Slags, ferronickel-manufg.

Repeated dose toxicity: inhalation

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

Test material information

Constituent 1

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.