Tin antimony grey cassiterite

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

Bioaccessibility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015-04-17 to 2015-10-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

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

Version / remarks:

2001

Deviations:

yes

Remarks:

Bioaccessibility testing: loading of 100 mg/L; five artificial physiological media agitated at 100 rpm, at 37 °C ± 2 °C; sampling after 2h and 24h; determination of antimony, tin and vanadium concentrations after filtration by ICP-OES and ICP-MS.

Principles of method if other than guideline:

The test was performed on the basis of OECD Series on Testing and Assessment No. 29 as well as according to the bioaccessibility test protocol provided by the monitor. The bioaccessibility protocol has been developed on the basis of relevant published methods ([1], [2], [3], [4] and [5]).

The aim of this test was to assess the dissolution of the pigment IPC-2018-003 (tin antimony grey cassiterite) in the artificial physiological media GST, GMB, ALF, ASW and PBS. 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.

Five different artificial physiological media with a single loading of test substance of 100 mg/Lwere used. The measurement of dissolved antimony, tin and vanadium concentrations after filtration were performed by ICP-OES and ICP-MS. Samples were taken after 2 and 24 hours agitation (100 rpm) at 37 ± 2 °C. The study was performed in triplicate with two additional method blanks per medium.

[1] Hanawa T. 2004. Metal ion release from metal implants. Materials Science and Engineering C 24: 745-752.
[2] Stopford W., Turner J., Cappelini D., Brock T. 2004. Bioaccessibility testing of cobalt compounds. Journal of Environmental Monitoring 5: 675-680.
[3] Midander K., Odnevall Walinder I., Leygraf C. 2007. In vitro studies of copper release from powder particles in synthetic biological media. Environmental Pollution 145: 51-59.
[4] European standard 1998. Test method for release of nickel from products intended to come into direct and prolonged contact with the skin (EN 1811)
[5] ASTM 2003. Standard test method for determining extractability of metals from art materials. ASTM D5517-03.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Tin antimony grey cassiterite

EC Number:

269-105-9

EC Name:

Tin antimony grey cassiterite

Cas Number:

68187-54-2

Molecular formula:

Sn(2-x-y)Sb(x)V(y)O4 0,04≤x≤0,50 0≤y≤0,10

IUPAC Name:

Tin antimony cassiterite

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material: Tin Antimony Grey Cassiterite (Pigment Black 23)
- Physical state: solid, grey powder, odourless
- Substance type: inorganic pigment

Test animals

Species:

other: in vitro (simulated human body fluids)

Details on test animals or test system and environmental conditions:

Test principle in brief:
- five different artificial physiological media,
- single loading of test substance of 100 mg/L,
- samples taken after 2 and 24 hours agitation (100 rpm) at 37 ± 2 °C,
- two method blanks per artificial media were tested; measurement (by ICP-OES and IPC-MS) of dissolved antimony, tin and vanadium concentrations after filtration
- the study was performed in triplicate

The aim of this test was to assess the dissolution of IPC-2018-003 (tin antimony grey cassiterite) in five artificial physiological media: Artificial lysosomal fluid (ALF, pH = 4.5), Artificial sweat solution (ASW, pH = 6.5), Gamble´s solution (GMB, pH = 7.4), Artificial gastric fluid (GST, pH = 1.5), Phosphate buffered saline (PBS, pH = 7.4). 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 gastrointestinal tract and by inhalation.

Administration / exposure

Duration and frequency of treatment / exposure:

Samples were taken after 2 h and 24h.

