Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test procedure in accordance with generally accepted scientific standards and described in sufficient detail.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report date:
2007

Materials and methods

Objective of study:
other: bioaccessibility
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Quantitative in-vitro bioaccessibility data were generated on released metal ions from nine different UGI (Upgraded Ilmenite) when exposed to synthetic biological media of different pH and chemical composition.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Slags, ilmenite electrothermal smelting
EC Number:
293-671-6
EC Name:
Slags, ilmenite electrothermal smelting
Cas Number:
91081-64-0
Molecular formula:
M3O5
IUPAC Name:
Slags, ilmenite electrothermal smelting
Details on test material:
- Name of test material (as cited in study report):
(I) Soreslag – QIT SO; Company. QIT Iron & Titanium; Sample I.D. SL2006-042
(II) UGS – QIT CL; Company. QIT Iron & Titanium; Sample I.D. SL2006-049
(III) RBM Sulphate slag – RBM SO; Company: Richards Bay Minerals; Sample I.D. 604441
(IV) RBM Chloride slag – RBM CL; Company: Richards Bay Minerals; Sample I.D. 604442
(V) Tinfos 77% TiO2 slag – Tinfos SO; Company: Tinfos; Sample I.D. X-01/07
(VI) Sulphate grade titania slag – NMW SO; Company: Namakwa; Sample I.D. SS-3992-11/10/06
(VII) Chloride grade slag – NMW CL; Company: Namakwa; Sample I.D. CIS-4418-02/01/07
(VIII) TiCor Sulphate slag – EXX SO; Company: Exxaro Sands; Sample I.D. MKT_SUL_061207_0000
(IX) TiCor Marketing Chloride slag – EXX CL; Company: Exxaro Sands; Sample I.D. MKT_CHL_061223_0000

TiO2 Pigment – KRO TiO2; Company: Kronos; Sample I.D. 0700203-001
(The titanium dioxide sample was tested for comparative reasons only)

- Substance type: technical product
- Physical state: solid, black brown granular
- Storage condition of test material: at room temperature
- Composition of test material, percentage of components: 100 % UGI
No further details are given.
Radiolabelling:
no

Test animals

Species:
other: not applicable - in vitro test
Strain:
other: not applicable - in vitro test
Sex:
not specified
Details on test animals or test system and environmental conditions:
not applicable - in vitro test

Administration / exposure

Route of administration:
other: not applicable - in vitro test
Vehicle:
other: not applicable - in vitro test
Details on exposure:
Test Media
Each test item was separately exposed to 4 different test media screening a relevant pH range from about 1.5 to 7.5. The test media were:
• Phosphate-buffered saline (PBS, pH 7.4), as a standard physiological solution that mimics the ion strength of human blood serum. It is widely used in the research and medical health care community as a reference test solution for comparison of data under simulated physiological conditions.
• Gamble’s solution (GMB, pH 7.4) which mimics interstitial fluid within the deep lung under normal health conditions.
• Artificial lysosomal fluid (ALF, pH 4.5) which simulates intracellular conditions in lung cells occurring in conjunction with phagocytosis and represents relatively harsh conditions.
• Artificial gastric fluid (GST, pH 1.5) mimics the very harsh digestion milieu of high acidity in the stomach.
The test media were chosen in order to simulate relevant inhalation scenarios (as far as practical) where the different Ti test items may enter the human body through inhalation and, subsequently by ingestion of inhaled particles that are translocated to the gastro-intestinal tract.
Duration and frequency of treatment / exposure:
The exposure periods were 2 hours and 24 hours.
Doses / concentrations
Remarks:
Doses / Concentrations:
5 ± 0.5 mg of each test item
No. of animals per sex per dose / concentration:
no animal were used
Control animals:
no
Positive control reference chemical:
For comparison, a TiO2 pigment was analysed in parallel.
Details on study design:
Experimental Procedure:
Triplicate slag samples were prepared for exposure in the different test media, each for two time periods. In addition, one blank sample (without addition of any test item) containing only the test solution was incubated together with the triplicates for each time period. 5 ± 0.5 mg of each test item was weighed and placed in a TPX Nalge® jar. 50 mL of the test solution was then added to the TPX Nalge® jar containing the powder sample, before incubated at dark conditions at 37 ± 2 °C. The solution was gently shaken (bi-linearly) with an intensity of 25 cycles per minute (no adjustment of solution volume to powder mass was made). After the exposure period, the samples were allowed to cool to ambient room temperature before the final pH of the test solution was measured. The test medium was then separated from the residual slag particles by centrifugation at 3000 rpm for 10 minutes. The supernatant solution was decanted into a LDPE storage flask and acidified to pH <2 (not needed in case of artificial gastric fluid) with 65% pure HNO3 prior to solution analysis (a standard procedure for metal analysis).

Metal analysis:
The release of metal constituents from the different test items were analysed by inductively coupled plasma optical emission spectroscopy (ICP-OES, Varian Vista Ax Pro), to determine the total amount of released Ti (primarily) as well as other trace elements of interest, e.g. Fe, V, Mg, Mn, Cr, Cu, from each test substance.
Details on dosing and sampling:
no
Statistics:
no data

Results and discussion

Preliminary studies:
no data

Toxicokinetic / pharmacokinetic studies

Details on absorption:
no data
Details on distribution in tissues:
no data
Details on excretion:
no data

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
no

Any other information on results incl. tables

Except for Ti, the primary element of interest, the release of various elements including Fe, V, Mg, Mn, Cr and Cu was determined. The following main conclusions are drawn:

• Large variations in specific surface area between the test items were observed (see attached report), ranging from 0.06 to 1.26 m2/g for the different UGI products, Titanium slags, and 8.54 m2/g for the TiO2 pigment.

• The released concentrations of Ti ions from all test items (often close to the limit of detection 0.12 μg/L) were generally low (see attached material). The Ti release was influenced by the composition and pH of the test media. The released concentrations increased with solution acidity, i.e. GMB ≤ PBS < ALF ≤ GST.

• Release of iron occurred from most test items, except KRO TiO2 and QIT CL, to a highly variable extent and also depending on the test medium

• Release of manganese occurred from most test items, except KRO TiO2 and QIT CL at a very low concentration for most slags for all media investigated.

• Relevant release of magnesium could only be observed in PBS and GST. Due to a high intrinsic magnesium content of GMB and ALF, no further evaluation of magnesium release was performed.

• Copper and chromium are not released to any relevant extent from any of the test items, except for the EXX SO slag in GMB after 24 hours of exposure.

• No release of vanadium was observed from any of the test items except for the QIT CL slag in all test media.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: very low bioaccessibility potential based on study results
see above