Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Section A3 Physical and Chemical Properties of Active Substance
Subsection
(Annex Point)
Method Purity/
Specification
Results
Give also data on test
pressure, temperature,
pH and concentration
range if necessary
Remarks/
Justification
GLP
(Y/N)
Reliability Reference Official
use only
3.1 Melting point, boiling
point, relative density
(IIA3.1)
0
3.1.1 Melting point
Melting pt. 1 EC Method A1 99.5% 151°C Yes 1 O’Conner, B
(2006)
Safepharm
Laboratories
x
Melting pt. 2 No data Anhydrous
form
153°C The active substance is a
naturally occurring substance
derived from a food source.
There will therefore be
variability in the active
substance when sourced
from different producers.
However, the specification is
for purity of 99.5% or
greater. It is therefore
considered that the
physicochemical
characteristics of the pure
form will be applicable to this
specification of the active
substance and that further
No
data
3 Daubert, TE et
al (1995)
Physical and
thermodynami
c properties of
pure chemicals.
Data Compliat.
Taylor and
Francis
x
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Section A3 Physical and Chemical Properties of Active Substance
Subsection
(Annex Point)
Method Purity/
Specification
Results
Give also data on test
pressure, temperature,
pH and concentration
range if necessary
Remarks/
Justification
GLP
(Y/N)
Reliability Reference Official
use only
physico-chemical studies are
not justified.
3.1.2 Boiling point
Boiling pt. EC Method A2 99.5% Decomposed from ca.
171°C at 102.83 kPa
prior to boiling
Yes 1 O’Conner, B
(2006)
Safepharm
Laboratories
x
3.1.3 Bulk density/
relative density
Bulk/rel. density 1 EC Method A3 99.5% Relative density: 1.65
E+03 kg/m3
Yes 1 O’Conner, B
(2006)
Safepharm
Laboratories
x
Bulk/rel. density 2 DIN 53912 Relative density: 1.665
kg/m3
The active substance is a
naturally occurring substance
derived from a food source.
There will therefore be
variability in the active
substance when sourced
from different producers.
However, the specification is
for purity of 99.5% or
No
data
4 CRC Handbook
of Chemistry
and Physics,
70th
Edn
x
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Section A3 Physical and Chemical Properties of Active Substance
Subsection
(Annex Point)
Method Purity/
Specification
Results
Give also data on test
pressure, temperature,
pH and concentration
range if necessary
Remarks/
Justification
GLP
(Y/N)
Reliability Reference Official
use only
greater. It is therefore
considered that the
physicochemical
characteristics of the pure
form will be applicable to this
specification of the active
substance and that further
physico-chemical studies are
not justified.
3.2 Vapour pressure
(IIA3.2)
Vapour pressure 1 OECD 104 99.5% Result: 1.6 E-10 Pa
Temp.: 25°C
Yes 1 O’Conner, B
(2006)
Safepharm
Laboratories
x
3.2.1 Henry´s Law Constant
(Pt. I-A3.2)
Calculated Result: 4.398E-14
Pa.m3/mole
x
3.3 Appearance
(IIA3.3)
3.3.1 Physical state Crystalline powder No
data
4 OECD SIDS
dossier
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Section A3 Physical and Chemical Properties of Active Substance
Subsection
(Annex Point)
Method Purity/
Specification
Results
Give also data on test
pressure, temperature,
pH and concentration
range if necessary
Remarks/
Justification
GLP
(Y/N)
Reliability Reference Official
use only
3.3.2 Colour White or colourless No
data
4 OECD SIDS
dossier
3.3.3 Odour No data
3.4 Absorption spectra
(IIA3.4)
Not applicable 99.5% Yes 1 O’Conner, B
(2006)
Safepharm
Laboratories
x
UV/VIS No significant
absorption at 290 nm
IR Consistent with
proposed structure
NMR Consistent with
proposed structure
MS Consistent with
proposed structure
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Section A3 Physical and Chemical Properties of Active Substance
Subsection
(Annex Point)
Method Purity/
Specification
Results
Give also data on test
pressure, temperature,
pH and concentration
range if necessary
Remarks/
Justification
GLP
(Y/N)
Reliability Reference Official
use only
3.5 Solubility in water
(IIA3.5)
including effects
of pH (5-9)
Water solubility EC Method A6 99.5% result: 65 – 69.9% w/w
temperature: 10, 20
and 30°C
pH: Substance ionises at
pH 5-9
Yes 1 O’Conner, B
(2006)
Safepharm
Laboratories
x
3.6 Dissociation constant
(-)
OECD 112 99.5% pK1 =3.01
pK2 = 4.50
pK3 = 5.87
Yes 1 O’Conner, B
(2006)
Safepharm
Laboratories
x
Various methods. Not stated 25°C
pK1 =2.63 – 3.44
pK2 =4.11 – 5.02
pK3 =5.34 – 6.55
The active substance is a
naturally occurring substance
derived from a food source.