Doses / concentrations

Dose / conc.:

100 other: mg of the test item /L artificial media

Details on study design:

Reagents
The water (resistivity >18 MΩ·cm.) used for this test was purified with a Pure Lab Ultra water purification system from ELGA LabWater, Celle, Germany.
- Nitric acid - “Supra” quality (ROTIPURAN® supplied by Roth, Karlsruhe, Germany).
- Hydrochloric acid – “instra-analyzed plus” quality (J.T. Baker, Griesheim, Germany).
- Sodiumhydroxide – pro Analysis quality (Chemsolute, Th. Geyer, Renningen, Germany)

Metal analysis
- Standards: single element standards were used as antimony, tin and vanadium standards (Merck Certipur Antimony ICP standard 1000 mg/L lot no. HC384311; Merck Certipur Tint ICP standard 1000 mg/L lot no. HC375770; Merck Certipur Vanadium ICP standard 1000 mg/L lot no. HC43452566; Darmstadt, Germany).
- Certified reference materials: quality control standards TM-25.4 (lot no. 0914) obtained from Environment Canada and multielement standards (Merck XVII, lot no. HC382226 – only antimony and tin; Merck XXI, lot no. HC42984673 – only vanadium, Darmstadt, Germany) were analyzed for total dissolved antimony, tin and vanadium by ICP-MS along with the samples to determine the accuracy of the applied analytical method. Furthermore the calibration solutions were measured along with the ICP-MS measurements as recalibration standards.

Instrumental and analytical set-up for the ICP-MS instrument:
Agilent 7700ce ICP-MS, Agilent Technologies, Waldbronn Germany
Nebulizer: Conical nebulizer, from Glass Expansion
Spray chamber: Scott Type spray chamber, from Agilent
Carrier gas flow: 0.93 L/min
Dilution Gas flow: 0.1 – 0.16 L/min
RF power: 1500 W
Isotopes: 121Sb, 123Sb, 118Sn, 119Sn, 120Sn, 51V and 103Rh (internal standard)

The applied LOD/LOQs were calculated as follows:
LOD: 3 x standard deviation of calibration blank divided by the slope of calibration line;
LOQ: 3 x LOD.

Calibration: blank, 0.1 μg/L, 0.25 μg/l, 0.5 μg/L, 0.75 μg/L, 1 μg/L, 2.5 μg/L, 5.0 μg/L, 7.5 μg/L, 10 μg/L, 12.5 μg/L, 15 μg/L, 17.5 μg/L, 20 μg/L, 22.5 μg/L and 25 μg/L.
(for mass balance measurement calibration points were blank, 1 µg/L, 2.5 µg/L, 5.0 µg/L, 7.5 µg/L, 10 µg/L, 25 µg/L, 50 µg/L, 75 µg/L and 100 µg/L).
Correlation factors (r): at least 0.999047

Determination of mass balance
To the residual, undissolved test item in the vessels, 80 mL aqua regia (3 : 1 mixture of concentrated hydrochloric and nitric acid) were added to the flasks after the test. The filters used for sampling were extensively rinsed with aqua regia. Solutions were sampled after at least 24 h, antimony, tin and vanadium were measured in at least one mass balance sample (vessel and filter/syringes) for each medium by ICP-MS, and the mass balance was calculated.

Details on dosing and sampling:

Loading:
Detailed loadings of the test vessels are given in "Any other information on materials and methods incl. tables".

Results and discussion

Toxicokinetic / pharmacokinetic studies

Toxicokinetic parameters

Toxicokinetic parameters:

other: bioaccessibility

Remarks:

Dissolution of Sb at a loading of 0.1 g/L: ALF 24h: 0.260 ± 0.007 µg/L; dissolution of Sn at a loading of 0.1 g/L: ALF 24h: 2.81 ± 0.05 µg/L; dissolution of V at a loading of 0.1 g/L: ALF 24h: 3.53 ± 0.04 µg/L

