Reaction mass of cobalt sulphide and nickel sulphide and trinickel disulphide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Meets generally accepted scientific standards, well documented and acceptable for publication.

Data source

Reference

Reference Type:

publication

Title:

Distribution of Various Nickel Compounds in Rat Organs After Oral Administration

Author:

ISHlMATSU S, KAWAMOTO T, MATSUNO K, KODAMA Y

Year:

1995

Bibliographic source:

Biological Trace Element Research. 49: 43-52.

Materials and methods

Objective of study:

distribution

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

10 mg Ni as Ni3S2 in 5% saline was administered to rats by gavage and sacrificed 24 hr after exposure.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Trinickel disulphide

EC Number:

234-829-6

EC Name:

Trinickel disulphide

Cas Number:

12035-72-2

Molecular formula:

Ni3S2

IUPAC Name:

trinickel disulfide

Details on test material:

- Name of test material (as cited in study report): Ni3S2

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
- Weight at study initiation: 200 g
- Acclimation period: 2 days

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 5% saline

Details on exposure:

VEHICLE
- Justification for use and choice of vehicle (if other than water): increased solubility

Duration and frequency of treatment / exposure:

single exposure

Doses / concentrations

Dose / conc.:

10 other: mg

Remarks:

Ni as Ni3S2

No. of animals per sex per dose / concentration:

8 males

Control animals:

yes, concurrent vehicle

Positive control reference chemical:

Not applicable.

Details on study design:

Not applicable.

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled (delete / add / specify): urine, blood, lung, liver, kidney, spleen, pacreas, heart, brain
- Time and frequency of sampling: 24 hr


METABOLITE CHARACTERISATION STUDIES
After weighing each organ, it was treated with a mixture of nitric acid and sulfuric acid until completely digested, and the solution was brought to a certain volume with 0.1N nitric acid. Blood samples were used for analysis after being diluted 10 times with 0.1N nitric acid. In addition, 24-h urine was collected by metabolic cage, and each 5 mL of urine was completely digested with nitric acid and brought to a certain volume with 0.1N nitric acid in the same way as the organs. The Ni concentration in the sample solution was determined by a flameless atomic absorption spectrophotometry; the detection limit was 1 ppb.

Statistics:

Not reported.

Results and discussion

Preliminary studies:

Preliminary data indicated that the soluble Ni compounds were excreted for the most part within 72 h after the oral administration and the retained amount of Ni in the organ was small. Therefore, the animals were sacrificed 24 h after the administration.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

In all, 0.47% of adminstered dose was absorbed (based on Ni levels in organs, blood, and urine) at 24 hr.

Details on distribution in tissues:

Exposure to Ni3S2 resulted in a significant increase in Ni levels in the lung, liver, and kidney.

Transfer into organs

Transfer into organs 1

Test no.:

#1

Transfer type:

other: mouth to lungs

Observation:

distinct transfer

Transfer into organs 2

Test no.:

#2

Transfer type:

other: mouth to liver

Observation:

distinct transfer

Transfer into organs 3

Test no.:

#3

Transfer type:

other: mouth to kidney

Observation:

distinct transfer

Transfer into organs 4

Test no.:

#4

Transfer type:

other: mouth to spleen

Observation:

no transfer detectable

Transfer into organs 5

Test no.:

#5

Transfer type:

other: mouth to pancreas

Observation:

no transfer detectable

Transfer into organs 6

Test no.:

#6

Transfer type:

other: mouth to heart

Observation:

no transfer detectable

Transfer into organs 7

Test no.:

#7

Transfer type:

other: mouth to brain

Observation:

no transfer detectable

Details on excretion:

> 93% of the absorbed dose (44ug/47ug) was excreted in the urine by 24-hrs post dose administration.

Toxicokinetic parameters

Test no.:

#1

Toxicokinetic parameters:

other: absorbed fraction of total oral dose: 0.47%

Metabolite characterisation studies

Metabolites identified:

no

Details on metabolites:

not relevant

Any other information on results incl. tables

Amount of Nickel 24 hr After Oral Exposure
	ug of Ni
	Organs	Blood	Urine	Total	AbsorbedFraction, %
Ni3S2	2.9 (2.0)	0.6 (0.4)	44 (16)	47 (15)	0.47

Date are Mean +/- (SD)

Nickel Concentrations in Organs Significantly Elevated at 24 Hours After Exposure

	Lung	Liver	Kidney
Ni3S2	0.17 (0.14)	0.07 (0.03)	1.2 (0.9)
Control	0.04 (0.01)	0.03 (0.01)	0.03 (0.01)

Applicant's summary and conclusion

Conclusions:

Low bioaccumulation potential based on study results
The authors concluded that these results suggest that the kinetic behavior of Ni compounds administered orally is closely related with the solubility of Ni compounds, and that the solubility of Ni compounds is one of the important factors for determining the health effect of Ni compounds.

Executive summary:

Ishimatsu et al. (1995) examined the solubility and distribution of eight Ni compounds (including Ni3S2) in rats following oral exposure. Solubility of 300 mg of each compound was measured in 50 mL of distilled water or saline. Of the 8 compounds examined, Ni3S2 exhibited relatively high solubility – 517-572 μg/mL versus ~ 1 and 4 μg/mL for green and black NiO, respectively. For oral exposure, each nickel compound was administered by gavage (10 mg in 5% saline) and rats were sacrificed 24 hr after exposure. No significant changes in body weight or organ weights (lung, liver, kidney, spleen, pancreas, heart, and brain) following Ni3S2 exposure were observed. Ni concentrations were measured in lung, liver, kidney, spleen, pancreas, heart, blood, and brain via atomic absorption spectrophotometry. Relative to levels of Ni in control tissues, Ni levels were significantly elevated in the lung (0.17 vs. 0.04 μg/g), liver (0.07 vs. 0.03 μg/g), and kidney (1.2 vs. 0.03 μg/g) of Ni3S2-treated animals. In all, only 0.47% of the administered Ni3S2 was measurable in organs, blood or urine 24 hr after exposure. The authors concluded that these results suggested that the kinetic behavior of Ni compounds administered orally is closely related with the solubility of Ni compounds, and that the solubility of Ni compounds is one of the important factors for determining the health effect of Ni compounds (however health effects were not evaluated in this study). STUDY RATED BY AN INDEPENDENT REVIEWER