Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The potential for a fibre to produce a toxic effect in the lung has often been described in terms of the 3Ds that is dose, dimension and durability. The dose refers to the dose in the lung parenchyma of the longer fibres that the macrophage cannot fully engulf and remove; the dimension refers firstly to the diameter which will determine if the fibre can be inhaled into the deep lung (i.e., if the fibre is ‘respirable’); and secondly to the length which determines whether the fibre can be engulfed and removed by the macrophage; and finally durability which determines how fast the fibre can dissolve and/or breakdown once deposited in the lung.

These factors combined influence what is most indicative of potential adverse health effects, that is, the cumulative number of the longer fibres remaining in the lung over time. In this regard, the dimension (both diameter for respirability and length for potential macrophage clearance) and durability or bio-solubility [ability of a fibre to dissolve in lung fluid] serve as modifiers of the dose. Fibre composition per se does not determine potential toxicity of the fibre; the primary determinant is fibber dose, and composition plays an important role in the fibres ability to persist in the lung (bio-persistence) and hence dose.

Long and short fibres differ in the way in which their elimination from the respiratory tract is affected by each of these mechanisms. Short fibres are taken up by macrophages and subjected to chemical dissolution/leaching within an acidic milieu while at the same time they are actively removed by these phagocytic cells primarily by the tracheal bronchial tree and the lymphatic system. In contrast, long fibres (longer than approximately 20 µm) which can only be incompletely phagocytised by macrophages, cannot be efficiently removed from the lung parenchyma by physical translocation but may be subjected to chemical dissolution/leaching at acidic pH where macrophages attach to the long fibres, and at neutral pH when in contact with the lung surfactant.
Fibres which deposit in the bronchial tree are removed from the lung via the mucociliary escalator and either expelled from the body by coughing or swallowed. If swallowed, the MMVF fibres will disintegrate rapidly at acidic gastric pH.
 
Absorption:
                     Skin:No data have been identified on dermal absorption. MMVF fibres are inorganic and it is evaluated that MMVF fibres have low potential for crossing biological membranes and that systemic exposure through dermal exposure is negligible.
      Conclusion:The most likely exposure routes for MMVF fibres are evaluated to be by inhalation and possibly by ingestion/swallowing following the inhalation for workers. Thus systemic exposure to MMVF fibres leading to toxic reactions is evaluated to be very unlikely.