Organisation for Economic Co-operation and Development

ENV/CBC/TG/RD(2022)16

For Official Use English - Or. English

18 March 2022
ENVIRONMENT DIRECTORATE
CHEMICALS AND BIOTECHNOLOGY COMMITTEE

Working Party of National Coordinators of the Test Guidelines Programme

Response to comments on the new draft Test Guideline on the Determination of the
Volume Specific Surface Area of Manufactured Nanomaterials

34th Meeting of the Working Party of the National Coordinators of the Test Guidelines Programme

Mar Gonzalez, Principal Administrator Manufactured Nanomaterials

Email: mar.gonzalez@oecd.org, Phone: +33 145 24 76 96

JT03491589
OFDE

This document, as well as any data and map included herein, are without prejudice to the status of or sovereignty over any territory, to the
delimitation of international frontiers and boundaries and to the name of any territory, city or area.
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Note by the Secretariat

1. This document contains the compiled responses to comments (RCOM) resulting from the 1 st WNT
commenting round for the new draft Test Guideline (TG) on the Determination of the Volume Specific
Surface Area of Manufactured Nanomaterials (Nov-December 2021). Inputs on the final round of
comments were made by experts from Japan, Korea, the Netherlands (NL), Sweden, the United States,
and BIAC.
2. The new draft TG is made available as document ENV/CBC/TG(2022)25. As an accompanying
document, the WNT is invited to take note of the JRC report on the Interlaboratory comparison on the
determination of the Volume Specific Surface Area (VSSA) of manufactured nanomaterials. The report
was made publicly available in June 2021 [LINK].
ACTION REQUIRED: The WNT is invited to take note of the responses to comments.

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RESPONSES TO COMMENTS RECEIVED FOLLOWING THE 1ST WNT COMMENTING ROUNDS ON THE DRAFT TG ON VSSA
(NOV-DECEMBER 2021)

# Deleg Para Line Expert Comments response

# #
1. GER GC GER congratulates the lead to this clear and helpful TG. Thank you for your support.
However, as the draft TG is mainly relying on ISO standards it remains open for the Several other TGs rely on ISO standards and such a
reader if the current draft TG can be deployed without consultation of the cited ISO statement has not been required for them. As all the
norms. Therefore, a clear statement on this is needed for the user of the TG within the participants in the ILT were able to work without
document consulting the ISO standards, we are convinced that
it may not be necessary in a majority of cases.

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# Deleg Para Line Expert Comments response

# #
2. Japan GC The VSSA value is obtained by multiplying the mass specific surface area by the skeletal Thank you so much for this clear support. Indeed,
density, and the BET method (ISO 9277:2010) is used for the mass specific surface area coordination with the ISO has been taking place.
and the gas pycnometry (ISO 12154:2014) is used for the skeletal density. In addition,
the importance of pre-treatment, such as degassing and pre-treatment problems in
these measurements, are clearly described.
Furthermore, inter-laboratory comparison tests were conducted to evaluate the
variability within and between laboratories, and it is clearly stated that the guideline
was developed after demonstrating that it is acceptable. In addition, it recommends
the use of reference materials appropriate to ensure the reliability of measurement
results, which we believe is a carefully prepared guideline at this stage.
In addition, the report on the VSSA measurement results, both for the mass specific
surface area and the skeletal density stipulates in detail the description of product
information and information on the characteristic structure of the nanomaterial, as
well as information on the measurement, including pre-treatment, and the VSSA
calculated from this information. Therefore, the VSSA measured by the procedures in
this guideline can be used as a reliable value for evaluating nanomaterials' behavior and
biological effects. However, considering the structural characteristics and diversity of
nanomaterials, it is essential to update the guidelines to be more suitable for the actual
conditions of nanomaterials in accordance with the future revision of ISO standards.
3. NL GC It is acknowledged that the text in this TG is succinct and ISO standards are needed as Thank you for this support. We tried to address all
well. Nevertheless, at some points this appears to influence clarity of the text and your comments below
further clarifications would be appreciated. This is further detailed in comments below.
4. NL GC There are inconsistencies in referencing when referring to several references together. Done
E.g. in line 7 reference is made to “(1)(2)(3)(4)(5)”, while in line 64 reference is made to
“(19), (5)”, and in line 103 to “(12), (13), (14), (15), and (16)”. Suggest to adjust to one
style only.

