REPORT SANITIZED DETERMINATION

OF THE WATER SOLUBILITY

OF 1,1,3,3-TETRAMETHYLBUTYL PEROXYPIVALATE .-.--____ NOTOX **Projec**

**~**

) NOTOX **Substan**

**,** -

·· · Page

1 of 13

·1,1,3,3-TETRAMETHYLBUTYLPEROXYPIVALATECONFIDENTIALITYSTATEMENTNOTOX'-----/.ThisreportcontainstheunpublishedresultsofresearchsponsoredbyAkzoNobelChemicalsB.V..Reproduction,issueordisclosuretothirdpartiesinanyformisnotpermittedwithoutpriorwrittenauthorizationfromthesponsor.•Page2-1,1,3,3-TETRAMETHYLBUTYL PEROXYPIVALATE STATEMENT

OF GLP COMPLIANCE NOTOX B.V., 's-Hertogenbosch,

The Netherlands The study described

in this report

has been correctly reported

and was conducted

in compliance

with the most recent edition

of: The OECD Principles

of Good Laboratory Practice which
are essentially

in conformity

with: The United States Food and Drug Administration.

Title

21 Code

of Federal Regulations

Part
58. The United States Environmental Protection Agency (FIFRA). Title

40 Code of Federal Regulations

Part 160. The United States Environmental Protection Agency (TSCA). Title

40 Code

of Federal Regulations

Part 792. Study Director Ir. M.J.C. Brekelmans **(~·;;·~~,**

Management J.A.M.W.

van Helvoirt **(i'!ea!I"Of-Gil~y**

.. """'\ Date: Page

3( 1,1,3,3-TETRAMETHYLBUTYL PEROXYPIVALATE QUALITY ASSURANCE STATEMENT

**,,r-~** NOT OX Project,_ **~/** NOTOX B.V., 's-Hertogenbosch,

The Netherlands This report

was audited

by the NOTOX Quality Assurance

Unit

to ensure that the methods

and results accurately reflect

the raw data. The dates

of Quality Assurance inspections

and audits

are given below. During

the on-site inspections procedures applicable

to this type

of study were inspected. DATES

OF QAU INSPECTIONS/AUDITS on-site inspection

(s) 15 July 1997 protocol inspection

(s) 22 May 1997 report audit

(s) 26 August
1997 Head

of Quality Assurance C.J. Mitchell
B.Sc. ··-------

· Page

4 REPORTING
DATES 15 July 1997 22 May 1997 26 August
19971,1,3,3-TETRAMETHYLBUTYL PEROXYPIVALATE SUMMARY

/
.. **-----~** NOTOX Projec( 'o,.,______:f The determination

of the water solubility

was based

on the following guidelines: OECD guideline

for testing

of chemicals

no. 105: 'Water Solubility", Adopted
July
27, 1995. EEC Directive
92/69 EEC, Part

A, Methods

for the determination

of physico· chemical properties,

A.6: "Water solubility'.

EEC Publication

no. L383, December
1992. Since 1,1,3,3-TETRAMETHYLBUTYL PEROXYPIVALATE

is

a liquid,

the column elution method

is not applicable, Therefore,

the flask method

was used for the determination

of the water solubility

of 1,1,3,3-TETRAMETHYLBUTYL PEROXYPIVALATE. The water solubility

of 1,1,3,3-TETRAMETHYLBUTYL PEROXYPIVALATE

at 19.5

± l.O'C

is

< 0.6 mg/1.

· Page

5

·

### ··- ···- ··- 

# ------------------, 

# 1,1,3,3-TETRAMETHYLBUTYL PEROXYPIVALATE PREFACE Sponsor Study Monitor Testing Facility Study Director Study plan TEST SUBSTANCE Identification Chemical

name CAS No. Description Batch Purity Test substance storage Stability
under storage conditions Expiry date

AKZO Nobel Chemicals

B.V. P.O. Box 247 3800

AE AMERSFOORT The Netherlands **~** 

# (_

.



