Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 282-762-6 | CAS number: 84418-50-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Not reported
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- publication
- Title:
- Pulmonary clearance and toxicity of zinc oxide instilled into the rat lung
- Author:
- Hirano S, Higo S, Tsukamoto N, Kobayashi E & Suzuki KT
- Year:
- 1 989
- Bibliographic source:
- Arch. Toxicol. 63(4):336-342
Materials and methods
- Objective of study:
- toxicokinetics
- Principles of method if other than guideline:
- Pulmonary toxicity of zinc oxide (ZnO) was evaluated by investigating the metabolic fate and inflammatory potency of ZnO instilled into the rat lung.
- GLP compliance:
- no
Test material
- Details on test material:
- - Name of test material (as cited in study report): Zinc oxide
- Obtained from Kanto Chemical Co., Ltd, Tokyo, Japan
Constituent 1
- Radiolabelling:
- no
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Clea Japan Co., Tokyo
- Weight at study initiation: 250-290 g
- Individual metabolism cages: yes/no
- Diet (e.g. ad libitum): Commercial chow (Oriental Yeast Co., Tokyo), ad libitum
- Water (e.g. ad libitum): Distilled water, ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 °C
- Humidity (%): 50 %
Administration / exposure
- Route of administration:
- intratracheal
- Vehicle:
- other: sterile physiological saline
- Details on exposure:
- - Preparation of dosing solution: Test material was milled for 5 min with a micro-pulvilizer (P-7, Fritsch Japan Co., Ltd, Yokohama, Japan) and the resulted particles were suspended in sterile physiological saline and sonicated in an ultrasonic cleaner before instillation
- Method of particle size determination: Electron microscope (JSM- 840, JEOL, Tokyo) after collecting the particles on a membrane filter of 0.03 µm pore size (Nuclepore Co., Pleasanton, Calif, USA)
- Particle size: < 2 µm, appeared to form aggregates of 10-20 particles - Duration and frequency of treatment / exposure:
- Duration of exposure:
- Time-course experiment: 1/3, 1, 2, 3, 5, 7, 14 and 21 d
- Dose response experiment: 2 d
Frequency of exposure: Single intratracheal instillation of 0.4 mL ZnO suspension
Doses / concentrations
- Remarks:
- Doses / Concentrations:
- Time-course experiment: 100 µg Zn/rat
- Dose response experiment: 0, 20, 50, 100, 200, 500 and 1000 µg Zn/rat
- No. of animals per sex per dose / concentration:
- Three
- Control animals:
- yes, concurrent vehicle
- Positive control reference chemical:
- No
- Details on study design:
- None
- Details on dosing and sampling:
- Time of sacrifice:
- Time-course experiment: 1/3, 1, 2, 3, 5, 7, 14 and 21 d after administration
- Dose response experiment: 2 d after administration
Bronchoalveolar lavage fluid (BALF): BALF was used for measurement of lactate dehydrogenase (LDH) and 13-glucuronidase activity; concentrations of protein and essential elements (S, P, Ca and Mg); and differential cell counts
Organs: Trachea, lung, heart, liver and kidneys were removed, rinsed, blotted and weighed; lung tissues were assayed for metallothionein (MT)
Zinc concentration in BALF pellet, liver and kidney tissues: Measured by an inductively coupled argon plasma-atomic emission spectrometer (JY48PVH, Seiko Instruments & Electronics Co., Ltd, Tokyo) - Statistics:
- Two tailed t-test
Results and discussion
- Preliminary studies:
- Not applicable
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Dose-response experiment: Percentage of Zn retained in the lung increased with the dose, but at doses lower than 50 µg Zn/rat exogenous Zn was not observed 2 d after instillation indicating that the rat lung was able to clear ZnO particles up to a dose of 50 µg Zn/rat at least within 2 d. At doses higher than 200 µg Zn/rat, Zn was retrieved proportionally to the dose of ZnO both in the supernatant and pellet of BALF suggested the role of solubilization of ZnO particles in the bronchoalveolar milieu in the clearance rate of ZnO from the lung.
- Details on distribution in tissues:
- - No measurable accumulation of Zn was observed in the liver and kidneys even at a dose of 1000 µg Zn/rat
- 20 µg Zn/rat was sufficient to develop maximum responses for β-glucuronidase activity and surfactant content in the bronchoalveolar lavage fluid
- Lactate dehydrogenase activity and protein content in the lavage fluid increased significantly at 20 µg Zn/rat
- Metallothionein (MT) was induced with a peak at 2 d. The content of MT was proportional to the dose of ZnO, but contributed little for the accumulation of Zn in the lung.
- Details on excretion:
- - ZnO particles were solubilised in the bronchoalveolar milieu and cleared from the lung with a half-life of 14 h.
