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Diss Factsheets

Administrative data

Endpoint:
additional toxicological information
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Type of study / information:
A study was conducted to determine the dissolution and bioaccessibility of test item in five artificial physiological test media (phosphate-buffered saline (PBS) (pH 7.2), artificial interstitial fluid (pH 7.4), artificial sweat solution (pH 6.5), artificial lysosomal fluid (pH 4.5) and artificial gastric fluid (pH 1.5)).
Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
other: Stopford W, Turner J, Cappelini D, Brock T 2003. Bioaccessibility testing of Cobalt compounds. Journal of Environmental Monitoring 5:675-680.
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: EEC guideline SANCO/3029/99 rev. 4 dated 11/07/00: Working document “Guidance for generating and reporting methods of analysis in support of residue data requirements for Annex II (part A, Section 4) and Annex III (part A, Section 5)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
antimony trioxide
IUPAC Name:
antimony trioxide
Constituent 2
Chemical structure
Reference substance name:
Titanium dioxide
EC Number:
236-675-5
EC Name:
Titanium dioxide
Cas Number:
13463-67-7
Molecular formula:
O2Ti
IUPAC Name:
Titanium(IV) oxide
Constituent 3
Chemical structure
Reference substance name:
Calcium oxide
EC Number:
215-138-9
EC Name:
Calcium oxide
Cas Number:
1305-78-8
Molecular formula:
CaO
IUPAC Name:
oxocalcium
Constituent 4
Chemical structure
Reference substance name:
Silicon dioxide
EC Number:
231-545-4
EC Name:
Silicon dioxide
Cas Number:
7631-86-9
Molecular formula:
O2Si
IUPAC Name:
dioxosilane
Test material form:
solid: particulate/powder
Specific details on test material used for the study:



STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature without particular precaution to avoid the light exposure

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: None

Results and discussion

Any other information on results incl. tables

Titanium dioxide is essentially insoluble in artificial interstitial fluid, in artificial sweat solution and in PBS solution, and slightly soluble in artificial gastric fluid (0.41%) and in artificial lysosomal fluid (0.26%).

 

Antimony oxide is slightly soluble in all artificial physiological test media (minimum release in artificial interstitial fluid and in PBS solution: 0.12%; maximum release in artificial gastric fluid: 0.33%).

 

The % of dissolution for titanium dioxide and for antimony oxide was calculated from the test item composition considering an initial Uverithe load of 100 mg. The maximum possible release for Titanium is 23350 µg/L, while for Antimony is 32245 µg/L.


TABLE 1a Uverithe:47Ti and123Sb concentrations and % of dissolution in Artificial gastric fluid (pH 1.5)

Artificial gastric fluid

(pH 1.5)

47Ti

(µg/L)

Titanium dioxide

(% of dissolution)

123Sb

(µg/L)

Antimony oxide

(% of dissolution)

T0

(*)

Mean

n.d.

-

n.d.

-

S.D.

-

-

RSD%

-

-

T2h

(**)

Mean

54.35

0.23

59.88

0.19

S.D.

3.31

6.91

RSD%

6.08

11.55

T8h

(**)

Mean

79.54

0.34

82.60

0.26

S.D.

1.73

5.51

RSD%

2.17

6.67

T24h

(**)

Mean

94.79

0.41

107.27

0.33

S.D.

5.96

8.83

RSD%

6.29

8.23

n.d.: lower than the Limit of Detection (L.O.D. = 0.50 µg/L for Ti and Sb).

(*) This valueis considered the contribution of the test medium.

(**) This valuewas calculated subtracting the relevant Control sample value, in order to consider the contribution of the test medium.

 The between-vessel variation was less than 20 % in accordance with OECD Series No. 29 (ENV/JM/MONO(2001)9).


TABLE 1b Uverithe:47Ti and123Sb concentrations and % of dissolution in Artificial lysosomal fluid (pH 4.5)

Artificial lysosomal fluid

(pH 4.5)

47Ti

(µg/L)

Titanium dioxide

(% of dissolution)

123Sb

(µg/L)

Antimony oxide

(% of dissolution)

T0

(*)

Mean

3.28

-

n.d.

-

S.D.

0.08

-

RSD%

2.37

-

T2h(**)

Mean

19.99

0.09

48.34

0.15

S.D.

1.01

3.99

RSD%

5.04

8.25

T24h

(**)

Mean

55.04

0.24

81.64

0.25

S.D.

1.21

0.46

RSD%

2.20

0.57

T72h

(**)

Mean

60.01

0.26

84.79

0.26

S.D.

1.38

0.95

RSD%

2.30

1.12

n.d.: lower than the Limit of Detection (L.O.D. = 0.50 µg/L for Sb).

(*) This valueis considered the contribution of the test medium.

(**) This valuewas calculated subtracting the relevant Control sample value, in order to consider the contribution of the test medium.

The between-vessel variation was less than 20 % in accordance with OECD Series No. 29 (ENV/JM/MONO(2001)9).


TABLE 1c Uverithe:47Ti and123Sb concentrations and % of dissolution in Artificial sweat solution (pH 6.5)

Artificial sweat solution

(pH 6.5)

47Ti

(µg/L)

Titanium dioxide

(% of dissolution)

123Sb

(µg/L)

Antimony oxide

(% of dissolution)

T0

(*)

Mean

n.d.

-

n.d.

