Nickel bis(dihydrogen phosphate)

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, well documented and acceptable for assessment

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:

Distribution of various nickel compounds in rat organs after oral administration.

Author:

Ishimatsu S, Kawamoto T, Matsuno K, Kodama Y.

Year:

1995

Bibliographic source:

Biol. Trace Elements Res. 49 (1): 43 – 52.

Materials and methods

Objective of study:

absorption

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

A particular Test Guideline was not specified in the study.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Nickel sulphate

EC Number:

232-104-9

EC Name:

Nickel sulphate

Cas Number:

7786-81-4

Molecular formula:

NiSO4

IUPAC Name:

nickel(2+) sulfate

Constituent 2

Reference substance name:

22.3% Ni

IUPAC Name:

22.3% Ni

Constituent 3

Reference substance name:

Wako Pure Chem. Ind., Japan

IUPAC Name:

Wako Pure Chem. Ind., Japan

Details on test material:

- Name of test material (as cited in study report): Nickel sulphate hexahydrate
- 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
- Analytical purity: 22.3% Nickel
- All other details on the test material was not reported or is not applicable.
- Other: A solubility test was performed. Three hundred milligrams of each compound was put into 50 mL of distilled water and saline.
The suspension was shaken for 1 wk at 37°C and filtered through a filter paper (Toyo filter paper, No. 5C, Ams., Japan) and
a membrane filter (pore size 0.22 um). The Ni concentration of the filtrate was determined by an atomic absorption spectrophotometry (Hitachi
Polarized Zeeman Effect Atomic Absorption Spectrophotometer, Model Z-8000, Ams., Japan).

Radiolabelling:

no

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kyudo Co., Ltd. (Ams., Japan).
- Age at study initiation: 10 wk of age
- Weight at study initiation: 200 g
- Fasting period before study: Not reported
- Housing: Glass metabolic cages
- Individual metabolism cages: Yes
- Diet (e.g. ad libitum): Not reported
- Water (e.g. ad libitum): Not reported
- Acclimation period: 2 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported

IN-LIFE DATES: Not reported

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 5% starch saline solution

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: Each Ni compound containing 10 mg of Ni was dissolved in a 5% starch saline solution and the solution was administered by gavage to the experimental animals. The control group was also given a 5% starch saline solution.

DIET PREPARATION
- Rate of preparation of diet (frequency): Not reported
- Mixing appropriate amounts with (Type of food): Not reported
- Storage temperature of food: Not reported

VEHICLE
- Justification for use and choice of vehicle (if other than water): Not reported
- Concentration in vehicle: 10 mg of Ni was dissolved in a 5% starch saline solution
- Amount of vehicle (if gavage): Not reported
- Lot/batch no. (if required): Not reported
- Purity: Not reported

HOMOGENEITY AND STABILITY OF TEST MATERIAL: Not reported

Duration and frequency of treatment / exposure:

One dose

Doses / concentrations

Remarks:

Doses / Concentrations:
10 mg of Ni

No. of animals per sex per dose / concentration:

8 males/group

Control animals:

yes

Positive control reference chemical:

None

Details on study design:

- Dose selection rationale: Not reported
- Rationale for animal assignment (if not random): Not reported

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, Distribution)
- Tissues and body fluids sampled: The lungs, liver, kidneys, spleen, pancreas, heart, brain, and blood were taken as samples for the
determination of Ni. The Ni concentration in the sample solution was determined by a flameless atomic absorption spectrophotometry.
- Time and frequency of sampling: 24 h after the administration.

METABOLITE CHARACTERISATION STUDIES: Not applicable

TREATMENT FOR CLEAVAGE OF CONJUGATES (if applicable): Not applicable

Statistics:

Student's T-test

Results and discussion

Preliminary studies:

Solubilities:
Ni-metal - 3.57 ug/ml in saline, 1.13 ug/ml in distilled water
NiSO4 - 32.4 g/100 g (reference value)
NiCl2 - 42.3 g/100 g (reference value)
Ni(NO3)2 - 54.3 g/100 g (reference value)

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The absorbed fraction in the rats given scarcely soluble compounds, was estimated to be 0.09% for the Ni-Metal group and 10-34% for the NiSO4,
NiCl2, and Ni(NO3)2 groups. NiCl2 absorption was 9.8%.

Following administration of a single dose of 10 mg nickel (nickel sulphate in 5% starch saline solution) by gavage to male Wistar rats, the absorbed fraction was 11% 24 hours after oral administration.

Details on distribution in tissues:

Ni Organ Concentrations: Significantly higher concentrations were found in the lungs, kidneys, and pancreas for the Ni-metal group.
Ni concentrations in all organs in the rats given NiSO4, NiCl2, and Ni(NO3)2 were significantly higher than those in the control rats.

Ni Distribution: About 84-87% of the Ni amount was found in the kidneys for the NiCl2 and NiSO4. The ratio in the kidneys for the Ni(NO3)2 and Ni-M groups was 73, and 51%, respectively.

On the other hand, the Ni amount in the liver was higher than that in the kidneys for the NiO(G) group, showing similar results as the control group. The ratio of Ni in the kidneys depended on the solubility of the administered Ni compound.

Transfer into organs

Test no.:

#1

Transfer type:

other: kidney and lung

Observation:

distinct transfer

Remarks:

significantly different than control

Details on excretion:

In the preliminary experiment soluble Ni compounds were excreted within 72 hours after the oral administration.
24 hours after oral administration NiCl2 was measured in the urine at 914 ug.

Toxicokinetic parameters

Toxicokinetic parameters:

other: none reported

Metabolite characterisation studies

Metabolites identified:

not specified

Details on metabolites:

not applicable

Applicant's summary and conclusion

Conclusions:

Following administration of a single dose of 10 mg nickel (nickel sulphate in 5% starch saline solution) by gavage to male Wistar rats, the absorbed fraction was 11% 24 hours after oral administration.

Executive summary:

STUDY RATED BY AN INDEPENDENT REVIEWER.