Barium carbonate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Remarks:

Bioaccessibility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2021-12-14 to 2022-06-21

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2022

Report date:

2022

Materials and methods

Objective of study:

bioaccessibility (or bioavailability)

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

An internationally agreed guideline does not exist for this test (e.g. OECD). This test was conducted on the basis of the guidance for OECD-Series on testing and assessment Number 318 and according to the nanoGRAVUR Standard Operation Procedure for static solubility testing of NM suspension v1.0. The test media were artificial physiological media: gastric simulation fluid (GSF), phosphate-buffered saline (PBS) and Gamble's solution (GMB)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Barium carbonate

EC Number:

208-167-3

EC Name:

Barium carbonate

Cas Number:

513-77-9

Molecular formula:

BaCO3

IUPAC Name:

barium carbonate

Test material form:

solid: nanoform

Radiolabelling:

no

Test animals

Species:

other: in vitro (simulated human body fluids)

Details on test animals or test system and environmental conditions:

Test Set-up
- three different artificial physiological media,
- single loading of test substance of 1 g/L,
- PBS and Gamble media: samples taken after 0.5, 2, 6 and 48 hours incubation at 37°C
- GSF media: samples taken after 0.5, 2 and 48 hours incubation at 37°C
- the study was performed in triplicate
- three vessels with test solution and two blanks were prepared per medium. The particle suspension was shaken for different time periods using an overhead shaker. The shaker was placed inside a climate chamber to guarantee a constant temperature of 37°C. After shaking, the suspension was centrifuged (5000 G) with a 5-10k Da membrane ultrafiltration Tube (Sartorius Vivaspin V15). The filtrate was afterwards analysed via Inductively Coupled Plasma Optical Emission Spectrometry (ICP OES) for the quantification of the Barium concentration.

The aim of this test was to assess the dissolution of Barium carbonate nano in three artificial physiological media: Phosphate buffered saline (PBS, pH 7.2-7.4), Gastric simulation fluid (GSF, 1.3-1.5) and Gamble’s solution (pH 7.2-7.4). The test media were selected to simulate relevant human-chemical interactions , e.g. a substance entering the human body by ingestion into the gastro-intestinal tract (GSF).

Administration / exposure

Duration and frequency of treatment / exposure:

Barium concentrations were determined after 0.5, 2, and 48 hours of incubation in PBS, Gamble and GSF. In Gamble and PBS media, barium concentrations were additionally determined after 6 h.

Doses / concentrations

Dose / conc.:

1 other: g of test item/L artificial media

Details on study design:

Test setup
Three replicate flasks per test medium (PBS, GSF and Gamble) were prepared with a loading of 1 g/L. In addition two blank samples were prepared per test medium. The test item was weighed into flasks, adjusted to volume with the respective artificial physiological medium and shaken for different time periods using an overhead shaker. The shaker was placed inside a climate chamber to guarantee a constant temperature of 37°C. Samples of Gamble and PBS medium were taken after 0.5, 2, 6 and 48 h and GSF samples after 0.5, 2 and 48 h. Barium concentrations were determined with ICP-OES after centrifugation (5000 g) with a 5-10k Da membrane ultrafiltration Tube.

Results and discussion

Main ADME results

Main ADME results 1

Type:

other: Bioaccessibility GSF, 0.5h

Results:

607 ± 5.8 mg Ba/L (dissolved)

Main ADME results 2

Type:

other: Bioaccessibility GSF, 2h

Results:

605 ± 21.2 mg Ba/L (dissolved)

Main ADME results 3

Type:

other: Bioaccessibility GSF, 48h

Results:

633 ± 15.3 mg Ba/L (dissolved)

Main ADME results 4

Type:

other: Bioaccessibility PBS, 0.5h

Results:

29.7 ± 0.3 mg Ba/L (dissolved)

Main ADME results 5

Type:

other: Bioaccessibility PBS, 2h

Results:

24.3 ± 2.3 mg Ba/L (dissolved)

Main ADME results 6

Type:

other: Bioaccessibility PBS, 6h

Results:

23.0 ± 1.4 mg Ba/L (dissolved)