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

Concentration of dissolved antimony in artificial physiological media:
Total Sb ± SD in sample vessels (corrected concentrations, corresponding to a loading of exactly 100 mg/L) with mean method blank subtraction (mean of 2 h and/or 24 h)
- GST 2h: 0.091 ± 0.012 µg/L (no subtraction, all method blanks below LOD)
- GST 24h: 0.446 ± 0.018 µg/L (no subtraction, all method blanks below LOD)
- GMB 2h: 0.004 ± 0.002 µg/L (no subtraction, all method blanks below LOD)
- GMB 24h: 0.016 ± 0.004 µg/L (no subtraction, all method blanks below LOD)
- ALF 2h:0.058 ± 0.001 µg/L (no subtraction, three method blanks below LOD, one method blank below LOQ)
- ALF 24h: 0.260 ± 0.007 µg/L (no subtraction, all method blanks below LOQ)
- ASW 2h: 0.032 ± 0.003 µg/L (no subtraction, all method blanks below LOD)
- ASW 24h: 0.139 ± 0.003 µg/L (no subtraction, all method blanks below LOD)
- PBS 2h: 0.096 ± 0.081 µg/L (method blanks: 0.062 ± 0.024 µg/L; one method blank below LOQ, three method blanks above LOQ)
- PBS 24h: 0.086 ± 0.004 µg/L (method blanks: 0.141 ± 0.003 µg/L; all method blanks above LOQ)

Concentration of dissolved tin in artificial physiological media
Total Sn ± SD in sample vessels (corrected concentrations, corresponding to a loading of exactly 100 mg/L) with mean method blank subtraction (mean of 2 h and/or 24 h)
- GST 2h: 0.069 ± 0.012 µg/L (no subtraction, all method blanks below LOD)
- GST 24h: 0.237 ± 0.029 µg/L (no subtraction, all method blanks below LOD)
- GMB 2h: All samples below LOD (all method blanks below LOD)
- GMB 24h: All samples below LOD (all method blanks below LOD)
- ALF 2h: 0.895 ± 0.013 µg/L (no subtraction, all method blanks below LOD)
- ALF 24h: 2.81 ± 0.05 µg/L (no subtraction, all method blanks below LOD)
- ASW 2h: 0.066 ± 0.015 µg/L (method blanks: 0.002 ± 0.002 µg/L; one method blanks below LOD, one method blank below LOQ, two method blanks above LOQ)
- ASW 24h: 0.397 ± 0.019 µg/L (method blanks: 0.010 ± 0.004 µg/L; all method blanks above LOQ)
- PBS 2h: 0.034 ± 0.015 µg/L (no subtraction, one method blank below LOD, three method blanks below LOQ)
- PBS 24h: 0.064 ± 0.009 µg/L (no subtraction, one method blank below LOD, three method blanks below LOQ)

Concentration of dissolved vanadium in artificial physiological media
Total V ± SD in sample vessels (corrected concentrations, corresponding to a loading of exactly 100 mg/L) with mean method blank subtraction (mean of 2 h and/or 24 h)
- GST 2h: 2.01 ± 0.12 µg/L (no subtraction, all method blanks below LOD)
- GST 24h: 3.74 ± 0.07 µg/L (no subtraction, all method blanks below LOD)
- GMB 2h: 2.36 ± 0.03 µg/L (no subtraction, three method blanks below LOD, one method blank below LOQ)
- GMB 24h: 3.07 ± 0.04 µg/L (method blanks: 0.032 ± 0.002 µg/L; all method blanks above LOQ)
- ALF 2h: 2.43 ± 0.03 µg/L (no subtraction, three method blanks below LOD, one method blank below LOQ)
- ALF 24h: 3.53 ± 0.04 µg/L (no subtraction, one method blank below LOD, three method blanks below LOQ)
- ASW 2h: 1.76 ± 0.10 µg/L (no subtraction, three method blanks below LOD, one method blank below LOQ)
- ASW 24h: 2.83 ± 0.03 µg/L (method blanks: 0.006 ± 0.004 µg/L; two method blanks below LOD, one method blank below LOQ, one method blank above LOQ)
- PBS 2h: 2.16 ± 0.14 µg/L (no subtraction, all method blanks below LOD)
- PBS 24h: 3.29 ± 0.03 µg/L (no subtraction, all method blanks below LOD)