-

S.D.

-

-

RSD%

-

-

T2h(**)

Mean

n.d.

0.00

18.58

0.06

S.D.

-

0.43

RSD%

-

2.30

T24h

(**)

Mean

1.01

0.00

37.50

0.12

S.D.

0.01

1.02

RSD%

1.02

2.73

T72h

(**)

Mean

1.62

0.01

47.56

0.15

S.D.

0.20

2.86

RSD%

12.07

6.01

T168h

(**)

Mean

2.79

0.01

48.40

0.15

S.D.

0.12

1.80

RSD%

4.39

3.71

n.d.: lower than the Limit of Detection (L.O.D. = 0.50 µg/L for Ti and Sb).

(*) This valueis considered the contribution of the test medium.

(**) This valuewas calculated subtracting the relevant Control sample value, in order to consider the contribution of the test medium.

The between-vessel variation was less than 20 % in accordance with OECD Series No. 29 (ENV/JM/MONO(2001)9).


TABLE 1d Uverithe:47Ti and123Sb concentrations and % of  dissolution in Phosphate buffered saline (PBS) (pH 7.2)

Phosphate buffered saline (PBS)

(pH 7.2)

47Ti

(µg/L)

Titanium dioxide

(% of dissolution)

123Sb

(µg/L)

Antimony oxide

(% of dissolution)

T0

(*)

Mean

5.97

-

< 1.00

-

S.D.

0.26

-

RSD%

4.41

-

T2h

(**)

Mean

1.76

0.01

19.97

0.06

S.D.

0.12

0.23

RSD%

6.84

1.18

T24h

(**)

Mean

2.48

0.01

38.14

0.12

S.D.

0.19

1.48

RSD%

7.83

3.87

<1.00 : lower than the Limit of Quantification (L.O.Q. = 1.00 µg/L for Sb) but higher than the Limit of Detection (L.O.D. = 0.50 µg/L for Sb)

(*) This valueis considered the contribution of the test medium.

(**) This valuewas calculated subtracting the relevant Control sample value, in order to consider the contribution of the test medium.

The between-vessel variation was less than 20 % in accordance with OECD Series No. 29 (ENV/JM/MONO(2001)9).


TABLE 1e Uverithe:47Ti and123Sb concentrations and % of dissolution Artificial interstitial fluid (pH 7.4)

Artificial interstitial fluid

(pH 7.4)

47Ti

(µg/L)

Titanium dioxide

(% of dissolution)

123Sb

(µg/L)

Antimony oxide

(% of dissolution)

T0

(*)

Mean

1.50

-

n.d.

-

S.D.

0.04

-

RSD%

2.70

-

T2h(**)

Mean

1.69

0.01

11.82

0.04

S.D.

0.19

0.61

RSD%

11.53

5.20

T24h

(**)

Mean

2.21

0.01

29.98

0.09

S.D.

0.17

2.18

RSD%

7.88

7.27

T72h

(**)

Mean

2.21

0.01

36.97

0.11

S.D.

0.17

3.54

RSD%

7.80

9.57

T168h

(**)

Mean

2.74

0.01

37.40

0.12

S.D.

0.26

2.97

RSD%

9.34

7.94

n.d.: lower than the Limit of Detection (L.O.D. = 0.50 µg/L for Sb).

(*) This valueis considered the contribution of the test medium.

(**) This valuewas calculated subtracting the relevant Control sample value, in order to consider the contribution of the test medium.

The between-vessel variation was less than 20 % in accordance with OECD Series No. 29 (ENV/JM/MONO(2001)9).


 



Applicant's summary and conclusion

Conclusions:
Titanium dioxide is essentially insoluble in artificial interstitial fluid, in artificial sweat solution and in PBS solution, and it is slightly soluble in artificial gastric fluid (0.41% released after 24 hours) and in artificial lysosomal fluid (0.26% released after 72 hours). The solubility of antimony oxide is very low in all artificial physiological test media. The lowest release of 0.12% was observed in artificial interstitial fluid after 168 and in PBS solution after 24 hours and maximum release of 0.33% was observed in artificial gastric fluid after 24 hours.
Executive summary:

A study was conducted to determine the dissolution and bioaccessibility of test item in five artificial physiological test media selected to simulate relevant human-chemical interactions (Martinez 2016).

The study was performed according the method described by Stopford et al. (2003) and SANCO/3029/99 guideline and is a GLP-compliant. This study is considered reliable without restrictions (Klimisch 1) and is suitable for use as a key study for this endpoint.

The dissolved amount of the test item was quantified by the mass concentration of titanium dioxide and antimony oxide in five artificial physiological test media (phosphate-buffered saline (PBS) (pH 7.2),artificial interstitial fluidor Gamble’s solution (pH 7.4), artificial sweat solution (pH 6.5), artificial lysosomal fluid (pH 4.5) and artificial gastric fluid (pH 1.5)) at specific time intervals using ICP-MS analysis. 

The results indicate that whilst titanium dioxide is essentially insoluble in artificial interstitial fluid, in artificial sweat solution and in PBS solution, it is slightly soluble in artificial gastric fluid (0.41% released after 24 hours) and in artificial lysosomal fluid (0.26% released after 72 hours).

The solubility of antimony oxide is very low in all artificial physiological test media. The highest release of antimony oxide of 0.33% was observed in artificial gastric fluid after 24 hours.