Benzene-1,3,5-tricarbonyl trichloride

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:

15-03-2022 to 23-05-2022

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Study conducted to recognised guidelines and guidance under GLP. All relevant validity criteria were met, with the exception of the 'repeatability criteria'. Applicant assessment indicates: the study can be considered acceptable with restrictions. This was given the corrosivity of the test item observed to equipment within the dry powder dispersion laser diffraction analysis study, and/or the inability to disperse in suitable non-aqueous solvents to test using wet module it can be considered the test item was satisfactorily tested. This is also with reference to the conclusion that the test item could be considered: inhalable under OECD 39 (2018). The proportion of test item having an inhalable particle size of < 100 μm was determined to be less than or equal to 3.55 % w/w using the laser diffraction analysis method - dry powder dispersion. Although the thoracic and respirable fractions appear non-existent due to absence of test item with < 10 μm particle size.

Qualifier:

according to guideline

Guideline:

ISO 13320 (Particle size analysis - Laser diffraction methods)

Deviations:

yes

Remarks:

Repeatability criteria not fulfilled, refer to 'Rationale for reliability incl. deficiencies' and/or 'Overall remarks, attachments' and 'Applicant's summary and conclusion' ; the test item was satisfactorily tested considering its corrosive properties.

Qualifier:

according to guideline

Guideline:

other: CIPAC MT 187

Version / remarks:

“Particle Size Analysis by Laser Diffraction”, Handbook K, 2007

Deviations:

yes

Remarks:

Repeatability criteria not fulfilled, refer to 'Rationale for reliability incl. deficiencies' and/or 'Overall remarks, attachments' and 'Applicant's summary and conclusion' ; the test item was satisfactorily tested considering its corrosive properties.

GLP compliance:

yes

Type of method:

Laser scattering/diffraction

Type of particle tested:

primary particle

Remarks:

The test item appeared to be white to pale yellow crystalline powder with some agglomerations. Lumps/agglomerations were carefully pulverised with a spatula to achieve a more constant distribution of the test material into the system prior to measurement.

Mass median aerodynamic diameter:

ca. 1 263 µm

Geometric standard deviation:

ca. 2.323

Remarks on result:

other: Information for Aero S module for dry powder dispersion: average MMAD: 1263 µm and average GSD 2.323 (GSD range: 2.131 - 2.509) where: n=6 ; See 'overall remarks, attachments' for further information.

Key result

Percentile:

D10

Mean:

298 µm

St. dev.:

57.4

Remarks on result:

other: n=6 ; average D10: 298 µm ; %STDVP was > 3% - see 'overall remarks, attachments' for further information.

Key result

Percentile:

D50

Mean:

ca. 980 µm

St. dev.:

56.3

Remarks on result:

other: n=6 ; average D50: 980 µm ; %STDVP was > 2.5% - see 'overall remarks, attachments' for further information.

Key result

Percentile:

D90

Mean:

ca. 2 150 µm

St. dev.:

57.5

Remarks on result:

other: n=6 ; average D90: 2150 µm ; %STDVP was < 4% - see 'overall remarks, attachments' for further information.

No.:

#1

Size:

< 100 µm

Distribution:

<= 3.55 %

Remarks on result:

other: The proportion of test item having an inhalable particle size of < 100 μm was determined to be < or = 3.55 % w/w (via the particle size histogram presented in the full study report) - see 'overall remarks, attachments' for further information

No.:

#2

Size:

< 10 µm

Distribution:

0 %

Remarks on result:

other: The proportion of test item having an inhalable particle size of < 10 μm (thoracic fraction) was determined to be 0 % w/w (at < 9.86 μm actual).

No.:

#3

Size:

< 1 µm

Distribution:

0 %

Remarks on result:

other: The proportion of test item having an inhalable particle size of < 1 μm (respirable fraction) was determined to be 0 % w/w .

1. The particle size distribution of the test item was analysed over the range 0.01 µm to 3500 µm. Analysis of the generated results indicates the test item contains particles with particle sizes above 3500 µm. However, due to the limitations of the Laser Diffraction analyzer equipment, this could not be confirmed.
2. See tables for detailed information on results. It was noted the %STDVP for D50 was > 2.5%, for D10 > 3% and for D90 < 4%. It can be concluded that the repeatability of the measured particle size distributions is above the acceptable limits proscribed by the applicable guidelines. Although the repeatability was not within the acceptance criteria for the D10 and D50, it was decided not to repeat the measurement due to the corrosiveness of the test item and visible corrosion damage caused to the test system. Further testing using Dry Powder Dispersion could not be performed.

