Zinc oxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

Organ biodistribution, clearance, and genotoxicity of orally administered zinc oxide nanoparticles in mice

Author:

Li C-H, Shen C-C, Cheng Y-W, Huang S-H, Wu C-C, Kao C-C, Liao,J-W and Kang J-J

Year:

2012

Bibliographic source:

Nanotoxicology, 6(7):746-56

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

not specified

Remarks:

the publication does not specify GLP compliance

Test type:

other: limit test

Limit test:

yes

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:

other: nano- and micromaterial

Details on test material:

uncoated ZnO nanoparticle:
- Diameter: 50 nm approximately
- Hydrodynamic diameter: 93.35 ± 14.53 nm

ZnO microparticles:
- Diameter: >100 nm
- Hydrodynamic diameter 1226.2 ± 120.4 nm

Other information: The suspensions of ZnO particles (stock concentration: 50 mg/mL) were prepared using anhydrous dimethyl sulfoxide (DMSO). ZnO-nanoparticle and ZnO microparticle were diluted with sterile water plus 1% hydroxypropyl methyl cellulose (HPMC) or culture medium, then mixed vigorously, sonicated, and then immediately applied to mice or human cells to minimize agglomeration. Finally, the DMSO concentration was less than 1% (in vivo study).

Test animals

Species:

mouse

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

- Rationale for the selection of the starting dose: Based on the result of another study (Yamaki & Yoshino 2009).

Doses:

5,000 mg/kg bw for both ZnO nanoparticle and microparticle

No. of animals per sex per dose:

5/sex/dose

Control animals:

yes

Details on study design:

Thirty mice were divided into three groups (five males and five females per group). Mice were fed with vehicle (control group), 5,000 mg/kg bw ZnO-nanoparticle suspension or 5,000 mg/kg bw ZnO-microparticles suspension. Dosed mice were conditioned for 14 d. The mortality and clinical behaviour were observed daily. Body weights were recorded twice weekly. At the end of the study (on Day 14), the mice were anaesthetised with isoflurane and blood (for serum biochemistry analysis) was collected from the orbital sinus, followed by gross necropsy. Tissue samples (for histopathologic examination) were taken and fixed in 10% neutral buffered formalin

Statistics:

All data were expressed as the mean ± SD from at least three independent experiments (N ‡ 3). The significance of the difference between the control and each experimental test condition was analysed by Student’s t-test. Statistically significant differences among groups were determined using one-way analysis of variance (ANOVA). A value of p < 0.05 was taken as statistically significant.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

Not observed

Clinical signs:

other: Not observed

Body weight:

other body weight observations

Remarks:

In comparison with vehicle control group, ZnO microparticles treated group showed a body weight reduction in both males (Days 5 and 10) and females (Days 5, 10, and 14); the body weight changes were unobvious in ZnO nanoparticle treated groups.

Gross pathology:

Decreased wet weights of the spleen, kidney, and liver were observed in ZnO microparticles treated females but not in ZnO nanoparticle treated males. However, no obvious gross pathological signs were found in the study.

Other findings:

All serum biochemistry measures were without any significant alternation except for marginal variations in certain parameters.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the study details, the LD50 value of both the ZnO nanoparticles and ZnO microparticles can be established at >5,000 mg/kg bw in mice.

Executive summary:

The study was conducted to examine the acute toxicity of both ZnO nanoparticles and ZnO microparticles in mice.

Thirty mice were divided into three groups (five males and five females per group). Mice were fed with vehicle (control group), 5,000 mg/kg bw ZnO-nanoparticle suspension or 5,000 mg/kg bw ZnO-microparticles suspension. Dosed mice were conditioned for 14 d.

All the mice survived throughout the testing period without exhibiting any abnormalities related to the test substances. In comparison with the vehicle control group, ZnO-microparticles treated group showed a body weight reduction in both males (Days 5 and 10) and females (Days 5, 10, and 14); the body weight changes were not obvious in ZnO-nanoparticle treated groups. All serum biochemistry measures were without any significant alterations except for marginal variations in certain parameters.

Based on the study details, the LD50 value of both the ZnO nanoparticles and ZnO microparticles can be established at >5,000 mg/kg bw in mice.