2.113**r::--::--:----::---:-----:--------~----_** ..___________,

15.00 20.00 25.00 30.00 35.00 40
..00 

### Solution of3MBA (100 mg/L) 

### 22-Feb-200 14711b031 2: Diode Array Range: 1.443e+1 1.08+1


# / Range: 1.966e+1 1.oe+1 15.73

10.00 15.00 30.00 

### [1] Water+

### test Item (LC·MS sample -2) 14711b024_' 2: DIode Array Range: 2.506e+1

7.**~** 5.
0.:'0**~1'h1""--- ·~rlh~~~~~~~~~~~~~~~~~~~~~ThM**  30.00 35.00 40.00 

# IIf

# '11\ Solution oftest item (100 mg/L) 22.Feb.200 14711b029 2: Diode Array Range: 1.298e+1 Test item 

# I 1.0e+1 7.

### ~ 5. 25.72 2. O. "-r....,...,J,
........."TT"1.."...,...,....,TTT'T"T"TTTT.,........,.....,.,..,.,......,......TTT".......-,-rrrrrrr-r"..,.,,..,..,...,l"""T'1rrr"'1'"T"M..,.,.,.,....,.,...,..,.T1 TIme 6.00 10.00

7.**~** 5.

O. 20.00 25.00 30.00 

## seA 2: DiodeArray 22·Feb-200

10.00 15.00 20.00 25.00 Fig. 15-1 UV chromatograms of LC-MS analysis for test solution (205 - 300nm) (LC·MS sample -2, qualitative analysis ofwater-soluble converted products), 

## -82­ 7.

2. 

## o. S. 0



### 945

### j[2] Sludge 

### +test Item**(LC~MS** 

### sample**~~** i14711b025 

### 22-Feb·200 2: Diode Array Range: 2.667e+1

## ------------------~~--------**~~nT~~~~~~~~Tn~~~~~~nT~~~Tn~~nTi~** a.GO 10.00 15.00 20.00 

### [3] Sludge 

### +test Item (LC·MS sample -2) 14711b026 1.0e+1 

## :it 5. 2. 

## a. . 25.00 3MID 35.00 40.00 

### 22·Feb·200

2: Diode Array Range: 2.664e+1**~~~MT~~~~~~MT~~~~~~~~~~~~~~~nma** .00 10.00 1 . '20.00 25.00 30.00 

### [4) Sludge 

### +

## test Item (LC·MS sample -2) 14711b027 1.0&+1 7 2.57

### ~ 5. 2. 0
.. 5.00. 10.00 15.00 

### [5J Control blank (LC-MS sample -2) 14711b028 1.0e+1 20.00 25.00 .00 35.00 40.00 

### 22-Feb
..20

2: DiodeArray Range: 2.7241+1

2: Diode Array Range: 2.676e+1

7.

2.

5;00 10.00 15.00 20.00 25.00 30.00 55.0.0 

## l't'll\ 

# 2a-elL 1, 12. Fig. 15-2 UV chromatograms of LC-MS analysis for test solution (205 - 300nm) (LC-MS sample -2, qualitative analysis ofwater-soluble converted products). 

## -83­ 946

### olution oftest item (100 mg/L) 22·Feb·200 14711b029 1: Scan ES+ TIC Test Item 

# 2U2; 1.50e8

5.00 10.00 15.00 

### Solution of3MBA (100 mg/L) 20.00 14711b031 1: Scan ES+ TIC 1.5Oea

3MBA 

# I :13.16 5.00 10.00 15.00 

### olution of SBA (100 mglL) 20.00 25.00 

### 3000 14111b030 1: ScanES+ TIC 1.50e8

S8A 

# I
16.78 5. 10.00 15.00 20.00 

### [1] Water 

### +test item (Le-MS sample -2) 25.00 30.00 14711b024_1

Test item

Fig. 16-1 Total ion chromatograms of LC-MS analysis for test solution (LC-MS sample -2, qualitative analysis ofwater-soluble converted**product~4** 7 

## -84­

### [2) Sludge +

### test item (LC·MS sample -2) 14711b025

1.66 A 

# \ o Testitem 

# 8 C \E / 22-Feb-20071,' 1: Scan ES+ TIC 1.5086 

# \ / af I

### T~~~~~8~.50~~~~~~~~~~~~~~~~~~~~:; ..,. I TJme

,........___-O50,;.;.0=-0 10.00 15.00 20.00 35.00 40;00 

### [3] Sludge + 

### test Item (LC-MS sample -2) 22·Feb·200 14711b026 1: Scan ES+

A 1.10 

# \

5.00 10.00 15.00 20.00 25,00 

### [6] Control blank (LC.MS sample .2) as.1<1 30.00 TIC 1.60ea

1: Scan ES+ TIC i.50eS

14711b02S 1: Scan ES+ 

### nc 1.50e8

1.88 33.18 20.00 25;00 

### ao.OO 35.00 

# M,'TaYlA.K,' Fig. 16·2 Total ion chromatograms of LC-MS analysis for test solution (LC-MS sample -2. qualitative analysis ofwater-soluble converted products). 

## -85­ 948

### [3] Sludge 

### +test item (LC-MS sample ·2) 14711b02e 2.67 6.**.~** 

## o.

14711b026 1.68 

## eo UV chromatogram (205

- 300 nm)

5.00 10.00 Total ion chromatogram A 

# \11.64 15.00 20.00 25.00 30.00 

### 22-Feb-200 2: Diode Array Range: 2.664e+1

33.0$::-_--,

35.00 40.00 1: Scan ES+ TIC 2.68e7**-~~TM~~~nT~~~~~~~~MT~~~~~~~MT~~~nme** 5. 10.00 15.00 .00 

### [3] Sludge 

### +

## test item (LC·MS sample .2) 14111b026 462 (8.539) Cm (452:4n.( 438:451+480:492)x1.5OO) 1 221 

### m

14711b02S 915 (18.912) 

### em (901:922-(885:893+931 :936)x1.500) 1 

### m 25.m

ill 600 BOO 1 1200 30.00 35.00 40.00 

### 22·Feb-20l> 1:ScatI ES+ 8.22e6 Mass spectrum ofpeak A

1::ScanES+ 1;81e5**~~!\Im** ofpeakB

1400 Fig. 17-1 Mass spectra ofwater-soluble converted products (LC-MS sample -2, sludge 

### + test item, vessel [3]). 

## -86­ 949Mass spectrum ofpeak E 14711b0261207 (22.309) Cm (1202:1213-(1196:1198+1219:1224)xl.500) 1: Scan ES+ 10 460 8.0785

Fig. 17-2 Mass spectra ofwater-soluble converted products (LC-MS sample -2, sludge
... test item, vessel [3]). 

### 13] Sludge +

### test item (LC-MS sample -2) 14711b026 946 (17.465) Cm (942:954-(931 :938+959:968)Xl .500) 1**~1**



# .**~**

1 458

423 14711b026 1168 (21.958) Om (1174: 1194-(1166:1171+1196:1201)x1.500) 1: Sean ES+ 3.82e5 Mass spectrum ofpeak D

## 22.Feb_200~ 1; Scan ESt

## a.56e5 Mass spectrum ofpeak C .



## -87­ 950

### [2] Sludge 

### + test item (LC-MS sample

## -=2)**22-Feb~200 14711bO,~~**  8 A 

## \ 9,50 Total ion chromatogram 1: Scan ES+ TIC 2.72e7**.~** 

# 11 5.00 10.00 15.00 20.00 25.00 30.00 35.00 40.00 14711b025 1: Scan ES+ 8·50 m/z

## 5~~~ 2.18

- 0

# "A
... 0

## roo 0., ,-,,0 

# t

"1 0 0 " , '0 00'" ",
.. ",. 0 0 0 , 0 0 " , 0
.... 0
.. ,' 0'''" 0
.. , .... , 5.00 10.00 15.00 20.00 25.00 30.00 35.00 40,00 14711b025 1: Scan ES+ 1j 3.<41 m/z

### = 221

# ~J. 0

## A,
.. 0
.. 0
.. , ..

# !., 0 0
.. ,. .. 0
.. 0

# :or 0 0 , 0 0
.. , .. 0 ., 0 0 0 0
.. 0
.. , ' , ,
.... 0 0 ,. , , 0
.. 0
.. ,'.­ 5.00 '10.00 15.00 20.00 25.00 30.00 35.00 4000 14711b025 1: Scan ES+ 

# 1J**~ ~=**  

# J,

0
... , 0
.. "
......

