1-[3-(Hydroxymethyl)pyridin-2-yl)-4-methyl-2-phenylpiperazine

Appearance / physical state / colour

Administrative data

Endpoint:

appearance / physical state / colour

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05 October 2017 - 01 March 2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

particle size distribution (granulometry)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05 October 2017 - 01 March 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

according to guideline

Guideline:

ISO 13320 (Particle size analysis - Laser diffraction methods)

Version / remarks:

2009

Qualifier:

according to guideline

Guideline:

other: CIPAC MT 187 (Particle size analysis by laser diffraction)

Version / remarks:

Handbook K, 2007

Principles of method if other than guideline:

According to REACH Article 13(3) tests on substances shall be conducted in accordance with the test methods laid down in a Commission Regulation or in accordance with other international test methods recognised by the Commission or the Agency as being appropriate. No particle size distribution test method is laid down in regulation (EC) No 440/2008. OECD 110 TG ‘Particle Size Distribution/Fibre Length and Diameter Distributions’ dates from 1981 and describes two methods in detail; both methods have restrictions and are not applicable to the entire size range. ECHA’s Guidance on information requirements and Chemical Safety Assessment-Chapter R.7a stipulates that many methods are available for particle size measurements but none of them is applicable to the entire size range. The guidance mentions Laser scattering/diffraction as a method for particles of all kind and makes reference to ISO 13320:2009.

According to Guidance document EUR 20268 (2002), the laser diffraction technique is applicable to particles of respirable and inhalable size. The MMAD can be calculated when density is known.

GLP compliance:

yes (incl. QA statement)

Remarks:

certificate issued on 13 Jan 2016

Type of method:

Laser scattering/diffraction

Type of particle tested:

primary particle

Type of distribution:

volumetric distribution

Specific details on test material used for the study:

Relative density: 1.19

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
The sample was observed to contain agglomerations and lumps of > 2000 μm. Test material was therefore manually sieved (2000 µm).
Result:
10.9% by weight had a particle size of > 2000 μm.
89.1% by weight had a particle size of < 2000 μm; this fraction was used for laser diffraction analysis.

Mass median aerodynamic diameter:

600.355 µm

Geometric standard deviation:

>= 2.166 - <= 2.172

Remarks on result:

other: The MMAD above is the average of 5 runs. GSD was calculated from d50/d15.78. The min. and max. GSD values of 5 runs are provided above. The St.dev. in the table below is the population standard deviation [µm].

Remarks:

Result based on the fraction of the sample which was < 2000 μm.

Key result

Percentile:

D10

Mean:

178.736 µm

St. dev.:

2.376

Key result

Percentile:

D50

Mean:

550.344 µm

St. dev.:

7.873

Key result

Percentile:

D90

Mean:

1 128.075 µm

St. dev.:

19.247

No.:

#1

Size:

< 10 µm

Distribution:

0.82 %

Remarks on result:

other: volume of sample (based on the fraction of the sample which was < 2000 μm)

Conclusion of visual and microscopic evaluation:

- visual observation: coarse to medium powder with some fines and larger solid lumps

- microscope using 3.2 objective lens : irregular shaped crystals; smallest individual particle size was approximately 9 μm and the largest individual size was approximately 864 μm

- microscope using 40 objective lens: single crystalline particles

Laser Diffraction Particle Size Analysis:

Coefficient of variation for D50 is < 3%; D10 and D90 are < 5%. These values are within the acceptable limits mentioned in the ISO 13320 standard.

Conclusions:

Manual sieve analysis showed that 10.9% (w/w) of the substance had a particle size of > 2000 μm and 89.1% (w/w) a particle size of < 2000 μm.
Laser diffraction results for the substance fraction < 2000 µm:
D10 = 178.736 µm, D50 = 550.344 µm and D90 = 1128.075 µm.
0.82% of the sample volume was determined to be < 10 µm.
The MMAD was calculated to be 600.355 µm.

Executive summary:

The particle size distribution of the substance was performed in a GLP study according to ISO 13320 and CIPAC MT 187.

The sample was observed to contain agglomerations and lumps of > 2000 μm. Manual sieve analysis was therefore performed: 10.9% (w/w) of the substance had a particle size of > 2000 μm and 89.1% (w/w) had a particle size of < 2000 μm. The laser diffraction analysis was conducted on the sample fraction < 2000 μm using the small volume wet module. Each result is the average of five runs.

Result for the fraction < 2000 µm: D10 = 178.736 µm, D50 = 550.344 µm and D90 = 1128.075 µm. 0.82% of the sample volume (fraction < 2000 μm) was < 10 µm. The MMAD was calculated to be 600.355 µm.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The appearance was determined by visual observation (direct and under a microscope). No guideline was followed for the appearance determination but sufficient details were given in the study report.

GLP compliance:

yes (incl. QA statement)

Remarks:

certificate issued 13 Jan 2016

Test material

Test material information

Constituent 1

Reference substance name:

{2-[(2R)-4-methyl-2-phenylpiperazin-1-yl]pyridin-3-yl}methanol; {2-[(2S)-4-methyl-2-phenylpiperazin-1-yl]pyridin-3-yl}methanol

EC Number:

700-296-8

Cas Number:

61337-89-1

Molecular formula:

C17-H21-N3-O

IUPAC Name:

{2-[(2R)-4-methyl-2-phenylpiperazin-1-yl]pyridin-3-yl}methanol; {2-[(2S)-4-methyl-2-phenylpiperazin-1-yl]pyridin-3-yl}methanol

Test material form:

solid: particulate/powder

Details on test material:

Physical appearance: white powder
Storage conditions: at room temperature

Results and discussion

Physical state at 20°C and 1013 hPa:

solid

Form / colour / odour

Key result

Form:

solid: particulate/powder

Colour:

White

Odour:

other: not determined

Substance type:

organic

Any other information on results incl. tables

By standard visual inspection, a test substance sample was observed to be a coarse to medium powder with some fines and larger solid lumps.

Based on observation using a 3.2 objective lens, the particles appeared to be irregular shaped crystals.

Based on observation using a 40 objective lens, the sample was observed to be made up of single crystalline particles.

Applicant's summary and conclusion

Conclusions:

The substance is a white powder at room temperature.