Zinc oxide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The study is comparable to a guideline study with acceptable restrictions. The study was not performed under GLP conditions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Objective of study:

other: dissolution

Principles of method if other than guideline:

The dissolution behaviour in lysosomal pH4.5 conditions was studied to simulate the
clearance by dissolution. The method is compliant with a draft OECD guidance (WPMN
Task 1.5), and was previously validated against in-vivo clearance (Koltermann-Jülly et al.
2018, Koltermann-Jülly et al. 2019, Keller et al. 2020).

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Zinc oxide

EC Number:

215-222-5

EC Name:

Zinc oxide

Cas Number:

1314-13-2

Molecular formula:

ZnO

IUPAC Name:

oxozinc

Test material form:

solid: nanoform, no surface treatment

Details on test material:

- Particle size distribution: D10 is 10.4 nm ; D50 is 18.2 nm ; D90 is 28.2 nm
- Shape of particles: spheroidal
- Surface area of particles: ca. 10 - 40 m2/g
- Crystal structure: hexagonal zincite crystalline phase
- Coating: no coating applied
- Dustiness: 12 mg/kg (respirable mass index)
- Dissolution rate (kmin): 378 ng/cm2/h

Radiolabelling:

no

Test animals

Details on test animals or test system and environmental conditions:

not applicable

Administration / exposure

Details on exposure:

not applicable

No. of animals per sex per dose / concentration:

not applicable

Control animals:

not relevant

Positive control reference chemical:

not applicable

Details on study design:

The flow-through setup was described in detail by several publications as an implementation of a
Continuous Flow System (CFS) according to ISO TR 19057 (ISO/TR19057 2017, Koltermann-Jülly et al. 2018, Keller et al. 2020, Keller et al. 2020). CFS is established as a screening method of the dissolution kinetics of mineral fibres (Guldberg 1995, IARC 2002, Wohlleben et al. 2017). A ZnO mass of M0 = 1 mg was weighed onto a membrane (cellulose triacetate, Sartorius Stedim Biotech GmbH, Goettingen, Germany: 47 mm diameter, 5 kDa pore size), topped by another membrane, and enclosed in flow through cells. The flow through cells at 37 ± 0.5 °C were kept upright to ensure that emerging air bubbles can leave the system and do not accumulate within the cell. The flow rate (V) was 48 mL/d; this corresponds to a ratio, SA/V around 0.02 h/cm, which was independently found to lead to correct predictions.(Keller et al. 2020) The PSF medium – previously validated for the purpose of particle dissolution (Stefaniak et al. 2005) and recommended by the ISO 19057– was employed to simulate the lysosomal compartment at pH 4.5. The programmable sampler drew 10 mL eluates twice per day. These were stabilised by 0.1N HNO3, and analysed by ICP-MS (Perkin Elmer Nexion 2000b).

Details on dosing and sampling:

A ZnO mass of M0 = 1 mg was weighed onto a membrane (cellulose triacetate, Sartorius Stedim Biotech GmbH, Goettingen, Germany: 47 mm diameter, 5 kDa pore size), topped by another membrane, and enclosed in flowthrough cells. The flow rate (V) was 48mL/d; this corresponds to a ratio, SA/V around 0.02 h/cm. The programmable sampler drew 10 mL eluates twice per day.

Statistics:

not specified

Results and discussion

Preliminary studies:

not applicable

Main ADME results

Main ADME results 1

Type:

other: dissolution

Results:

k min 378ng/cm2/h

Main ADME results 2

Type:

other: dissolution

Results:

k max 323ng/cm2/h

Toxicokinetic / pharmacokinetic studies

Details on absorption:

not applicable

Details on distribution in tissues:

not applicable

Details on excretion:

not applicable

Any other information on results incl. tables

The dissolution of test material T0420 was tested in lysosomal conditions (pH4.5). The fitted halftime from exponential decay was 0.19 days. The dissolution rate obtained from the conversion of the fitted halftime (kmin) was 378ng/cm2/h.
The highest observed dissolution rate in a single sampling interval (kmax) was 323ng/cm2/h.

Applicant's summary and conclusion

Conclusions:

The dissolution of test material T0420 was tested in lysosomal conditions (pH4.5). The dissolution rate obtained from the conversion of the fitted halftime (kmin) was 378ng/cm2/h.
The highest observed dissolution rate in a single sampling interval (kmax) was 323ng/cm2/h.

Executive summary:

ZnO test item T0420 was tested in a continuous flow through system in lysosomal conditions at pH4.5 to simulate clearance by dissolution.