Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2013-10-08 to 2014-03-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Objective of study:
bioaccessibility
Test guideline
Qualifier:
no guideline available
Deviations:
not applicable
Principles of method if other than guideline:
This report measured bioaccessibility of aluminium nitride in body fluid simulants as a surrogate for bioavailability.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
- Name of test material (as cited in study report): Aluminum Nitride
- Analytical purity: 65.8% Aluminum
- Lot/batch No.: 12877
Radiolabelling:
no

Test animals

Details on test animals and environmental conditions:
not applicable

Administration / exposure

Details on exposure:
not applicable
Duration and frequency of treatment / exposure:
not applicable
Doses / concentrations
Remarks:
Doses / Concentrations:
0.1 g test substance in 50 mL of simulated fluid
No. of animals per sex per dose:
not applicable
Control animals:
other: not applicable
Positive control:
not applicable
Details on study design:
Aluminium nitride was extracted in simulated leaching fluids for two time periods: 2 hrs and 24 hrs. The extractions were performed using 0.1 gram of sample in 50 mL of simulated fluid. A shaker water bath at a temperature of 37±2 °C was used. All extractions were performed in duplicate. The extracts were analyzed for soluble aluminium using EPA Method #200.8 (ICP/MS). Results were reported as µg Al/g sample, % Al release/Al content.
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

Details on metabolites:
not applicable

Bioaccessibility

Bioaccessibility testing results:
see below (Table 1-5)

Any other information on results incl. tables

Table 1: Soluble Aluminum in Simulated Gastric fluid

Extraction time in h

Weight used

µg Aluminum /g Sample

% Aluminum release/ Aluminum content

2 hours

0.1003

14,955

2.27

0.1002

17,166

2.61

24 hours

0.1000

69,300

10.5

0.1005

61,443

9.34

 

Table 2: Soluble Aluminum in Simulated Interstitial fluid

Extraction time in h

Weight used

µg Aluminum /g Sample

% Aluminum release/ Aluminum content

2 hours

0.1002

469

0.07

0.1001

549

0.08

24 hours

0.1008

685

0.10

0.1001

729

0.11

 

Table 3: Soluble Aluminum in Simulated Lysosomal fluid

Extraction time in h

Weight used

µg Aluminum /g Sample

% Aluminum release/ Aluminum content

2 hours

0.1002

1.262

0.19

0.1009

1.303

0.20

24 hours

0.1030

23.738

3.61

0.1036

23.745

3.61

 

Table 4: Soluble Aluminum in Artificial Perspiration

Extraction time in h

Weight used

µg Aluminum /g Sample

% Aluminum release/ Aluminum content

2 hour

0.1003

319

0.05

0.1008

288

0.04

24 hours

0.1000

1.590

0.24

0.1001

1.913

0.29

 

Table 5: Soluble Aluminum in PBS

Extraction time in h

Weight used

µg Aluminum /g Sample

% Aluminum release/ Aluminum content

2 hour

0.1009

50

0.01

0.1010

45

0.01

24 hours

0.1004

55

0.01

0.1005

65

0.01

 

 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
In conclusion, the release of aluminium ions from aluminium nitride is low in artificial body fluids. The more acidic the simulated fluid, the more aluminium ions are released, i.e. up to 9.92 % in simulated gastric fluid (pH 1.5), and 3.61 % in simulated lysosomal fluid (pH 4.5) after 24 hours.
Executive summary:

This report measured bioaccessibility of aluminium nitride as a surrogate for bioavailability. To do this the soluble aluminium was measured using EPA Method #200.8 (ICP/MS) after incubation of aluminium nitride in simulated body fluids (simulated gastric fluid, simulated interstitial fluid, simulated lysosomal fluid, and artificial perspiration). Results were reported as µg Al/g sample and % Al release/Al content.

Overview of Al released in the different simulated body fluids:

Medium

t in h

% Al-release

Simulated gastric fluid

2

2,44%

24

9,92%

Simulated interstitial fluid

2

0,08%

24

0,11%

Simulated lysosomal fluid

2

0,20%

24

3,61 %

Artificial perspiration

2

0,05%

24

0,27 %

PBS

2

0,01%

24

0,01 %

 

The bioavailability in artificial body fluids ranged from 0.05% (artificial perspiration and interstitial fluid) to 9,92 % (simulated gastric fluid). The maximum solubility was determined at acidic pH. Based on the results, the bioavailability of aluminium nitride would be expected to be low in all tested artificial body fluids except gastric acid. Bioavailability strongly depends on the route of administration.