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# Deleg Para Line Expert Comments response

# #
5. BIAC GC The use of VSSA to estimate the size of a particle population has historically been a We interpret this comment as supportive to the
useful tool to evaluate the type of materials being investigated when compared with current draft TG. Thank you
particle sizing data at full dispersion. i.e., the equation (8 / VSSA) x 1000 gives a size in
nm that is a useful check for the status of a material and what the VSSA actually
represents. This is good not only for identifying materials that are predominantly nano-
objects versus nanostructured particles; but also by identifying when a material may
behave more like a molecule than a particle as measured in a dispersed state. Some
materials may have rather small particle sizes but their VSSA are low reflective of their
ability to assemble at the molecular scale during drying. Noting the use of VSSA as a
simple screening tool for a first approximation for identifying the nature of particle
materials might be useful as an informative contribution.

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# Deleg Para Line Expert Comments response

# #
6. BIAC GC It might have been missed, but a specification of the analytical balance to be used does
not appear to be given. Since samples may be loaded in two different instruments to
determine the VSSA, the mass measurement going into each is important, as this will
impact the overall uncertainty. There should be some note on the requirements for
the analytical balance or a reference to a standard and when mass measurement
should occur (e.g., after heat treatment to remove water)
It seems that the comment refers to the weighting
of the degassed mass (done in an analytical balance)
before introducing the test sample in the BET and
pycnometer and starting the SSA and density
measurements.
In the SOP used during the ILC, a balance with a 0.1
mg precision was indicated in the materials and
apparatus section. The same indication was also
present in the SOPs provided by experts (BAM,
CSIC..).
Some commercial instrumentation allows for
weighing the sample amount “in situ”, and specific
measurement and calibration instructions are
provided by the producer. Of course, the
microbalance must be properly calibrated using
traceable mass pieces
While in the ISO standard for BET there seems to be
no indication on the precision of the balance, the
standard for pycnometry refers to weighting the
materials in an analytical balance readable, without
estimation, to at least 0.1% of the sample.
Some text has been added in paragraph 48 (SSA, test
conditions and Skeletal density test conditions) to
address the comment.

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# Deleg Para Line Expert Comments response

# #
7. GER 1 5ff Additional background regarding VSSA should be added. As stated “This physical- The VSSA can be calculated by multiplying SSA with
chemical property may influence the behaviour and biological effects of manufactured skeletal density, as explained in this TG. As a result
nanomaterials” is true, but the provided references refer nearly exclusively to specificSSA and VSSA are directly related to each other. The
surface area (SSA) with the unit m²/g. observed effects attibuted to SSA can hence be
NC Agree extrapolated to VSSA and extra references are
therefore considered not needed.
8. GER 1 10 It is stated that information on VSSA may provide information that helps to estimate The explanation can be the same as for previous
environmental fate of nanomaterials. To our experiences it is unclear how VSSA (alone) comment, only the reverse transformation is
can provide such information and therefore there is a need for justification by further needed Nevertheless, as the commenter hints, VSSA
explanation and references. Otherwise we recommend to delete that part of the in itself is not a common dose metric for assessing
sentence. NC Agree NM toxicity, SSA is mostly used, instead. We do use
VSSA as a proxy for NM classification
A small change in wording has been included.
9. GER 1 14 Full stop missing Thanks. Corrected
NC Editorial
10. NL 1 12 Suggest to clarify: [...] in some cases, they data on VSSA can be used [...] Wording corrected Thank you

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# Deleg Para Line Expert Comments response

