Zinc bis(dihydrogen phosphate)

Basic toxicokinetics

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:

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

Remarks:

Test according to state-of-the-art operating procedures for testing of metal bioelution.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Objective of study:

bioaccessibility (or bioavailability)

Test guideline

Qualifier:

according to guideline

Guideline:

other: ASTM D5517-07: Standard Test Method for determining the extractability of metals from art materials - ASTM, 2007 (American Society for Testing and Materials).

Principles of method if other than guideline:

The release/dissolution of lead from Zn alloy R1 (massive) with Pb concentration = 0.481% in simulated gastric fluid was measured. The resulting value is termed bio-accessibility, and is defined as the fraction of a substance that is soluble under physiological conditions and therefore potentially available for absorption into systemic circulation. The simulated gastric fluid represents an exposure-relevant exposure route (oral exposure). The compound was introduced as powder in a test item / solution ratio of 2000 mg/L during 2 hours.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Zinc

EC Number:

231-175-3

EC Name:

Zinc

Cas Number:

7440-66-6

IUPAC Name:

zinc

Constituent 2

Reference substance name:

Lead

EC Number:

231-100-4

EC Name:

Lead

Cas Number:

7439-92-1

Molecular formula:

Pb

IUPAC Name:

lead

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Rezinal nv, Dellestraat 17, B-3550 Zolder, Belgium; Batch N°: LB 17/027
- Expiration date of the lot/batch: stable over time
- Purity test date:
0.481 % lead [7439-92-1] and 99.4 % zinc [7440-66-6]

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature, in the dark.
- Stability under test conditions:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: epoxy embedding


FORM AS APPLIED IN THE TEST (if different from that of starting material) : epoxy embedded Zinc alloy R1 massive

Results and discussion

Preliminary studies:

not applicable

Main ADME results

Main ADME results 1

Type:

other: bioaccessibility

Results:

gastric fluid (2hours): as %Pb released of total Pb content: 0.038%

Main ADME results 2

Type:

other: bioaccessibility

Results:

gastric fluid (2hours): as %Zn released of total Zn content: 2.0%

Toxicokinetic / pharmacokinetic studies

Details on absorption:

not applicable

Details on distribution in tissues:

not applicable

Details on excretion:

not applicable

Metabolite characterisation studies

Metabolites identified:

not measured

Details on metabolites:

not applicable

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

gastric fluid (2hours): as %Pb released of total Pb content: 0.038
gastric fluid (2hours) as %Zn released of total Zn content: 2.0%

Any other information on results incl. tables

Zinc alloy R1, massive (surface loading 0.001681 m²/L) 2h gastric at pH 1.5

Analyte		X±Sbetween	CV between
Lead (Pb) (assay 0.481 %)	dissolution	3.69 ± 0.26 μg/L	7 %
	absolute Pb release	1.84 ± 0.13 μg/g	7 %
	% of available Pb eluted	0.038 %
	Pb release/surface	2.2 mg/m²

Zinc (Zn) (assay 99.4 %)	dissolution	40.5 ± 1.3 mg/L	3 %
	absolute Zn release	20.3 ± 0.7 mg/g	3 %
	% of available Zn eluted	2.0 %
	Zn release/surface	24 g/m²

X= Average of 3 test vessels (0.2µm filtration) S = Standard deviation CV: Coefficient of variation (%)

Applicant's summary and conclusion

Conclusions:

Bio-elution test according to state-of-the-art procedures, useful for determining dissolution capacity of Pb / Zn in gastric fluid.
The dissolution in gastric fluid is used to estimate bioavailability after oral exposure

Executive summary:

During this on epoxy embedded Zinc alloy R1 massive, the following could be observed after 2 hours of exposure to simulated gastric fluid (pH 1.5):

at a surface loading of 16.81 cm²/L (2 g/L surface equivalent), it was shown that:

o For lead an average value of 3.69 μg/L Pb (CVbetween-vessel = 7 %; N = 3) was found after 2 hours of extraction, corresponding with a lead release of 0.038 % (or 2.2 mg/m²).

o For zinc an average value of 40.5 mg/L Zn (CVbetween-vessel = 3 %; N = 3) was found after 2 hours of extraction, corresponding with a zinc release of 2.0 % (or 24 g/m²).

The results can be assumed reliable since the test conditions stayed constant during the experiment.