Method Purity/ Results Remarks/ GLP Reliability Reference

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


Document IIIA


Subsection

(Annex Point)

Method Purity/

Specification

Results




range if necessary

Remarks/

Justification

GLP

(Y/N)


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









No

data

4 CRC Handbook

of Chemistry

and Physics,

70th

Edn

x


Document IIIA


Subsection

(Annex Point)

Method Purity/

Specification

Results




range if necessary

Remarks/

Justification

GLP

(Y/N)


use only


considered that the

physicochemical






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


Document IIIA


Subsection

(Annex Point)

Method Purity/

Specification

Results




range if necessary

Remarks/

Justification

GLP

(Y/N)


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


Document IIIA


Subsection

(Annex Point)

Method Purity/

Specification

Results




range if necessary

Remarks/

Justification

GLP

(Y/N)


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










considered that the

physicochemical


No

data

2 Serjeant EP,

Dempsey B.

Ionisation

constants of

organic acids in

aqueous

solution. IUPAC

Chemical Data

Series – No. 23.

Pergamon

Press


Document IIIA


Subsection

(Annex Point)

Method Purity/

Specification

Results




range if necessary

Remarks/

Justification

GLP

(Y/N)


use only





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.


Document IIIA


Subsection

(Annex Point)

Method Purity/

Specification

Results




range if necessary

Remarks/

Justification

GLP

(Y/N)


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


Document IIIA


Subsection

(Annex Point)

Method Purity/

Specification

Results




range if necessary

Remarks/

Justification

GLP

(Y/N)


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


Document IIIA


Subsection

(Annex Point)

Method Purity/

Specification

Results




range if necessary

Remarks/

Justification

GLP

(Y/N)


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)


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


Document IIIA


BOILING POINT (3.1.2)


Date July 2009


justification


See comment on melting point



Remarks None


Date November 2009

Results and discussion Deleted unnecessary “1” in table by myself


Reliability

Acceptability OK

Remarks


Date May 2010

Remarks OK


Document IIIA


Bulk density/relative density (3.1.3)


Date July 2009


justification


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


endpoint. See comment on melting point

Acceptability Acceptable after check and presenting signed document

Remarks None


Date November 2009

Results and discussion


Reliability

Acceptability OK


Date May 2010

Remarks OK


Document IIIA


VAPOUR PRESSURE (3.2)


Date July 2009


justification





Remarks None


Date November 2009

Results and discussion Deleted unnecessary “1” in table by myself


Reliability

Acceptability OK

Remarks


Date May 2010

Remarks OK


Document IIIA


Henry’s Law Constant (3.2.1)


Date July 2009


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


Date November 2009

Results and discussion OK

Conclusion

Reliability

Acceptability OK

Remarks


Date May 2010

Remarks OK


Document IIIA


Absorption spectra (3.4)


Date July 2009


justification





Remarks None


Date November 2009



Reliability

Acceptability OK

Remarks


Date May 2010

Remarks OK


Document IIIA


Solublility in water (3.5)


Date July 2009


justification


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.




Remarks None


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


Date May 2010

Remarks Correction made OK


Document IIIA


Dissociation constant (3.6)


Date July 2009


justification





Remarks None


Date November 2009



Reliability

Acceptability OK

Remarks


Date May 2010

Remarks OK


Document IIIA


Solubility in organic solvents, including the effect of temperature on

solubility (3.7)


Date July 2009


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


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


Date May 2010

Remarks New GLP study performed and data inserted


Document IIIA


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


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


Document IIIA


Partition coefficient n-octanol/water (3.9)


Date July 2009


justification


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


endpoint. See comment on melting point

Acceptability Acceptable after check and presenting signed document

Remarks None


Date November 2009



Reliability

Acceptability OK

Remarks


Date May 2010

Remarks OK


Document IIIA


Thermal stability (3.10)


Date July 2009


justification





Remarks None


Date November 2009



Reliability

Acceptability OK


Date May 2010

Remarks OK


Document IIIA


Flammability (3.11)

Relative Self-Ignition Temperature


Date July 2009


justification

The purity of the active test product is not specified in the document.


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


Date November 2009


Conclusion OK

Reliability

Acceptability OK


Date May 2010

Remarks OK


Document IIIA


Surface tension (3.13)


Date July 2009


justification





The writing “surface tension 2” has to be deleted. The value “1” next to surface

tension 1 can also be removed.

Remarks None


Date November 2009

Results and discussion Deleted unnecessary “1” and “surface tension 2” in table by myself


Reliability

Acceptability OK


Date May 2010

Remarks OK


Document IIIA


Explosive properties (3.15)


Date July 2009


justification





See comment on Flammability


Remarks None


Date November 2009



Reliability

Acceptability OK


Date May 2010

Remarks OK


Document IIIA


Oxidizing properties (3.16)


Date July 2009


justification





See comment on Flammability


Remarks None


Date November 2009



Reliability

Acceptability OK


Date May 2010

Remarks OK

Documents

Method Purity/ Results Remarks/ GLP Reliability Reference