# #
11. Swed 1 5-14 Perhaps mention that this paragraphs primarily concerns nanomaterials in powder The reviewer correctly states that the described
en form? If nanoparticles are dispersed into e.g. plastics such that they form solid methods are only applicable to materials in powder
nanocomposites, the specific surface area of the nanoparticles in the composite is still
form. While the paragraph, and the TG as a whole,
large, but since they cannot disappear from the composite they are a much smaller applies implicitly to powders only, we have included
threat against human health than free nanoparticles in powder form. This can be an explicit reference to powdered materials in the
clarified even though §13 states that nanocomposites are not included in this report. given paragraph, and in paragraphs 14 and 15, as
requested by the reviewer.
Paragraph 13 does not address composite materials
in its most generic meaning, but it addresses
specifically coated and composite nanoparticles. To
avoid confusion for the reader, we revised the
paragraph accordingly.
12. Swed 2 15 Perhaps write out the unit of VSSA? The unit (m2/cm3) has been inserted, as requested
en by the reviewer.
13. GER 7 35 Add “as”: “However, as ISO….allows a rapid…” Done
14. NL 7 37 Suggest to make the last part a separate sentence, i.e. “This documentary standard is See previous comment
used in this TG.”
15. NL 8 44 Suggest to include ISO 5725 part 5 in the reference list and limit the text in this Done
paragraph accordingly.
16. NL 8 45 Suggest to clarify: “[...] within each laboratory [...]” The term within-laboratory is generally used by ISO
and metrology communities when referring to
variability within a laboratory. Since the two words
are functioning together, we have now connected
the words by a hyphen.

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# Deleg Para Line Expert Comments response

# #
17. GER 10 471ff One important issue is the harmonisation of terminology and definitions in various TGs We agree that coherence among TGs is important.
and and GDs for environmental fate testing of nanomaterials (see previous discussions on We have, so far, not identified any contradiction
anne this at the WNT meeting in April 2020). The list of definitions used in this annex is quite with other OECD documents. We decided to keep
x on long. Please make sure that the used definitions are in line with the definitions used for the definitions that allow to use this TG without
defin these terms in other OECD documents, e.g. all terms regarding adsorption/absorption, needing to consult the ISO standards, as has been
ition isotherms, density and for sure “particle” might be already cited elsewhere and required generally by the National Coordinators.
s shouldn`t be contradicting. From our experiences at WNT, it will not be sufficient and
satisfactory to just mention that these definitions only apply to this TG. In order to avoid
deviations, one solution might be deleting those definitions from the annex which are
already used in the cited ISO norms and definitions which are not absolutely necessary
for the understanding of the draft TG. However, important definitions which are
needed in the TG (and should remain) of course include surface area, SSA, VSSA,
density.
18. NL 11 56 Suggest to add references for the ISO documents to clarify (they are in the reference Done
list already).
19. GER 12 65 As “NM” as abbreviations for “nanomaterial” is neither introduced nor used in other Changed as suggested by NL in next comment
paragraphs of this document, we recommend to change to “nanomaterial”.
20. NL 12 65 The statement appears broader applicable than nanomaterials. Suggest to replace Done
“NM” by “material to be measured”.
21. BIAC 12 65 Suggest to change to not “unintentionally” modified. In some cases, an organic coating The paragraph refers to changes during the
may be intentionally removed for analysis, for example. measurement or preparation of the material
whose VSSA is to be measured (this could also be a
treated sample, but the measurement or
preparation should not additionally modify it.

