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Toxicological information

Toxicological Summary

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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

A large number of key and supporting studies have evaluated repeated dose toxicity by the inhalation route. These studies have been carried out on a variety of different SAS materials. Overall, the effects displayed by these studies show a similar picture of pathology for both non-surface treated and surface treated SAS.

 

In some studies, dose-dependent and particle-related local inflammation in lung and lung-associated tissues (lymph nodes) have been observed, accompanied by corresponding changes of inflammatory markers in the bronchoalveolar fluid. There are no substantial different pathological findings when comparing different SAS grades. Test item-related changes in lungs are dose-dependent and characterized by increased perivascular infiltration, alveolar macrophages and macrophage aggregations, as well as macrophage type II hyperplasia. Accordingly, reactive changes have been observed in BALT (bronchus-associated lymphoid tissues) and regional lymph nodes. Any clinical effects or morphological changes of other tissues indicating systemic toxicity are not associated with SAS exposure. Observed effects are not substance-specific, all respirable particles will show such response directly after exposure.

 

Concerns on the toxicity of SAS materials are mainly based on the publication by Reuzel et al. (1991, Food Chem Toxicol 29:341-354), which documented indications for the occurrence of lung fibrosis in a 13-week inhalation study with 3 different SAS forms. An expert pathology working group (PWG) subsequently re-evaluated and discussed this finding by re-analysing the identical lung sections as used by Reuzel et al. according to current histopathological standards. This expert group concluded that irreversible changes, such as fibrosis and granulomas were not induced by any of the 3 SAS forms in the 13-week inhalation study (PWG Report, Hardisty et al. 2016; Weber et al., 2018, Toxicology Research and Application, Vol. 2, p. 1-17).

 

ECHAs decision on substance evaluation pursuant to article 46(1) of Regulation (EC) No 1907/2006 for silicon dioxide requested additional sub-chronic toxicity studies in rats via the inhalation route with fully characterized forms of pyrogenic SAS to examine the induction of pulmonary fibrosis as main toxicological endpoint. Such studies have been carried out with the high BET pyrogenic SAS ‘CAB-O-SIL S-17D’ and the low BET pyrogenic SAS ‘AEROSIL® OX 50’. Neither of these 2 key studies evidenced lung fibrosis or, correspondingly, increases in collagen content even after extending the post-inhalation recovery period up to 12 months.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population