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Diss Factsheets

Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The bioaccessability study described in this report was performed according to the "Draft Guidance for RIP 3.6: Bioavailability and Read-Across for Metals and Minerals". GLP study.
Cross-reference
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Objective of study:
absorption
Test guideline
Qualifier:
according to guideline
Guideline:
other: Draft Guidance for RIP 3.6: Bioavailability and Read-Across for Metals and Minerals
Principles of method if other than guideline:
The bioaccessability of nickel oxalate dihydrate was assessed in bioaccessibility studies using simulated gastric, interstitial, and lysosomal (cytosol) fluids. Duplicate extractions were performed at 2, 72 and 72 hours, respectively, and analyzed by inductively coupled plasma mass spectrometry (ICP-MS) for nickel content.
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
nickel (II) oxalate dihydrate
IUPAC Name:
nickel (II) oxalate dihydrate
Constituent 2
Reference substance name:
6018-94-6
Cas Number:
6018-94-6
IUPAC Name:
6018-94-6
Details on test material:
- Name of test material (as cited in study report): nickel oxalate dihydrate
- Molecular formula (if other than submission substance): NiC2O4.2H2O
- Molecular weight (if other than submission substance): 182.7 g/mol
- Structural formula attached as image file (if other than submission substance): see Figure 1
- Physical state: no data
- Analytical purity: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: no data
Radiolabelling:
no

Test animals

Species:
other: not applicable

Administration / exposure

Route of administration:
other: not applicable
Details on study design:
GASTRIC
Each extraction was performed using 0.1 g of sample in 50 mL of synthetic 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 time of 2 hours. Once complete, the solutions were removed from the bath. The solutions were filtered through a 0.45 µm filter and the pH was verified. The filtrates were collected in 8 oz. disposable plastic bottles and kept in a 35 °C incubator until analyzed.

INTERSTITIAL
Each extraction was performed using 0.1 g of sample in 50 mL of synthetic interstitial fluid (pH = 7.4 ± 0.2). Samples were weighed into acid washed 250 mL amber Erlenmeyer flasks. Simulated interstitial 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 HCI 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 time of 72 hours. Once complete, the solutions were removed from the bath. The solutions were filtered through a 0.45 µm filter and the pH was verified. The filtrates were collected in 8 oz. disposable plastic bottles and kept in a 35 °C incubator until analyzed.

LYSOSOMAL
Each extraction was performed using 0.1 g of sample in 50 mL of synthetic lysosomal Fluid (pH = 4.5 to 5.0). Samples were weighed into acid washed 250 mL amber Erlenmeyer flasks. Lysosomal 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 time of 72 hours. Once complete, the solutions were removed from the bath. The solutions were filtered through a 0.45 µm filter and the pH was verified. The filtrates were collected in 8 oz. disposable plastic bottles and kept in a 35 °C incubator until analyzed.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
GASTRIC FLUID
- After 2 hours, 9155 and 9450 ug Ni/g sample (0.92 and 0.95%) were extracted from duplicate samples of synthetic gastric fluid.
- In the blank, < 25 ug Ni/g sample was detected in both replicates.

INTERSTITIAL FLUID
- After 72 hours, 3530 and 3955 ug Ni/g sample (0.35 and 0.40%) were extracted from duplicate samples of synthetic interstitial fluid.
- In the blank, < 25 ug Ni/g sample was detected in both replicates.

LYSOSOMAL (CYTOSOL) FLUID
- After 72 hours, 75,500 and 74,260 ug Ni/g sample (7.6 and 7.4%) were extracted from duplicate samples of synthetic lysosomal fluid.
- In the blank, < 25 ug Ni/g sample was detected in both replicates.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results

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