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# Deleg Para Line Expert Comments response

# #
22. GER 13 67ff This paragraph refers to the limitation of the TG in relation to NMs used in the ILC. In Thank you for this valid and important comment. In
other words, this paragraph defines the applicability of the TG. This should be clearly addressing the elaborated concern, we have revised
stated at the very beginning, as the ILC carried out so far does not considered the paragraph 13, i.e. we now explicitly acknowledge
application of the TG to the outlined NMs, “e.g. coated nanomaterials, composite that the applicability of the described methods has
nanomaterials, microporous nanomaterials and nanomaterials with very high SSA”. only been demonstrated for the types of materials
There are therefore uncertainties remain as to whether the TG is accurate and valid for used in the ILC and that unknown uncertainties may
these NMs. arise when applying the methods to other types of
materials, and in particular materials with a higher
complexity.
23. GER 13 75- This sentence is a copy-paste from the last sentence of the previous paragraph. Is a Indeed. Deleted
77 repetition really needed here?
NC Please Clarify
24. NL 13 69- Suggest to clarify: “Such materials may pose challenges when using ISO 12154 and Done Thanks
70 calculating VSSA. High surface area materials can produce values of skeletal density that
are smaller than the actual value (18), [...]”
25. NL 13 75- The last sentence of this paragraph appears to be in a bigger font size. Corrected
77
26. BIAC 14 79 “…and are disperse…” It is not clear what is meant here, but any nanomaterial in dry Indeed, wording changed as per NL comments
form is agglomerated so, “dispersed” may not be an appropriate term. below
27. BIAC 14 79 I would suggest removing the pore diameter specification if it is not provided for the Mesopores have by (ISO) definition ISO/DIS 15901-
other. Also the statement is a generalization so “approximately” or “predominantly” 2(en) a size between 2 and 50 nm. The size reported
should be considered rather than a sharp division. here relates to this definition. Macropores are (as
defined in the same ISO document) larger than 50
nm.
28. NL 14 79- Suggest to clarify: “[...] and are disperse solids that are either, nonporous, mesoporous Done. Thanks
80 with pore diameter between 2–50 nm, and or to macroporous solids.”

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# Deleg Para Line Expert Comments response

# #
29. NL 14 80- In contrast with the “on the other hand” these sentences appear to tackle the same Thank you for the revision, which improves the
85 issue to some extent. Suggest to clarify, e.g.: readability of the given section. We changed your
“The technique is not suitable for substances, which are microporous solids, although text a bit more, to be more accurate
a specific annex is included in ISO 9277:2010, which contains a specific strategy for
measurement of surface area for these substances as well. On the other hand, tThe BET
gas adsorption model is inappropriate at small pores sizes (smaller than ca. 2 nm) and
a correction may be needed for microporous solids, depending on the nanomaterial
(adsorbent) and the gas (adsorptive) used. ISO 9277:2010 contains an annex that
outlines a specific strategy to allow measurement of surface area for these substances.”
30. NL 17 112 Please add a reference for the recommendation of the use of krypton. Added
31. US 17 The apparent absence of factoring in possible adverse effects of agglomeration and Paragraph 17 addresses the physical principle of gas
aggregation of nanomaterials, which could affect the determinations. I find that item adsorption (e.g. through weak van der Waals forces)
#17 in a way seems to be alluding on agglomeration (e.g., van der Waals), but not sure. on the external surface of particles. We believe that
A further clarification is needed. the current paragraph does not allude on the weak
forces that may keep individual particles together as
agglomerates and, therefore, no revisions are made.
However, the reviewer is correct that nanomaterials
are often sensitive to agglomeration and
aggregation. It is known that the BET method can
significantly underestimate the surface area of
aggregated nanoparticles. In paragraph 14 we have
now inserted a statement that BET applies only to
non-aggregated particles.
32. US 17 111- It is not clear why krypton is recommended for nanomaterials with a very small specific A rationale is provide in reference 18. Now added
112 surface area. For nitrogen and argon, a clear rationale was provided in the previous reference.
sentences.
33. Japan 19 A typo. Change Emmet to Emmett. Corrected

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# Deleg Para Line Expert Comments response