Any other information on results incl. tables

Method validation summary ICP-MS

validation parameter	results	Comment
Selectivity	similar data with two different gas modes or two different Isotopes and same gas mode	-
Linearity	applied calibration functions were linear	correlation coefficient at least 0.999047
Limit of detection	Sb: 0.001 – 0.018 µg/L Sn: 0.001 – 0.223 µg/L V: 0.003 – 0.055 µg/L
Limit of quantification	Sb: 0.004 – 0.054 µg/L Sn: 0.002 – 0.669 µg/L V: 0.008 – 0.166 µg/L
Accuracy measurement / Reproducibility testsample and mass balance samples measurements	Mean recovery for CRM TM-25.4 (dilution factor 5): Sb: 99.1 ± 4.3 % (n = 34) Sn: 102 ± 4.5 % (n = 33) V: 97.4 ± 5.3 % (n = 34)	Low concentration range (certified with 23.8 µg Sb/L - diluted 4.76 µg Sb/L; 23.8 µg Sn/L – diluted 4.76 µg/L; 27.4 µg V/L – diluted 5.48 µg V/L)
Trueness test samples	Quality control standard Merck XVII: Sb: 103 ± 2.0 % (n = 2) Sn: 96.1 ± 1.9 % (n = 2)	Mid concentration range (10 µg/L)
Trueness test samples	Quality control standard Merck XVII: Sb: 113 ± 3.0 % (n = 26) Sn: 96.6 ± 7.9 % (n = 26)	High concentration range (20 µg/L)
Trueness test samples	Quality control standard Merck XXI: V: 98.5 ± 6.1 % (n = 26)	High concentration range (20 µg/L)
Trueness mass balance samples	Quality control standard Merck XVII: Sb: 102 ± 4.5 % (n = 5) Sn: 95.7 ± 3.8 % (n = 5)	High concentration range (50 µg/L)
Trueness mass balance samples	Quality control standard Merck XXI: V: 93.2 ± 3.5 % (n = 5)	High concentration range (50 µg/L)
Trueness test samples	Recalibration standard: Sb: 100 ± 3.2 % (n = 29) Sn: 99.7 ± 2.6 % (n = 28) V: 96.4 ± 5.7 % (n = 29)	Low concentration range (5 µg/L)
Trueness mass balance samples	Recalibration standard: Sb: 92.1 ± 3.5 % (n = 5) Sn: 96.7 ± 2.5 % (n = 5) V: 93.7 ± 3.3 % (n = 5)	Mid concentration range (25 µg/L)
Trueness test samples/mass balance samples	Fortification of samples: Sb: 93.2 – 106 % Sn: 94.5 – 104 % V: 92.2 – 113 %

Fortification

For fortified test samples, recoveries were in the range of 93.2 – 106 % for Sb, 94.5 – 104 % for Sn and 92.2 – 113 % for V.

Fortification of Sb in test samples

sample	measured concentration [µg/L]	calculated level after addition [µg/L]	recovery [µg/L] / [%]
GST vessel 1 sample b 2h	0.108	0.154	0.158 / 102
GST vessel 2 sample b 2h	0.096	0.148	0.148 / 100
GST vessel 1 sample b 24h	0.464	2.81	2.80 / 99.5
GST vessel 3 sample b 24h	0.459	0.556	0.559 / 100
GMB vessel 1 sample a 2h	0.005	0.087	0.081 / 93.2
GMB vessel 2 sample b 24h	0.020	1.68	1.64 / 97.6
ASW vessel 1 sample a 2h	0.030	0.103	0.100 / 96.6
ASW vessel 1 sample a 24h	0.138	0.425	0.414 / 97.3
ALF vessel 1 sample a 2h	0.55	0.120	0.124 / 103
ALF vessel 1 sample a 24h	0.266	0.511	0.500 / 97.9
PBS vessel 3 sample a 2h	0.176	1.73	1.72 / 99.7
PBS vessel 2 sample a 24h	0.235	3.41	3.36 / 98.6
Mass balance sample vessel 1 ALF (dilution factor 2)	0.639	33.8	35.9 / 106
Mass balance sample vessel 1 ASW (dilution factor 2)	0.431	17.0	17.6 / 104

