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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
DNEL related information

Local effects

Acute/short term exposure
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

Introduction: 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.

                     Oral:No data have been identified on oral absorption. However, MMVF fibres degrade at acidic pH resulting in dissolution and breakage into to smaller fibres (length less than 20 μm). Also, as they are inorganic it is evaluated that MMVF fibres have low potential for crossing biological membranes and that systemic exposure through oral exposure is negligible.

                     Inhalation:No data have been identified on absorption following inhalation. However, in the chronic inhalation studies of MMVF (e.g. McConnell, 1994), the liver, spleen, kidneys and heart were routinely examined histopathologically with no exposure related lesions observed in these organs in any of the studies of MMVF thus indicative of no systemic effects. MMVF fibres are inorganic and it is evaluated that MMVF fibres have low potential for crossing biological membranes and that systemic exposure following inhalation is negligible. Regarding the further fate in the lung see metabolism below.

 

Distribution:No data have been identified on distribution.

 

Metabolism:The fate of fibres deposited on surfaces within the respiratory system depends on two different but simultaneously occurring processes: dissolution and disintegration (T. Hesterberg et al., 1996; T. W. Hesterberg et al., 1998b; Muhle et al., 1997; Zoitos et al., 1997).

Dissolution:MMVF fibres exhibit a moderate degree of leaching (Goldberg et al., 1998; Searl et al. 1999). Hence, following in vivo inhalation it has been demonstrated that the composition of MMVF fibres changes with time in the lungs, with a depletion in Na2O, CaO and MgO and a corresponding relative enrichment in SiO2and Al2O3(Lehuede et al., 1997). Furthermore, MMVF fibres have been shown to develop surface etching and deterioration (Lehuede et al., 1997).

 

Studies show that MMVF fibres dissolve rapidlyin vitroin a simulated lung fluid at pH 7.4 (Guldberg et al., 2002; Kamstrup et al., 1998; Knudsen et al., 1996). For this fibre type the dissolution rate kdisis 23 ± 11 ng x cm-2x hour-1(Zoitos et al.. 1997). The dissolution of MMVF 21 is about two times faster at pH 4.8 than at pH 7.4 (Christensen et al. 1994).

 

Furthermore, rats exposed to MMVF fibres (30 mg/m3; 6 hour/day, 5 days/week for 2 years) showed lung concentrations for fibres with lengths >20 μm of 3, 5, 11, 13 and 10 x105fibres per mg dry lung at sampling times of 3, 6, 12, 18 and 24 months, respectively (McConnell, et al., 1994). These findings are consistent with early attainment of a balance between continued exposure and dissolution (i.e., lower biopersistence) of this fibre type.

 

                     Disintegration:Since the dissolution of MMVF 21 is about two limes faster at pH 4.8 than at pH 7.4 (Christensen et al. 1994) the fastest in vivo dissolution is expected in the phagolysosomes of alveolar macrophages where the pH is about 4.8 (Kreyling et al., 1991). Therefore, the part of a long fibre involved in a macrophage should dissolve faster, will become thinner and could be a location where the fibre is brcaking (Bellmann et al. 1994). The shorter fibres will be removed from the lung either by the lymphatic system or via the mucociliary escalator and either expelled from the body by coughing or swallowed. If swallowed, the MMVF fibres will dissolve rapidly at acidic gastric pH (Bernstein, 2007).

 

Excretion:Clearance of fibres from the lung occurs through physiological clearance by alveolar macrophages, in vivo dissolution of fibres in the extracellular fluid and the breakage of long fibres into short segments (T. W. Hesterberg, et al., 2001; Yu et al., 1998). The shorter broken fibres are removed from the lung either by the lymphatic system or 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.

 

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.

 

 

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

MMVF no nota Q

 

Introduction: 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.

                     Oral:No data have been identified on oral absorption. However, MMVF fibres degrade at acidic pH resulting in dissolution and breakage into to smaller fibres (length less than 20 μm). Also, as they are inorganic it is evaluated that MMVF fibres have low potential for crossing biological membranes and that systemic exposure through oral exposure is negligible.

                     Inhalation:No data have been identified on absorption following inhalation. However, in the chronic inhalation studies of MMVF (e.g. McConnell, 1994), the liver, spleen, kidneys and heart were routinely examined histopathologically with no exposure related lesions observed in these organs in any of the studies of MMVF thus indicative of no systemic effects. MMVF fibres are inorganic and it is evaluated that MMVF fibres have low potential for crossing biological membranes and that systemic exposure following inhalation is negligible. Regarding the further fate in the lung see metabolism below.

 

Distribution:No data have been identified on distribution.

 

Metabolism:The fate of fibres deposited on surfaces within the respiratory system depends on two different but simultaneously occurring processes: dissolution and disintegration (T. Hesterberg et al., 1996; T. W. Hesterberg et al., 1998b; Muhle et al., 1997; Zoitos et al., 1997).

Dissolution:MMVF fibres exhibit a moderate degree of leaching (Goldberg et al., 1998; Searl et al. 1999). Hence, following in vivo inhalation it has been demonstrated that the composition of MMVF fibres changes with time in the lungs, with a depletion in Na2O, CaO and MgO and a corresponding relative enrichment in SiO2and Al2O3(Lehuede et al., 1997). Furthermore, MMVF fibres have been shown to develop surface etching and deterioration (Lehuede et al., 1997).

 

Studies show that MMVF fibres dissolve rapidlyin vitroin a simulated lung fluid at pH 7.4 (Guldberg et al., 2002; Kamstrup et al., 1998; Knudsen et al., 1996). For this fibre type the dissolution rate kdisis 23 ± 11 ng x cm-2x hour-1(Zoitos et al.. 1997). The dissolution of MMVF 21 is about two times faster at pH 4.8 than at pH 7.4 (Christensen et al. 1994).

 

Furthermore, rats exposed to MMVF fibres (30 mg/m3; 6 hour/day, 5 days/week for 2 years) showed lung concentrations for fibres with lengths >20 μm of 3, 5, 11, 13 and 10 x105fibres per mg dry lung at sampling times of 3, 6, 12, 18 and 24 months, respectively (McConnell, et al., 1994). These findings are consistent with early attainment of a balance between continued exposure and dissolution (i.e., lower biopersistence) of this fibre type.

 

                     Disintegration:Since the dissolution of MMVF 21 is about two limes faster at pH 4.8 than at pH 7.4 (Christensen et al. 1994) the fastest in vivo dissolution is expected in the phagolysosomes of alveolar macrophages where the pH is about 4.8 (Kreyling et al., 1991). Therefore, the part of a long fibre involved in a macrophage should dissolve faster, will become thinner and could be a location where the fibre is brcaking (Bellmann et al. 1994). The shorter fibres will be removed from the lung either by the lymphatic system or via the mucociliary escalator and either expelled from the body by coughing or swallowed. If swallowed, the MMVF fibres will dissolve rapidly at acidic gastric pH (Bernstein, 2007).

 

Excretion:Clearance of fibres from the lung occurs through physiological clearance by alveolar macrophages, in vivo dissolution of fibres in the extracellular fluid and the breakage of long fibres into short segments (T. W. Hesterberg, et al., 2001; Yu et al., 1998). The shorter broken fibres are removed from the lung either by the lymphatic system or 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.

 

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.