Reaction mass of calcium hydrogen phosphonate and dialuminium tricalcium hexaoxide

Particle size distribution (Granulometry)

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

particle size distribution (granulometry)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Test procedure in accordance with national standards DIN 55992-1:2006 and ECHA TGD R7a

Qualifier:

according to guideline

Guideline:

DIN 55992-1 (Determination of a parameter for the dust formation of pigments and extenders - Part 1: Rotation method)

Version / remarks:

12 May 1981

Deviations:

no

GLP compliance:

no

Type of method:

cascade impaction

Type of distribution:

volumetric distribution

Mass median aerodynamic diameter:

9.9 µm

Geometric standard deviation:

3.6

Percentile:

other: Total dustiness

Mean:

<= 11.932 other: %

Remarks on result:

other: % refers to total substance mass

Percentile:

other: Inhalable fraction

Mean:

<= 8.677 other: %

Remarks on result:

other: % refers to total substance mass

Percentile:

other: Thoracic fraction

Mean:

<= 6.16 other: %

Remarks on result:

other: % refers to total substance mass

Percentile:

other: Respirable fraction

Mean:

<= 2.979 other: %

Remarks on result:

other: % refers to total substance mass

Percentile:

other: Deposition in respiratory tract

Remarks on result:

other: MPPD model calculation of deposition of total dustiness in the respiratory tract: : Head region: 64 %, Tracheo-bronchial region: 1.4 % and alveolar region: 4.3 %

No.:

#1

Size:

<= 32.4 µm

Distribution:

<= 71.51 %

Remarks on result:

other: size refers to average aerodynamic diameter of total dustiness i.e. the proportion of dust arising from solid substances under processing, handling and transportation conditions (119.32 mg/g = 11.93 % of powdery substance)

No.:

#2

Size:

<= 15.8 µm

Distribution:

<= 58 %

Remarks on result:

other: see passage #1

No.:

#3

Size:

<= 8.13 µm

Distribution:

<= 45.37 %

Remarks on result:

other: see passage #1

No.:

#4

Size:

<= 4.06 µm

Distribution:

<= 23.39 %

Remarks on result:

other: see passage #1

No.:

#5

Size:

<= 2.04 µm

Distribution:

<= 8.93 %

Remarks on result:

other: see passage #1

No.:

#6

Size:

<= 0.99 µm

Distribution:

<= 3.1 %

Remarks on result:

other: see passage #1

No.:

#7

Size:

<= 0.47 µm

Distribution:

<= 0.71 %

Remarks on result:

other: see passage #1

Calculated MMAD and GSD values were used as input parameters for the prediction of the fractional deposition behaviour in the respiratory tract applying the Multiple Path Particle Dosimetry model (MPPD)(ver.2.11).

Deposition in head (naso-pharyngeal) region: 89.1 %

Deposition in tracheo-bronchial region: 1.4 %

Deposition in pulmonal (alveolar) region: 4.3 %

This values refer to the total dustiness i.e. the proportion of dust arising from solid substances under processing, handling and transportation conditions (119.32 mg/g = 11.93 % of powder substance).

Only very few amounts of the total dustiness fraction (4.3 %) will reach the pulmonary (alveolar) region. The vast majority of inhaled dust will be withheld in the naso-pharyngeal (head) region (89.1 %) and minor amounts in the tracheobronchial region (1.4 %). Deposits in the alveolar region would not get directly absorbed as the substance is an poorly soluble dust. The alveolar dust deposits would mainly be engulfed by alveolar macrophages. The macrophages will then either translocate particles to the ciliated airways or carry particles into the pulmonary interstitium and lymphoid tissues. Poorly water-soluble dusts depositing in the nasopharyngeal region could be coughed or sneezed out of the body or swallowed. Dusts depositing in the tracheo-bronchial region would mainly be cleared from the lungs by the mucocilliary mechanism and swallowed (c.f. ECHA TGD R7a, R.7.12.2.1).

Thus, direct inhalative systemic bioavailability is unlikely due to the deposition behaviour, crystalline structure and limited solubility.

Executive summary:

The “physical” particle size distribution does not necessarily reflect the particle size of dusts/aerosols that may be formed under relevant and practical workplace conditions (for example, during manual operations such as bag filling and emptying or under mechanical agitation as in mixing and weighing operations). Therefore, the particle size distribution of the airborne fraction of a test substance "reaction mass of calcium hydrogen phosphonate and dialuminium tricalcium hexaoxide" grenerated during mechanical agitation was determined using the rotating drum method according to DIN 55992-1:2006 (Determination of a parameter for the dust formation of pigments and extenders - Part 1: Rotation method) (modified Heubach Method).

Inhalable, thoracic and respirable fraction were calculated from the particle size distribution (cumulative frequency distribution) and the characteristic lines defined for inhalable, thoracic and respirable fractions in accordance with DIN EN 481.