# ) 

# ------'"'"""-------- NOTOX B.V. Hambakenwetering

3 5231

DD 's-Hertogenbosch The Netherlands 

# c

--- ____________

_) Start:

01 July 1997 Completed:

15 August
1997 1,1,3,3-TETRAMETHYLBUTYL PEROXYPlVALATE Propaneperoxic

acid, 2,2-dimethyl-,1,1,3,3- tetramethylbutyl

ester (9CI) 22288-41-4 

# < nJourless liquid re-e-GepH·rtcafe

of Analysis In freezer

in the dark Stable Not indicated The sponsor

is responsible

for the completeness

and GLP Compliance

of all test substance

data. PURPOSE

AND PRINCIPLE The purpose

of the study
was

to evaluate

the solubility

of the test substance

in water. To determine

the water solubility

of the test substance,

two different methods

can

be used

: The column elution method

for solubilities<

10·• g/1. - The flask method

for **solubilities~**



# 10-

2 

# g/1. Page

6

-1,1,3,3-TETRAMETHYLBUTYLPEROXYPIVALATENOTOXProject")GUIDELINESThestudyproceduredescribedinthisreportwasbasedonthefollowingguidelines:OrganizationforEconomicCo-operationandDevelopment(OECD},OECDguidelinefortestingof chemicalsno.105:'WaterSolubility',AdoptedJuly27,1995.EuropeanEconomicCommunity(EEC),EEC-Directive92/69EEC,PartA,Methodsforthedeterminationofphysico-chemicalproperties,A.6:'Watersolubility'.EECPublicationno.L383,December1992.ARCHIVINGNOTOXB.V.willarchivethefollowingdataforatleast10years:protocol,report,testsubstancereferencesampleandrawdata.TESTSYSTEMANDRATIONALEDoubledistilledwater.Thetestsystemisrecognizedbytheinternationalguidelines(EEC,OECD).VALIDATIONOFTHETESTPROCEDUREThetestmethodasoutlinedinthisreportisvalidatedperiodically,using4-nitrophenoland2,4-dichlorophenoxyaceticacidalternately.TheresultsareinaccordancewiththecriteriaofOECDGuidelineNo.105"Watersolubility'(1995).-Page7·

# 1,1,3,3-TETRAMETHYLBUTYL PEROXYPIVALATE PERFORMANCE

OF THE TEST Preliminary

test



# (~~ NOTOX 

# Proj~J 30 ml test substance

was stirred
with

50 ml double distilled
water

in

a climate
room

at approximately

20'C 

# for

2 

# days. Main study Since 1,1,3,3-TETRAMETHYLBUTYL PERDXYPIVALATE

is

a liquid,

the column elution method

is not applicable, Therefore,

the flask method

was used for the determination

of the water solubility

of 1,1,3,3-TETRAMETHYLBUTYL PEROXYPIVALATE. Approximately

440



# mg (i.e approximately

0.5 ml)
of the test substance

was weighed
into each

of three Erlenmeyer flasks.

To each flask,

100

ml double distilled
water
was added.

The flasks were securely closed

and placed

on

a magnetic stirring device.

The content

of each flask
was stirred

for 24,
48 

# or 72 

# hours

at 19.5

± 

# 1.0'C. Preparation

of

a blank: 100

ml double distilled
water
was stirred

for
72 

# hours

at 19.5

± 

# 1.0'C. 

# The blank solution

was pretreated

and analysed identically

as the water samples
from the main study. pH measurements: Each clear water sample from the main study
was diluted

in

a 

# 9:1 (v/v) 

# ratio with

a 0.1
M NaC1 solution,
prior

to pH measurement. - Page

8

### ···-- 

# ···------------, 

# 1,1,3,3-TETRAMETHYLBUTYL PEROXYPIVALATE METHOD

OF CHEMICAL ANALYSIS The concentration

of 1,1,3,3-TETRAMETHYLBUTYL PEROXYPIVALATE

was determined

using

a High Performance.Liquid Chromatographic

method. 1,1,3,3·TETRAMETHYLBUTYL PEROXYPIVALATE

is

a liquid with

a lower density than water. Samples

of the water phase were taken using

a volume pipette. To avoid contamination,

the outside
part

of the volume pipette which came in contact
with the sample,

was dried thoroughly
before emptying

the pipette

in the centrifugation

tube. Sample pretreatment preliminary

test 5 

# ml was taken from the water phase

and centrifuged

(5 

# min, 3500

g, 20°C). Then,

2.5

ml was taken from the centrifuged

water phase

and centrifuged

a second time (same conditions). Thereafter

1.0

ml was taken

and this water sample

was centrifuged

a third time (same conditions).