Table 1: Test results - Particle Size Analysis (Dry Powder Dispersion)

	Run 1	Run 2	Run 3	Run 4	Run 5	Run 6	Mean	STDVP	%STDVP
Volume weighted mean	1110	1090	1220	1090	1110	1080	1120	51.6	4.62
Mode	1160	1170	1220	1080	1080	1090	1130	59.3	5.22
D10 (10% of material is ≤)	275	236	399	283	326	270	298	57.4	19.3
D50 (50% of material is ≤)	979	950	1090	951	976	933	980	56.3	5.74
D90 (90% of material is ≤)	2170	2160	2260	2110	2120	2100	2150	57.5	2.67
GSD	2.381	2.509	2.131	2.362	2.210	2.343	2.323	0.134	5.758
MMAD	1263

All results are in µm.
0% by volume of sample was seen to be < 10.00 µm.

Conclusions:

The test item contains particles with particle sizes above 3500 µm which could not be analysed. The proportion of test item having an inhalable particle size of < 100 μm was determined to be less than or equal to 3.55 % w/w using the laser diffraction analysis method - dry powder dispersion. Repeat testing was not possible due to test item corrosivity and visible damage to the test system. The test item could be considered: inhalable. Although the thoracic and respirable fractions appear non-existent due to absence of test item with < 10 μm particle size. Laser diffraction analysis by wet module was not possible due to an inability to disperse in available non-aqueous solvents and test item incompatibility with aqueous solvents.

Executive summary:

The test item particle size was evaluated using laser diffraction analysis according to ISO 13320 : 2009 “Particle Size Analysis – Laser Diffraction Methods” and/or CIPAC MT 187 “Particle Size Analysis by Laser Diffraction”, Handbook K (2007) under GLP. The test item appeared to be white to pale yellow crystalline powder with some agglomerations (determined by the test facility). The test is conducted to determine the particle size distribution of the test item by means of Laser Diffraction Analysis, using the Aero S for dry powder dispersion. Various tests were performed to determine the correct parameters, most suitable feed procedure and dispersion pressures and once identified the test item was analysed using the Malvern Mastersizer 3000 Laser Diffraction Analyser. Six (n=6) runs were conducted to ensure repeatability of results. During initial testing, large lumps or agglomerations were formed within the test item container. The test system became blocked by the lumps causing measurements to halt. Therefore, the test item lumps/agglomerations were carefully pulverised with a spatula to achieve a more constant distribution of the material into the system prior to further measurement. The lumps/agglomeration pre-treatment was carefully focused on lumps/agglomeration break-up and not on pulverising the powdered/granular test item.
The test item contains particles with particle sizes above 3500 µm which could not be analysed.
The test item had the following averaged properties following six runs (n=6) :
MMAD (mass median aerodynamic diameter) 1263 μm
d10 - 10 % of material is 298 μm
d50 - 50 % of material is 980 μm
d90 - 90 % of material is 2150 μm
volume of sample < 10.00 μm: 0%
It was noted the %STDVP for D50 was > 2.5%, for D10 > 3% and for D90 < 4%. It can be concluded that the repeatability of the measured particle size distributions is above the acceptable limits proscribed by the applicable guidelines. Although the repeatability was not within the acceptance criteria for the D10 and D50, repetition of the measurement could not be completed due to the corrosiveness of the test item and visible corrosion damage caused to the test system. Further testing using Particle Size Analysis (Wet Module) could not be performed. The test item has incompatibility with aqueous solvents and may form corrosive solutions. Therefore, aqueous solvents could not be utilised. With the limited number of potential solvents, including: Corn oil, Peanut oil, Isoparaffin G, PEG300 and Silicone Oil, were tested and found to give poor dispersibility of the test item (was seen to ‘sink to the bottom’ of the sample/solvent container). It was determined there was no suitable dispersant that could be used for particle size analysis using the wet module. Further testing could not be performed. It can be concluded, the proportion of test item having an inhalable particle size of < 100 μm was determined to be less than or equal to 3.55 % w/w using the laser diffraction analysis method - dry powder dispersion. The test item could be considered: inhalable. Although the thoracic and respirable fractions appear non-existent due to absence of test item with < 10 μm particle size.

Description of key information

Particle Size Distribution: ca. 3.55% w/w with particle size < 100 μm, no particles < 10 μm, ISO 13320 : 2009 - Laser Diffraction Analysis - Dry Powder Dispersion module, 2022

The test item contains particles with particle sizes above 3500 µm which could not be analysed.