There will therefore be
variability in the active
substance when sourced
from different producers.
However, the specification is
for purity of 99.5% or
greater. It is therefore
considered that the
physicochemical
characteristics of the pure
No
data
2 Serjeant EP,
Dempsey B.
Ionisation
constants of
organic acids in
aqueous
solution. IUPAC
Chemical Data
Series – No. 23.
Pergamon
Press
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Section A3 Physical and Chemical Properties of Active Substance
Subsection
(Annex Point)
Method Purity/
Specification
Results
Give also data on test
pressure, temperature,
pH and concentration
range if necessary
Remarks/
Justification
GLP
(Y/N)
Reliability Reference Official
use only
form will be applicable to this
specification of the active
substance and that further
physico-chemical studies are
not justified.
3.7 Solubility in organic
solvents, including the
effect of temperature
on solubility
(IIIA3.1)
CIPAC Method
181 and EC
Method A6
99.7 –
100.3%
Hexane ≤ 7.84 E-05 g/L
Diethyl ether = 7.34 g/L
Methanol > 250 g/L
Y 1 Fox JM and
White DF
(2010) Citric
acid:
Determination
of solubility in
organic
solvents.
Harlan
laboratories
3.8 Stability in organic
solvents used in b.p.
and identity of
relevant breakdown
products
(IIIA3.2)
The active substance will not
be used in organic solvents in
the biocidal product.
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Section A3 Physical and Chemical Properties of Active Substance
Subsection
(Annex Point)
Method Purity/
Specification
Results
Give also data on test
pressure, temperature,
pH and concentration
range if necessary
Remarks/
Justification
GLP
(Y/N)
Reliability Reference Official
use only
3.9 Partition coefficient n-
octanol/water
(IIA3.6)
including effects
of pH (5-9)
log Pow 1 EC Method A8 99.5% result: Pow ≤ 1.75 E-04,
log Pow ≤ -3.76
temperature: 21°C
pH: Substance ionises at
pH 5-9
Yes 1 O’Conner, B
(2006)
Safepharm
Laboratories
x
log Pow 2 Similar to shake
flask method
Not stated result: 0.019
temperature: 20°C
pH:
No
GLP
not
compu
lsory
at
time
of
study
2 Collander R
(1951) the
partition of
organic
compounds
between
higher alcohols
and water.
Acta Chem.