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34. NL 20 119 For consistency, suggest to the font style of “p/p0” to italic. Changed
35. GER 21 130 Please specify if it should be “”and types IV” or “and type IVa” Clarified now, according to Ref 15
NC Please clarify
36. Japan 21 144 It will be helpful if recommended value of am is written in the TG (0.162 for nitrogen Recommended numbers for cross-sectional areas
and 0.142 for argon ?). (am) for N2, Kr, Ar, and other frequently used
adsorptives are given in Thommes et al (15) and
ISO 9277 (16). They gives values for N2 0.162, Kr
0.202, Ar: 0.138 (77.4K) and 0.142 (87.4 K).
Footnote added in paragraph 17
37. GER 21 Figur Figure caption. In para 21 refers to types of isotherms and the caption to classes of Done
e1 isotherms. Please harmonise.
38. US 21 129- It would be helpful to the reader if a statement regarding the associated solid types for The other types of sorption isotherms are outside
130 the other isotherms (i.e., Ia, Ib, III, V, and VI) is included. the scope of the TG. However, a statement has been
inserted in paragraph 21 guiding the reader directly
to the IUPAC reference (15), in which detailed
information on the six types of isotherms can be
found.
39. US 21 131 What does “B” in the isotherm II plot mean? Reversible Type II isotherms are given by the
physisorption of most gases on nonporous or
macroporous
adsorbents. The shape is the result of unrestricted
monolayer-multilayer adsorption up to high p/p0. If
the
knee is sharp, Point B – the beginning of the middle
almost linear section – usually corresponds to the
completion
of monolayer coverage.

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# Deleg Para Line Expert Comments response

# #
40. BIAC 28 176 Please refrain from using “known ‘bulk” in “’bulk material density’”. The term “bulk The he term “known bulk density” was not well
density” has a very different meaning and may cause confusion. Instead maybe chosen as it indeed can cause confusion. We
indicate “material density” to avoid confusion. Avoid using “known” since it is being welcome the reviewer’s alternative suggestion,
measured because it is not known. Suggest to use “commonly reported material which has been inserted in paragraph 28.
density”
41. BIAC 29 187- Not all of the materials used in the ILC are certified reference materials. This OK. Changes made
191 terminology has a specific meaning and must be placed into context for what
measurement. I am not aware of a certified reference material for VSSA. Note in table
1 the NIST material is clearly labelled an SRM and NOT a CRM. Perhaps just indicate
“reference materials” and remove “certified”.
42. BIAC 191 Table The product name is given for only one reference material. Unless the intent is to In Table 1, we only list those reference materials
1 provide product names for all of them (when they exist) this should be removed. that were used within conducted ILC study In
avoiding giving the impression that the user should
only use those reference materials listed in Table 1,
we now explicitly refer to the COMAR database
whether other commercially available reference
materials for BET can be found.
43. BIAC 191 Table The explanation of the asterisk would likely confuse the reader. Either remove or We agree that the previous footnote (asterisk) is
1 replace with a different explanation. For instance: “Although NIST SRM 1898 and KRISS confusion and welcome the alternative proposal
301-03-001 represent the same TiO2 product, the reference materials are prepared made.
from different commercial lots and have significantly different specific surface areas.
44. BIAC 31 203 This section seems to promote JRC materials over others. I would suggest broadening Wording changed
this out to include BAM, NIST, etc. and refer back to the materials in the ILC.
45. NL 29 189- Please check whether the reference is correct (ILC report is reference 19). This may Thank you. Done
191 need to be checked throughout the document.

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# Deleg Para Line Expert Comments response

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46. Korea 29 Table Corrected
1

KRISS 301-03-001 TiO2* 57.00 1.32

Aeroxide P25

47. Japan 209 Does 'sample preparation' mean the degassing step? If so, please change the 'sample No. sample preparation is used in a more general
preparation' to 'degassing step' to unify the expression in the document. meaning as described in paragraph 31.
48. Japan 33- Description focuses only on the multipoint method. Don't we need to give guidance on A footnote has been added to refer to the single-
36 the other popular methods like the single-point and the carrier gas methods? point method
49. GER 37 236- How relevant is that sentence as the scope of the TG is inorganic uncoated The scope is not limited to inorganic uncoated
238 nanomaterials? Please clarify nanomaterials. There are just uncertainties and
measures of caution that must be taken for these
materials, as stated in several paragraphs of the
draft TG
50. NL 37 238 Typo: “(18)” Corrected thanks
51. US 37 236- Would this statement be applicable to the nanoscale version of these cellulose and Please explain.
238 some low density polymeric materials?

