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EC number: 231-718-4 | CAS number: 7699-45-8
- 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
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- Nanomaterial pour density
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- Endpoint summary
- Stability
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- 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
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- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
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- Specific investigations
- Exposure related observations in humans
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- Additional toxicological data

Acute Toxicity: inhalation
Administrative data
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- migrated information: read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Study period:
- Not applicable
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for data waiving:
- other:
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:
- Unnamed
- Year:
- 1 989
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The potential of the test material to induce respiratory adverse effects/damage to the lungs in Porton Wistar rats was investigated using intra-tracheal instillation of the test material as a single dose. Oedema resulting from the treatment was assessed by increases in lung wet weight together with elevation in the levels of a purified alveolar surface protein fraction derived from the perfused lungs. The formation of a protein rich oedematous fluid is a common early response to toxic substances.
The toxicity of the test material can be correlated with pulmonary oedema inducing capacity, since protein rich oedematous fluid is a common early response to toxic substances.
Assessment of oedematous reaction is carried out by determination of increased in lung wet weight together with elevated levels of a purified alveolar surface protein fraction derived from lungs which had been totally perfused of blood. - GLP compliance:
- not specified
- Test type:
- other: Biochemical and pathological study in lungs
- Limit test:
- no
Test material
- Reference substance name:
- Zinc chloride
- EC Number:
- 231-592-0
- EC Name:
- Zinc chloride
- Cas Number:
- 7646-85-7
- IUPAC Name:
- zinc dichloride
- Details on test material:
- - Name of test material (as cited in study report): Zinc chloride
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- - Weight at study initiation: 150 -200 g
- Diet (e.g. ad libitum): Commercial diet
- Water (e.g. ad libitum): Tap water
Administration / exposure
- Route of administration:
- other: Intratracheal
- Type of inhalation exposure:
- other: Intratracheal
- Vehicle:
- other: water
- Details on inhalation exposure:
- Not applicable
- Analytical verification of test atmosphere concentrations:
- not specified
- Concentrations:
- 1. Investigation of rat lung response at different dose levels: 0.25, 0.5, 1.0, 2.0, 4.0 and 5.0 mg/kg bw
2. Investigation dose levels which produce early alveolar oedema: 0.25, 0.5, 1.0 or 1.5 mg/kg bw
3. Investigation of the effects of the perfusion procedure: 1.5 mg/kg bw
4. Investigation of the time course of oedema and any signs of fibrogenesis: 2.5 mg/kg bw
5. Histopatholgical examination of lungs: 2.5 mg/kg bw - No. of animals per sex per dose:
- 1. Investigation of lung response at low dose: 4
2. Investigation of rat lung response at different dose levels: Not reported
3. Investigation of dose level which produces early alveolar oedema: 6
4. Investigation of the effects of the perfusion procedure: 10
5. Investigation of the time course of oedema and any signs of fibrogenesis: 6
6. Histopatholgical examination of lungs: 10 - Control animals:
- yes
- Details on study design:
- - Duration of observation period following administration:
1. To investigate lung response at low dose: 2 and 4 wk
2. To investigate rat lung response at different dose levels: 12 h and 7 d
3. To investigate dose level which produces early alveolar oedema: 20 h
4. To investigate the effects of the perfusion procedure: 20 h
5. To investigate the time course of oedema and any signs of fibrogenesis: 6, 18, 28, 48, 72 h, 7 d and 14 d
6. Histopatholgical examination of lungs: 6, 28, 72 h, 7 d and 14 d
- Necropsy of survivors performed: yes
EXAMINATION
- Examination performed for different groups:
1. To investigate lung response at low dose: Lung wet weight and alveolar surface protein levels
2. To investigate rat lung response at different dose levels: Histopathological examination
3. To investigate dose level which produces early alveolar oedema: Concentration of protein in the lavage fluid
4. To investigate the effects of the perfusion procedure: Lung wet weight and alveolar surface protein levels
5. To investigate the time course of oedema and any signs of fibrogenesis: Lung wet weight, alveolar surface protein levels after all time intervals (6, 18, 28, 48, 72 h, 7 dand 14 d) and lung dried weight and hydroxyproline in the total lavaged lung after 7 and 14 d
6. Histopatholgical examination of lungs
- Other examinations: Biochemical analysis using standard techniques - Statistics:
- Statistical analysis of the data was carried out using an unpaired Student's t-test and differences between mean values were considered significant when P < 0.05.
Results and discussion
- Preliminary study:
- Not applicable
Effect levelsopen allclose all
- Sex:
- male
- Dose descriptor:
- other: Elevated alveolar surface protein and lung wet weight
- Effect level:
- 0.3 other: mg/kg bw
- Exp. duration:
- 14 d
- Sex:
- male
- Dose descriptor:
- other: intra-alveolar oedema with charecteristic eosinophilic fluid accumulation and fibrin clots
- Effect level:
- > 0.5 other: mg/kg bw
- Exp. duration:
- 12 h
- Sex:
- male
- Dose descriptor:
- other: interstitial fibrosis
- Effect level:
- 2.5 other: mg/kg bw
- Exp. duration:
- 14 d
- Sex:
- male
- Dose descriptor:
- other: Fibrogenic response
- Effect level:
- 2.5 other: mg/kg bw
- Exp. duration:
- 7 d
- Mortality:
- Not reported
- Clinical signs:
- other: Not observed
- Body weight:
- Not observed
- Gross pathology:
- Not observed
- Other findings:
- - Other observations:
1. Results for investigation of lung response at low dose after 2 or 4 wks: See Table 1
2. Results for investigation of rat lung response at different dose levels:
- Histologic (intra-alveolar oedema) evaluation after 12 h of instillation: Very slight, moderate and severe distribution of intra-alveolar oedema was observed at 1, 4 and 5 mg/kg bw respectively. Interstitial oedema was observed.
