Tin titanium zinc oxide

Specific investigations: other studies

Link to relevant study record(s)

Reference

Endpoint:

chemobiokinetics general studies

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2017-07-21 to 2017-09-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD 29 ‘Guidance document on transformation/dissolution of metals and metal compounds in aqueous media’

Version / remarks:

2001

Principles of method if other than guideline:

Two different artificial physiological media, single loading of test substance of 100 mg/L, measurement of dissolved tin, titanium and zinc concentrations after filtration, samples taken after 2 and 24 hours agitation (100 rpm) at 37 ± 2 °C, two additional method blanks per medium. The study was performed in triplicate. The aim of this test was to assess the dissolution of the test substance in the set of artificial physiological 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 into the gastro-intestinal tract or through the skin.

GLP compliance:

yes (incl. QA statement)

Type of method:

other: in chemico

Endpoint addressed:

other: Bioaccessibility

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch No. of test material: 0014981472
- Expiration date of the Batch: 2026-02-13

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

Examinations:

- ICP-OES analysis
- ICP-MS analysis

Solution pH values

After preparation of the artificial physiological media, solution pH was adjusted to their respective target pH. The target pH in all media before addition of test substance was in the nominal range. During the study, the pH of GST medium remained stable in the method blank vessels and the test vessels. Therefore, a possible effect of the test substance can be excluded. In ASW medium, the pH in all vessels (including method blank vessels) decreased from the start of the study to the 2 h sampling point (6.32 – 6.35 in test sample vessels, 6.33 and 6.31 in method blank vessels). During the measurement of the pH at sampling point 24 h a further decrease of the pH in the method blank vessels was observable (5.86 and 5.89) and in the test vessels a decrease in mainly the same range as the method blank vessels was observable (5.93, 5.94 and 5.95). Due to the mainly same pH in test and method blank vessels an effect of the test substance can be excluded.

Temperature control

The test was performed in an incubated laboratory shaker (Shaking incubation cabinet, Minitron, INFORS AG, Bottmingen, Switzerland) at 100 rpm. The temperature was adjusted to 37.5 in a thermostatically controlled shaking cabinet to reach a temperature of 37 ± 2°C in the media. The temperature in thermostatically controlled shaking cabinet was confirmed by a certified thermometer and a thermo data logger.

Analytical measurements

The results of the ICP-OES and ICP-MS measurements of total dissolved Sn, Ti and Zn concentrations in samples are presented in the following tables.

Table 5: Concentration of dissolved tin in artificial physiological media

Media and sample	LOD/LOQ of Sn measurement series	Total Sn ± SD in method blanks	Without method blank subtraction		With mean method blank subtraction (mean of 2 h and/or 24 h)
			Total Sn ± SD in sample vessels without method blank	Total Sn ± SD in sample vessels (corrected concentrations, corresponding to a loading of exactly 100 mg/L)	Total Sn ± SD in sample vessels	Total Sn ± SD in sample vessels (corrected concentrations, corresponding to a loading of exactly 100 mg/L)
GST 2h	LOD: 0.010 μg/L LOQ: 0.030 μg/L	All method blanks below LOD	253 ± 30.3 μg/L	253 ± 30.3 μg/L	No subtraction	No subtraction
GST 24h	LOD: 0.010 μg/L LOQ: 0.030 μg/L	All method blanks below LOD/LOQ	136 ± 3.34 μg/L	136 ± 3.41 μg/L	No subtraction	No subtraction
ASW 2h	LOD: 0.028 μg/L LOQ: 0.083 μg/L	All method blanks below LOD/LOQ	11.5 ± 4.61 μg/L	11.5 ± 4.61 μg/L	No subtraction	No subtraction
ASW 24h	LOD: 0.028 μg/L LOQ: 0.083 μg/L	All method blanks below LOQ	154 ± 5.59 μg/L	154 ± 5.59 μg/L	No subtraction	No subtraction

 

