Zinc nitrate

Repeated dose toxicity: other routes

Administrative data

Endpoint:

repeated dose toxicity: other route

Remarks:

oropharyngeal aspiration

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

other: not rated according to Klimisch et al.

Rationale for reliability incl. deficiencies:

other:

Remarks:

The references contained in this summary entry represent in vivo experiments with investigat ions on repeated dose toxicity (route: oropharyngeal aspiration) with very limited value for risk assessment purposes. The references do not fulfil the criteria for quality, reliability and adequacy of experimental data for the fulfilment of data requirements under REACH and hazard as sessment purposes (ECHA guidance R4 in conjunction with regulation (EC) 1907/2006, Annexes VIIX). The information contained therein were included for information purposes only.

Data source

Reference

Reference Type:

publication

Title:

Pulmonary and hemostatic toxicity of multi-walled carbon nanotubes and zinc oxide nanoparticles after pulmonary exposure in Bmal1 knockout mice

Author:

Luyts, K. et al.

Year:

2014

Bibliographic source:

Particle and Fibre Toxicology 11:61.

Materials and methods

Principles of method if other than guideline:

Luyts, K. et al. (2014):
Test substance: zinc oxide nanoparticles, (BASF Z-Cote; zinkite, uncoated, primary size: 100 nm, NM110) obtained from the European Commission Joint Research Centre Nanomaterials Repository; X-ray diffraction size: 70 to >100 nm (by TEM analysis); size: 20-250/50-350 nm; Brunauer-Emmett-Teller (BET) surface area: 14 m²/g
Doses/Concentrations: 6.4 or 12.8 μg per aspiration (concentrations: 256 or 512 μg/mL)
No. of animals per sex per dose: not specified
Exposure duration: 5 consecutive weeks
Exposure frequency: once a week
Negative control: sterile water containing 2 vol% mouse serum
Positive control: not specified
Method of aerosol generation: not specified
Observation period: not specified
Parameters investigated: analysis of the number of macrophages, neutrophils, eosinophils and lymphocytes in the broncho-alveolar lavage (BAL) fluid by the DiffQuick method (Medical Diagnostics,
Düdingen, Germany); GSSG/GSH measurements (reduced (GSH) and oxidized (glutathione disulfide, GSSG)) in the left lung by UPLC/MS-MS and LC/MS-MS analysis; cytokine measurements in the remaining lobes of the right lung using the MSD mouse pro-inflammatory 7-plex (IFN-γ, IL-1β, IL-6, IL-10, IL-12p70, KC/GRO, TNF-α); measurement of partial thromboplastin time (aPTT), the prothrombin time (PT) and plasma levels of coagulation factors (F) VII, FVIII and fibrinogen in the blood serum; histological examination of the superior lobe of the right lung and heart, analysis of the arc/bow of the aortic tissues by incubation with antibodies and the biotinyl tyramide kit.

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:

OZn

IUPAC Name:

oxozinc

Test material form:

solid: nanoform

Test animals

Species:

other: Luyts, K. et al. (2014): Bmal1−/− and Bmal1+/+ mice (C57BL/6 J)

Sex:

male/female

Administration / exposure

Route of administration:

other: Luyts, K. et al. (2014): oropharyngeal aspiration

Results and discussion

Effect levels

Remarks on result:

other:

Remarks:

Luyts, K. et al. (2014): ZnO NPs seemed to suppress the inflammatory (decreased neutrophils in Bmal1−/− mice) and oxidative response (increased total glutathione in Bmal1−/− mice), but were also procoagulant with a significant increase of the coagulation factor FVIII. The procoagulant effects, as well as the significant correlations between the pulmonary endpoints (inflammation and oxidative stress) and hemostasis parameters were more pronounced in Bmal1−/− mice than in Bmal1+/+ mice.

Applicant's summary and conclusion

Conclusions:

No conclusion can be drawn from the above publications due to lack of quality, reliability and adequacy of the experimental data for the fulfilment of data requirements under REACH.

The references contained in this summary entry represent in vivo experiments with investigations on repeated dose toxicity with very limited value for risk assessment purposes. All references do not fulfil the criteria for quality, reliability and adequacy of experimental data for the fulfilment of data requirements under REACH and hazard assessment purposes (ECHA guidance R4 in conjunction with regulation (EC) 1907/2006, Annexes VII-X). The information contained therein were included for information purposes only.

Luyts, K. et al. (2014):
The non-physiological route of administration via oropharyngeal aspiration is not guideline conform and not suitable to assess acute inhalation toxicity. Only two dose groups were tested which does not allow a dose-response related analysis. Furthermore, the number of test animals per sex per dose are not stated. Also, the experimental design is insufficiently documented (e. g. information about the test material (purity), test animals (initial body weight, acclimation period) and the environmental conditions (temperature, humidity)). Only selected parameters investigated (coagulation, inflammatory and oxidative stress parameters) and the investigated endpoints are not required for building an expert judgment and further assessment of the test substance under REACH (ECHA guidance R4 in conjunction with regulation (EC) 1907/2006, Annex VII-X).