# 1.,
......'
..,'
0 0 0 10 , , ., , .. , , ' , "
.. " 0 ,. 0
.. , .. 0 0 ,
.. 0 0 , 0 0 0 0 ,. " 0 ,'
..... 5.00 10.00 15.00 20.00 25;00 30;00 35.00 40.00 14711b025 1: Scan ES+ 100 Ut aa.14 mlz =281



# -J .""'1"" 0

# ,1.""~,, " ,,,..,. 0 "" o",! _0' .",,.,

# M.,...l,pi!f'¥~**~** 5;00 10.00 15.00 20.00 2s.oo 30.00 35.00 40,00 14711b025 1: Scan ES-+ 1.81 2.27.5 

# 11 '1' mlz 

### =321



# .." 1", 000

# "I\'~,0
..

# ,~'-1"''''' 0

# 1~

# ....,**""''''~\i4!,** If
....oM,

# ~..I~I**".~** 'I'" 0' , 5.00 10.00 15.0() 20.00 25.oo30J)!) 35.00 40.00 

# ;5.... ,...**'~,=E:;'**

:100..,
.. 0' ,,,, 0"

# o"'~'~, 0'0"

# "t.

0 0"0""" ,"0 .,' 0

# "1'" 0,0 0

# ~ 0 0'"

# ,,:.47 ,n"'" 5.00 10.00 1'5.00 20.00 25.00 30.00 35.00 40.00

, 1: Scan ES+ m/z =361 1.16



### Fig. 17-3 Mass spectra ofwater-soluble converted products (LC-MS sample -2, sludge 

### + test item, vessel [2]. mass chromatograms). 

## -88­ 951

# ----- [2] Sludge 

### +test item (LC-MS sample .2) 22·Feb·200 14711b025 Total ion cnromatooram 1: Scan ES+

5.00

11.50 '# 1.1& 1.66

­ TIC 2.ne7 

# \ B A 33.12

8.50

10.00 15.00 25.00 30.00 35.00 40.00 1: Scan ES+

mlz

## =221 1.48e6

5.00 10.00 16.00 20,00 25.00 30.00 36.00 40.00 147110025 1; Scan ES+ 1**~** mlz 

### = 239 1.5486 .'# 11.82 1.79

5.00 10.00 15.00 20.00 26;00 30.00 35.00 40.00 14711b025 1: Scan ES+ . 1 17.<18 mlz

# = 323 7.26$5 22,31 

# .,.
6.0 10.00 15.00 20.00 25.00 30.00 35.00 40,00 14111b025 1: Scan ES+ 174 m/z

# = 341 1 7.G485

'if.
5.00 15.00 25.00 30.00 35.00 40.00 14711b025 1: Scan ES+ 1 17.4& mlz::: S63 4.46e

5.00 10.00 15.00 20.00 25.00 30;00 

### 36.00 40.00 14711b025 1: Scan ES+**t7J~4** mlz

# =379 1.41e5 

# .,. us 39.41) 5.00 10.00 15.00 20.00 25.00 

# !'t'll\ lao'

# ? . 2.1.2. 

# h**.-rq~k,\** Fig. 17-4 Mass spectra ofwater-soluble converted products (LC-MS sample -2, sludge + test item, vessel [2}. mass chromatograms). 

## -89­ 1



### 9527 

### [2] Sludge 

### +test Item (LC-MS sample -2) 

### 22-Feb-200 14711b025
. 1.66 Talal Ion chromatogram 1: Scan ES+ TIC 2.72e7 A B 

# \ 3$..12**.~** 6.50 5.00 10.00 15.00 20.00 25.00 30.00 35.00 40.00 j14711bOZ5 1: Scan ES+ 16.111 m/z '" 321 1.81 

# ! ' 2.27e5 220t**~** 5JlO 10.00 15.00 

### :mOO 15.00 30.00 35.00 40.00 14711b025 1: Scan ES+ 21.98 1 mlz '" 42$ 

### 4.02e5**~** M.1. 5.00 10.00 15.00 20.00 25.00 30:00 35.00 40.00 14111bG25 1: ScanES+



### Fig. 17-5 Mass spectra afwater-soluble converted products (LC-MS sample -2. sludge + test item. vessel [21. mass chromatograms). 

### 953 

## -90­ 1

5.00 35.00 

## I Lf11\ 2U18 m/z =441 4.66e5 if. 84 5.00 10.00 15.00 20.00 25.00 

### 30.00 35.00 40.00 14711b025 1: Scan ES+ 21.81 m/z =456 7.57e5 'tit

6.00 10.00 20.00 25.00 40.00 14711.b025 1; Scan ES+ 21.98**mtz=~** 1 2.46eS

'tit aM 5.00 10.00 15.00 

### .20:00 30.00 35.00 40.00 14711b025 1: ScanES+ 21.$& mtz ;::479 1.8185[2] Sludge 

### +test item (LC-MS sample 

### -2) 14711b025
. 1.66 Total Ion chromatogram A 

# \ 8.50 5.00 10.00 15.00 20.00 14111b025 1

5.00 10.00 15.00 20.00 14711b025 1

15.00 20.00 14711b025 1

5
..00 10.00 15.00 20.00 14711b025 1

5.00 

## ie.oo 16.00 20.00 14711b02& 1

5.00 10.00 15.00 20.00 14711b02S 1 26.00 30.00

25.00 30.00

25.78

25.00 

### 30.00

2UO 22-Feb-200 1: Scan ES+ TIC 2.72e7

35.00 40.00 1: ScanES+ 7.2565

35.00 40.00 1:ScanES+



### mIz=42& 9.7885

35.00 40.00 1: Scan ES+

mlz= 1.3586 17••' mlz=323

26.00 30.00 36;0040.00 1: Scan ES+

m/z =480 1.2Se6

26.00 

### 30.00 3ttOO 40.00 1: Scan ES+



### mlz =-465 5.78e5

25.00 SO.OO 35.00 40.00 1: Scan ES+

m/z =481 2.SSe5

5.00 10.00 15.00 20.00 26.00 SO.OO 

# I**~f]** 

## 1 \ 

## Mo7, )..., 12.. Fig. 17-6 Mass spectra ofwater-soluble converted products (LC-MS sample 

### -2. sludge + test item, vessel 

### [21. mass chromatograms). 

## -91­ 954

## 1 [3] Sludge 

## +test Item (LC·MS sample -2) 22-Feb-200 14711b026

# ~S4 \7.{ 

# \.1 2578 38,06

--.......II.M.I.".,....,.. lu..
.**..-~** Total ion chromatogram Test item 1: Scan E5+­ 1M 

### BeE TIC A D 33,14 26897 

# I
a# 

# 1j 5.00 10,00 15.00 20.00 25.00 30.00 3500 40,00 14111b026 , 1: Scan ES+

# 8~'52**m/Z6~3!;~** 2.18
# ..

# l,
... OJ'"

# ",~" ""''''"" ",
.. , 1" "'"' .• ''' 

### 'j'
.. .,,,,,,,,.. r....'
.. ,,' 5.00 10.00 15.00 20.00 25.00 30.00 35.00 40.00 14'l11b026 1: Scan ES+ 

# 1:1 mlz ::

# 221 8.54 

# "J., AI' "'t'
..

# ",t"""
..,',
..

# ,~r",,, "'1''' ",
.. ,""""",,,,, ,...." ,
..,".'" 5.00 10.00 15.00 20.00 25.00 SO.OO 35.00 40.00 14711b026 1: Scan ES+ 

# 1:) 8.52 m/z::' 

# j ,, '" ',',,,.,,,,

# ,!. j , , , , , , • , , , ' , , ,

# t·,,,,',,.,,,,,,,,,,,'.,.".,.,.,,,,',,,,,,,•,"',.. 5.00 10.00 15.00 20.00 25.00 30.00 35.00 40.00 14711b026 1; Scan E8+ 