Table 6: Concentration of dissolved titanium in artificial physiological media

Media and sample	LOD/LOQ of Ti measurement series	Total Ti ± SD in method blanks	Without method blank subtraction		With mean method blank subtraction (mean of 2 h and/or 24 h)
			Total Ti ± SD in sample vessels without method blank	Total Ti ± SD in sample vessels (corrected concentrations, corresponding to a loading of exactly 100 mg/L)	Total Ti ± SD in sample vessels	Total Ti ± SD in sample vessels (corrected concentrations, corresponding to a loading of exactly 100 mg/L)
GST 2h	LOD: 0.456 μg/L LOQ: 1.37 μg/L	All method blanks below LOD	29.2 ± 4.38 μg/L	29.2 ± 4.37 μg/L	No subtraction	No subtraction
GST 24h	LOD: 0.456 μg/L LOQ: 1.37 μg/L	All method blanks below LOD	222 ± 3.97 μg/L	222 ± 3.94 μg/L	No subtraction	No subtraction
ASW 2h	LOD: 0.033 μg/L LOQ: 0.100 μg/L	All method blanks below LOD	0.472 ± 0.191 μg/L	0.472 ± 0.191 μg/L	No subtraction	No subtraction
ASW 24h	LOD: 0.033 μg/L LOQ: 0.100 μg/L	All method blanks below LOD/LOQ	26.2 ± 1.27 μg/L	26.2 ± 1.27 μg/L	No subtraction	No subtraction

  

Table 7: Concentration of dissolved zinc in artificial physiological media

Media and sample	LOD/LOQ of Zn measurement series	Total Zn ± SD in method blanks	Without method blank subtraction		With mean method blank subtraction (mean of 2 h and/or 24 h)
			Total Zn ± SD in sample vessels without method blank	Total Zn ± SD in sample vessels (corrected concentrations, corresponding to a loading of exactly 100 mg/L)	Total Zn ± SD in sample vessels	Total Zn ± SD in sample vessels (corrected concentrations, corresponding to a loading of exactly 100 mg/L)
GST 2h	LOD: 0.077 μg/L LOQ: 0.231 μg/L	All method blanks above LOQ; 1.37 ± 0.20 μg/L	458 ± 21.7 μg/L	458 ± 21.7 μg/L	457 ± 21.7 μg/L	457 ± 21.7 μg/L
GST 24h	LOD: 0.077 μg/L LOQ: 0.231 μg/L	All method blanks above LOQ; 3.24 ± 1.32 μg/L	2545 ± 90.8 μg/L	2544 ± 90.4 μg/L	2542 ± 90.8 μg/L	2542 ± 90.4 μg/L
ASW 2h	LOD: 0.580 μg/L LOQ: 1.74 μg/L	All method blanks below LOD	11.0 ± 7.50 μg/L	11.0 ± 7.50 μg/L	No subtraction	No subtraction
ASW 24h	LOD: 0.580 μg/L LOQ: 1.74 μg/L	All method blanks below LOD	184 ± 1.11 μg/L	184 ± 1.10 μg/L	No subtraction	No subtraction

 

Mass balance calculation

Mass balance dissolved zinc concentrations in vessels and filters as measured by ICP-OES indicate no complete dissolution of the pigment in the physiological media after addition of aqua regia to the sample vessels. Due to the observations during the mass balance test item was still visible which could be a result of insoluble parts of the test item. The results and the recovery of zinc in the weighted test item are compiled in Table 8 (only zinc given).

