Nickel(2+) hydrogen citrate

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: basic data given

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Long term toxicologic assessment of nickel in rats and dogs.

Author:

Ambrose, A. M. et al.

Year:

1976

Bibliographic source:

Journal of Food Science and Technology 13, 181-187

Reference 2

Reference Type:

secondary source

Title:

Nickel Sulphate, CAS-No.: 7786-81-4, EINECS-No.: 232-104-9, RISK ASSESSMENT Final version March 2008, Chapters 0, 1, 2, 4, 5, 6 & 7 – human health only

Author:

Danish Environmental Protection Agency

Year:

2008

Bibliographic source:

European Union Risk Assessment Report

Materials and methods

Objective of study:

other: distribution and excretion

Principles of method if other than guideline:

Two year feeding-study in dogs. Within this study, tissue storage of nickel as well as nickel excretion in the urine and feces were examined.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

nickel sulphate hexahydrate

IUPAC Name:

nickel sulphate hexahydrate

Details on test material:

- Name of test material (as cited in study report): nickel sulfate hexahydrate
- Molecular formula (if other than submission substance): NiSO4x6H2O
- Analytical purity: no data
- Composition of test material, percentage of components: 22.3% nickel

Radiolabelling:

no

Test animals

Species:

dog

Strain:

Beagle

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: about 6 months
- Housing: individually
- Individual metabolism cages: no
- Diet (e.g. ad libitum): finely ground dog kibbled meal (Radiston Purina, St. Louis, Missouri)
- Water (e.g. ad libitum): water was mixed in the diet

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: diet

Details on exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): daily
- Mixing appropriate amounts with (Type of food): Nickel sulfate was added to the basic diet in amounts calculated to yield the required dose. Weighed amounts of feed, 400 g/d through the first 22 weeks and 450 g/d thereafter, moistened and thoroughly mixed with an equal weight of water, were offered to the dogs.

Duration and frequency of treatment / exposure:

daily for 2 years

Doses / concentrations

Remarks:

Doses / Concentrations:
100, 1000 and 2500 ppm
In week two, the high concentration was adjusted to 1500 ppm because auf severe gastrointestinal effects (emesis, salivation, gastrointestinal irritation). At two-week intervals this dietary nickel level was again raised to 1700, 2100 and 2500 ppm, without any effects.

No. of animals per sex per dose / concentration:

3

Control animals:

yes, plain diet

Details on study design:

Feed consumed was recorded daily and body weights were recorded weekly.

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces
- Time and frequency of sampling: At approx. 12 months, one week collections of excreta were made on one dog of each sex and dose level for analyses of nickel content. During the 23rd and 24th months, one week collections were made on two dogs of each sex and diet level, and three successive weekly collections were made from two other dogs of each sex and diet level. The sixth dog of each sex on each of the nickel-containing diets for 24 months returned to the control diet. Two successive one-week collections of excreta were made following passage of charcoal-marked feces.


At autopsy, specimens of bone, liver, kidney, lung, skeletal muscle and fat were taken from each dog for nickel analysis. Feces were oven-dried and ground and tissue nickel was determined on wet basis (spectrophotometric method of Alexander et al. 1946).

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

Tissue analyses on bone, liver, kidney, lung, skeletal muscle and fat indicated limited retention of Ni. Highest values found were for kidney (4-7 ppm in dogs recieving 2500 ppm), and in one dog 1.6 ppm was found after withdrawal of nickel-containing diet for two weeks.

Details on excretion:

Approx. 1 to 3% of the ingested nickel was excreted in the urine.
Data on excretion in feces showed variable amounts of Ni, inconsistent with the amounts in diet and ingested.