The two and three times centrifuged

water samples
were analysed undiluted. Sample pretreatment

main study From each Erlenmeyer
flask, duplicate samples
were taken

and centrifuged five successive

times

at 41700

g and 20°C for

5 minutes.

The five times centrifuged

water samples
were diluted

by

a 

# factor

2 

# with acetonitrile prior

to analysis. Analytical
method Column Mobile phase Flow Detection Injection volume Calibration solutions LiChrospher

100 

# RP-8,

125

x 

# 4 (I.D.)

mm; d =5 **~m** 

# (Merck, Darmstadt, Germany) 68/40 

# {v/v) acetonitrile (HPLC-grade,
Labscan Limited

Co., Dublin, Ireland)/Milli·Q

water (Mi1lipore
Corp., Bedford,

MA, USA) 1 

# ml/min UV at !..= 

# 205



# nm 100
**~1** 

# From two stock solutions

with concentrations

between

0.8 

# and 1.1 g/1
of 1,1,3,3-TETRAMETHYLBUTYL PEROXYPIVALATE

in acetonitrile, dilutions

in mobile phase were prepared

for calibration purposes. · Page

9

.1,1,3,3-TETRAMETHYLBUTYLPEROXYPIVALATENOTOXDATAHANDLINGGeneraln1.Mean:X=1,LXin1=12.Maximumdeviation:[(highestvalue-lowestvalue)/mean]x100%3.Limitofdetection:Thelimitofdetectionisdefinedastheabsoluteamountof1,1,3,3·TETRAMETHYLBUTYLPEROXYPIVALATEatwhichthepeakheightisthreetimesthenoiselevel(ratiosignaltonoiseisthree(SIN=3)).Basedonthenoiseandsignalmeasurement,thelimitofdetectionwascalculated.Calibration1.Inthechromatogramofthestandardsolution,onesmallpeakandonelargepeakwereobserved.Frominformationsuppliedbythesponsor,itwasunderstoodthatthelargepeakderivesfromthemajorcomponentof1,1,3,3-TETRAMETHYLBUTYLPEROXYPIVALATEwhereasthesmallpeakderivesfromanimpurityinthetestsubstance.QuantitativeanalyseswerebasedonthelargestpeakintheHPLCchromatogramof1,1,3,3-TETRAMETHYLBUTYLPEROXYPIVALATE.2.Response:R=Peakareatestsubstance[units]Responsefactor:RF=Rc[units•1/mg]Rresponsecalibrationsolution[units]Cconcentrationoftestsubstanceincalibrationsolution[mg/1]Forthemeasurementsofthepreliminarytest,themeanRFwascalculatedfrom4RFvalues.2.Calibrationcurve:Theresponsewascorrelatedwiththeconcentrationtestsubstance,usinglinearregressionanalysis(leastsquaresmethod).R=a•C+bRresponsecalibrationsolution[units]C=concentrationoftestsubstanceincalibrationsolution[mg/1]aslope[units'l/mg]b=intercept[units]Forthemeasurementsofthemainstudy,acalibrationcurvewasconstructedfromsixdatapoints.·Page101,1,3,3-TETRAMETHYLBUTYL PEROXYPIVALATE Samples 1. Concentration 1,1,3,3-TETRAMETHYLBUTYL PEROXYPIVALATE

in samples: or

R

' d C

;

·

·

·

·

·

·
·

·

·

·

·

·

·

·

·

[ mg 11] RF (R·b)

•
d c; ·········--·--·

(mg/1] a R

; response sample (units] d
**~** dilution factor Rf; mean response factor calibration solutions [units'l/mg] a