Scand. V5:771-
780
x
3.10 Thermal stability,
identity of relevant
breakdown products
(IIA3.7)
OECD 113 99.5% Thermally stable and
stable in air up to at
least 150oC
Yes 1 O’Conner, B
(2006)
Safepharm
Laboratories
x
3.11 Flammability, EC Method A10 99.5% Not highly flammable Yes 1 Tremain, S x
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Section A3 Physical and Chemical Properties of Active Substance
Subsection
(Annex Point)
Method Purity/
Specification
Results
Give also data on test
pressure, temperature,
pH and concentration
range if necessary
Remarks/
Justification
GLP
(Y/N)
Reliability Reference Official
use only
including auto-
flammability and
identity of
combustion products
(IIA3.8)
(2006)
Safepharm
Laboratories
Relative Self-Ignition
Temperature
EC Method A16 99.5% None below melting
temperature
Yes 1 Tremain, S
(2006)
Safepharm
Laboratories
x
3.12 Flash-point
(IIA3.9)
Test not applicable to solids
Flash-point 1
Flash point 2
3.13 Surface tension
(IIA3.10)
Surface tension EC Method A5 99.5% result: 73.6 mN/m for a
1.01g/l solution
temperature: 21°C
Yes 1 O’Conner, B
(2006)
Safepharm
Laboratories
x
3.14 Viscosity
(-)
result:
temperature:
Test not applicable to solids
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Section A3 Physical and Chemical Properties of Active Substance
Subsection
(Annex Point)
Method Purity/
Specification
Results
Give also data on test
pressure, temperature,
pH and concentration
range if necessary
Remarks/
Justification
GLP
(Y/N)
Reliability Reference Official
use only
3.15 Explosive properties
(IIA3.11)
EC Method A14 99.5% Predicted to be
negative based upon
structure
Yes 1 Tremain, S
(2006)
Safepharm
Laboratories
x
3.16 Oxidizing properties
(IIA3.12)
EC Method A17 99.5% Predicted to be
negative based upon
structure
Yes 1 Tremain, S
(2006)
Safepharm
Laboratories
x
3.17 Reactivity towards
container material
(IIA3.13)
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Evaluation by Competent Authorities
MELTING POINT (3.1.1)
EVALUATION BY RAPPORTEUR MEMBER STATE
Date July 2009
Evaluation of applicant’s
justification
A GLP document is always signed. This is not the case.
The reliability of Melting pt.2 has been changed from 2 to 3. No data are
available on the method and on the GLP. Based on a reference book, one can
not say (reliability 2) that the melting point has been determined by a method
comparable to the OECD 102 method.
Two melting points are given pt. 1 and pt. 2. An explanation should be given
why two different melting points are taken up in this report. Only one study is
selected for the final result. The OECD 102 method is preferred and GLP is better
compared to “No data”.
We accept that only the reliable study for melting point should be O’Conner, B
(2006) Safepharm Laboratories Study No 2189/001 should be considered for this
endpoint. The signed copy of this study was submitted in the updated version of
the dossier submitted to the Belgian CA in May 2006
Conclusion The signed document has to be scanned
Acceptability Acceptable after presenting signed document
Remarks None
COMMENTS FROM RAPPORTEUR MEMBER STATE
Date November 2009
Results and discussion
Conclusion OK - Signed document submitted in 2008
Reliability
Acceptability OK
Comments from Industry
Date May 2010
Remarks OK
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Evaluation by Competent Authorities
BOILING POINT (3.1.2)
EVALUATION BY RAPPORTEUR MEMBER STATE
Date July 2009
Evaluation of applicant’s
justification
A GLP document is always signed. This is not the case.
See comment on melting point
Conclusion The signed document has to be scanned
Acceptability Acceptable after presenting signed document
Remarks None
COMMENTS FROM RAPPORTEUR MEMBER STATE
Date November 2009
Results and discussion Deleted unnecessary “1” in table by myself
Conclusion OK - Signed document submitted in 2008
Reliability
Acceptability OK
Remarks
Comments from Industry
Date May 2010
Remarks OK
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Evaluation by Competent Authorities
Bulk density/relative density (3.1.3)
EVALUATION BY RAPPORTEUR MEMBER STATE
Date July 2009
Evaluation of applicant’s
justification
A GLP document is always signed. This is not the case.
The second value 1.665 kg/m3 is 1000 times lower then the first value 1.65 e+03
kg/m3. This has to be checked.
