDY RATED BY AN INDEPENDENT REVIEWER.