Main ADME results 7

Type:

other: Bioaccessibility PBS, 48h

Results:

16.7 ± 0.6 mg Ba/L (dissolved)

Main ADME results 8

Type:

other: Bioaccessibility Gamble, 0.5h

Results:

99.8 ± 0.4 mg Ba/L (dissolved)

Main ADME results 9

Type:

other: Bioaccessibility Gamble, 2h

Results:

120 ± 0.0 mg Ba/L (dissolved)

Main ADME results 10

Type:

other: Bioaccessibility Gamble 6h

Results:

77 ± 0.0 mg Ba/L (dissolved)

Main ADME results 11

Type:

other: Bioaccessibility Gamble 48h

Results:

46 ± 1.0 mg Ba/L (dissolved)

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

Please refer to "any other information on results incl. tables" below.

Any other information on results incl. tables

Barium concentrations in simulated artificial body fluids

The bioaccessibility of barium carbonate nano was determined in vitro by simulating dissolution under physiological conditions considered to mimic artificial body fluids with a loading of 1 g test item/L. Dissolved barium concentrations were operationally defined as the dissolved Ba fraction after centrifugation (5000 G) with a 5-10k Da membrane ultrafiltration Tube (Sartorius Vivaspin V15). The barium background concentration in all media used for the test was ≤ 0.04 mg/L and therefore no background correction was performed.  The dissolved Ba fractions are summarized in Table 2.

 

Table 2: Dissolved barium concentrations in various artificial physiological media after exposure to Barium carbonate nano (BM020)

Medium	Sampling time (hours)	Conc. Ba of method blanks (mg/L)	Conc. Ba in test solutions (mg/L)	Mean Ba conc. ± SD (mg/L)
GSF	0.5	0.037 0.039	610 610 600	606.7 ± 5.8
	2	-	590 620	605.0 ± 21.2
	48	LOD	650 620 630	633.3 ± 15.3
PBS	0.5	LOD	29 30 30	29.7 ± 0.3
	2	-	23 27 23	24.3 ± 2.3
	6	-	24 22	23.0 ± 1.4
	48	0.030 0.031	16 17 17	16.7 ± 0.6
Gamble	0.5	LOD	100 99 100	99.8 ± 0.4
	2	-	120 120 120	120 ± 0.0
	6	0.038 0.038	77 77	77 ± 0.0
	48	0.031 0.030	45 47 46	46 ± 1.0

 

The highest solubility for Barium was found in the gastric simulant fluid with the lowest pH value, nearly 100% of the Ba was dissolved. In GSF the solubility remained constant during the incubation period of 48 hours. In Gamble and PBS the materials show a decrease in the solubility over time. Usually, an increase in solubility over time would expected, which reaches a material, temperature and pH dependent equilibrium. The results of these two media show i.e. initially increasing and later decreasing solubility. A possible explanation could be that initially dissolved barium ions re-combine with other substances of the medium (e.g. phosphates) and precipitate. 

 

Solution pH

During the study, the pH of all media incl. blanks remained stable.

 

Temperature

The test solutions were placed in a climate chamber with a constant temperature of 37 °C to simulate the human body temperature.

 

Applicant's summary and conclusion

Conclusions:

The bioaccessibility of barium carbonate nano was determined in vitro by examining dissolution in artificial body fluids at 37°C. At a loading of 1 g test item/L (corresponding to 696 mg Ba/L), dissolved barium concentrations (operationally defined as the dissolved Ba fraction after centrifugal filtration (5-10 kDa) were determined with 607, 605 and 633 mg Ba/L after 0.5, 2 and 48 h in artificial gastric fluid (GSF, pH = 1.3), respectively, corresponding to a maximum mean released barium fraction of 91% after 48h.
With mean concentrations of 29.7, 24.3, 23.0 and 16.7 mg Ba/L after 0.5, 2, 6 and 48 h incubation, dissolved barium concentrations in phosphate buffered saline (PBS, pH = 7.3) were lower. Mean barium concentrations in Gamble´s solution (GMB, pH = 7.3) were determined at 100, 120, 77 and 46 mg Ba/L after 0.5, 2, 6 and 48 hours of incubation, respectively.