Two bulk/rel. densities are given 1 and 2. An explanation should be given why
two different bulk/rel. densities are taken up in this report. Only one study is
selected for the final result. The OECD 109 method is preferred and GLP is better
compared to “No data”.
Conclusion The right value of rel density has to be checked. The signed document has to be
scanned
We accept that only the reliable study for relative density should be O’Conner, B
(2006) Safepharm Laboratories Study No 2189/001 should be considered for this
endpoint. See comment on melting point
Acceptability Acceptable after check and presenting signed document
Remarks None
COMMENTS FROM RAPPORTEUR MEMBER STATE
Date November 2009
Results and discussion
Conclusion OK - Signed document submitted in 2008
Reliability
Acceptability OK
Comments from Industry
Date May 2010
Remarks OK
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Evaluation by Competent Authorities
VAPOUR PRESSURE (3.2)
EVALUATION BY RAPPORTEUR MEMBER STATE
Date July 2009
Evaluation of applicant’s
justification
A GLP document is always signed. This is not the case.
See comment on melting point
Conclusion The signed document has to be scanned
Acceptability Acceptable after presenting signed document
Remarks None
COMMENTS FROM RAPPORTEUR MEMBER STATE
Date November 2009
Results and discussion Deleted unnecessary “1” in table by myself
Conclusion OK - Signed document submitted in 2008
Reliability
Acceptability OK
Remarks
Comments from Industry
Date May 2010
Remarks OK
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Evaluation by Competent Authorities
Henry’s Law Constant (3.2.1)
EVALUATION BY RAPPORTEUR MEMBER STATE
Date July 2009
Evaluation of applicant’s
justification
Our recalculation comes out a different value compared to the one presented
here.
Conclusion The value of Henry coefficient has to be checked. The values taken for
calculation have to be taken from this database.
The calculation was taken from the OECD SIDS dossier and was not calculated
using the Safepharm reported values for VP and water solubility.New value
based on these numbers included.
Acceptability Not Acceptable
Remarks None
COMMENTS FROM RAPPORTEUR MEMBER STATE
Date November 2009
Results and discussion OK
Conclusion
Reliability
Acceptability OK
Remarks
Comments from Industry
Date May 2010
Remarks OK
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Evaluation by Competent Authorities
Absorption spectra (3.4)
EVALUATION BY RAPPORTEUR MEMBER STATE
Date July 2009
Evaluation of applicant’s
justification
A GLP document is always signed. This is not the case.
See comment on melting point
Conclusion The signed document has to be scanned
Acceptability Acceptable after presenting signed document
Remarks None
COMMENTS FROM RAPPORTEUR MEMBER STATE
Date November 2009
Results and discussion OK
Conclusion OK - Signed document submitted in 2008
Reliability
Acceptability OK
Remarks
Comments from Industry
Date May 2010
Remarks OK
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Evaluation by Competent Authorities
Solublility in water (3.5)
EVALUATION BY RAPPORTEUR MEMBER STATE
Date July 2009
Evaluation of applicant’s
justification
A GLP document is always signed. This is not the case.
From the first column it seems another value of water solubility would have
been given: “water solubility 2”. This is not the case. So “water solubility 2” and
“1” should be removed.
The ranking of ionisation has been studied at pH from 5 to 9 and not at all pH.
Conclusion The signed document has to be scanned
See comment on melting point
Acceptability Acceptable after presenting signed document
Remarks None
COMMENTS FROM RAPPORTEUR MEMBER STATE
Date November 2009
Results and discussion Deleted unnecessary “1” and “Water solubility 2” in table by myself
Conclusion OK after correction that pH has been done from 5 to 9.
Reliability
Acceptability OK
Remarks
Comments from Industry
Date May 2010
Remarks Correction made OK
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Evaluation by Competent Authorities
Dissociation constant (3.6)
EVALUATION BY RAPPORTEUR MEMBER STATE
Date July 2009
Evaluation of applicant’s
justification
A GLP document is always signed. This is not the case.
