Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
Acute/short term exposure
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

1. Toxicological endpoints

Acute toxicity:

High doses of calcium silicate (CS, >5000 mg/kg bw) failed to produce adverse effects after oral ingestion in experimental animals.

No experimental data have been located following acute inhalation exposure to CS. Aerosol levels that were technically achievable under experimental conditions with synthetic amorphous silica (SAS) are acutely non-toxic and clearly sub-lethal (=< 2 mg/L). This is also assumed for CS.

Genotoxicity

CS gave no evidence of a mutagenic potential in various in-vitro and in-vivo studies, additionally supported by negative results obtained with structure-analogous silica in standard tests as well as in an in-vitro/ex-vivo assay for gene mutation, following inhalation exposure of rats to SAS for 13 weeks.

Carcinogenicity:

CS provided no evidence of a carcinogenic potential in a limited 2y feeding study in rats, consistent with the negative results from longterm feeding studies in rat and mouse using structure-analogous SAS. In a comparative life-span carcinogenicity study using the intrapleural rat model, synthetic amorphous sodium aluminium silicate (NAS), administered at a cancer-producing dose for fibres, induced no mesotheliomas. In synopsis of all genotoxicity, carcinogenicity along with various long-term inhalation studies with CS, NAS, and SAS, it is concluded that there is no evidence of a carcinogenic potential of synthetic amorphous CS after oral ingestion or inhalation exposure.

Reproduction toxicity:

CS did not induce adverse effects on intra-uterine development in three animal species.

No impact on reproductive parameters is expected by prolonged exposure to CS, given the inherent properties of this substance class, and based on limited data from synthetic amorphous silica (SAS), the parent substance of CS.

Repeated-dose toxicity:

Dermal and oral exposure are not relevant toxicological issues, based on the inherent substance properties and experimental evidence. The long-term oral NOAEL value, the highest dose tested in a 2y feeding study in rats receiving CS, was approx. 3000 mg/(kg bw*d).

Prolonged inhalation exposure (readacross, analogy approach):

The limited experimental data after prolonged exposure to calcium silicate in rats and guinea pigs (up to 24 months) provides evidence that no definite differences in effects exist between synthetic amorphous silica (SAS) and calcium silicate (CS). However, no NOEC can be derived from this study, as only one single high and adverse exposure concentration was applied (Columbia 1966).

Therefore, the analogy approach is adopt by making use of experimental data obtained with SAS, in particular for deriving the NOEC: The inhalation of respirable particles of synthetic amorphous silica (SAS) produces a time- and dose-related inflammation response of the lung tissue in animal studies. Progressive events following excess exposure are characterised as “interstitial fibrosis/early nodular fibrosis/incipient fibrosis”. However, a progression process of any lesion has not been observed like that seen after quartz exposure, i.e. all observations suggest reversibility. There are no signs of classical nodular silicosis or a lymphatic-type pneumoconiosis. On the other hand, crystalline silica produces persistent lung inflammation even at much lower exposure levels [Johnston et al. 2000].

2. Experimental No-Observable-Adverse-Effect Concentration (NOAEC)

After 5 exposures (6 h/d) to 1 mg/m3 (respirable), no tissue reaction was observed (see 7.5.3: ASASP 2003a, b, c). After 13 weeks at 1.3 mg/m3 (respirable), there was no morphological tissue effect that could be considered as a pathological manifestation (slight reversible collagen stimulation and no significant increase in lung weight) [see 7.5.3: Degussa 1987].

Based on the pathological relevance of effects, 1 mg/m3 (respirable) was established as NOEC (short-term) and NOAEC(sub-chronic). This appears to be justified also in light of the fact that the sub-chronic study was conducted with a pyrogenic SAS which appears to induce more marked tissue responses than the precipitated SAS type. 

The short-term LOAEC(5 d) was 5.4 mg/m3for the pyrogenic SAS, but this concentration was more of a NOAEC for the precipitated types [see 7.5.3: ASASP 2003 a,b,c]. The low exposure level did not provide any evidence of an accumulation of adverse effects over time.

Under comparable test conditions, we expect that synthetic amorphous calcium silicate shows the same behaviour.

3. Particle size distribution of the aerosols used in inhalation studies as compared with dusts under technical application:

The particle size and morphology rather than particle composition is the determinant of inflammatory response in the lung.

The respirable fractions of the experimental SAS aerosols that consisted of particles with aerodynamic diameters of =< 5 µm represented >= 50 wt%, those consisting of particles with aerodynamic diameters of =< 10 µm represented > 80 wt%.

In the commercial products, that fraction of particles in the whole-size range of air-borne particles according to EN/DIN 481 that is potentially able to reach the thoracic and alveolar site (respirable fraction) is below 1 vol% (= wt%) (see: Endpoint summary of 4. "Physical chemical properties_Particle characteristics" and entries of chapter 4.5).

Under comparable test conditions, we expect that synthetic amorphous calcium silicate shows the same behaviour.

4. Derivation of the DNEL(inhalation)

With reference to the German OEL of 4 mg/m3 for synthetic amorphous silicas (inhalable fraction) [stipulated by entry into the TRGS]

, it is proposed also adopting this value as DNEL for structure-analogous calcium silicate.

It is based on a scientific evaluation of the German scientific committee, Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe ("MAK-Kommission") (MAK Germany/Austria/Switzerland) [MAK 1994]. The principles of this evaluation correspond to those published by the European "Scientific Committee on Occupational Exposure Limits, SCOEL".

This procedure is in compliance with the rules laid down in the CSA guidance, Chapter R 8 (ECHA 2008, R 8, Appendix R.8 -13).

Aspects of MAK´s proposal for an OEL for synthetic amorphous silica:

The MAK Commission clearly confined this OEL to highly disperse synthetic amorphous silica (SAS) and excluded other forms of silicas that – although radiographically amorphous – tend to exhibit a crystalline character: these include tempered or calcinated amorphous silica, silica glasses, silica fumes and similar types. They argue that these types show a particle-size distribution generally different from that of SAS, while the experimental toxicological response pattern resembles that of crystalline silicas following inhalation. While deciding, the Commission took into account that under occupational and use conditions SAS forms aggregates and agglomerates with particle sizes of up to 100 µm, i.e. representing a particle distribution distinctly beyond the critical respirable fine-particle spectrum, and that the pulmonary effects showed complete reversibility during a recovery period [MAK 1994]. The OEL represents the inhalable fraction of dust, which is related to the available epidemiological exposure data. Animal test results are related to respirable dust fraction.

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Reference:

MAK (1994): Gesundheitsschädliche Arbeitsstoffe. Toxikologisch-arbeitsmedizinische Begründung von MAK-Werten (Maximale  Arbeitsplatz-Konzentrationen).Amorphe Kieselsäuren, Deutsche Forschungsgemeinschaft (DfG), closed 10 April 1989, VCH  Verlagsgesellschaft mbH, Weinheim 1994

ECHA (2008): Guidance on information requirements and chemical safety assessment: Chapter R.8: Characterisation of dose [concentration]-response for human health, May 2008 [information_requirements_r8_en]

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General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

Dermal, oral and inhalation exposure are not relevant toxicological issues, based on the inherent substance properties and experimental evidence. Therefore, DNEL values are not derivable for the general population.