## 10J 33

## mlZa~ 

# T '10 

# #J fI

# J\.rz'~\f'! tI,

# II'~"I,','b, i • ••

### t" 

# ,'I,.III f

# Ii, 1'1';

# I., "ftj" 

## 11'./;

## 1'.*"1'

# L**1"~** ",'1./1'1'1 5.00 10.00 16.00 20.00 25.00 30.00 35.00 40.00 14711b02e 1: Scan ES+

# 1~**~ ~::m**  

# t**~ ~~** **~~** 

# ",J"
...", "t'''""'" ,., 'I'

# ,t,.,r,l
.., II'" 10104• .,.,...,.., ",
... " 5.1)0 10.00 15.00 20.00 25.00 30.00 35.00 40.00 14711b026 1: Scan E8+ 

### ':] ,.... mlzo.,.



# "J,, .It, ,'''',.. ,,' •,

# 'r',."",.,..

# ,L,..,,,......."'..,,,**"~,,**

# ..,, .........I" .".,.....,'­ .5,00 10.00 15.00 .20.00 25.00 30.00 35.00 40.00 14711b026
. 1: Scan ES+ 

# 1j' '. j1Ua
.

# ml29~ ""1$$ #..
. . 2U2 31.0
. 

# f
,if

I

# J\.,Wl'

# t.·,**,~~tf'"** 

# jt:AI:!\-:-i;'**~~ 1"I~1t~"/'U1¥1:,.;Jt'111''''''';fi\·.f.I~~~~h~**  TIme

# I 5,00 10.00**.~.** .--15.0020.:..00 .:.25.00_ 30.00**~....!§.,~** __ 40.00
. 

# it{ 'll , 

## 1"'0

# '1, '1, 2.1..**~L** 

# To-rtA.k\ Fig. 17-7 Mass spectra of water-soluble converted products (LC-MS sample -2, sludge + test item, vessel [3], mass chromatograms). 

## -92­ 955

### [3] Sludge 

### +teat Item (LC-MS sample -2) 14711b026 Total ion chromatogram 1.118 A E Test item BCD 

# I

14711b026 1 ex:!

Ul
1-4711b026 1 _10 1.1'

14711b026 1

14111b028

14711b026 1

# '"

14711b028 1 5.00

5.00

5.00

5.00

5.00 

## lit'll\ 

# \ 8,.5,4

10.00

10.00

10.00

'0.00

10.00

10.00 

# \ /**~u(** 26.78
20.00 25.00 30.00

15.00 20.00 25.00 30.00 17.60

.21.1' 15:.00 20.00**~5.00** 30.00

Wt

1!1.oo 2tl00 26.00 30.00

15.00 20.00 25.00 30.00 17M

tUO 20.00 26.130 30.00 17$2 

### 22-Feb-200 1:ScanES+ TIC 2.8887

35.00 40.00 1: Scan ES+

mlz =221 1.6186

35.00 40.00 1: Scan ES+



### m1z= 1;7

35.00 ' 40.00 1: Scan ES+

m/Z= 6.17eS

36.00 40.00

35;00

35.00 1: Scan ES+ mlz =341 6.

40.00 1: SCan ES+



### mIz= 383



## ...

40.00 1: SCan ES+

mJz
.. &1$ 1.6385

Fig. 17-6 Mass spectra ofwater-soluble converted products (LC-MS sample -2. sludge 

### +

### test item, vessel [3], mass chromatograms). 

## -93­ 956

### [3] Sludge 

### +test item (LC·MS sample -2) 14711b()26
. tee 

### T oIallQn chromatogram B C 

# \1 33.14 

## .l#!

5.00 10.00 15.00 20.00 25.00 30.00 35.00 14711b026 10 1.86 111.73 21.9<1

5.00 10.00 15.00 20.00 30.00 35.00 14711b026 21M 1

5.00 10.00 15.00 20.00 26.00 30.00 35.00 14711b026

lit 25.77 3$.811

21:88 1'# 3&;17



# .,.
5.00 10.00 15;00 

### 20.00 2$.00 30.00 14711b026 21.88 1 5.00 10.00 15.00 20.00 26.00 ·30.00 35.00 14711b026 21.98 1

35.00

35.00

5.00 

# (tt111\ '# 28.," 5.00 10.00 15.00 20.00 25.00**3O~00** 14711b026 21;" '1**~** 1.77 

### 22-Feb-200 1: Scan ES+ TIC 2.6687

40.00 1: Scan ES+



### mlz

# = 321 21985

40.00 1: Scan ES+

m/z= 4 4.00eS

40.00 1: Scan ES+

m/z:;; 441 4.6485

40.00 1: Scan ES+

m/z

# = 458 6.5ge6

40.00 1: Scan E$+

mlz

# = 483 1.S1e6

40.00 1: Scan ES+



### mlz

# = 47t 1.58e5



### Fig. 17·9 Mass spectra ofwater-soluble converted products (LC·MS sample -2. sludge + test item, vessel [3J. mass chromatograms). 

## -94­ 957

### [3] Sludge 

### + test item (LC-MS sample ·2) 

### 22-Feb-200 14711b026
. 1: Scan ES+ A 

# \ 8.54 1.68 Totailon chromatogram TIC 2me1**.~** 5.00 10.00 15.00 20.00 25.00 30,00 35.00 40.00 14711b026 1: Scan ES+ 17.>48 m/z=323 6.i7e5

5.00 10.00 15.00 20;00 25.00 30.00 36.00 40.00 141'flb026 1: Scan ES+

14711b026 1: Scan ES+ 1 m/z= 1.1
26.77
6.00 10.00 1S.00 20.00 25.00 30.00 35.00 40.00 14711b026 1: Scan 

### es+ 22JJ1 mlz =4&0 10 1.4118

6.00 10.00 15.00 20.00 25.00 30.00 35.00 40.00 14711b026 1: Scan ES+ m/z :;:4$$ 1**~U1e5**

15.00 20.00 25.00 30.00 

### 35.00 40:00 1: Scan ES+



### (lC-MS sample -2. sludge + test item. vessel [3], mass chromatograms). 

### 958 

## -95­ 1

5.00 10.00 22.31

15.00 20.00 25.00 m/z=425 1.02

40.00



### mIz =481 U8e5

Fig.17-10 Mass spectra ofwater-soluble converted products

### [4] Sludge 

### +test item (LC-MS sample -2) 

### 22-Feb-200 14711**b~~:o** Total ion chromatogram 1: Scan ES+ 1 A C TIC 2.76e7 3U4 .;fl \ 8.1>4 5.00 10.00 15.00 20.00 25.00 30.00 35.00 40.00 14711b027 1: Scan ES+ 1

# J 8.54 mlz

# = 137 

# '}
..l
...,'·· "



# ,l,., ,,'1
.. " , ' ,,, I ' , , •I ' " ., " • ., ••', " ••• ., " " , '
... , ' " , , '
.. , 5.00 10.00 15.00 20.00 25.00 30.00 35.00 40.00 14711b027 1: Scan ES+ 

# 'j, ,A,.•. 'I , , ••

# ,I,,..,", "., ...:r." ,.."
.." .,"
.., ........,, .........,'

# :t
221 5.00 10.00 15.00 20.00 2.5.00 30..00 40.00 

# 35.00 14711b027 1: Scan ES+ 8,6l1 mlz

# = 239 

# 'j
.....""
'I ' ,
.. ,

# ,t,,'" ,,,,, " ,•, 'I ' , 

## "I".,," ,.,'
.. "" ".,,'" " ,,'. ," ' " ,.'

# 8' 5..00 10.00 15.00 20.00 25.00 30.00 35.00 40.00 14711b027 1:ScanES+ 

# 1j Sf .1O M**mlz3~** 

# '3"'".·,. I'

# ",jL,,,.,

# "~ ,",",,,,,r'",t,•

# to"
.. 'f'
....'/. ",.., 

# 1

....

### iI.

# "I, 5.00 10.00 15.00 20J)0 25.00 30.00 35.00 40.00 14711b027 1: Soan ES+ 

# 1j 1.85 m/z

## = 

# 321 t 11l.l1l1 :lUI 2.00e 

# '"
..! 1 

### m ., , .. "'.,,.,,
.......".,.

# ,1
.., 

# .1.,"'"",.,\**.~,.** 

# "",...
.., ...1\ 6.00 10.00 15.00 20.00 25.00 30.00 35.00 40.00 14711b027 1: Soan ES+ 

# 1:] 339 18,91 m/z

# = 

# "'1
. ...""","""""
........\'.,.'t.".",,..,",·,,·""".To"'" , .•",.,..,'"
....­ 5.00 10.00 16.00 20.00 25.00 30.00 35.00 40.00

# ~4j711b0121':1**1:~~::~** 16.95
\lUl1 ."., It'\''N

## t,l/IjAI';""'uf,'*4

# r'1·tA~¥r'~ 4014

# '''flI1.'I't·Jt~'''''jlIr\''''I'¥~+''''t~.;'''·f.~ TIme 5,00 10.00 15.00 20.00 2s.o0 30.00 35.00 40.00 

# I If

## 11 l \ 

# 19o7, 9... 1.."l.. 

# h \\o..r-L\

# k,' Fig, 17-11 Mass spectra ofwater-soluble converted products (LC-MS sample -2, sludge + test item, vessel [4J. mass chromatograms). 

