Diammonium 5-(hexylsulfonyl)-2-{[3-methyl-2,7-dioxo-1-(3-sulfonatobenzoyl)-2,7-dihydro-3H-naphtho[1,2,3-de]heterocycle-6-yl]amino}benzenesulfonate

Particle size distribution (Granulometry)

Administrative data

Endpoint:

particle size distribution (granulometry)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08 January 2009 to 26 February 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of inspection: 19 August 2008; Date of signature: 04 March 2009

Type of method:

determination of fibre length and diameter distributions

Type of distribution:

volumetric distribution

Test material

Test material information

Results and discussion

Particle size

Percentile:

D50

Remarks on result:

other: Too few particles were of a size less than 10.0 µm to allow accurate assessment of mass median aerodynamic diameter.(migrated from fields under 'Mass median diameter' as D50 percentile. No source field for Standard deviation.)

Particle size distribution at different passages

Particle size distribution at different passages 1

No.:

#1

Size:

> 100 µm

Distribution:

34.8 %

Remarks on result:

other: Proportion of test material having an inhalable particle size less than 100 µm using the sieve method.

Particle size distribution at different passages 2

No.:

#2

Size:

> 10 µm

Distribution:

<= 0.431 %

Remarks on result:

other: Proportion of test material having a thoracic particle size less than 10.0 µm using the Cascade Impactor method.

Particle size distribution at different passages 3

No.:

#3

Size:

> 5.5 µm

Distribution:

<= 0.16 %

Remarks on result:

other: Proportion of test material having a respirable particle size less than 5.5 µm using the Cascade Impactor method

Any other information on results incl. tables

Screening test (sieve method)

The results of the sieving procedure are shown in the following table:

Table 2

Sieve aperture size (µm)	100
Mass of test material transferred to sieve (g)	10.07
Mass of test material passed through sieve (g)	3.50
Test material less than sieve aperture size (%)	34.8

Definitive test (cascade impactor method)

Determination 1

The results of the cascade impactor method are shown in the following table:

Table 3   Determination 1

Cup Number	ParticleCollected (µm)	Cup Masses (g)
		Pre-sampling	Post-sampling	Difference
1	>10.0	86.1243	88.9262	2.8019
2	5.5 - 10.0	85.3993	85.4076	0.0083
3	2.4 - 5.5	85.9171	85.9192	0.0021
4	1.61 - 2.4	85.6346	85.6355	0.0009
5	0.307 - 1.61	85.7978	85.7996	0.0018
Filter	<0.307	0.1223	0.1224	0.0001

Amount of test material found in artificial throat: 0.25 g.
Total amount of test material recovered from impactor cups, filter and artificial throat: 3.07 g.

The cumulative amounts found for the individual particle size cut-points (µm) are shown in the following table:

Table 4   Determination 1

Cup Number	Particle Size Cut-points (µm)	Cumulative Mass of Test Material (g)	Cumulative Amount of Test Material (%)
2	10.0	0.0132	0.431
3	5.5	0.0049	0.160
4	2.4	0.0028	9.14 x 10^-2
5	1.61	0.0019	6.20 x 10^-2
Filter	0.307	0.0001	3.26 x 10^-3

Determination 2

The results of the cascade impactor method are shown in the following table:

Table 5   Determination 2

Cup Number	ParticleCollected (µm)	Cup Masses (g)
		Pre-sampling	Post-sampling	Difference
1	>10.0	86.1248	89.0369	2.9121
2	5.5 - 10.0	85.4004	85.4074	0.0070
3	2.4 - 5.5	85.9194	85.9195	0.0001
4	1.61 - 2.4	85.6385	85.6394	0.0009
5	0.307 - 1.61	85.8027	85.8029	0.0002
Filter	<0.307	0.1179	0.1179	0

Amount of test material found in artificial throat: 0.08 g.
Total amount of test material recovered from impactor cups, filter and artificial throat: 3.00 g.

The cumulative amounts found for the individual particle size cut-points (µm) are shown in the following table:

Table 6   Determination 2

Cup Number	Particle Size Cut-points (µm)	Cumulative Mass of Test Material (g)	Cumulative Amount of Test Material (%)
2	10.0	0.0082	0.273
3	5.5	0.0012	4.00 x 10^-2
4	2.4	0.0011	3.67 x 10^-2
5	1.61	0.0002	6.67 x 10^-3
Filter	0.307	0	0

Determination 3

The results of the cascade impactor method are shown in the following table:

Table 7   Determination 3

Cup Number	ParticleCollected (µm)	Cup Masses (g)
		Pre-sampling	Post-sampling	Difference
1	>10.0	86.1232	89.0183	2.8951
2	5.5 - 10.0	85.3995	85.4062	0.0067
3	2.4 - 5.5	85.9185	85.9189	0.0004
4	1.61 - 2.4	85.6349	85.6353	0.0004
5	0.307 - 1.61	85.7991	85.7994	0.0003
Filter	<0.307	0.1177	0.1177	0

Amount of test material found in artificial throat: 0.13 g.
Total amount of test material recovered from impactor cups, filter and artificial throat: 3.03 g.

The cumulative amounts found for the individual particle size cut-points (µm) are shown in the following table:

Table 8   Determination 3

Cup Number	Particle Size Cut-points (µm)	Cumulative Mass of Test Material (g)	Cumulative Amount of Test Material (%)
2	10.0	0.0078	0.257
3	5.5	0.0011	3.63 x 10^-2
4	2.4	0.0007	2.31 x 10^-2
5	1.61	0.0003	9.89 x 10^-3
Filter	0.307	0	0

The overall cumulative amounts of test material with a particle size less than 10.0 µm (%) from Determinations 1 to 3 are shown in the following table:

Table 9

Determination	Cumulative Amount of Test Material Less Than 10.0 µm (%)	Mean Cumulative Amount of Test Material Less Than 10.0 µm (%)
1	0.431	≤0.431
2	0.273
3	0.257

The overall cumulative amounts of test material with a particle size less than 5.5 µm (%) from Determinations 1 to 3 are shown in the following table:

Table 10

Determination	Cumulative Amount of Test Material Less Than 5.5 µm (%)	Mean Cumulative Amount of Test Material Less Than 5.5 µm (%)
1	0.160	≤0.160
2	4.00 x 10^-2
3	3.63 x 10^-2

Applicant's summary and conclusion

Conclusions:

Particle size data acquired for the test material are shown in the table below.

Executive summary:

Particle size data have been acquired using a procedure designed to comply with the European Commission technical guidance document 'Particle Size Distribution, Fibre Length and Diameter Distribution' (June 1996), which satisfies the requirents of OECD Guideline 110. 

The results are as follows:

Measurent	Method	Result
Proportion of test material having an inhalable particle size less than 100 µm	Sieve	34.8%
Proportion of test material having a thoracic particle size less than 10.0 µm	Cascade Impactor	≤0.431%
Proportion of test material having a respirable particle size less than 5.5 µm	Cascade Impactor	≤0.160%