The test item had the following averaged properties following six runs (n=6) :
MMAD (mass median aerodynamic diameter) 1263 μm
d10 - 10 % of material is 298 μm
d50 - 50 % of material is 980 μm
d90 - 90 % of material is 2150 μm
volume of sample < 10.00 μm: 0%
It was noted the %STDVP for D50 was > 2.5%, for D10 > 3% and for D90 < 4%. It can be concluded that the repeatability of the measured particle size distributions is above the acceptable limits proscribed by the applicable guidelines. Although the repeatability was not within the acceptance criteria for the D10 and D50, repetition of the measurement could not be completed due to the corrosiveness of the test item and visible corrosion damage caused to the test system. Further testing using Particle Size Analysis (Wet Module) could not be performed. With the limited number of potential solvents, including: Corn oil, Peanut oil, Isoparaffin G, PEG300 and Silicone Oil, were tested and found to give poor dispersibility of the test item (was seen to ‘sink to the bottom’ of the sample/solvent container).

Applicant asseessment indicates that: a regulatory conclusion to the study was, the proportion of test item having an inhalable particle size of < 100 μm was determined to be less than or equal to 3.55 % w/w using the laser diffraction analysis method - dry powder dispersion. The test item could be considered: inhalable under OECD 39 (2018). Although the thoracic and respirable fractions appear non-existent due to absence of test item with < 10 μm particle size.

Additional information

Key study : ISO 13320 : Laser Diffraction Analysis - Dry Powder Dispersion module, 2022 : The test item particle size was evaluated using laser diffraction analysis according to ISO 13320 : 2009 “Particle Size Analysis – Laser Diffraction Methods” and/or CIPAC MT 187 “Particle Size Analysis by Laser Diffraction”, Handbook K (2007) under GLP. The test item appeared to be white to pale yellow crystalline powder with some agglomerations (determined by the test facility). The test is conducted to determine the particle size distribution of the test item by means of Laser Diffraction Analysis, using the Aero S for dry powder dispersion. Various tests were performed to determine the correct parameters, most suitable feed procedure and dispersion pressures and once identified the test item was analysed using the Malvern Mastersizer 3000 Laser Diffraction Analyser. Six (n=6) runs were conducted to ensure repeatability of results. During initial testing, large lumps or agglomerations were formed within the test item container. The test system became blocked by the lumps causing measurements to halt. Therefore, the test item lumps/agglomerations were carefully pulverised with a spatula to achieve a more constant distribution of the material into the system prior to further measurement. The lumps/agglomeration pre-treatment was carefully focused on lumps/agglomeration break-up and not on pulverising the powdered/granular test item.
The test item contains particles with particle sizes above 3500 µm which could not be analysed.
The test item had the following averaged properties following six runs (n=6) :
MMAD (mass median aerodynamic diameter) 1263 μm
d10 - 10 % of material is 298 μm
d50 - 50 % of material is 980 μm
d90 - 90 % of material is 2150 μm
volume of sample < 10.00 μm: 0%
It was noted the %STDVP for D50 was > 2.5%, for D10 > 3% and for D90 < 4%. It can be concluded that the repeatability of the measured particle size distributions is above the acceptable limits proscribed by the applicable guidelines. Although the repeatability was not within the acceptance criteria for the D10 and D50, repetition of the measurement could not be completed due to the corrosiveness of the test item and visible corrosion damage caused to the test system. Further testing using Particle Size Analysis (Wet Module) could not be performed. The test item has incompatibility with aqueous solvents and may form corrosive solutions. Therefore, aqueous solvents could not be utilised. With the limited number of potential solvents, including: Corn oil, Peanut oil, Isoparaffin G, PEG300 and Silicone Oil, were tested and found to give poor dispersibility of the test item (was seen to ‘sink to the bottom’ of the sample/solvent container). It was determined there was no suitable dispersant that could be used for particle size analysis using the wet module. Further testing could not be performed. It can be concluded, the proportion of test item having an inhalable particle size of < 100 μm was determined to be less than or equal to 3.55 % w/w using the laser diffraction analysis method - dry powder dispersion. The test item could be considered: inhalable. Although the thoracic and respirable fractions appear non-existent due to absence of test item with < 10 μm particle size.

Applicant assessment indicates: the study can be considered acceptable with restrictions. This was given the corrosivity of the test item observed to equipment within the dry powder dispersion laser diffraction analysis study, and/or the inability to disperse in suitable non-aqueous solvents to test using wet module it can be considered the test item was satisfactorily tested. This is also with reference to the conclusion that the test item could be considered: inhalable under OECD 39 (2018). Although the thoracic and respirable fractions appear non-existent due to absence of test item with < 10 μm particle size.