### 959 

## -96­

### [4] Sludge 

### +test item (LC·MS sample -2) 

### 22·Feb·200 14711b027 1: Scan ES+ 1.70 Total ion chromatogram 

# \1 30.69 22.29 21i.77 

# \ D 

# \/E 

# I TIC B 

## c Test item 2.78e7 33.14 

### .at

7 6.00 10.00 15.00 20.00 25.00 30.00 35.00 40.00 14711b027 1: Scan ES+ 17.60**~** m/z

## = 221 1.40et1 1.77 "#­

5.00 10.00 15.00 20.00 25.00 30.00 35.00 40.00 1: Scan ES+ 17.50 mlz 

### =239 1.51t6

5.00 10.00 16.00 20.00 30.00 35.00 40.00 14711b027 1: Scan ES+ 17.110 mlz =$23 5.21e5 22.31 il

5.00 10.00 15.00 20.00 25.00 30.00 35.00 40.00 14711b027 1: Scan ES+ 1 17.48 m/z

## = 341 S.53e5



### MO 10.00 15.00 20.00 26.00**~OO** 

### 85.00 40.00 14111b027 1: Scan ES+

5.00 10.00 15.00 20.00 25;00 30.00 35.00 40.00 141.11b027 1: Scan ES+ 17.62 m/z

# =379 

### 10 1.48e6 IP. U1

15.00 

## l(Jot']
... 1, 1.l.. 

# tv\,**lcnr~k\** Fig. 17-12 Mass spectra ofwater-soluble converted products (LC-MS sample -2, sludge"" test item, vessel [4], mass chromatograms). 

### 960 

## -97­ 1 17.50 mlz

# = 363 

## a 

# '* ,,1$1

25;()OSG.QO1 [4] Sludge 

### +test item**(LC~MS** sample .2) 22-Feb.200 14711b027 1: Scan ES+ 1.70 Total ion chromatogram TIC B C 278e7 A 33.14 .# 

# \ 8.54 T 

# \!

5.00 10.00 15.00 20.00 25.00 30.00 35.00 40.00 14711bO:27 1: ScanES+ 1.85 mlz;;; 321 21.98 2.0065 16.89 it
5.00 10.00 15.00 20.00 25.00 30.00 35.00 40.00 14711b027 1: Scan ES+ 1 2U8 m/z =<423 3,**~**
5.00 10.00 15.00 20.00 25.00 30.00 35.00 40.00 14711b027 1: Scan ES+ 1 218& m/z =441 4.4985**~** ••1" 5,00 10.00 15.00 20.00 25.00 30.00 35.00 40.00 14711b027 1: Scan ES+ 1 2U4 mlz =458 S.06a '/I.

5.00 10.00 16.00 20.00 26.00 30.00 35.00 40.00 14711b027 1: Scan ES+

5.00 10.00 15;00 20.00 25.00 30.00 35.00 40.00 14711b027 1: Scan ES+ 21
.... m/z 

### =47.**1.~** 

# .,. 1.&7 3O.U 

### { l.{-

## fj 

## l\ 

## lo07, L,**~2.** 10.00 15.00 20. 1 2U8 m/z =<183 2.18es


# .,. 1.17 WIG

Fig. 17-13 Mass spectra ofwater-soluble converted products (LC-MS sample -2, sludge 

### + test item, vessel [4J. mass chromatograms). 

## -98­ 9617 [4] Sludge 

### +test item (LC-MS sample -2)**22-Feb~200** . 14711b027
. 1: Scan ES+ 1.70 Total Ion chromatogram TIC 

# \ B

# \1 C 2.78e7 A 3U4 .<It 8.5.4 5.00 10.00 15.00 20.00 25.00 30.00 35.00 40.00 14711b027 1: Scan ES+ 17.50 1 m/z =323 5.21e5 22.31 'it 5;00 11100 15.00 20.00 25.00 30.00 35.00 40.00 14711b027 1: Scan ES+ 1 22.31 mlz :;425 9.11e5**~** 21$.77 5.00 10.00 15.00 20.00 25.00 30.00 35.00 40.00 14711bG27 1: Scan ES+ 1 22.28 mlz=44S 1.18e8 

### <It

5.00 1D.OO 15.00 20.00 2s.o0 30.00 

## as.oo 40.00 14711b027 1: Scan ES+ mlz ::_ 1 22.28 tileS**~** 6.00 10,00 15•.00 20.00 26.00 30.00 

## as.oo 40.00 14711b027 1: Scan ES+ 22.21 m/z =465 5.9385 'at
5.00 

## to.no 15.00 20.00 25.00 30.00 35.00 4D.CO 14711b027 1: Scan ES+ ZUt mlz =46.1 3.2ge5**~** Time 10.00 16.00 20.00 25.00 40.00

### l.o-o~, 

## 1. 12.. 

## 111\

_ TQ.. r1A

# KI' Fig. 17-14 Mass spectra ofwater-soluble converted products (LC-MS sample -2, sludge + test item, vessel [41. mass chromatograms). 

## -99­ 1



### 962

### Study No.14711 

## Peak A

......

## -....-_.....................

### -_

### ............

# -............

## --_....................................................

## - 

# --.



# · · · · · · ·

m/z Fragment ions 261 

# (M 

# + Na)+ 239 (M 

# + H)+ 221 

# 137 (M - 

# H20 + H)+ ( M - 3MBA 

# + H20+ H

# t

Fig.17 - 15 Mass spectra 

### ofwater-soluble converted products (LC-MS sample -2, sludge 

## +test item, presumed fragment ions of peak A). 

### Date 

## J..C907·S-J I Name 

# 7.**I<ff~~p.../**



## -100­ 9636 

### [5] Control blank (LC-MS sample -2) 22-Feb-200 14711b028 1: Scan ES+

# '~l

# T Tol"'oooh,,,,,,log"'m

# ,.i:.~

# "~,, '1""1

# ""1""'.••.,n. ;;:" ii·;; ;,;;;....

# 2:::::::**5~OO** 10.00 15,00 20.00 25.00 30.00 .35.00 40.00 14111b028 1: Selin ES+ 

# 111.83 miL 

### = 13., 

# ..\.L••**~~~~,..~663"** 5.00 1OJlO 15.00 2tlOO 25.00 30.00 35.00 40,00 14711b026 1: Scan ES+ 

# 1:11 Ul

$

# m1Z1~8: 

# :1 ,....,...,..,.,.,.,'"
.. ... 1\
...."
...

## """,.4\'10,

# ~,L.""~''''M-II 5.00 10.,00 1.5.00 20.00 25.00 80.00 35.00 40.00 14711b028 1: Scan ES+ 

# j 

# T**mll,~l:**



# "'ll.¥.."_,,, """"t
....'I
..

# W!I'No

# /!~.1.,...,~1"" ...

# .,..!~~ 5,00. 10.00 1.6.00 20.00 28.00 30.00 35.00 40,00 14711bD28 1: Scan ES+ 

# 10J**~3.16** 

### m/z =261 

# J "

# ~, , I I 

### I' ,.." '" I'" " 

# ",,,"'rO I I """ "I

# 't'"''"•.t¥I• .,

# 'Io/'fL11."'11
...... 5.00
. 10,00 15.00 20.00 25.00 30.00 35.00 40.00 14711b028· 1: SCln ES+ 

# 'I**~=~** 

# '1,- ,.,..,,-""'1",,

# 11'."'
......"'.,."
..../'I
...."
....., "..,14\ooj
....

# ,./w..,..,.:­

5.00 10.00 16.00 20.00 25.00 30.00 35.00 40.00 14711b028 1: Scan ES+ t**~=_** 2.77e4



# ['+t-t \\ loa!\ 

## '1,-22.. 

# M

# .1CAY"Vl.k,' Fig. 18-1 Mass chromatograms ofwater-soluble converted products (LC-MS sample -2, control blank). 

## -101­ 964

### Control blank (LC·MS sample -2) 4711b028 Total ion chromatogram

5.00 10.00 15.00 20.00 30.00



### 5.00 10.00 15.00 20.00 30.00

Mass chromatograms ofwater-soluble converted products 1: Scan ES+ mlz

# = 221

35.00 40.00 1: Scan ES+

m/z= 1

35.00 40.00 1: ScanES+

mlz=

(LC-MS sample -2, control blank). 