Such particle size distribution data have previously been used within EU Risk Assessments (Zinc, Nickel, Copper, Lead, and Antimony trioxide) for predicting particle-size dependent deposition behaviour in the respiratory tract. The Heubach method provides a “total dustiness” value indicating the propensity of a material to become airborne, thus serving as an indicator of the mobility and inhalability under workplace conditions. If an assessment of the toxicological potential of a substance when inhaled by humans is necessary, not only the inhalability but also the fractional deposition behaviour in the respiratory tract should be considered. The aerodynamic particle size distribution (PSD) is parameterised by the mass median aerodynamic diameter (MMAD) and the geometric standard deviation (GSD). This PSD can be used to assess the potential of particles to be inhaled and at a higher tier examination, to deposit in a specific region of the respiratory tract. The latter is considered to be most relevant for toxicological considerations as effects can only be caused by particles that deposit, i.e. that are not exhaled. Further on, resorption and clearance, and thus systemic bioavailability highly depends on the region of the respiratory tract where the dust is deposited. Mass Median Aerodynamic Diameter (MMAD): 9.9 μm, Geometric Standard Deviation (GSD): 3.6 µm Total dustiness: 119.32 mg/g (11.93 % of total substance mass) DIN 55992-1:2006 (Determination of a parameter for the dust formation of pigments and extenders - Part 1: Rotation method) Inhalable fraction: 86.77 mg/g (8.7 % of total substance mass) Thoracic fraction: 61.60 mg/g (6.2 % of total substance mass) Respirable fraction: 29.79 mg/g (3 % of total substance mass) Calculated from the particle size distribution (cumulative frequency distribution) and the characteristic lines defined for inhalable, thoracic and respirable fractions in accordance with DIN EN 481. Applying the Multiple Path Particle Dosimetry model (MPPD)(ver.2.11), calculated MMAD and GSD values were used as input parameters for the prediction of the fractional deposition behaviour in the respiratory tract. Only very few amounts of the total dustiness fraction (4.3 %) will reach the pulmonary (alveolar) region. The vast majority of inhaled total dustiness fraction will be withheld in the naso-pharyngeal (head) region (89.1 %) and minor amounts in the tracheobronchial region (1.4 %).

Reference 2

Endpoint:

particle size distribution (granulometry)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1997-06-04 to 1997-06-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP, Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 110 (Particle Size Distribution / Fibre Length and Diameter Distributions)

Version / remarks:

12 May 1981

Deviations:

no

GLP compliance:

yes

Type of method:

cascade impaction

Type of distribution:

other: multistage impactor and sieving

No.:

#1

Size:

< 63 µm

Distribution:

<= 100 other: mass %

No.:

#2

Size:

< 12 µm

Distribution:

ca. 50 other: mass %

No.:

#3

Size:

< 1 µm

Distribution:

ca. 44.5 other: mass %

Substance "reaction mass of calcium hydrogen phosphonate and dialuminium tricalcium hexaoxide" is a powder with a rate of:

- 100 mass-% < 63 µm

- 50 mass-% < 12 µm (MMD)

- 44.5 mass-% < 1 µm

SIEVING resulted in particle sizes:

< 63 µm: 100 Mass-%

MULTISTAGE IMPACTOR particle size distribution determination resulted in particle sizes:

< 0.32 µm: 17.08 Mass-%

0.32 to < 0.66 µm: 15.48 Mass-%

0.66 to < 1.36 µm: 22.23 Mass-%

1.36 to < 2.71 µm: 19.32 Mass-%

2.71 to < 5.43 µm: 17.36 Mass-%

5.43 to < 10.55 µm: 5.04 Mass-%

10.55 to < 21.62 µm: 1.46 Mass-%

21.62 to < 63 µm: 2.03 Mass-%

The density of the testing material was determined with a Helium-density-measuring-apparatus.The multiple determination resulted in the value 2.245 +/- 0.09 g/cm³.

 

Conclusions:

- 100 mass-% < 63 µm
- 50 mass-% < 12 µm (MMD)
- 44.5 mass-% < 1 µm

Executive summary:

The particle size distribution of substance "reaction mass of calcium hydrogen phosphonate and dialuminium tricalcium hexaoxide" (a.i. 90 -95 %) was measured in a study according to OECD Guideline 110 (Particle Size Distribution / Fibre Length and Diameter Distributions), 1981.

The substance is a powder with a rate of:

- 100 mass-% < 63 µm

- 50 mass-% < 12 µm (MMD)

- 44.5 mass-% < 1 µm

The density of the testing material was determined with a Helium-density-measuring-apparatus. The multiple determinations resulted in the value 2.245 +/- 0.09 g/cm³.