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# Deleg Para Line Expert Comments response

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52. NL 39 243- Suggest to clarify: Done, thanks
246 “Consecutive volume measurements may show a consistent increase or decrease in
surface values. Such a cCorrelation of the measurement result with the measurement
number, resulting in increasing or decreasing surface values, indicates interaction
between the sample/ and the gas, or an incomplete removing of atmospheric gases
during the degassing step. In the first caseWhen interaction is observed, the gas used
for the measurement should be substituted by another gas (19).
53. BIAC 40 246 It may be beneficial to provide examples of commonly applied alternative gases. N2, Ar, Kr have already mentioned as possible gases.
No need to repeat here.
54. NL 44 261- This sentence specifically refers to “with nitrogen, argon and argon at cryogenic As Kr is seldom used, we consider this unnecessary.
262 temperatures”. In paragraph 17 krypton is also specifically mentioned as a The user can find guidance in reference (16)
recommended adsorbate to determine specific surface area. Please clarify which
technique is considered most suitable for physisorption measurements with krypton.
55. NL 45 266 Suggest to clarify footnote 5, e.g. Thanks, done
“Essentially, both experimental configurations are very similar. They both consist of a
have fixed size sample chamber and a reference chamber connected by tubes, a
pressure-measuring sensor and three valves. The only difference being is the position
of the pressure-measuring sensor in relation to the valve that connectsing the sample
chamber to the reference chamber.”
56. BIAC 45 267- In pycnometry, the volume must be measured. Is there a reference for an example Please note that in pycnometry the skeletal volume
268 where it is calculated? I believe some instruments may provide a mass analysis with is calculated from the volume of the measuring cell,
the volume analysis to give density but not a calculation for skeletal volume. Please the volume of the reference cell, and the pressure
revise. readings before and after the gas expansion step
and equilibrium. The applied formula depends on
the configuration of the particular instrument used.
57. Swed 48 281 Perhaps write out the unit of VSSA? Done
en

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# Deleg Para Line Expert Comments response

# #
58. GER 49 289 There is similar information on the test material that needs to be reported for surface This is indeed correct. However, we prefer to keep
ff area and density. It might be worth to mention it just once at the beginning. NC Please it as it is, because some users may wish to determine
consider independently both properties.
59. NL 49 299 This is the only place where the abbreviations TGA and DSC are used. Please explain. Done
60. Japan 319 Please consider to include the pressure range of linearity and the correlation coefficient Done
to in the test report.
322
61. NL 49 355- A closing bracket appears to be missing. Added
356
62. NL Anne 473- Please provide references for the different definitions. This will facilitate transparency Care has been taken that these definitions are the
x 513 and help avoid conflicting definitions in different OECD TGs and/or ISO-documents. same as in the relevant ISO documents and the
references used. No conflicts have been identified
with other OECD TGs. No changes done
63. NL Anne 485- It is assumed that this definition is for “dead volume” (as used in line 310). The term Indeed. Corrected
x 486 “free space” is not used elsewhere in the text (the text “also known as ‘free space’” in
the definition further suggests this definition was intended for a different term).
64. NL Anne 490- Typo’s: “[...] with a width [...]” (to be consistent with the definition for “macropore”). Corrected. Thank you
x 491
65. NL Anne 496- Suggest to clarify: Corrected. Thanks
x 497 “Open pore: pore not totally enclosed by its walls and hence not (potentially)
interconnecting with other pores and not accessible to fluids

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