## -102­ 965

### [5} Control blank (LC·MS sample ·2) 14711b028 1.88 Total ion chromatogram _ilt

8 5.00 1O,GO 15.00 20.00 25.00 30.00 147f1bC28 1 1.$6 \\1:

5.00 10.00 15.00 20.00 25.00 30.00 14711b028**~** 5.00 10.00 16.'00 20.00 26.00 

### 30.00 14711b028 1 UlS**~**
5.00 10.00 20.00 26.00 SO.OO 14711b028 1'tit
5
..00 10.00 16.00 20.00 25.00· 30.00



# l

# eel \, Fig. 18-3 Mass chromatograms ofwater-soluble converted products (LC-MS sample -2, control blank). 

## -103­ 22·Feb·200 1: Scan ES+ TIC 2.66e7

35.00 40.00 1: Scan ES+

m/z '" 321 1.86e5

35.00 40.00 1: Scan ES+

m/z 

### =423 3.00e4

40.00 1: Scan ES+

mlz = 441 1.248

35.00 40.00 1: ScanES+

m/z= 458 1.1685

35.00 40.00 1: Scan ES+

mlZ=
...

## es e.611a4

3$.00 40.00 1: Scan ES+

m/z

# = 47 6.15e4



### 966

### Control 

### blank (LC·MS sample -2) 14711bG28
. 1.68 Total ion chromatogram
.'lIt

14711b028 5.00

5.00 10.00 15.00

10.00 15.00 20.00 25.00 3CI.OO

20.00 25,00 3Q.00

Mass chromatograms ofwater-soluble converted products (LC-MS sample -2, control blank). 35.00 40.00 1: Scan ES+

mil. =

35.00 40.00 1: Scan ES+

m/z =

.00 1: ScanES+

m/z=



### 967 14711b028 10 1.118



## -104­StudyNo. 14711 Wavelength 190.00

- 340.00 Date Sample Solvent Reference Scp. IS, 2006 

### Testitem Acetonitrile ScaleLimit SlitWUlth Scan Speed Sampling Pitch I.MOO O.lHIOO (UV)2.0nm 200mnlmin 0.500000 Mooo- -0,\000 :...0
...**~.''I**

)..
..**~,.** ',flill Cell 10mmx lOmm, quartz Instrument rASCO V-560 Photometric Mode Abs Analyst Note**H.~~** SO.OmgIL

Chemicals Evaluation and Research Institute, Japan KurumeLaboratory 

# 1.5r-------------------------------------

____________**~**

Abs A forHPLC (2IOnm) 0.5



### o
- - - -- - --- - ---- - - -- ••:.:"::_"!"-

# ""-----------------1 -0.1 L-L

___....;L

___-L

___....L-

___-'-

___...I..-_--' 190 200 250 300 340 Wavelength[nm] PeakLlst 1: t94.00 ( 0.9057) 

### Fig.19 UV spectrum oftestitem.



## -105­ 968

### Standard solution 25.0 mgll 

### 10-Dec-200 1471';005 4:**ScanES~** 1 TIC 1.24&5 

### Total ion chromatogram 

# /

%

tI,(11



### .2.00 400 

### 8.00 

### Standard solution 

## 26.0 mgIL 14711a005 35 (3.B39) 

## em (33:38-(40:42+30:32)x1.500) 

### 4:ScanES

### 1 185.2 9.41!i3 

### Mass spectrum ofpentaerythritol (M + CH3COof I·_·_··_···
___ ______

### ··t___... ,**··~** , (M + HCOO)­



### 969 Fig. 20 - 1 Mass spectrum of pentaerythritol,


## -106­

### tandard solution 25.0 mg/L 10-Dec-200 14711a005 4: Scan ES10 Total ion chromatogram TIC 

### 1.24eS

3.01**18~~~~~~~~~~~~~~~~~~~~~~~** 14711a005 4: Scan ES3.114 

### m/z

### = 171 9.2263 

### 1

%**o~~~~~~~~~~~~~~~~~~~~~~~~~** 14711a005 4: Scan ES

### 10 

### m/z

# =181 

### 2.3084



### %**o~~~~~~~~~~~~~~~~~~~~~~~** 14711a005 4: Scan ES3 

### m/z

# = 195 

### 1 3.8764



### Fig. 20 - 2 Mass spectrum ofpentaerythritol. (mass chromatograms)

## -107­ 970

### Solution of 3MSA (50.0mg/L) 14711xoo2 

## 23-F.IJ..200 1: Scan ES

### TIC 4.0184 1

%

% Total ion chromatogram 

# / 

# Elli::1**~~~~~~~~~~~~~~~~~~~~~~TIme**

. (M - Hf 17.50 20.00 

### 23-Feb-200 1: Scan E8­ 9.63e3 

### Mass spectrum of3MBA



## .-............................................., 

# . 

# . .**~~~.rnM~Mm.~~mm~~~~~~~~~~~~~~~~** 100 120 140 160 180 200 220 240 2$0 280 300 320 340 

# itt'1ll It>(1 ,**2.~** 

# 1.3**r"TaI"L.,.k~** Fig. 21 - 1 Mass spectrum of 3MBA.


## -108­ 971

### Solution of3MBA (50.0mg/L) 

### 23..feb-2.00 14711xOOZ 1: Scan ES10 4.85 Total ion chromatogram TIC 

### 4.0184**16~~~~~~~~~~TN~~~~~~~~~~~~** 

### 14711x002 ,1: Scan ES

### 1 

### m/z

# =11 2.7

%



### 0.00 2.50 

### 5.00 7;50 

### 2007, 1.1) Fig. 21 - 2 Mass spectrum of3MBA (mass chromatogram)

## -109­ 972

### 10 

### Solution ofSBA (60.0mg/L) 23-Feb-200 14711x001 1: Scan ES11.37 

### TIC 268e4 Total ion chromatogram



### % 

# fB;;:1

15.00

Mass spectrum of SBA



# I 

# ?J**H0yYS,-~.** 

# & f S OH
MaSs number (M);238



### I

# tr11\**2ao~.. 1.~).**  

# 3 Fig. 22 - 1 Mass spectrum of SSA.



### -110­ 

### 973

### Solution of SBA (50.0mg/L) 

### 23-Feb-200'i! 14711xOO1 1: Scan 

## Es-l 11.37 10 Total ion chromatogram TIC 2.68&4



### • -.4**1a~~~~~~~~~~~~~~~~~~~~~~~~** 14711><001 1: Scan ES11.37 m/z:: 237 1 1.74e4



### 0.00 2. 

### 5.00 7.50 10;00 12.50. 

### 15.00 

## { tf'lll "loo?, L 

## 1.l Fig. 22 - 2 Mass spectrum of SBA. (mass chromatogram)


### -111­ 974

### IT

60

50 

### C:-H**~tr, -~-~--.------~--.--.--.-**  

# .. I I



### , , , I !
__**~** __**~** __**~** ___**~** _____ l
__ • __**~wP_.** 

## ___**~**

## __ 0:0

Str. , I**-------------~-~-** 

## ..**--~.--~ .-------.-~~-~----------~--.-------------~--**  

## •
4000 3000 2000 1500 1000 800 l/em 

### Instrument**~** 

### Shimadzu IRPrestige-21 StudyNo. 

### : 14711 Sample :Testitem Method :Neat Date ! 

### September 19, 2006 

### Name

### :H\(::.~
Fig.23 ·1 

### IR spectrumoftest itemmeasured before experimental start.



## -112­ 975

### • • 40 100

80



## ,**8O~--··---·----i**



### 29' --.--------- -_._--­

.••-._.- •.