See comment on melting point
Conclusion The signed document has to be scanned
Acceptability Acceptable after presenting signed document
Remarks None
COMMENTS FROM RAPPORTEUR MEMBER STATE
Date November 2009
Results and discussion OK
Conclusion OK - Signed document submitted in 2008
Reliability
Acceptability OK
Remarks
Comments from Industry
Date May 2010
Remarks OK
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Evaluation by Competent Authorities
Solubility in organic solvents, including the effect of temperature on
solubility (3.7)
EVALUATION BY RAPPORTEUR MEMBER STATE
Date July 2009
Evaluation of applicant’s
justification
The reliability of solubility has been changed from 2 to 3. No data are available
on the method and on the GLP. Based on a reference book, one can not say
(reliability 2) that the solubility has been determined by a method comparable
to the requirements of today. The references of the study date to 1948, 1949.
Therefore the statement that “further physicochemical studies are not
justified” is not accepted.
The units of the 100 g should be checked and corrected also in doc. IIA. Please
don’t use shortcuts of the words.
There is no agreement with doc IIA in case of ethyl acetate and amyl acetate.
Please check.
Conclusion Although the Merck Index is a reference book, the values would be more
reliable with a more recent study following the required guidelines..
The active substance is used as a coating for a facial tissue. The coating is
formulated and applied to the base coat outside the EU. There will be no use of
the active substance in an organic solvent from the proposed biocidal use. The
information provided from the reference book is considered to be sufficient for
determining if any organic solvents used in analytical methods outlined in the
submitted data are valid for the use. The data is not required for risk
assessment purposes so it it therefore considered that the handbook data is
sufficient for the intended purpose and a new study is not scientifically justified
Acceptability Acceptable after major revision
Remarks
COMMENTS FROM RAPPORTEUR MEMBER STATE
Date November 2009
Results and discussion See remark in table. The way how solubility of the compound in different
solvents have been calculated is wrong.
We also not agree with the comment given that a more recent study is not
needed. The requirements in the guiding document are not taking the purpose
of the biocide into account.
Conclusion Not OK
Reliability 4. Not reliable
Acceptability Major revision needed
Remarks
Comments from Industry
Date May 2010
Remarks New GLP study performed and data inserted
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
COMMENTS FROM RAPPORTEUR MEMBER STATE
Date May 2010
Results and discussion The new data are fine. Please remove the first study out of this report. The
study is not using SI units and the transformation industry proposes is not
correct. I mentioned several times for example that it is not correct to equal
2.17 g/100g to 21700 mg/L saturated solution for ether. All these data have to
be removed out of the study.
Conclusion New study is OK, first study has to be removed
Reliability 1
Acceptability Acceptable when first study results are removed
Remarks
Comments from Industry
Date June 2010
Remarks First study removed from table
Comments from Rapporteur Member State
Date June 2010
Remarks OK
COMMENTS FROM INDUSTRY
Date July 2010
Evaluation of rapporteur's
comments
OK
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Evaluation by Competent Authorities
Partition coefficient n-octanol/water (3.9)
EVALUATION BY RAPPORTEUR MEMBER STATE
Date July 2009
Evaluation of applicant’s
justification
A GLP document is always signed. This is not the case.
The second value 0.019 is 100 times higher then the first value 1.75 e-04. This
has to be checked.
Two Pow values are given 1 and 2. An explanation should be given why two
different Pow values are taken up in this report. Only one study is selected for
the final result. The OECD 107 method is preferred and GLP is better compared
to “No GLP”.
