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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study was performed before EU/OECD protocol establishment and no guideline is mentioned. Long-term data on inhalation toxicity for slags, ferronickel-manufg. is not available for the whole substance. Until a relevant study is performed on slags, ferronickel-manufg., it was attempted to identify possible adverse effects based on data for its recognised constituents, even though the results cannot be applied directly, due to the way the constituents are bound in the matrix of the substance and are not as bioavailable as the free substances that are examined. So, the results must be taken into consideration with care.

Data source

Reference
Reference Type:
publication
Title:
Pulmonary reaction to metallic aluminum powders
Author:
Gross P., Harley R.A., Detreville R.T.
Year:
1973
Bibliographic source:
Arch. Environ. Health 26:227–236

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Study performed before EU/OECD protocol establishment
GLP compliance:
no
Remarks:
Study performed before EU/OECD protocol establishment
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Aluminium oxide
EC Number:
215-691-6
EC Name:
Aluminium oxide
Cas Number:
1344-28-1
Molecular formula:
Al2O3
IUPAC Name:
Aluminium Oxide
Details on test material:
Dust aerosol characterised by particle size by count: 66% < 1 μm, 25% 1 to 4 μm, 9% > 4 μm, mean diameter: 0.8μ m, specific surface area: 6.3 m2/gm, total grease: 0%, Al2O3 content:99.8%

Test animals

Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
30 rats in 6 chambers exposed to 75 mg Al2O3/m3 for 6 months (6h/day, 5d/wk). Average concentration measured by dividing the weight of accumulated dust/filter/day by the volume of air passed through the chamber/day

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
air
Remarks on MMAD:
MMAD / GSD: particle size by count: 66% < 1 μm, 25% 1 to 4 μm, 9% > 4 μm, mean diameter: 0.8μm
Details on inhalation exposure:
30 rats in 6 chambers exposed to 75 mg Al2O3/m3 for 6 months (6h/day, 5d/wk)
Analytical verification of doses or concentrations:
no
Details on analytical verification of doses or concentrations:
Average concentration measured by dividing the weight of accumulated dust/filter/day by the volume of air passed through the chamber/day
Duration of treatment / exposure:
6 months
Frequency of treatment:
6h/day, 5d/wk
Doses / concentrations
Remarks:
Doses / Concentrations:
75 mg/m3
Basis:
other: Average concentration measured by dividing the weight of accumulated dust/filter/day by the volume of air passed through the chamber/day
No. of animals per sex per dose:
no specific data available
Details on study design:
30 rats in 6 chambers exposed to 75 mg Al2O3/m3 for 6 months (6h/day, 5d/wk)
Positive control:
No

Examinations

Observations and examinations performed and frequency:
No data
Sacrifice and pathology:
Animals were sacrificed after 6 months on the experiment and examined for pathological and clinical signs.
Statistics:
no data

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
No mortalities up to 6 months after exposure initiation
Mortality:
no mortality observed
Description (incidence):
No mortalities up to 6 months after exposure initiation
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
Lungs of rats exposed at 6 months contained foci of clustered alveoli with well preserved swollen macrophages engorged with Al2O3 particles. No abnormal proliferation of the macrophages.
Urinalysis findings:
no effects observed
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Description (incidence and severity):
Lungs of rats exposed at 6 months contained foci of clustered alveoli with well preserved swollen macrophages engorged with Al2O3 particles. No abnormal proliferation of the macrophages.
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
Lungs of rats exposed at 6 months contained foci of clustered alveoli with well preserved swollen macrophages engorged with Al2O3 particles. No abnormal proliferation of the macrophages.
Histopathological findings: neoplastic:
no effects observed
Details on results:
No mortalities up to 6 months after exposure initiation. Lungs of rats exposed at 6 months contained foci of clustered alveoli with well preserved swollen macrophages engorged with Al2O3 particles. No abnormal proliferation of the macrophages. No alveolar proteinosis or lipid pneumonitis

Effect levels

Dose descriptor:
NOAEC
Effect level:
>= 75 mg/m³ air
Based on:
act. ingr.
Remarks:
Aluminium Oxide
Sex:
not specified
Basis for effect level:
other: see 'Remark'

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
From this subchronic study a NOAEC of 75mg Al2O3/m3 can be established. Based on the typical aluminum oxide content of our substance a NOAEC of 1250 mg Electrofurnace slag/m3 and 7500mg Converter slag/m3 can be established, which makes the hazard from the inhalation of ferronickel slags insignificant. Additionally, granulometry results on ferronickel slags show that only about 6% of the test item consists of particles with size less than 5 µm, which form the majority of the tested substance (see also Endpoint 4.5 - Particle Size Distribution). As a result there is an overestimation of risk due to Ferronickel slags inhalation based on Aluminium Oxide results. Nevertheless these results will be taken into account for long-term inhalation risk assessment.
Executive summary:

30 rats in 6 chambers were exposed to 75 mg Al2O3/m3 for 6 months (6h/day, 5d/wk). Average concentration measured by dividing the weight of accumulated dust/filter/day by the volume of air passed through the chamber/day

No mortalities up to 6 months after exposure initiation. Lungs of rats exposed at 6 months contained foci of clustered alveoli with well preserved swollen macrophages engorged with Al2O3 particles. No abnormal proliferation of the macrophages. No alveolar proteinosis or lipid pneumonitis

From this subchronic study a NOAEC of 75mg Al2O3/m3 can be established. Based on the typical aluminum oxide content of our substance a NOAEC of 1250 mg Electrofurnace slag/m3and 7500mg Converter slag/m3 can be established, which makes the hazard from the inhalation of ferronickel slags insignificant. Additionally, granulometry results on ferronickel slags show that only about 6% of the test item consists of particles with size less than 5 µm, which form the majority of the tested substance (see also Endpoint 4.5 - Particle Size Distribution). As a result there is an overestimation of risk due to Ferronickel slags inhalation based on Aluminium Oxide results. Nevertheless these results will be taken into account for long-term inhalation risk assessment.

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