SIEVING resulted in particle sizes:

< 63 µm: 100 Mass-%

MULTISTAGE IMPACTOR particle size distribution determination resulted in particle sizes:

< 0.32 µm: 17.08 Mass-%

0.32 to < 0.66 µm: 15.48 Mass-%

0.66 to < 1.36 µm: 22.23 Mass-%

1.36 to < 2.71 µm: 19.32 Mass-%

2.71 to < 5.43 µm: 17.36 Mass-%

5.43 to < 10.55 µm: 5.04 Mass-%

10.55 to < 21.62 µm: 1.46 Mass-%

21.62 to < 63 µm: 2.03 Mass-%

Description of key information

Mass Median Aerodynamic Diameter (MMAD): 9.9 μm, Geometric Standard Deviation (GSD): 3.6 µm
Total dustiness: 119.32 mg/g (11.93 % of total substance mass)
DIN 55992-1:2006 (Determination of a parameter for the dust formation of pigments and extenders - Part 1: Rotation method)
Inhalable fraction: 86.77 mg/g (8.7 % of total substance mass)
Thoracic fraction: 61.60 mg/g (6.2 % of total substance mass)
Respirable fraction: 29.79 mg/g (3 % of total substance mass)
Calculated from the particle size distribution (cumulative frequency distribution) and the characteristic lines defined for inhalable, thoracic and respirable fractions in accordance with DIN EN 481.
Applying the Multiple Path Particle Dosimetry model (MPPD)(ver.2.11), calculated MMAD and GSD values were used as input parameters for the prediction of the fractional deposition behaviour in the respiratory tract.

Only very few amounts of the total dustiness fraction (4.3 %) will reach the pulmonary (alveolar) region. The vast majority of inhaled total dustiness fraction will be withheld in the naso-pharyngeal (head) region (64.0 %) and minor amounts in the tracheobronchial region (1.4 %).

Additional information

The “physical” particle size distribution does not necessarily reflect the particle size of dusts/aerosols that may be formed under relevant and practical workplace conditions (for example, during manual operations such as bag filling and emptying or under mechanical agitation as in mixing and weighing operations). Therefore, the particle size distribution of the airborne fraction of a test substance "reaction mass of calcium hydrogen phosphonate and dialuminium tricalcium hexaoxide" generated during mechanical agitation was determined using the rotating drum method according to DIN 55992-1:2006 (Determination of a parameter for the dust formation of pigments and extenders - Part 1: Rotation method) (modified Heubach Method).

Inhalable, thoracic and respirable fractions were calculated from the particle size distribution (cumulative frequency distribution) and the characteristic lines defined for inhalable, thoracic and respirable fractions in accordance with DIN EN 481.

Such particle size distribution data have previously been used within EU Risk Assessments (Zinc, Nickel, Copper, Lead, and Antimony trioxide) for predicting particle-size dependent deposition behaviour in the respiratory tract. The Heubach method provides a “total dustiness” value indicating the propensity of a material to become airborne, thus serving as an indicator of the mobility and inhalability under workplace conditions. If an assessment of the toxicological potential of a substance when inhaled by humans is necessary, not only the inhalability but also the fractional deposition behaviour in the respiratory tract should be considered. The aerodynamic particle size distribution (PSD) is parameterised by the mass median aerodynamic diameter (MMAD) and the geometric standard deviation (GSD). This PSD can be used to assess the potential of particles to be inhaled and at a higher tier examination, to deposit in a specific region of the respiratory tract. The latter is considered to be most relevant for toxicological considerations as effects can only be caused by particles that deposit, i.e. that are not exhaled. Further on, resorption and clearance, and thus systemic bioavailability highly depends on the region of the respiratory tract where the dust is deposited.

Mass Median Aerodynamic Diameter (MMAD): 9.9 μm, Geometric Standard Deviation (GSD): 3.6 µm

Total dustiness: 119.32 mg/g (11.93 % of total substance mass)

DIN 55992-1:2006 (Determination of a parameter for the dust formation of pigments and extenders - Part 1: Rotation method)

Inhalable fraction: 86.77 mg/g (8.7 % of total substance mass)

Thoracic fraction: 61.60 mg/g (6.2 % of total substance mass)

Respirable fraction: 29.79 mg/g (3 % of total substance mass)

Calculated from the particle size distribution (cumulative frequency distribution) and the characteristic lines defined for inhalable, thoracic and respirable fractions in accordance with DIN EN 481.

Applying the Multiple Path Particle Dosimetry model (MPPD)(ver.2.11), calculated MMAD and GSD values were used as input parameters for the prediction of the fractional deposition behaviour in the respiratory tract. Only very few amounts of the total dustiness fraction (4.3 %) will reach the pulmonary (alveolar) region. The vast majority of inhaled total dustiness fraction will be withheld in the naso-pharyngeal (head) region (64.0 %) and minor amounts in the tracheobronchial region (1.4 %).