Table 8

Media	Value for dissolved zinc after addition of aqua regia		In samples [mg]	Calculated value Zn [mg]	Nominal amount [mg] #	Recovery [%]
	Vessels [mg]	Filters/syringes [mg]
GST vessel 1	2.77	0.042	0.124	2.94	8.8	33.4
GST vessel 2	2.81	0.034	0.116	2.96	8.8	33.6
GST vessel 3	2.74	0.037	0.121	2.9	8.8	32.9
ASW vessel 1	5.34	0.001	0.008	5.35	8.8	60.8
ASW vessel 2	4.51	0.013	0.008	4.53	8.8	51.5
ASW vessel 3	5.57	0.005	0.008	5.58	8.8	63.4

* Measured dissolved zinc includes the amount of zinc in test solutions after addition of aqua regia, the amount of zinc rinsed of used filters and syringe and the amount of zinc removed with samples during the study.

Example: 2.77 mg (amount Zn in vessel) + 0.042 mg (amount Zn in syringe/filters) + 0.124 mg (Zn in samples) = 2.94 mg

# nominal amount Zn = 17.6 g in 100 g test item  8.80 mg Zn in 50 mg test item  nominal amount 8.80 mg * initial weight mg / 50 mg

Example: 8.80 mg Zn * 50.014 mg test item / 50 mg = 8.80 mg Zn

Description of key information

The dissolution of tin and titanium can be regarded as neglible. Considering a nominal amount of 34 mg/100 mg for tin and 20.9 mg/100 mg for titanium in the pigment only 0.4 % tin and approx. 1 % titanium were maximally measured in artificial sweat or gastrointestinal fluid after a period of 24 hours. Nearly 15 % of the theoretical zinc content in 100 mg had dissolved in the gastrointestinal fluid and only 0.1 % in the artifical sweat after 24 hours.

Additional information

A study was performed at the Fraunhofer Institute for Molecular Biology and Applied Ecology (Fraunhofer IME, Schmallenberg, Germany) with the objective to investigate the dissolution of the pigment in the artificial physiological media GST and ASW. 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 or by inhalation. The dissolved amount of test item was specified by the mass concentration of the substance in the test media under the applied test conditions after separation of undissolved test item by filtration (filtration through a 0.2 μm polyethersulphone membrane syringe filter). The total dissolved amount was determined by measuring the total concentrations of dissolved Sn, Ti and Zn, in this filtrated solution. The test was performed on the basis of OECD Series on Testing and Assessment No. 29 (2001; ENV/JM/ MONO(2001)9) [4]: “Guidance Document on Transformation / Dissolution of Metals and Metal Compounds in Aqueous Media” as well as according to the bioaccessibility test protocols according to different literature.

For the experimental setup the test item was weighed into flasks, adjusted to volume with the respective artificial physiological medium (loading of approx. 100 mg/L) and agitated at 100 rpm at 37°C ± 2°C. Samples were taken after 2h and 24h. The total dissolved tin, titanium and zinc concentrations of sampled solutions were determined after filtration by ICP-OES and ICP-MS. Under the conditions of this test (flasks with different artificial physiological media; inorganic pigment loadings of approx. 50 mg per 500 mL (i.e. 100 mg/L), at 37°C, sampling after 2h and 24h), the measured concentrations of dissolved tin, titanium and zinc were as shown below:

Comment on presentation of results:

The nominal loading in this test was 100 mg/L. However, due to weighing uncertainties the actual loadings range from 100.000 mg/L to 100.028 mg/L in the 6 test vessels. For the sake of simplicity, the tables and graphs in this summary chapter show the corrected concentrations, corresponding to a loading of exactly 100 mg/L and the not corrected concentrations according to the actual loadings (with and without method blank subtraction if method blanks above LOQ).

