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Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment.
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008

Materials and methods

Objective of study:
other: Leaching of nickel matte samples in syntethic biological fluids (termed bioaccessibility).
Test guideline
Qualifier:
no guideline available
Deviations:
not applicable
Principles of method if other than guideline:
In situations where the bioavailability of a metal substance is not known or not feasible to determine experimentally, the amount of ion “available for absorption” may be measured using in vitro methods. In this application the dissolution (e.g., elution or extraction) of metal ion from surrogate (synthetic) tissue fluids is measured. The resultant value is termed bioaccessibility and is defined as the amount of a substance (e.g., metal ion) available for absorption. This report measured bioaccessibility of nickel matte samples as a surrogate for bioavailability.
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
Matte, nickel
EC Number:
273-749-6
EC Name:
Matte, nickel
Cas Number:
69012-50-6
Molecular formula:
Not applicable
IUPAC Name:
Nickel matte
Details on test material:
Composition(s) tested:

Nickel Sulphidic Matte with Copper >8% (including Cobalt 0.1 -<1%) [Results also apply to: Nickel Sulphidic Matte with Copper >8% (including Cobalt ≥1 - <3%)]

Nickel Sulphidic Matte (including Cobalt 0.1 -<1%) [Results also apply to: Nickel Sulphidic Matte (including Cobalt ≥1 - <3%)]

Nickel Metallic Matte (including Cobalt ≥3%) [Results also apply to: Nickel Metallic Matte (including Cobalt 0.1 -<1%) and Nickel Metallic Matte (including Cobalt ≥1 - <3%)]






Radiolabelling:
no

Test animals

Species:
other: not applicable
Strain:
other: not applicable
Details on test animals or test system and environmental conditions:
Not applicable

Administration / exposure

Route of administration:
other: not applicable
Vehicle:
other: not applicable
Details on exposure:
Not applicable
Duration and frequency of treatment / exposure:
Not applicable
Doses / concentrations
Remarks:
Doses / Concentrations:
Not applicable
No. of animals per sex per dose / concentration:
Not applicable
Control animals:
other: not applicable
Positive control reference chemical:
Not applicable
Details on study design:
For each matte group tested the methods utilized included:

Gastric fluid:
Each extraction was performed using 0.1 gram of sample in 50 ml of Simulated Gastric Fluid (pH < 1.5). Samples were weighed into acid washed 250 ml amber Erlenmeyer flasks. Gastric Fluid was added to the flasks and they were then swirled to mix compound and fluid. The pH was checked for each solution and adjusted if necessary with 2N HCl.
The opening of the flasks were covered with parafilm and aluminum foil. The flasks were then placed in a preheated 37° C reciprocal shaker bath. The samples were allowed to shake for the required extraction times. Once complete, the solutions were removed from the bath. The pH was checked and the solutions were filtered through a 0.45 um filter. The filtrates were collected in 8 oz. disposable plastic bottles and kept in a 35° C incubator until analyzed.

Alveolar fluid:
Each extraction was performed using 0.1 gram of sample in 50 ml of Simulated Alveolar Fluid (pH = 7.4 + 0.2). Samples were weighed into acid washed 250 ml amber Erlenmeyer flasks. Simulated Alveolar Fluid was added to the flasks and they were then swirled to mix compound and fluid. The pH was checked for
each solution and adjusted if necessary with 2N HCl or 1N NaOH. To keep the extraction pH at 7.4, 5% CO2 in Nitrogen was bubbled into the solution at a rate of 50 cc/min. The bubbling solutions were placed in a preheated 37° C
reciprocal shaker bath. The samples were bubbled and allowed to shake for the required extraction times. Once complete, the solutions were removed from the bath. The pH was checked and the solutions were filtered through a 0.45 um filter. The filtrates were collected in 8 g disposable plastic bottles and kept in a 35° C incubator until analyzed.

Artificial Perspiration:
Each extraction was performed using 0.1 gram sample in 50 ml of Artificial Perspiration (pH = 6.5 + 0.1). Samples were weighed into acid washed 250 ml amber Erlenmeyer flasks. Perspiration was added to the flasks and they were then swirled to mix compounds and fluid. The pH was checked for each solution and adjusted if necessary with 2N HCl or 1 N NaOH. The opening of the flasks were covered with parafilm and aluminum foil. The flasks were then placed in a preheated 37° C water bath. No shaking was performed. Once the extraction time was complete, the solutions were removed from the bath. The pH was checked and the solutions were filtered through a 0.45 um filter. The filtrates were collected in 8 oz. disposable plastic bottles and kept in a 35° C incubator until analyzed.
Details on dosing and sampling:
Not applicable
Statistics:
Not applicable

Results and discussion

Preliminary studies:
Not applicable

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Not applicable
Details on distribution in tissues:
Not applicable
Details on excretion:
Not applicable

Metabolite characterisation studies

Metabolites identified:
not measured
Details on metabolites:
Not applicable

Any other information on results incl. tables

Data on elemental content percent release over time (range of 2-72 hours) in various in synthetic biological fluids for each nickel matte type (assessed at 2 gram/liter) are listed in the following tables.