; slope [units'l/mg] b = intercept (units] 2. The water solubility

of

a test substance

is specified

by the saturation

mass concentration

of the test substance

in water

at

a given temperature

and

is expressed

in g/1. 3. Because

the water solubility

of 1,1,3,3-TETRAMETHYLBUTYL PEROXYPIVALATE

was<

100 g/1,

no correction

for the mass fraction

of the test substance

in the water phase
was made. Page

111,1,3,3-TETRAMETHYLBUTYLPEROXYPIVALATERESULTSPreliminarytestNOTOXProjeetAfterboththesecondandthirdcentrifugationstep(5min.,3500g),theconcentration1,1,3,3-TETRAMETHYLBUTYLPEROXYPIVALATEinthewaterphasewasdeterminedtobe8mg/1.Becausethetestsubstanceisacolourlessliquid,thereweresomedoubtsifallundissolvedtestsubstancewasseparatedfromthewaterphase.Therefore,itwasdecidedtoregardthecentrifugationstepscriticallyduringthemainstudy.Ahigherrelativecentr1fuga1fieldwaschosen(Smin,41700g)foreachcentrifugationstepduringthemainstudyandcentrifugationwasrepeateduntilthetestsubstanceconcentrationinthewatersampleshadbecomestable.MainstudySince1,1,3,3·TETRAMETHYLBUTYLPEROXYPIVALATEisaliquid,thecolumnelutionmethodisnotapplicable,Therefore,theflaskmethodwasusedforthedeterminationofthewatersolubilityof1,1,3,3-TETRAMETHYLBUTYLPEROXYPIVALATE.Thecalibrationcurve(0.25·1.49mg/1;sixconcentrations)hadacorrelationcoefficientof0.991andarelativestandarddeviationinresponseof8.5%.Eachcalibrationsolutionwasmeasuredinduplicate.Forcalibrationsolutions0.50mg/1,thedeviationbetweenthetworesponseswasbetween6and18%whilethedeviationbetweenthetworesponseswas48%forthe0.25mg/1calibrationsolution.Duplicateanalysesofthepretreatedwatersamplesshoweddeviationsinresponsebetween24and200%.Basedonalltheseresults,itwasconcludedthatthemethodofchemicalanalysisisnotsatisfactoryatthislowconcentrationlevel.Consideringtheresponsesofthepretreatedwatersamples,itwasfoundthatthesewereallbelowtheresponsesofthe0.25mg/1calibrationsolution.Thesignaltonoiseratiowas<3inthechromatogramsofthe0.25mgllcalibrationsolution,i.ebelowthelimitofdetection.Thereforeitwasconcludedthatthetestsubstanceconcentrationsinthepretreatedwatersampleswereallbelowthelimitofdetection.Thelimitofdetectionwasdeterminedfromtwochromatogramsofthe0.50mg/1calibrationsolution.Thenoiselevel(meanheight)wasdeterminedtobe4mm(attenuationoftheintegrationunit:2).Inthesamechromatograms,themeanpeakheightofthetestsubstancepeakwas21mm.Therefore,thelimitofdetectionwasdeterminedtobe0.3mg/1ataninjectionvolumeof100(i.e.31ngabsolute).Becausethewatersamplesweredilutedbyafactortwo,thewatersolubilitywascalculatedtobe<0.6mg/1.ThepHofthewatersamplesfromthemainstudyweredeterminedtobe·>---Inconclusion,thewatersolubilityof1,1,3,3-TETRAMETHYLBUTYLPEROXYPIVALATEat19.5±1.0"Cis<0.6mg/1.Page12/"-·...__NOTOXProject-------AKZONOBELCertificateofAnalysis.ICS-331.'.,name·rrade'niime·aatii"li'hurrtber:1,1,§i-tetramethylbutylperoxypivalale_;__Trigonox425(.:_..·._.·,':'·'-------'.' '.-·{,,../\--.·Test..-.-·'·::'·...··(Filiicod!).;_;·..'·_·-:'>;..\''//Page13-CentralResearch-------------------,\\.,---,.."•.............................-----------'........................