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Toxicological information

Basic toxicokinetics

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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:
August 26,2008
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Not GLP - not enough details on test material
Cross-reference
Reason / purpose:
reference to other study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Internale Guideline from Nipera
Deviations:
not specified
Principles of method if other than guideline:
1) SIMULATED 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 pH was checked for each solution and adjusted if necessary with 2N HCl.The flasks were covered with parafilm and aluminium foil.The flasks were paklced in a preheated 37°C reciprocal shaker bath.The samples were allowed toshake for the required exctraction times.Once complete, the solutions were removed from the bath.The pH was checked and solution were filtered trough a 0.45 µm filter. The filtrated were collected in 8 oz. disposable plastic bottle and kept in a 35°c incubator until analyzed by EPA method #200.8 (ICP/MS).

2)SIMULATED ALVEOLAR FLUID
Each extraction was performed using 0.1 gram of sample in 50 ml of Simulated Alveolar fluid (pH=7.4 ± 0.2). Sample 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 exctaction pH at 7.4,5% CO2 in Nitrogen was bubbled and alloed to shake for the required extraction times.Once complete, the solutions were removed from the bath. The pH was checked and solutions were filtered trough a 0.45 µm filter. The filtrates were collected in 8 g disposable plastic bottles and kept in a 35°C incubator until analyzed.

3)Artificial Perspiration
Each extraction was performed using 0.1 gram of sample in 50 ml of Simulated Alveolar fluid (pH=6.5 ± 0.1). Sample were weighed into acid washed 250 ml amber Erlenmeyer flasks. Perspiration was added to the flasks and they were then swirled to mix compound and fluid.The opening of the flasks were covered with parafilm and aluminum foil.The flask were then placed in a preheated 37°C water bath. No shaking was performedOnce the extraction was complete, the solution were removed from bath. The pH was checked and solutions were filtered trough a 0.45 µm filter. The filtrates were collected in 8 oz. disposable plastic bottles and kept in a 35°C incubator until analyzed.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report):nickel fluoride N111B-PTL (32.18% Nickel)
As Nickel is 32.18% of the powder, it is assumed that the starting material is NiF2*4H2O
Radiolabelling:
no

Results and discussion

Any other information on results incl. tables

Simulated Gastric fluid   
Extraction time ug Nickel/
g Sample
% Nickel/
g Sample
% Nickel Release/
Nickel content
2 hours 262.77 26.3 81.7
267.090 (dup) 26.7 83
5 hours 264.875 26.5 82.3
270.300 (dup) 27 84
24 hours 261.53 26.1 81.3
271.390 (dup) 27.1 84.3
72 hours 273.86 27.4 85.1
282.115 (dup) 28.2 87.7

Simulated Alveolar fluid  
Extraction time ug Nickel/
g Sample
% Nickel/
g Sample
% Nickel Release/
Nickel content
 
2 hours 116.6 11.7 36.2  
117.100 (dup) 11.7 36.4  
5 hours 115.31 11.5 35.8  
131.110 (dup) 13.1 40.7  
24 hours 132.015 13.2 41  
129.950 (dup) 13 40.4  
72 hours 134.76 13.5 41.9  
136.185(dup) 13.6 42.3  

Artificial Perspiration  
Extraction time ug Nickel/
g Sample
% Nickel/
g Sample
% Nickel Release/
Nickel content
2 hours 305.97 30.6 95.1
 2 hours 316.535 (dup) 31.7 98.4
5 hours 304.695 30.5 94.7
 5 hours 313.545 (dup) 31.4 97.4
24 hours 312.62 31.2 97.2
 24 hours 311.220 (dup) 31.1 96.7
72 hours 320.895 32.1 99.7
 72 hours 318.27 31.8 98.9

Applicant's summary and conclusion