Table68. Results of bioaccessibility studies ona representative sample from theNickel Matte (sulphidic high-copper) group

% Release in Artificial Gastric Fluid

Element

2 hr

5 hr

24 hr

72 hr

Cobalt

3.0

4.5

29.1

37.3

Cobalt (duplicate)

3.0

5.6

29.3

38.2

Copper

0.37

0.22

0.01

0.06

Copper (duplicate)

0.36

0.21

0.02

0.06

Arsenic

-

-

-

-

Arsenic (duplicate)

-

-

-

-

Nickel

1.2

1.9

14.2

28.7

Nickel (duplicate)

1.0

2.2

14.9

27.7

% Release in Artificial Alveolar Fluid

Element

2 hr

5 hr

24 hr

72 hr

Cobalt

-

-

-

-

Cobalt (duplicate)

-

-

-

-

Copper

-

-

-

-

Copper (duplicate)

-

-

-

-

Arsenic

-

-

-

-

Arsenic (duplicate)

-

-

-

-

Nickel

0.01

0.03

0.03

0.03

Nickel (duplicate)

0.01

0.03

0.03

0.04

% Release in Artificial Perspiration

Element

2 hr

5 hr

24 hr

72 hr

Cobalt

-

-

0.93

1.7

Cobalt (duplicate)

-

-

0.85

1.7

Copper

0.03

0.07

0.15

0.38

Copper (duplicate)

0.02

0.06

0.15

0.38

Arsenic

-

-

-

-

Arsenic (duplicate)

-

-

-

-

Nickel

0.04

0.06

0.25

0.90

Nickel (duplicate)

0.04

0.06

0.25

0.92

Table69. Results of bioaccessibility studies on a representative sample from theNickel Matte (sulphidic low-copper) group

% Release in Artificial Gastric Fluid

Element

2 hr

5 hr

24 hr

72 hr

Cobalt

3.0

4.5

29.1

37.3

Cobalt (duplicate)

3.0

5.6

29.3

38.2

Copper

0.37

0.22

0.01

0.06

Copper (duplicate)

0.36

0.21

0.02

0.06

Arsenic

-

-

-

-

Arsenic (duplicate)

-

-

-

-

Nickel

3.1

9.6

23.3

41.5

Nickel (duplicate)

3.3

9.8

24.3

43.5

% Release in Artificial Alveolar Fluid

Element

2 hr

5 hr

24 hr

72 hr

Cobalt

-

-

-

-

Cobalt (duplicate)

-

-

-

-

Copper

-

-

-

-

Copper (duplicate)

-

-

-

-

Arsenic

-

-

-

-

Arsenic (duplicate)

-

-

-

-

Nickel

-

0.01

0.01

0.01

Nickel (duplicate)

0.01

-

0.01

0.01

% Release in Artificial Perspiration

Element

2 hr

5 hr

24 hr

72 hr

Cobalt

-

-

0.43

0.48

Cobalt (duplicate)

-

-

0.48

0.60

Copper

-

-

-

-

Copper (duplicate)

-

-

-

-

Arsenic

-

-

-

-

Arsenic (duplicate)

-

-

-

-

Nickel

0.01

0.03

0.13

0.37

Nickel (duplicate)

0.02

0.03

0.14

0.41

Table70. Results of bioaccessibility studies on a representative sample from the Nickel Matte (metallic) group

% Release in Artificial Gastric Fluid

Element

2 hr

5 hr

24 hr

72 hr

Cobalt

3.0

6.4

46.7

101.3

Cobalt (duplicate)

3.2

6.5

46.5

98.2

Copper

1.1

0.77

0.48

0.67

Copper (duplicate)

1.2

0.82

0.51

0.67

Arsenic

-

-

-

9.8

Arsenic (duplicate)

-

-

-

9.8

Nickel

1.9

4.9

26.7

77.8

Nickel (duplicate)

2.3

5.7

26.5

77.0

% Release in Artificial Alveolar Fluid

Element

2 hr

5 hr

24 hr

72 hr

Cobalt

-

-

-

-

Cobalt (duplicate)

-

-

-

-

Copper

-

-

-

-

Copper (duplicate)

-

-

-

-

Arsenic

-

-

-

-

Arsenic (duplicate)

-

-

-

-

Nickel

-

0.01

0.02

0.02

Nickel (duplicate)

-

0.01

0.02

0.02

% Release in Artificial Perspiration

Element

2 hr

5 hr

24 hr

72 hr

Cobalt

-

-

0.25

0.83

Cobalt (duplicate)

-

-

0.22

0.75

Copper

-

-

0.13

0.13

Copper (duplicate)

-

-

0.15

0.15

Arsenic

-

-

-

-

Arsenic (duplicate)

-

-

-

-

Nickel

0.02

0.06

0.31

1.19

Nickel (duplicate)

0.02

0.06

0.23

1.16

 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: Data are available for toxicokinetic analysis of nickel mattes and read-across assessments to nickel and nickel-containing substances.
Executive summary:

STUDY RATED BY AN INDEPENDENT REVIEWER