_••.• -------­



## ------- ----.---­

------------ .. -----------­



### , 

# ..!



### - ...---- --- -- "'1-- - ,.., - - - .. - - - ­ ..... - - - - - ......... - - ­ 

### , ...

# ---­

## ---

# ­'...

## -- 

## -:-­ I 

## , I



# . . -..-.....--------...---s-..
r...---....-...--..-**~**

## ------....-------:- "!' 

### "
I 

### • I I I**OI-r~~~r_~4r_r~~.-r_+_~_r~~~r_r_,__r_r~--r_r_~or_r_;** 4000 3000


### Instrument Study No. Sample Method Date 

### Name 2000 1500 1000 500 

### lIcm



### : ShimadzuIRPrestige-21 : 14711 .:Testitem

:Neat :February26, 2007 

## : fjzt 

# ak

Fig.23- 2 IRspectrum oftest

### item measured after

### experimental completion.



## -113­ 976",



### Reference 

### IR spectrum 

### suppliedby 

### sponsor.



### -114­ 977

# Mff:I

# yiiA**1t~~W~ffiffi1iJf5E~~**

# ~$* 

# iIIS !fftg£**~ {~~~WO)~~&** **v~~~O)m}fllJ** 

# h: MT

# 6**r~f=tn-r**

## {~6**~~Mff~~~MT** 

# 6**£~~-fr1ltiB~1itl£~f1~~~£ ~,** **r~e~~1J&~~~~v'--Ct'j:,****~m{~¥:~ji~~f*6**

## ~~slfLr.J~~~-fl~m{~¥:~j(&**V~=fI~tJ!{~*****~:w,~t*****61f1ft1:O)wm~0)~ ~ ~~7EfJ)** **6~'~m** 

# 4**~~~mJET** 

# 6**~~1itl£~ ~~** 

# MT**6lttf§~cil~** 

# L- 

# --Cv'6 2:. 

# C: 

# :fr**1it~** 

# L

# *To t.ljO,**1lt~O)fr~WjrFl~t'j:,*****1lt~.O)~ft** 

# s**7J~** 

# G 

# 1m:' L--C 3**iFrFl~** 

# C: L-

# *To**~JJt** 

### 1 6 

## &f: 1 2

## J1 2 2 F.3



# MfB$A**{~~~j{~fnIi."6jf~#l~**

## !Aii*.~m**.~.!A.*$g/.-T§2.7%****~~~~~,~~~~~&V~~~~.**

978

# ,,' 

# CERI
ReceiptNo. 827-08-D-3387

STUDY CODE: XlS-0908



## FINAL REPORT

STABILITY ANALYSIS OF KarenzMT (Mixture ofPEMB and PE3MB), HOMOGENEITY, STABILITY AND CONCENTRATION ANALYSES OF THE TEST SUBSTANCE FORMULATION

March 2009

Hita Laboratory Chemicals Evaluation and Research Institute, Japan


### -i 

### 979X18-0908



### STATEMENT

TITLE OF STADY Stability Analysis of KarenzMT (Mixture of PEMB and PE3MB), Homogeneity, Stability and Concentration Analyses ofthe Test Substance Fonnulation (Study Code: Xl8-0908)

I, 

### the undersigned, hereby declare that this report provides a correct English translation of

### the final report (Study Code: X1S-0908, issued on March 16,2009).



### Yuji Kusune, M.S. Date Hita Laboratory Chemicals Evaluation and Research Institute, Japan

-ii­ 

### 980

### XlS-0908

GLP STATEMENT Hita Laboratory Chemicals Evaluation and Research Jnstitute, Japan Sponsor:
_____ Sho:wa Denko K.K. Title: Stability Analysis ofKarenzMT (Mixture of PEMB and PE3MB)' Homogeneity. Stability and Concentration Analyses ofthe Test Substance Formulation Studv Code: Xl&:-_Q908
I, the undersigned, hereby declare that this study was conducted in compliance with "Concerning Standard of the Testing Facilities Conducting the Test Relating to the New Chemical Substances" on Japanese GLP (Notification No. 1121003 ofthe PharmaceuticaJ and Food Safety Bureau, 

### MHLW, No.3 (November 17,2003) ofthe Manufacturing Industries Bureau, METl & 

### No. 031121004 oftile Environmental Health Department, MOE (November 21,2003»). I also confirmed that this report accurately reflected the raw data and the test data were valid.

Study Director: Signed in original
__ March 16, 2009 Yuji Kusune, M.S_

-iH­ 

### 981X18·0908
QUALITY ASSURANCE STATEMENT Hita Laboratory Chemicals Evaluation and Research Institute, Japan Sponsor: Showa Dcnko K.K. Title: Stability Analvsis of K,!!:cnzMT (Mixture of PEMB and PE3MB). lIomogeneity, Stabilityand Concentration Analvses ofthe Test Substance Formulation Study Code: X 18-0908
This study was inspected by Quality Assurance Unit of Hita Laboratory, Chemicals Evaluation and Research Institute, Japan. The dates inspected and the dates reported these reslilts to the study director and management are as follows Date Reported to Study Phase Date ofInspection Director and Management Protocol October 10, 2008 lR Spectrum ofTest S October 14, 2008 Homogeneity and Stability Analyses ofTest Substance October 14,2008 October 14, 2008 Formulation Confinnation ofthe Answer from October 17, 2008 October 17, 2008 Study Director (Protocol) Amendment to Protocol October 27,2008 October 27, 2008 Concentration Analysis cfTest November 6, 2008 November 6, 2008 Substance Formulation Amendment to Protocol (No.2) November 10, 2008 November 10,2008 Raw Data and Draft Final Repmt February 24, 2009 February 24, 2009 ReinspeClion ofRaw Data and February 27,2009 February 27, 2009 Draft Final Report Amendment to Protocol (No.3) March 12,2009 March 12, 2009 Draft Final Report (Second Time) March 12, 2009 March 12,2009 Final Report March 

### 16, 2009 March 

### 16, 2009 I, the undersigned, hereby declare that this report provides an accurate description ofthe methods and procedures used in this study, and that the reported results accurately reflect obtained raw data. Head, Quality Assurance Unit: March 16, 2009 Ryuichiro Mizuguchi, B.S. iv 

### 982X18-0908

TABLE OF CONTENTS Page TITLE ................................................................................................................................ 3 SPONSOR
......................................................................................................................... 3 'l'ESTING FACILITY
............................................................_........_............................... 3 PURPOSE OF STUDY
..................................................................................................... 3 GLP COMPLIANCE
........................................................................................................ 3 PERIOD OF STUDY
........................................................................................................ 3 STORAGE AND RETENTION PERIOD OF DATA
........................................................ 4 RETENTION OF ORIGfNAL DOCUMENTS
................................................................ 4 STUDY DIRECTOR AND PERSONS CONCERNED WITH THE STUDY AND THE OPERATION
...............

## on.................................................................................................. 4 APPROVAL BY AUTI·IOR
.............................................................................................. 4 SUMMARY
...................................................................................................................... 5 MATERlALS
.................................................................................................................... 6 1. TEST SUBSTANCE
................................................................................................... 6 METHODS
........................................................................................................................ 7 1. SUBJECT STUDY
.....................................................................................;............... 7 2. STADlLITY ANALYSIS OF THE TEST SUBSTANCE
......................................... 7 3. HOMOGENEITY, STABILITY Al\D CONCENTRATION ANALYSES OF THE TEST SUBSTANCE FORMULATION
..;.................................................................. 8
THE ENVIRONMENTAL FACTORS THAT MIGHT IIAVE AFFECTED THE RELIABILITY OF THE STUDY RESULTS
................................................................. 12 RESULTS AND DISCUSSION
....................................................................................... 12 1. RESULTS
...............................................................................;................................. 

### J2 2. DISCUSSION
............................................................................................................ 13

-1­ 

### 983Xl 8-0908

TABLES Homogeneity and stability analyses ofthe test substance formulation 14 2 Concentration analysis ofthe dose formulation
........................................................ 14
FIGURES IR spectrum measured priortothe administration period
......................................... 15 2 IR spectrum measured afterthe end ofthe administration period
............................ 15
REFERENCE IR spectrum provided 

### by the sponsor ....................................................................... 15



### -2­ 

### 984

### X18-0908
Study Code: X18-0908 Test Substance Code: HR7645 Sponsor Code: S-0170
TITLE Stability Analysis of KarenzMT (Mixture of PEMB and PE3MB), Homogeneity, Stability and Concentration Analyses ofthe Test Substance Formulation SPONSOR Showa Denko K.K. 13-9, Shiba Dalmon I-chome, Minato-ku, Tokyo 105-8518, Japan TESTING FACILITY Hita Laboratory Chemicals Evaluation and Research Institute, Japan 822, 3-chome, Ishii-machi, Hita, Oha 877-0061, Japan PURPOSE OF STUDY The purpose ofthis study is to determine the stability ofthe test substance during the dosing period, and homogeneity, stability and concentration of the test substance in formulation in "Twenty-Eight-Day Repeated-Dose Oral Toxicity Study ofKarenzMT (Mixture ofPEMB and PE3MB) in Rats" (Study Code: B11-0908). GLP COMPLIANCE This study was conducted in compliance with "Concerning Standard of the Testing Facilities Conducting the Test Relating to 

