3-(biphenyl-4-yl)-6-(4-chlorophenyl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione

Particle size distribution (Granulometry)

Administrative data

Endpoint:

particle size distribution (granulometry)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Testing was conducted between 29 April 2009 and 17 June 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 the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

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 Signature: 04/03/09 Date of Inspection: 19/08/08

Type of distribution:

other:

Test material

Test material information

Constituent 1

Reference substance name:

3-{[1,1'-biphenyl]-4-yl}-6-(4-chlorophenyl)-1H,2H,4H,5H-pyrrolo[3,4-c]pyrrole-1,4-dione

EC Number:

700-341-1

Cas Number:

105194-34-1

Molecular formula:

C24H15ClN2O2

IUPAC Name:

3-{[1,1'-biphenyl]-4-yl}-6-(4-chlorophenyl)-1H,2H,4H,5H-pyrrolo[3,4-c]pyrrole-1,4-dione

Constituent 2

Reference substance name:

3-(biphenyl-4-yl)-6-(4-chlorophenyl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione

IUPAC Name:

3-(biphenyl-4-yl)-6-(4-chlorophenyl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione

Details on test material:

Sponsor's identification : PDE-28
Description : red powder
Purity : 97%
Batch number : 1RF-8017
Date received : 23 March 2009
Storage conditions : room temperature, in the dark

Results and discussion

Particle size

Percentile:

D50

Mean:

other: Too few particles were of a size less than 10.0 µm to allow accurate assessment of mass median aerodynamic diameter. EXAMPLE

Remarks on result:

other: 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:

93.7 %

Particle size distribution at different passages 2

No.:

#2

Size:

< 10 µm

Distribution:

<= 0.15 %

Particle size distribution at different passages 3

No.:

#3

Size:

< 5.5 µm

Distribution:

<= 0.07 %

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)	9.44
Test material less than sieve aperture size (%)	93.7

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	86.1216	88.7792	2.6576
2	5.5 - 10.0	85.4438	85.4475	0.0037
3	2.4 - 5.5	85.9145	85.9140	-0.0005[1]
4	1.61 - 2.4	85.6294	85.6292	-0.0002*
5	0.307 - 1.61	85.7944	85.7943	-0.0001*
Filter	<0.307	75.0847	75.0849	0.0002

Amount of test material found in artificial throat: 0.33 g.
Total amount of test material recovered from impactor cups, filter and artificial throat: 2.9907 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	0.0039	0.13
3	5.5	0.0002	<0.01
4	2.4	0.0002	<0.01
5	1.61	0.0002	<0.01
Filter	0.307	0.0002	<0.01

 

[1]Insignificant weight loss noted, within anticipated balance tolerance. Value of 0.0000 g used in further calculations.

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	86.1279	88.9110	2.7831
2	5.5 - 10.0	85.4436	85.4456	0.0020
3	2.4 - 5.5	85.9142	85.9146	0.0004
4	1.61 - 2.4	85.6286	85.6289	0.0003
5	0.307 - 1.61	85.7936	85.7941	0.0005
Filter	<0.307	75.0774	75.0776	0.0002

Amount of test material found in artificial throat: 0.17 g.
Total amount of test material recovered from impactor cups, filter and artificial throat: 2.9565 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	0.0034	0.12
3	5.5	0.0014	0.05
4	2.4	0.0010	0.03
5	1.61	0.0007	0.02
Filter	0.307	0.0002	<0.01

 

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	86.13	89.0296	2.8996
2	5.5 - 10.0	85.4441	85.4466	0.0025
3	2.4 - 5.5	85.9143	85.9151	0.0008
4	1.61 - 2.4	85.6293	85.6298	0.0005
5	0.307 - 1.61	85.7945	85.7952	0.0007
Filter	<0.307	75.0827	75.0827	0.0000

Amount of test material found in artificial throat: 0.11 g.
Total amount of test material recovered from impactor cups, filter and artificial throat: 3.0141 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	0.0045	0.15
3	5.5	0.0020	0.07
4	2.4	0.0012	0.04
5	1.61	0.0007	0.02
Filter	0.307	0.0000	0.00

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	0.13	≤0.15
2	0.12
3	0.15

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	<0.01	≤0.07
2	0.05
3	0.07

Discussion:

Too few particles were of a size less than 10.0 µm to allow accurate assessment of mass median aerodynamic diameter.

Due to a high degree of variance for the less than 5.5 µm particle size data, an overall limit value has been reported. For consistency, a limit value has been reported for the less than 10.0 µm data also.

Representative sampling was ensured by rolling the sample container for approximately ten minutes and sampling from the top, middle and bottom prior to definitive testing.

The inhalable fraction is defined as the mass fraction of particles which can be inhaled by nose or mouth, the thoracic fraction is defined as the mass fraction of particles that passes the larynx and the respirable fraction is defined as the mass fraction of particles that reaches the alveoli.

Applicant's summary and conclusion

Conclusions:

Measurement Method Result
Proportion of test material having an inhalable particle size less than 100 µm Sieve 93.7%
Proportion of test material having a thoracic particle size less than 10.0 µm Cascade Impactor ≤0.15%
Proportion of test material having a respirable particle size less than 5.5 µm Cascade Impactor ≤0.07%

Executive summary:

Particle Size Distribution:

 Particle size data have been acquired using a procedure designed to comply with the European Commission technical guidance docunt 'Particle Size Distribution, Fibre Length and Diater Distribution' (June 1996), which satisfies the requirements 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	93.7%
Proportion of test material having a thoracic particle size less than 10.0  µm	Cascade Impactor	≤0.15%
Proportion of test material having a respirable particle size less than 5.5 µm	Cascade Impactor	≤0.07%