Silicon carbide

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Comparable to guideline study with limitations which do not impair the overall conclusion from the data. Sufficiently detailed description of the test procedure in accordance with scientific standards (critical supporting information given, such as species tested, substance identity and dosing procedure).

Materials and methods

GLP compliance:

not specified

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose/head only

Remarks:

oronasal

Vehicle:

other: unchanged (no vehicle)

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Dust concentration was measured gravimetrically with a Cassella instrument (Johannesburg Convention for Fine Dusts) and monitored continuously by a Tyndallometer (Hundt-µ Digital, Wetzlar, Germany).

Duration of treatment / exposure:

total exposure time: 50h

Frequency of treatment:

The animals were exposed for 5 hours a day on five consecutive days, followed by a rest period of two days and a re-exposure period of five consecutive days.

Doses / concentrations

Remarks:

Doses / Concentrations:
20 mg SiC / m³ respirable air
Basis:
analytical conc.

No. of animals per sex per dose:

first inhalation series: 50 animals
second inhalation series: 42 animals

Control animals:

yes, sham-exposed

other: quartz... (see attached file)

Results and discussion

Results of examinations

Organ weight findings including organ / body weight ratios:

no effects observed

Details on results:

- SiC produced no significant changes in organ weights at any time of observation.
- In the first series high total cell numbers as well as alveolar macrophages were found in the lavage fluid three days after the end of inhalation in the SiC group. SiC produced no specific stimulation of granulocytes. Similar results were found in the second series of studies. The number of cells in lavage fluid was similar in the sham control and SiC group over the entire experimental period. Exposure to SiC did not result in a noticeable shift in the numbers of alveolar macrophages, lymphocytes, and granulocytes in the total cell number.
- In both series the total amount of LSF phospholipids was not changed in animals exposed to SiC. SiC induced no alterations in the LSF subfractionswith values corresponding to those of the untreated control animals.
- Regarding the lung function control animals as well as animals exposed to SiC showed similar maximum flow values (>8.5 ml/s).
- 23% of the initial amount of SiC dust that was determined on day 3 was found in the lungs 90 days after inhalation.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Executive summary:

The question of lung damage as a result of exposure to silicon carbide (SiC) was investigated by inhalation experiments to obtain information on the qualitative response of lung tissue to the test substance (SiC). For comparison, quartz, kaolinite, and tempered clay dusts were used. The indices for the effects of the dusts studied were organ weights, numbers of bronchoalveolar cells, lung surfactant phospholipid concentrations including subfractions, and lung clearance. Exposure to the test samples was carried out according to the Essen inhalation model in two independent series. The results of the two series were similar: Compared with sham controls, exposure to SiC did not affect the indices studied. Even at a low dose (a quarter of the SiC dose) quartz gave pronounced deviations in all indices. In particular, an increase in granulocytes indicated toxic properties of the dust. The long term elimination of quartz from the lung was worse than that of SiC. The kaolinite and tempered clay dusts were intermediate between SiC and quartz based on several of the indices studied. It is concluded that SiC is deposited practically inert in the lung.