Toxicokinetic parameters
- Test no.:
- #1
- Toxicokinetic parameters:
- half-life 1st: 14 h
Metabolite characterisation studies
- Metabolites identified:
- no
- Details on metabolites:
- Not applicable
Any other information on results incl. tables
Table 1. Time-course and dose-response changes in lung wet weight and metallothionein content in the lung
|
Time after instillation (days) |
|||||||
1/3 |
1 |
2 |
3 |
5 |
7 |
14 |
21 |
|
Lung wet weight (g) |
0.87 |
1.33* |
1.48 |
1.41* |
1.30* |
1.49* |
1.24* |
1.23 |
± 0.04 |
± 0.04 |
± 0.19 |
± 0.04 |
± 0.10 |
± 0.07 |
± 0.02 |
± 0.13 |
|
Metallothionein (µg/lung) |
2.2 |
3.8 |
7.8* |
2.9 |
2.1 |
2.6 |
2 |
2.3 |
± 0.44 |
± 0.4 |
± 0.82 |
± 0.38 |
± 0.37 |
± 0.3 |
± 0.22 |
± 0.08 |
|
|
Control |
Dose of ZnO (µg Zn/rat) |
||||||
20 |
50 |
100 |
200 |
500 |
1000 |
-
|
||
Lung wet weight (g) |
0.87 |
1.1 |
1.46* |
1.48 |
1.39 |
1.76* |
1.99* |
|
± 0.06 |
± 0.05 |
± 0.09 |
± 0.19 |
± 0.14 |
± 0.09 |
± 0.09 |
||
Metallothionein (µg/lung) |
2.2 |
1.7 |
5.2 |
7.8* |
11* |
21* |
29* |
|
± 0.26 |
± 0.26 |
± 1.6 |
± 0.82 |
± 1.7 |
± 0.64 |
± 3.6 |
Data are presented as means ± SEM
* Significantly different from control value
Bronchoalveolar lavage fluid (BALF):
- Concentrations of protein & essential elements (S, P, Ca and Mg): The protein content increased with the dose and reached a plateau at 200 µg Zn/rat. S, Ca, and Mg content peaked at 2 d and returned to their control levels after 7-14 d, while P content showed a maximum value at 5 d and even at 7 d its content was still 3.8 times higher than the control value. S, Ca and Mg increased with the dose up to 200 µg Zn/rat and appeared to plateau at this dose level. However, the profile of P content again showed a different pattern from those of S, Ca and Mg contents. A dose level of 20 µg Zn/rat produced a maximum response in the P content
- Differential cell counts: Polymorphonuclear leukocytes (PMNs) peaked at 2 d, while 5 d for the macrophages in their peak, cells reached maximum values at 200-500 µg Zn/rat in the dose-response profiles.
Applicant's summary and conclusion
- Conclusions:
- low bioaccumulation potential based on study results
The results indicated that the rat lung was able to clear ZnO particles up to a dose of 50 g Zn2+/rat at least within two days. No measurable accumulation of Zn was observed in the liver and kidneys even at a dose of 1000 µg Zn2+/rat . - Executive summary:
Pulmonary toxicity of zinc oxide (ZnO) was evaluated by investigating the metabolic fate and inflammatory potency of ZnO instilled into the rat lung.
Groups of three rats received single intratracheal instillations of ZnO suspension at a dose of 100 µg Zn/rat in the time-course experiment or received 20, 50, 100, 200, 500 and 1000 µg Zn/rat and were killed 2 d after treatment in the dose-response experiment.
ZnO particles were solubilised in the bronchoalveolar milieu and cleared from the lung with a half-life of 14 h. Metallothionein (MT) was induced with a peak at 2 d. The content of MT was proportional to the dose of ZnO, but contributed little for the accumulation of Zn in the lung.
A dose of 20 µg Zn/rat was sufficient to develop maximum responses for β-glucuronidase activity and surfactant content in the bronchoalveolar lavage fluid. Moreover, the activity of lactate dehydrogenase and protein content in the lavage fluid increased significantly at 20 µg Zn/rat.
The results indicated that the rat lung was able to clear ZnO particles up to a dose of 50 g Zn2+/rat at least within two days. No measurable accumulation of Zn was observed in the liver and kidneys even at a dose of 1000 µg Zn2+/rat .
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
![ECHA](/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/echa_logo.png)
Embora a ECHA disponibilize muito material em linha na sua língua, uma parte desta página está disponível apenas em inglês. Mais informações sobreas práticas de multilinguismo da ECHA.
Bem-vindo ao sítio Web da ECHA O navegador Internet Explorer 7 (e versões anteriores) não é totalmente suportado por este sítio Web. Por favor atualize o seu Internet Explorer para uma versão mais recente.
Este sítio Web utiliza cookies a fim de garantir a melhor experiência possível nos nossos sítios Web.
Saiba mais sobre como utilizar cookies.