3. Results for investigation of dose level which produces early alveolar oedema and alveolar surface protein, after 20 h of instillation:
- Lung wet weight: Slight increase was observed, except for 0.25 mg/kg bw (not significant)
- Alveolar suface protein: Dose dependent increase, ranging from 5-50 mg, was observed
- Others: Upto 1.5 mg/kg bw, no visible signs of lung haemorrhage and red blood cells were observed in the lavage
4. Results for investigation of effects of perfusion procedure after 20 h: No significant changes in lung weight or in the alveolar surface protein were observed for perfused and non-perfused rat lungs
5. Results for investigation of time course of oedema and any signs of fibrogenesis: See Table 2
6. Results of histopatholgical examination of lungs at 6, 28, 72 h, 7 d and 14 d post-instillation: Interstitial fibrosis was observed in all the lungs after 14 d post-instillation
Any other information on results incl. tables
Table 1: Results for investigation of lung response at low dose (0.3 mg/kg bw) after 2 or 4 wks:
Time after Instillation (weeks) |
Treatment
|
n
|
Lung wet wt (g) as mean ± SD |
Alveolar surface protein (mg/rat) as mean ± SD |
2 |
Distilled water |
4 |
1.27 ± 0.08 |
3.5 ± 1.4 |
Zinc chloride |
4 |
1.27 ± 0.04 |
4.6 ± 3.9 |
|
4 |
Distilled water |
4 |
1.47 ± 0.15 |
4.3 ± 1.4 |
Zinc chloride |
4 |
1.72 ± 0.32 |
34.4 ± 50.5 |
n = No. of animals
* = Significantly different from controls by Student's t-test for unpaired samples
Table 2: Results for effect of 2.5 mg/kg bw zinc chloride on lung oedema and alveolar surface protein at different time intervals and lavaged lung dry weights, and hydroxyproline levels (indicator of fibrogenesis) after 7 and 14 d post-exposure
Treatment |
Time after instillation |
n |
Lung wet weight (g) as mean ± SD |
Alveolar surface protein (mg) as mean ± SD |
Dry lung weight (g) as mean ± SD |
Hydroxyproline (mg/lung) as mean ± SD |
Control |
6 h |
6 |
1.29 ± 0.38 |
5.41 ± 2.43 |
- |
- |
Zinc chloride |
6 h |
6 |
1.97 ± 0.74 |
51.17 ± 40.09* |
- |
- |
Zinc chloride |
18 h |
6 |
1.95 ± 0.34 |
30.09 ± 13.28 |
- |
- |
Control |
28 h |
4 |
1.10 ± 0.17 |
5.59 ± 2.46 |
- |
- |
Zinc chloride |
28 h |
6 |
2.80 ± 0.71* |
71.97 ± 14.88* |
- |
- |
Zinc chloride |
2 d |
5 |
2.21± 0.66 |
37.76 ± 25.85 |
- |
- |
Control |
3 d |
4 |
1.09 ± 0.04 |
3.25 ± 0.28 |
- |
- |
Zinc chloride |
3 d |
6 |
2.43 ± 0.64* |
36.91± 1.76* |
- |
- |
Control |
7 d |
4 |
1.13 ± 0.08 |
5.18 ± 2.08 |
0.188 ± 0.010 |
2.12 ± 0.26 |
Zinc chloride |
7 d |
6 |
2.05 ± 0.47* |
9.99 ± 4.02 |
0.222 ± 0.023* |
3.59 ± 0.88* |
Control |
14 d |
5 |
1.17 ± 0.12 |
4.16 ± 0.69 |
0.166 ± 0.069 |
1.80 ± 0.25 |
Zinc chloride |
14 d |
6 |
1.57 ± 0.42 |
13.77 ± 7.83* |
0.202 ± 0.069 |
3.46 ± 1.56 |
n = No. of animals
* = Significantly different from controls by Student's t-test for unpaired samples
Applicant's summary and conclusion
- Interpretation of results:
- sligthly toxic
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Significant lung damage, in terms of oedematous reaction, was induced in rats on single intra-tracheal instillation of zinc chloride
- Executive summary:
A number of single intra-tracheal instillation studies were performed in Wistar rats to investigate the delayed respiratory adverse-effects, and the potential of zinc chloride to damage the lungs.
In the study for investigation of pulmonary effects at low dose (0.3 mg/kg bw), a delayed elevated alveolar surface protein, with accompanying increased lung wet weight were observed after 4 wks. These effects correlated histologically with the quantitative biochemical assay for alveolar surface protein in a lavage fluid fraction.
Histopathological studies confirmed the induction intra-alveolar oedema at 12 h post-instillation of different dose levels (0.25-5 mg/kg bw) and interstitial fibrosis in the lungs at 2.5 mg/kg bw, after 14 d. The oedematous reaction in individual animals, after 20 h at 0.25-1.5 mg/kg bw, were variable, but the overall effect was dose dependent.
The onset of oedema, was rapid with maximal effects being noted within 3 days when high doses (2.5 mg/kg bw) of test material were instilled. However, in majority of the animals the severe oedematous reaction regressed between 3 and 7 d. In some animals, adjudged by histochemistry and elevated lung hydroxyproline, evidence of a fibrogenic response was observed 7 d post-exposure.
Hence, significant lung damage, in terms of oedematous reaction was induced in rats, on single intra-tracheal instillation of zinc chloride.
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