Registration Dossier

Administrative data

Description of key information

The effects of repeated exposure to silicon particles were recently investigated in a subchronic inhalation study. The results showed no signs of systemic toxicity. The main findings were very mild, local inflammatory effects observed in the lungs and lung-associated lymph nodes. No severe exposure-related effects were observed. No other studies on repeated dose toxicity of silicon were available. 
Repeated dose toxicity data on synthetic amorphous silicon dioxide and calcium silicate show that the silicon ion does not cause systemic target organ toxicity after oral exposure. The comparative in vitro data on the dissolution kinetics of silicon and synthetic amorphous silica in different artificial biological fluids show that the dissolution of silicon from silicon particles in vitro is similar or lower than that of synthetic amorphous silica. Therefore, the bioavailabity of silicon from silicon particles is likely to be similar or lower than that of synthetic amorphous silica. Based on read-across, no systemic toxicity is expected from oral exposure to silicon.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
No key studies available on silicon. Read-across to amorphous silicon dioxide is justified, and robust studies available on that substance.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
16 mg/m³
Study duration:
subchronic
Species:
rat
Quality of whole database:
Robust guideline study with silicon according to OECD 413 .

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEC
4 mg/m³
Study duration:
subchronic
Species:
rat
Quality of whole database:
Robust guideline study with silicon according to OECD 413 .

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Repeated dose systemic toxicity

No systemic effects were observed after subchronic exposure of rats to silicon particles by inhalation. Furthermore, repeated dose toxicity data on synthetic amorphous silicon dioxide show that the silicon ion does not cause systemic target organ toxicity after ingestion. The comparative in vitro data on the dissolution kinetics of silicon and synthetic amorphous silica in different artificial biological fluids show that the dissolution of silicon from silicon particles in vitro is similar or lower than that of synthetic amorphous silica. Therefore, the bioavailabity of silicon from silicon particles is likely to be similar or lower than that of synthetic amorphous silica. Also, repeated dose toxicity data on calcium silicate do not show any systemic toxicity. Calcium silicate can be used as a read-across substance for silicon since it is a sparingly soluble silicon compound which releases silicon in the body. Thus, based on read-across to amorphous silicon dioxide and calcium silicate, no systemic toxicity is expected from oral exposure to silicon. 

Repeated dose local toxicity

The main target organs for exposure to silicon by inhalation are the lungs. Repeated exposure to silicon particles in the alveolar size range at 16 mg/m3 resulted in very mild local inflammatory effects in the lungs and lung-associated lymph nodes. No statistically significant effects were observed at lower exposure doses.

Two epidemiological studies among the workers exposed to synthetic amorphous silica did not show any effects on lung function (Wilson et al. 1979; Choudat et al. 1990). Recent epidemiological studies from the silicon/ferrosilicon industry suggest the increased prevalence of COPD and decline in lung function (FEV1) of the exposed workers. The latest studies by Johnsen and co-workers (e.g., Johnsen et al. 2010) correlate these with cumulative dust exposure. The effect was seen both in FeSi/Si metal

and FeMn/SiMn/FeCr plants. Increasing evidence has accumulated showing that COPD may be related to workplace exposure to dusts, fumes and gases in general. It has been estimated that for COPD a population attributable risk of 15-20% is caused by occupational dusts/fumes. Therefore, the increased risk of COPD reported in the metallurgical industry is likely to be a general dust/fume exposure-related phenomenon rather than a specific effect of silicon or silica fumes formed during the process. Since silicon particles are only a minor component of these dusts present in silicon/ferrosilicon factories, no firm conclusions on the inhalation toxicity of silicon can be made based on these studies. 


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Read-across to oral study with amorphous silicon dioxide (silica gel).

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
Guideline study with silicon according to OECD 413.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
Guideline study with silicon according to OECD 413.

Justification for classification or non-classification

In a 90-day inhalation toxicity study on silicon particles, no systemic effects were observed. Very slight inflammatory effects in the lungs and lung-associated lymph nodes were reported at the highest dose tested (16 mg/m3). These findings were considered not to support classification of silicon since 1) the effects were rated as very slight in severity, 2) were only observed at a dose leading to increased retention of particles in the lungs (moderate lung overload), and 3) were clearly distinct from the severe progressive inflammatory effects observed with quartz (1 mg/m3). The findings following inhalation exposure to silicon particles are likely to be predominantly caused by general, non-substance-specific, effects of poorly soluble particles at lung burdens exceeding the capacity of the macrophage-mediated alveolar clearance.

No significant adverse effects have been reported for synthetic amorphous silica after repeated oral exposure. Based on the knowledge about the comparative dissolution kinetics of silicon from silicon particles and from synthetic amorphous silica (see Chapter 'Toxicokinetics'), it can be concluded that silicon is also of low toxicity after repeated oral exposure. Based on dissolution data, metallic impurities of silicon are not likely to have an impact on the toxicity of silicon (see Chapter 'Toxicokinetics').

No classification is suggested.

A detailed justification paper discussing the interpretation of the 90-day inhalation study results is attached in Section 13 of the Iuclid dossier.