Fortification of Sn in test samples

sample	measured concentration [µg/L]	calculated level after addition [µg/L]	recovery [µg/L] / [%]
GST vessel 1 sample b 2h	0.083	0.138	0.144 / 104
GST vessel 2 sample b 2h	0.062	0.125	0.129 / 103
GST vessel 1 sample b 24h	0.273	2.68	2.68 / 99.8
GST vessel 3 sample b 24h	0.233	0.405	0.397 / 98.0
GMB vessel 2 sample b 24h	<LOD^#	1.67	1.62 / 97.4
ASW vessel 1 sample a 2h	0.70	0.130	0.132 / 102
ASW vessel 1 sample a 24h	0.439	0.626	0.622 / 99.3
ALF vessel 2 sample a 2h	0.907	1.44	1.44 / 99.9
ALF vessel 2 sample a 24h	2.79	3.53	3.58 / 101
PBS vessel 3 sample a 2h	0.029	1.68	1.69 / 101
PBS vessel 2 sample a 24h	0.055	3.35	3.42 / 102
Mass balance sample vessel 1 ALF (dilution factor 2)	2.86	35.2	36.2 / 103
Mass balance sample vessel 1 ASW (dilution factor 2)	2.09	18.1	17.1 / 94.5

^#Solutions with concentrations below the LOD/LOQ were also fortified. However, a recovery of ± 15 % may not be realistic as concentrations in the original (unfortified) sample below the LOD may be lower than the noise ratio and concentrations below the LOQ are between the noise ratio and a real (quantifiable) signal. For solutions with concentrations below the LOD/LOQ, a recovery of ± 25 % - 30 % is more realistic.

Fortification of V in test samples.

sample	measured concentration [µg/L]	calculated level after addition [µg/L]	recovery [µg/L] / [%]
GST vessel 1 sample b 2h	2.18	1.53	1.49 / 97.3
GST vessel 2 sample b 2h	2.05	1.45	1.44 / 99.8
GMB vessel 1 sample a 2h	2.34	1.64	1.62 / 98.3
GMB vessel 2 sample b 24h	3.18	3.78	3.68 / 97.3
ASW vessel 1 sample a 2h	1.72	1.23	1.22 / 99.6
ASW vessel 1 sample a 24h	2.90	2.26	2.27 / 100
ALF vessel 2 sample a 2h	2.46	2.47	2.52 / 102
ALF vessel 2 sample a 24h	3.49	3.99	4.20 / 105
PBS vessel 3 sample a 2h	2.02	2.34	2.16 / 92.2
PBS vessel 2 sample a 24h	3-33	4.44	4.16 / 93.6
Mass balance sample vessel 1 ASW (dilution factor 2)	2.20	18.1	20.5 / 113
Mass balance filter of vessel 1 GST (dilution factor 2)	0.543	17.0	16.2 / 95.0

As further quality assurance measurement, routine analyses of method blank samples were performed with the same pretreatment as the test samples.

Antimony concentration in method blanks

- GST, GMB, ASW: All samples below LOD

- ALF: All samples below LOD/LOQ

- PBS: One method blank 2h below LOQ, three above LOQ:

2h -> 0.062 ± 0.024 µg/L; 2h method blanks by factor 2.56 below 2h samples; 24h method blanks all above LOQ: 24h -> 0.125 ± 0.004 µg/L; 24h method blanks by factor 1.69 below 24h samples

Tin concentration in method blanks

- GST, GMB, ALF: All samples below LOD

- ASW: One method blank 2h below LOD, one below LOQ, two above LOQ:
2h -> 0.002 ± 0.002 µg/L; 2h method blanks by factor 33.0 below 2h samples; 24h method blanks all above LOQ: 24h -> 0.010 ± 0.004 µg/L; 24h method blanks by factor 43.1 below 24h samples