Table 1: Concentration of dissolved tin in artificial physiological media

Media and sample	LOD/LOQ of Sn measurement series	Total Sn ± SD in method blanks	Without method blank subtraction		With mean method blank subtraction (mean of 2 h and/or 24 h)
			Total Sn ± SD in sample vessels without method blank	Total Sn ± SD in sample vessels (corrected concentrations, corresponding to a loading of exactly 100 mg/L)	Total Sn ± SD in sample vessels	Total Sn ± SD in sample vessels (corrected concentrations, corresponding to a loading of exactly 100 mg/L)
GST 2h	LOD: 0.010μg/L LOQ: 0.030μg/L	All method blanks below LOD	253 ± 30.3 μg/L	253 ± 30.3 μg/L	No subtraction	No subtraction
GST 24h	LOD: 0.010μg/L LOQ: 0.030μg/L	All method blanks below LOD/LOQ	136 ± 3.34 μg/L	136 ± 3.41 μg/L	No subtraction	No subtraction
ASW 2h	LOD: 0.028μg/L LOQ: 0.083μg/L	All method blanks below LOD/LOQ	11.5 ± 4.61 μg/L	11.5 ± 4.61 μg/L	No subtraction	No subtraction
ASW 24h	LOD: 0.028μg/L LOQ: 0.083μg/L	All method blanks below LOQ	154 ± 5.59 μg/L	154 ± 5.59 μg/L	No subtraction	No subtraction

 

Table 2: Concentration of dissolved titanium in artificial physiological media

Media and sample	LOD/LOQ of Ti measurement series	Total Ti ± SD in method blanks	Without method blank subtraction		With mean method blank subtraction (mean of 2 h and/or 24 h)
			Total Ti ± SD in sample vessels without method blank	Total Ti ± SD in sample vessels (corrected concentrations, corresponding to a loading of exactly 100 mg/L)	Total Ti ± SD in sample vessels	Total Ti ± SD in sample vessels (corrected concentrations, corresponding to a loading of exactly 100 mg/L)
GST 2h	LOD: 0.456μg/L LOQ: 1.37μg/L	All method blanks below LOD	29.2 ± 4.38 μg/L	29.2 ± 4.37 μg/L	No subtraction	No subtraction
GST 24h	LOD: 0.456μg/L LOQ: 1.37μg/L	All method blanks below LOD	222 ± 3.97 μg/L	222 ± 3.94 μg/L	No subtraction	No subtraction
ASW 2h	LOD: 0.033μg/L LOQ: 0.100μg/L	All method blanks below LOD	0.472 ± 0.191 μg/L	0.472 ± 0.191 μg/L	No subtraction	No subtraction
ASW 24h	LOD: 0.033μg/L LOQ: 0.100μg/L	All method blanks below LOD/LOQ	26.2 ± 1.27 μg/L	26.2 ± 1.27 μg/L	No subtraction	No subtraction

  

Table 3: Concentration of dissolved zinc in artificial physiological media

Media and sample	LOD/LOQ of Zn measurement series	Total Zn ± SD in method blanks	Without method blank subtraction		With mean method blank subtraction (mean of 2 h and/or 24 h)
			Total Zn ± SD in sample vessels without method blank	Total Zn ± SD in sample vessels (corrected concentrations, corresponding to a loading of exactly 100 mg/L)	Total Zn ± SD in sample vessels	Total Zn ± SD in sample vessels (corrected concentrations, corresponding to a loading of exactly 100 mg/L)
GST 2h	LOD: 0.077μg/L LOQ: 0.231μg/L	All method blanks above LOQ; 1.37 ± 0.20 μg/L	458 ± 21.7 μg/L	458 ± 21.7 μg/L	457 ± 21.7 μg/L	457 ± 21.7 μg/L
GST 24h	LOD: 0.077μg/L LOQ: 0.231μg/L	All method blanks above LOQ; 3.24 ± 1.32 μg/L	2545 ± 90.8 μg/L	2544 ± 90.4 μg/L	2542 ± 90.8 μg/L	2542 ± 90.4 μg/L
ASW 2h	LOD: 0.580μg/L LOQ: 1.74μg/L	All method blanks below LOD	11.0 ± 7.50 μg/L	11.0 ± 7.50 μg/L	No subtraction	No subtraction
ASW 24h	LOD: 0.580μg/L LOQ: 1.74μg/L	All method blanks below LOD	184 ± 1.11 μg/L	184 ± 1.10 μg/L	No subtraction	No subtraction