rac-(1R,4S,4aR,8R,8aS)-9-(dichloromethylidene)-8-hydroxyoctahydro-1,4-methanonaphthalen-5(1H)-one

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:

weight of evidence

Study period:

17 Jun 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: CIPAC method 187

Deviations:

no

GLP compliance:

yes

Type of method:

Laser scattering/diffraction

Type of particle tested:

primary particle

Type of distribution:

volumetric distribution

Remarks on result:

not measured/tested

Remarks:

MMAD and GSD not determined

Key result

Percentile:

D50

Mean:

1.99 µm

Remarks on result:

other: RSD: ± 5%

Percentile:

D90

Mean:

5.89 µm

Remarks on result:

other: RSD: ± 22.6%

Percentile:

D10

Mean:

0.78 µm

Remarks on result:

other: RSD: ± 1.8%

The final values for the mean particle size and the relative standard deviations have been quoted correct to one place of decimal, based on the 3 determinations.

Determination	Median D(50)	Percent undersize D(10)	Percent undersize D(90)
1	1.900 µm	0.771 µm	4.878 µm
2	2.130 µm	0.803 µm	7.766 µm
3	1.943 µm	0.776 µm	5.012 µm
average	1.99 µm	0.78 µm	5.89 µm
relative standard deviation	5.0 %	1.8 %	22.6 %

Conclusions:

The particle size distribution of the test item has been determined using laser diffraction. The average results are:
- Median particle size (D50): 1.99 µm
- Percent undersize (D10): 0.78 µm
- Percent undersize (D90): 5.89 µm

Executive summary:

The particle size distribution of test substance was determined by using the sieving method in accordance with the CIPAC method 187 under GLP conditions. It was found that that median particle size (D50) was 1.99 µm, the (D10) was 0.78 µm and the D90 was 5.89 µm.

Reference 2

Endpoint:

particle size distribution (granulometry)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

19 Feb 2015 to 16 Mar 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

other: European Commission Guidance Document EUR 20268 ‘Determination of Particle Size Distribution, Fibre Length and Diameter Distribution of Chemical Substances’

Version / remarks:

2002

Deviations:

no

GLP compliance:

yes

Type of method:

other: Sieve analysis and cascade impactor analysis

Type of particle tested:

primary particle

Type of distribution:

volumetric distribution

Remarks on result:

not determinable

Remarks:

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

No.:

#1

Size:

< 100 µm

Distribution:

70.5 %

No.:

#2

Size:

< 10 µm

Distribution:

<= 0.4 %

No.:

#3

Size:

< 5.5 µm

Distribution:

< 0.2 %

Table1: Sieve Analysis Results

Measurement	Result
Mass of test item transferred to sieve	10.12 g
Mass of test item passed through sieve	7.13 g
Percentage of test item less than 100 µm	70.5%

Table 2 Cascade Impactor Collected Masses

Collection Stage	Particle Size Range Collected (µm)	Collected Mass (g)
		Run 1	Run 2	Run 3
Artificial throat	n/a	0.40	0.27	0.24
Cup 1	>10.0	0.5230	0.7691	0.7971
Cup 2	5.5 to 10.0	0.0014	0.0012	0.0020
Cup 3	2.4 to 5.5	0.0001	0.0000	0.0003
Cup 4	1.61 to 2.4	0.0001	0.0006	0.0008
Cup 5	0.307 to 1.61	0.0001	0.0002	0.0005
Final Filter	<0.307	0.0001	0.0001	0.0002
Total mass of collected test item		0.9248	1.0412	1.0409

Table 3 Cascade Impactor Calculated Results

Particle Size Cut Points (µm)	Cumulative Mass (g)			Cumulative Percentage (%)
	Run 1	Run 2	Run 3	Run 1	Run 2	Run 3
<10.0	0.0018	0.0021	0.0038	0.2	0.2	0.4
<5.5	0.0004	0.0009	0.0018	<0.1	<0.1	0.2
<2.4	0.0003	0.0009	0.0015	<0.1	<0.1	0.1
<1.61	0.0002	0.0003	0.0007	<0.1	<0.1	<0.1
<0.307	0.0001	0.0001	0.0002	<0.1	<0.1	<0.1

Conclusions:

The granulometric (particle size) distribution of test substance was determined. By sieve analysis, the percentage of test item having an inhalable particle size of less than 100 µm was determined to be 70.5%. By cascade impactor analysis, the percentage of test item having a thoracic particle size of less than 10.0 µm and respirable particle size of less than 5.5 µm was determined to be ≤0.4% and <0.2% respectively.

Executive summary:

The particle size distribution of test substance was determined by using the sieving method in accordance with European Commission Technical Guidance Document EUR 20268 and GLP. It was found that the percentage of test item having an inhalable particle size of less than 100 µm was determined to be 70.5% (sieve analysis) and the percentage of test item having a thoracic particle size of less than 10.0 µm and respirable particle size of less than 5.5 µm was determined to be ≤0.4% and <0.2% respectively (cascade impactor analysis).

Description of key information

Median particle size D(50) = 1.99 µm, D(10) = 0.78 µm, D(90) = 5.89 µm, Laser scattering/diffraction, CIPAC 187, Das 2015

Inhalable particle size of less than 100 µm was determined to be 70.5% (sieve analysis) and the percentage of test item having a thoracic particle size of less than 10.0 µm and respirable particle size of less than 5.5 µm was determined to be ≤0.4% and <0.2% respectively (cascade impactor analysis), EUR 20268, O'Connor 2015.