### the New Chemical Substances" on Japanese GLP (Notification No. 1121003 of the Pharmaceutical and Food Safety Bureau, MHLW, No.3 (November 17, 2003) ofthe Manufacturing Industries Bureau, MET! & 

### No. 031121004 of the Environmental Health Department, MOE (November 21, 2003)). PERIOD OF STUDY Commencement ofStudy: October 9,2008 Initiation ofExamination (Initiation ofAnalysis): October 14, 2008 Termination ofExamination (Tennination ofAnalysis): December 26, 2008 Completion ofStudy: March J

### 6, 2009



### -3 

### 985

### X1S-090&



### STORAGE AND RETENTION PI<:RIOD OF DATA The raw data, protocol, study contract documents, test substance information, final report and other record documents will be retained 

### in the archive ofthe Hita Laboratory ofour organization for the same period of 

### B11-0908 paper data. After termination of the retention period, any measures taken 

### will be done so with the approval ofthe sponsor.


### RETENTION OF ORIGINAL DOCUMENTS An original protocol and an original final report will be retained at Hita Laboratory. The copies oftheir original that 

### the study director 

### will be recognized to be accurate copy will be sent to the sponsor.


### STUDY DIRECTOR AND PERSONS CONCER'l'iED WITH TH.E STUDY AND THE OP.ERATION Study director: Yuji Kusune, 

### M.S. Study staff: Masaru Suzuki, B.S. (Analysis ofthe test substance) Saori Takakura, 1.L.A.T., I.A.C.L.C.T. (Preparation ofthe test substance formulation) 

### APPROVAL BY AUTHOR Study director: Signed in original March 16, 2009 Yuji Kusune, M.S. Analytical Chemistry Section HitaLaboratory



### -4­ 

### 986

### Xl8-0908

SUMMARY
The test substance (KarenzMT (Mix.ture of PEMB and PE3MB)) was stable during the dosing period ofsubject study (Study Code: B

### 11-0908). The test substance in 10.0 and 0.25 

### w/v% formulations was stable for 8 days after preparation at cold and dark place and showed good homogeneity. The concentration oftest substance in 

### 10.0, 1.5 and 0.25 

### w/v% dose fomlUJations for subject study was acceptable level.



### -5 

### 987

### XI 8-0908

MATF.RIALS



## .....**~:** 

## .....**!~~T~.~r~.~T.~~~~.(l.~.:t:!?~~I!Q~.f.~.9.Y.!IJ.~~lJ.#X.lli~~r.9.N~9.~)'** 

## ......__...__._.._ .._ ....;


# . ,



### -6­ 

### 988X1S-0908



### 1.8 Storage Conditions Stored at room temperature (cabinet No. 1 in test substance storage room, tolerance temperature: IO-30°C). Actual temperature between received of test substance to termination of examination was 19.0-22.4°C. It satisfied tolerance. Avoid oxidizing agent. 

### 1.9 Handling 

### Precaution Glove, mask, cap, goggles and lab coat were worn. The test substance was treated in the draft since the test substance has characteristic odor.



### METHODS 1. SUBJECT STUDY Twenty-Eight-Day Repeated-Dose Oral Toxicity Study of KarcnzMT (Mixture ofPEMB and PE3MB) in Rats (Study Code: 

### B 11-0908) 

### 2. STABIUTY ANALYSIS OFTHETEST SUBSTANCE The infrared (JR) spectrum was measured by IR spectrophotometer before and after the dosing period ofsubject study. 2.1 Measurementof

### IR I) rnstrument 

### JR spectrophotometer: 

### FT-nO (HORlBA, Ltd.) 2) Condition Wave number: 4600 cm- I

- 400 cm-' 3) Pre-Treatment Potassium bromide neat 2.2 Criteria forJudgment IR spectrum orthc tcst substance that measured prior to dosing in our laboratory should be identical with provided from the sponsor. The test substance was judged to be stable when there are no differences in the IR spectrums at before and after dosing period.



### -7­ 

### 989

### XIS-0908

3. HOMOGENEITY, STABILITY AND CONCENTRATION ANALYSES OF THE TEST SUBSTANCE }<'ORMULATION In the homogeneity analysis, the samples were taken (n=l) from the upper, middle and lower layers of formulations immediately after preparation, respectively. These samples were pretreated and measured (11=1) with high performance liquid chromatography (HPLC). [n the stability analysis, the formulations were stored at cold and dark place for 8 days, and the sample was taken (n=I) from the middle layer of the formulations at point of measurement (3 days and 9days after preparation). These samples were pretreated and measured (n=l) with HPLC. 

### III the concentration analysis, the samples were taken (n=l) from the middle layer ofdose formulations immediately after preparation for subject study. These samples were pretreated and measured (n=l) with HPLC. 3.1 The Test SubstanceFormulation I) Homogeneity and Stability Analyses (1) Concentration 10.0 and 0.25 w/v% (2) Preparation Method Weighed 5.00 g oftile test substance in a beaker, and mixed with olive oil to make 50 mL, and used as 10.0 w/v% fOimulation. Accurate 2.5 mL of 10.0 w/v% formulation was diluted with olive oil to make toO mL, and used as 0.25 

### w/v% formulation. Vehicle: olive oil (Lot No. 0460YS, Fujimi Pharmaceutical) 2) Concentration Analysis The 10.0, 1.5 and 0.25 

### w/v% dose formulations at first preparation for subject study were used. 3.2 Outline ofAnalytical Method The analytical method was decided, according to results of validation of the analytical method 011 non-GLP at the test facility. I) Validation ofthe Analytical Method (!) Preparation for Measurement Sample

a) Standard Stock Solution for Validation ofthe Analytical Method Weighed 0.10187 g of the test substance, dissolved in 2-propanol to make 100 mL, and used this solution as 1018.7 llg!mL standard stock solution for validation ofthe analytical method. b) Sample for Specificity The standard stock solution for validation ofthe analytical method was diluted with 2-propanol to make 50.9 /lg/mL standard solution and 50.9 /lg!mL 8 

### 990X18-0908
vehicle-containing standard solution (containing 2 v/v% vehicle (olive oil)). 2-Propanol was lIsed as solvent blank, and vehicle blank (containing 2 v/v% vehicle) was prepared. c) Sample for Linearity The standard stock solution for validation ofthe analytical method was diluted with 2-propanol to make 25.5, 50.9'1 and 1 02**~lglmL** standard solutions. 

## *I: Itwas used 50.9**~lglmL** standard solution ofsample for specificity. d) Sample for Accuracy and Repeatability Standard solutions (concentration: 25.5, 50.9 and 102**~glmL,** eaeh concentration: n=3) were prepared in the same way ofsample for linearity. (2) Specificity Samples for specificity were measured with HPLC. The variation of detection value (total peak area) of the test substance between standard solution with and without vehicle was -2.0%. Therefore, it was confirmed that the result of variation satisfied criteria for judgment (within ±5%). In the results of HPLC analysis of solvent blank and vehicle blank, it was confirmed there were no background and interfering peaks at the elution peak position oftest substance. (3) Linearity Samples for linearity were measured with HPLC. The calibration curve was made by the concentration of the test substance in the horizontal line and the detection value of test substance in the vertical line. The coefficient of correlation ofcalibration curve which was obtained from least square**wa~** R=0.999. Therefore, it was confirmed that the result of linearity satisfied criteria for judgment (more than 0.999). (4) Accuracy and Repeatability Samples for accuracy and repeatability were measured with HPLC. The concentrations of the test substance were calculated with regression formula that was obtained at linearity. Accuracy and repeatability were calculated with these values. Accuracy of25.5 llg/mL standard solution was 0.4, -3.1 and -0.4%. Accuracy of50.9 IlglmL standard solution was -0.4, -1.2 and -1.0%. Accuracy of 102 IlglmL standard solution was 0.0, 0.0 and 1.0%. Repeatability of25.5, 50.9 and I021lglmL standard solution was 1.9, 0.4 and 0.6%, respectively. It was confirmed that the result of accuracy and rcpeatability satisfied criteria for judgment (accuracy: within ±IO%, repeatability: less than 5%).