- PBS: All samples below LOD/LOQ

Vanadium concentration in method blanks

- GST: All samples below LOD

- GMB: Three method blanks 2h below LOD, one below LOQ; all method blanks 24h above LOQ: 24h -> 0.032 ± 0.002 µg/L; 24h method blanks by factor 99.1 below 24h samples

- ALF: All samples below LOD/LOQ

- ASW: Method blanks 2h all below LOD/LOQ; two method blanks 24h below LOD, one method blank below LOQ, one method blank above LOQ -> 0.006 ± 0.004 µg/L; 24h method blanks by factor 465 below 24h samples

- PBS: ???

Applicant's summary and conclusion

Conclusions:

On the basis of OECD Series on Testing and Assessment No. 29 as well as according to a bioaccessibility test protocol, which has been developed on the basis of relevant published methods, the dissolution of the pigment IPC-2018-003 (tin antimony grey cassiterite) in the artificial physiological media (GST, GMB, ALF, ASW and PBS) with a single loading of 100 mg/L, agitation (100 rpm) at 37 °C ± 2 °C and sampling after 2 and 24 h, was determined. The measurement of dissolved antimony, tin and vanadium concentrations after filtration were performed by ICP-MS. The study was performed in triplicate with two additional method blanks per medium.

Concentration of dissolved antimony in artificial physiological media:
Total Sb ± SD in sample vessels (corrected concentrations, corresponding to a loading of exactly 100 mg/L) with mean method blank subtraction (mean of 2 h and/or 24 h)
- GST 2h: 0.091 ± 0.012 µg/L
- GST 24h: 0.446 ± 0.018 µg/L
- GMB 2h: 0.004 ± 0.002 µg/L
- GMB 24h: 0.016 ± 0.004 µg/L
- ALF 2h:0.058 ± 0.001 µg/L
- ALF 24h: 0.260 ± 0.007 µg/L
- ASW 2h: 0.032 ± 0.003 µg/L
- ASW 24h: 0.139 ± 0.003 µg/L
- PBS 2h: 0.096 ± 0.081 µg/L
- PBS 24h: 0.086 ± 0.004 µg/L

Concentration of dissolved tin in artificial physiological media
Total Sn ± SD in sample vessels (corrected concentrations, corresponding to a loading of exactly 100 mg/L) with mean method blank subtraction (mean of 2 h and/or 24 h)
- GST 2h: 0.069 ± 0.012 µg/L
- GST 24h: 0.237 ± 0.029 µg/L
- GMB 2h: All samples below LOD
- GMB 24h: All samples below LOD
- ALF 2h: 0.895 ± 0.013 µg/L
- ALF 24h: 2.81 ± 0.05 µg/L
- ASW 2h: 0.066 ± 0.015 µg/L
- ASW 24h: 0.397 ± 0.019 µg/L
- PBS 2h: 0.034 ± 0.015 µg/L
- PBS 24h: 0.064 ± 0.009 µg/L

Concentration of dissolved vanadium in artificial physiological media
Total V ± SD in sample vessels (corrected concentrations, corresponding to a loading of exactly 100 mg/L) with mean method blank subtraction (mean of 2 h and/or 24 h)
- GST 2h: 2.01 ± 0.12 µg/L
- GST 24h: 3.74 ± 0.07 µg/L
- GMB 2h: 2.36 ± 0.03 µg/L
- GMB 24h: 3.07 ± 0.04 µg/L
- ALF 2h: 2.43 ± 0.03 µg/L
- ALF 24h: 3.53 ± 0.04 µg/L
- ASW 2h: 1.76 ± 0.10 µg/L
- ASW 24h: 2.83 ± 0.03 µg/L
- PBS 2h: 2.16 ± 0.14 µg/L
- PBS 24h: 3.29 ± 0.03 µg/L