Non-graphitic carbon fibre

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

Bioaccessibility study in vitro

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2019-03-12 to 2019-06-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Objective of study:

bioaccessibility (or bioavailability)

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Series on Testing and Assessment No. 29 (23-Jul-2001): Guidance document on transformation/dissolution of metals and metal compounds in aqueous media

Deviations:

not specified

Principles of method if other than guideline:

An internationally agreed guideline does not exist yet for this test (e.g. OECD). Therefore, the test was performed on the basis of the guidance for OECD-Series on testing and assessment Number 29 and bioaccessibility methods applied in published studies [Midander K. et al. 2007. Enviromental Pollution 145: 51-59.; ASTM 2003. ASTM D5517-03]
Test conditions: Two artificial physiological media GST and PBS composition, one single loading of the test substance, i.e. 100 mg/L, measurements of dissolved TC and NPOC concentrations after 2 and 24 hours of agitation at 37 °C.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

carbon

EC Number:

701-026-1

Cas Number:

7440-44-0

Molecular formula:

C up to (C80N5H16O)n

IUPAC Name:

carbon

Specific details on test material used for the study:

- Batch No: 2399606
- Expiration date of the lot/batch: 08 December 2026
- Appearcane of test material: black powder

Radiolabelling:

no

Test animals

Species:

other: not applicable

Strain:

other: not applicable

Details on species / strain selection:

not applicable

Sex:

not specified

Administration / exposure

Route of administration:

other: in vitro study

Vehicle:

unchanged (no vehicle)

Details on exposure:

not applicable

Duration and frequency of treatment / exposure:

Not applicable

Doses / concentrations

Dose / conc.:

100 other: mg/L

Remarks:

Loading

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:

Please refer to box "Any other information on materials and method incl. tables".

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

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

The concentrations of non-purgeable organic carbon (NPOC) in the test media GST and PBS for all method blanks and samples were below the LOQ (0.712 mg/L) but above the LOD (0.186 mg/L). To calculate the dissolution of the non-purgeable organic carbon in the test media, a standardisation for values below the LOQ was performed. Therefore, individual sample values below the LOQ were set to LOQ/2 (0.356 mg/L) and these calculated concentrations were used for evaluation. The calculated concentrations in method blanks as well as the calculated concentrations in the samples were in the same order of magnitude and therefore a dissolution of the test item in GST or PBS medium is not distinguishable from the method blanks. The concentrations of total carbon (TC) in the method blank and test samples for the test medium PBS were all above the LOQ and for the test medium GST mainly all method blank and sample concentrations were above the LOQ. The concentrations in sample vessels were in the same order of magnitude as the method blank concentrations and therefore a dissolution of the test item in PBS or GST medium is not distinguishable. This observation is confirmed by the background corrected concentrations from the method blank.
For detailed results please refer to the tables in the box "Any other information on results incl. tables".

Any other information on results incl. tables

Table 1: NPOC concentrations of artificial physiological media (filtrated through a 0.45 µm membrane)

Medium & time	LOD/LOQ of NPOC measurement series [mg/L]	Mean NPOC ± SD of method blanks [mg/L]	Without background correction	With background correction
			Mean NPOC ± SD of test item[mg/L]	Mean NPOC of test item[mg/L]
GST 2h	LOD: 0.186 LOQ: 0.712	= 0.457± 0.142 (three samples below, one sample above LOQ)	= 0.356 (all samples below LOQ)	Negative value (-0.10)
GST 24h		= 0.624± 0.107 (two samples below and two samples above LOQ)	= 0.510± 0.268(samples of one vessel above, other samples all below LOQ)	Negative value (-0.11)
PBS 2h	LOD: 0.186 LOQ: 0.712	= 0.356 (all samples below LOQ)	= 0.438± 0.142(one sample above, all other samples below LOQ)	0.08 mg/L
PBS 24h		= 0.480± 0.176(three samples below, one sample above LOQ)	= 0.356 (all samples below LOQ)	Negative value (-0.12)

Samples below LOQ were used for calculation of mean by LOQ/2 (Commission Directive 2009/90/EC of 31 July 2009].

Table 2: TC concentrations of artificial physiologocal media (filtered through a 0.45 µm membrane)

Medium & time	LOD/LOQ of TC measurement series [mg/L]	Mean TC ± SD of method blanks [mg/L]	Without background correction	With background correction
			Mean TC ± SD of test item[mg/L]	Mean TC of test item[mg/L]
GST 2h	LOD: 0.186 LOQ: 0.712	0.832± 0.059	0.755± 0.399 (two samples below LOQ)	Negative value (-0.08)
GST 24h		1.07± 0.035	1.01± 0.266	Negative value (-0.06)
PBS 2h	LOD: 0.186 LOQ: 0.712	2.91± 0.07	2.87± 0.08	Negative value (-0.05)
PBS 24h		3.36± 0.27	3.26± 0.14	Negative value (-0.10)

Samples below LOQ were used for calculation of mean by LOQ/2 (Commission Directive 2009/90/EC of 31 July 2009].

Applicant's summary and conclusion

Conclusions:

To determine the dissolution of carbon in the arteficial body fluids GST and PBS the soluble amount of the test item was specified by measuring the total carbon content as TC as well as the dissolved organic carbon as non-purgeable organic carbon (NPOC) in the test media. In the NPOC measurement, the calculated concentrations in method blanks as well as the calculated concentrations in the samples were in the same order of magnitude and therefore a dissolution of the test item in GST or PBS medium is not distinguishable from the method blank. In the TC measurement, the concentrations in sample vessels were in the same order of magnitude as the method blank concentrations and therefore a dissolution of the test item in PBS or GST medium is not distinguishable. This observation is confirmed by the background corrected concentrations from the method blank.

The release of niobium ions from Niobium oxide is very low in artifical body fluids. Based on the results, the bioavailability of Niobium oxide can be considered to be very low for all routes of administration.

Executive summary:

A study was conducted to estimate the bioaccessibility of non-graphitic carbon fibre in different artificial media. The test media were selected to simulate relevant human-chemical interactions (as far as practical), i.e. a substance entering the human body by ingestion. Furthermore, only artificial gastric fluid (GST) and PBS (phosphate buffered saline that mimics the ionic strength of human blood serum) were chosen for testing due to the fact that in all other media a carbon source is used for the media. The soluble amount of the test item was specified by measuring the total carbon content as TC as well as the dissolved organic carbon (DOC) as non-purgeable organic carbon (NPOC) in the test media under the applied test conditions after separation of undissolved test item by filtration (filtration through a 0.45 µm PET membrane syringe filter; Polyester filter). For the experimental setup, the test item was weighed into flasks, adjusted to volume with the respective artificial physiological medium (loading of 100 mg/L) and agitated at 100 rpm at 37 °C ± 1 °C. Samples of GST and PBS medium were taken after 2 h and 24 h. The TC concentrations were determined as TC and the DOC as NPOC by a SHIMADZU TOC- V CPH Analyzer.

In the NPOC measurement, the calculated concentrations in method blanks as well as the calculated concentrations in the samples were in the same order of magnitude and therefore a dissolution of the test item in GST or PBS medium is not distinguishable from the method blank. In the TC measurement, the concentrations in sample vessels were in the same order of magnitude as the method blank concentrations and therefore a dissolution of the test item in PBS or GST medium is not distinguishable. This observation is confirmed by the background corrected concentrations from the method blank.