Conclusion The right value of log Pow has to be checked. The signed document has to be
scanned
We accept that only the reliable study for relative density should be O’Conner, B
(2006) Safepharm Laboratories Study No 2189/001 should be considered for this
endpoint. See comment on melting point
Acceptability Acceptable after check and presenting signed document
Remarks None
COMMENTS FROM RAPPORTEUR MEMBER STATE
Date November 2009
Results and discussion OK
Conclusion OK - Signed document submitted in 2008
Reliability
Acceptability OK
Remarks
Comments from Industry
Date May 2010
Remarks OK
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Evaluation by Competent Authorities
Thermal stability (3.10)
EVALUATION BY RAPPORTEUR MEMBER STATE
Date July 2009
Evaluation of applicant’s
justification
A GLP document is always signed. This is not the case.
See comment on melting point
Conclusion The signed document has to be scanned
Acceptability Acceptable after presenting signed document
Remarks None
COMMENTS FROM RAPPORTEUR MEMBER STATE
Date November 2009
Results and discussion OK
Conclusion OK - Signed document submitted in 2008
Reliability
Acceptability OK
Comments from Industry
Date May 2010
Remarks OK
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Evaluation by Competent Authorities
Flammability (3.11)
Relative Self-Ignition Temperature
EVALUATION BY RAPPORTEUR MEMBER STATE
Date July 2009
Evaluation of applicant’s
justification
The purity of the active test product is not specified in the document.
A GLP document is always signed. This is not the case.
Conclusion A justification to demonstrate the purity of the used product is needed.
The signed document has to be scanned
The signed copy of this study was submitted in the updated version of the
dossier submitted to the Belgian CA in May 2006
Batch number S504023 was tested for purity in Safepharm Report no.
2189/0002 submitted under endpoint A4.1.
Acceptability Acceptable after justification.
Remarks None
COMMENTS FROM RAPPORTEUR MEMBER STATE
Date November 2009
Results and discussion OK
Conclusion OK
Reliability
Acceptability OK
Comments from Industry
Date May 2010
Remarks OK
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Evaluation by Competent Authorities
Surface tension (3.13)
EVALUATION BY RAPPORTEUR MEMBER STATE
Date July 2009
Evaluation of applicant’s
justification
A GLP document is always signed. This is not the case.
See comment on melting point
Conclusion The signed document has to be scanned
Acceptability Acceptable after presenting signed document
The writing “surface tension 2” has to be deleted. The value “1” next to surface
tension 1 can also be removed.
Remarks None
COMMENTS FROM RAPPORTEUR MEMBER STATE
Date November 2009
Results and discussion Deleted unnecessary “1” and “surface tension 2” in table by myself
Conclusion OK - Signed document submitted in 2008
Reliability
Acceptability OK
Comments from Industry
Date May 2010
Remarks OK
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Evaluation by Competent Authorities
Explosive properties (3.15)
EVALUATION BY RAPPORTEUR MEMBER STATE
Date July 2009
Evaluation of applicant’s
justification
The purity of the active test product is not specified in the document.
A GLP document is always signed. This is not the case.
Conclusion A justification to demonstrate the purity of the used product is needed.
The signed document has to be scanned
See comment on Flammability
Acceptability Acceptable after justification.
Remarks None
COMMENTS FROM RAPPORTEUR MEMBER STATE
Date November 2009
Results and discussion OK
Conclusion OK - Signed document submitted in 2008
Reliability
Acceptability OK
Comments from Industry
Date May 2010
Remarks OK
Kimberly-Clark Europe Ltd Citric Acid Dec. 2014
Document IIIA
Evaluation by Competent Authorities
Oxidizing properties (3.16)
EVALUATION BY RAPPORTEUR MEMBER STATE
Date July 2009
Evaluation of applicant’s
justification
The purity of the active test product is not specified in the document.
A GLP document is always signed. This is not the case.
Conclusion A justification to demonstrate the purity of the used product is needed.
The signed document has to be scanned
See comment on Flammability
Acceptability Acceptable after justification.
Remarks None
COMMENTS FROM RAPPORTEUR MEMBER STATE
Date November 2009
Results and discussion OK
Conclusion OK - Signed document submitted in 2008
Reliability
Acceptability OK
Comments from Industry
Date May 2010
Remarks OK