(4aR*, 8aR*)-1-bromo-4a,5,9,10,11,12-hexahydro-3-methoxy-6H-benzofuro[3a,3,2-ef] [2]benzazepin-6-one hydrochloride (1:1)

Particle size distribution (Granulometry)

Link to relevant study record(s)

Reference

Endpoint:

particle size distribution (granulometry)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001-10-22 to 2002-03-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: European Commission, Document ECB/TM/February 1996: "Particle Size Distribution Fibre Length and Diameter Distribution", Guidance Document using the laser diffraction method.

Deviations:

no

Remarks:

There were no circumstances that may have affected the quality or integrity of the data.

Principles of method if other than guideline:

The above mentioned guideline contains several different methods for the determination of the particle size distribution. These are, between others sieving, microscopic examination, sedimentation, gravitational settling examination, cascade impaction and laser scattering / diffraction. In the present study the laser scattering / diffraction was applied.

GLP compliance:

yes (incl. QA statement)

Remarks:

Certificate from the Swiss GLP monitoring Authority.

Type of method:

Laser scattering/diffraction

Type of distribution:

volumetric distribution

Specific details on test material used for the study:

- Batch n°: RT002102G4A311
- Analytical purity: 99.4%
- Expiration date: 25 March 2002
- Storage condition: at room temperature

Percentile:

other: D5

Mean:

0.7 µm

St. dev.:

0.03

Percentile:

D10

Mean:

0.9 µm

St. dev.:

0.061

Percentile:

D50

Mean:

2.8 µm

St. dev.:

0.148

Percentile:

D90

Mean:

8.3 µm

St. dev.:

0.41

Visual examination (magnification 400) showed small colourless, crystalline structures.

Table 1. Percentage of the test substance T002102 particles below 1, 5 and 10 um as relevant particle size for the human health (exposure via inhalation).

um	1. Run%	2. Run%	3. Run %	4. Run%	Mean %	Stand. Dev
<1.0	10.47	12.60	10.20	13.11	11.60	1.47
<5.0	75.00	75.35	74.61	75.65	75.15	0.45
<10	94.12	92.34	94.70	92.14	93.33	1.28

Conclusions:

The particle size of T002102 was found to range from about 0.5 µm to 175 µm using the laser diffraction apparatus (range between 0.3 µm and 300 µm). The mass median diameter (MMD) was determined to be 2.8 µm.

Description of key information

The particle size distribution of the substance was determined in a GLP study performed according to European Commission, Document ECB/TM/February 1996: "Particle Size Distribution Fibre Length and Diameter Distribution", Guidance Document using the laser diffraction method without deviations (Tognucci, 2002). This K1 study concludes that the particle size of the substance ranges between 0.5 and 175 µm, with a median mass diameter of 2.8 µm. 

Additional information

The GLP study of Tognucci (2002) to determine the particle size distribution of T002102 according to the test guideline of the European Commision ECB/TM/February 1996 "Particle Size Distribution, Fibre Length and Diameter Distribution" concluded that the mass median diameter (MMD) was 2.8 µm using the laser diffraction apparatus in the range between 0.3 µm and 300 µm. The particle size distribution ranged from approximately 0.5 µm to 175 µm.

This study is considered reliable (Klimisch 1) and assigned as key study for this endpoint.