### -9­ 991Xl 8-0908

2) Preparation for Standard Solution Weighed 0.10 113 g ofthe test substance dissolved in 2-propanoJ to make 100 mL, and used this solution as 1011.3 J.LglmL standard stock solution. Accurate 1 mL of standard stock solution diluted with 2-propanol to make 20 mL, and 50.6**~lglmL** standard solution was prepared. 3 ) Pre-Treatment Formulations were mixed well using a magnetic stirrer. (I) 10.0 w/v% Formulation (Homogeneity, Stability and Concentration Analyses) Accurate 0.5 mL of formulation was dissolved in 2-propanol to make 50 mL. Accurate 1 mL ofthis solution was diluted with 2-propanol to make 20 mL, and served as an analytical sample (dilution rate: 2000). (2)1.5 w/v% Formulation (Concentration Analysis) Accurate 0.5 mL of formulation was dissolved in 2-propanol to make 30 mL. Accurate 2 mL ofthis solution was diluted with 2-propanol to make 10 mL, and served as an analytical sample (dilution rate: 300). (3) 0.25 w/v% Formulation (Homogeneity, Stability and Concentration Analyses) Accurate 0.5 mL offormulation was dissolved in 2-propanol to make 25 mL, and served as an analytical sample (dilulion rate: 50). 4) Conditions ofHPLC Analysis (l)Instruments (HPLC7) Interface: D-7000IF (Ilitachi, Ltd.) Pump: L-7100 (Hitachi, Ltd.) Auto sampler: L-7200 (Hitachi, Ltd.) UV-VIS detector: L-7400 (Hitachi, Ltd.) Column oven: L-7300 (Hitachi, Ltd.) Data processor: D-7000 HPLC System manager (Hitachi, Ltd.) (2) Conditions Column: L-column ODS (4.6 mm I.D. x 50 mm, CERI) Column temperature: 40°C Mobile phase: 0.5 v/v% phosphoric acid solution/acetonitrile 45/55 (v/v) Flowrate: 1 mUmin Wavelength: 210 nm Injection volume: 

### 3.3 J)ata Processing 1) Detection Value A total peak area was used as the detection value. 2) Quantitative Analytical Method In validation ofthe analytical method, the result of linearity was a straight line range 

### -10­ 

### 992

### XI 8-0908

of25.5, 50.9 and 102 !!glmL standard solutions, and it passed through the origin ofthe coordinates. Therefore, the concentrations ofanalytical samples were determined by single level calibration. 3) Calculation ofthe Test Substance Concentration in Formulation Concentration of test substance in each sample (C: w/v%) 

### was calculated with the equation shown below and rounded offto three significant figures. C =0

### CsxAxD Asx 10000 Cs: Test substance concentration in standard solution (/lglmL) As: Detection value oftest substance in standard solution A: Detection value oftest substance in each analytical sample D: Dilution rate in each analytical sample 

### 3.4 Criteria ror Judgment 1) 

### Homogeneity Analysis The test substance wasjudged as homogeneous dispersion in vehicle ifa coefficient of variation (CV) was within 5%. The CV was calculated using the following equation: CV(%)

# =Standard deviation for concentration oftest substance in each x 100 

### Mean concentration oftest substance in each layer
2) 

### Stability Analysis The test substance was judged as stable state in vehicle if a rate to the nominal concentration for the actual concentration (R.N.) and a rate to 

### the mean concentration immediately after preparation for the actual concentration (R.P.) were within the range of 

### 1OO±I0%. The R.N. and R.P. werecalculated using the following equation: Actualconcentration x] 

### 00 R.N.{%) Nominalconcentration R.P.(%) '" Actual concentration x I 

### 00 Mean concentration immediately after preparation 3) Concentration Analysis It was confirmed that R.N. was within the range of 100±10%. The R.N. was calculated using the following equation:

11

­ 

### 993

### XIS-0908

R.N.(%) "". Actualconcentration xl00 Nominal concentration



### ENVIRONMENTAL FACTORS THATMIGHTHAVE AFFECTED RELIABILITY OF STUDY RESULTS There were no factors that might have affected the reliability ofthe study data.



### RESULTS AND DISCUSSION 1. RESULTS 1.1 StabilityAnalysis oftheTellt Substance IR spectrum of test substance provided by the sponsor (Reference I) 

### was identical with that measured before dosing period for subject study (Figure 1). 

### There were no differences in the IR spectra between before and after dosing period (Figures 1, 2). 

### 1.2 Homogeneity, Stability and Concentration Analyses of tbe Test Substance Formulation J) Homogeneity and Stability Analyses The results ofhomogeneity and stability analyses ofthe test substance formulation are shown in Table I. (1) Homogeneity Analysis CY of 10.0 and 0.25 

### w/v% formulations were 0.6 and 1.0%, respectively. The results satisfied criteria forjudgment. (2) Stability Analysis

a) 10.0 

### w/v% Formulation At immediately after preparation, R.N. were 101 to 102%. At 3 days after preparation, R.N. was 100%, and R.P. was 98.0%. At 9 days after preparation, R.N. was 101%, and R.P. was 99.0%. All the results ofR.N. and R.P. satisfied criteria forjudgment. b) 0.25 w/v% Formulation At immediately after preparation, R.N. were 102 to 104%. At 3 days after preparation, R.N. was 102%, and R.P. was 99.6%. At 9 days alter preparation, R.N. was 102%, and R.P. was 100%. All the results ofR.N. and R.P. satisfied criteria forjudgment. 

### -12­ 

### 994X18-0908


### 2) Concentration Analysis The results of concentration analysis of the test substance formulation are shown in Table 2. R.N. of 10.0, 1.5 and 0.25 

### w/v% dose fomlUlations were 

### 99.1 to 

### 101%. All the results satisfied criteria fot"judgment. 

### 2. DISCUSSION Thetest substance was stable during the dosing period ofsubject study. The test substance 

### ill 10.0 and 0.25 

### w/v% formulations was stable for 8 days after preparation at cold and dark place and showed good homogeneity. The concentration of test substance in 10.0, 1.5 and 0.25 

### w/v% dose formulations for subject study was acceptable level.



### 13­ 995

### XIS-090S
, I 

### I . 

### Tablel H

### omoenelty and 

### stabT 1ltv 

### ana vses 01 t 

### le test sub

### stance ormu atlon Nominal

cone. (w/v%) 

### Time point of measurement Layer of measurement Actual cone. (w/v%) 

### R.N. (%) 

### Mean cone. (w/v%) 

### R.P. (%) CV (%)



### 10.0 Immediately after prcparation Upper 10.2 102 10.2 

# - 0.6 Middle 10.2 102 Lower 10.1 101 3 days after preparation Middle 10.0 100



# - 98.0 

# - 9 

### days after preparation Middle 10.1 101 

# . 99.0 

# -

0.25 Immediately aftcr preparation Upper 0.259 104 0.256 

# . 1.0 Middle 0.254 102 Lower 0.256 102 3 days after preparation Middle 0.255 102


# - 99.6


# - 9 days after preparation Middle 0.256 102


# - 100


# - R.N.: Rate to the nominal concentration R.P.: Rate to the concentration measured immediately after preparation CV; 

### Coefficient ofvariation ]'fhd f; 

### I . Table

### 2 ConcentratlOn analYSIS 0 

### t e ose ormu atlOn Date ofanalysis Nominal cone. (w/v%) 

### Actual cone. (w/v%) 

### R.N. 

### (%) 10.0 9.91 99.1 

### November 6, 2008 1.5 

### 1.51 101 0.25 0.250 100 R.N.: Rate to the nominal concentration

14 

### 996

### Xl 8-0908**~~,,~,.~"** lOOO 400.0 

### Figul'e I 

### IR spectrum measured priorto the administration period

Figure 2 

### IR spectrum measured afterthe end ofthe administration period

_L'

__-' 1000 

### Reference I lR spectrum provided by

### the sponsor

- J5­ 

### 997PAGE 1 OF 25 PAGES



### Mixture

### of PEMB and PE3MB: MICRONUCLEUS TEST IN olliE MOUSE PRO
..IECT NUMBER: 

### 0145/0219

AUTHOR: 

### L Flanders

STUDY SPONSOR: TEST FACILITY: 

### Showa Denko K.K. Harlan Laboratories Ltd 13-9, Shiba Daimon 1-Chome Shardlow Business Park Minato-ku Shardlow TOKYO 105-8518 Derbyshire JAPAN 

### DE722GD UK 

### Telephone: +44 (0) 1332 792896 Facsimile: +44 (0) 1332 799018 0145-02191LF



### 998PROJECT NUMBER: 014510219 PAGE 2 

### QUALITYASSURANCE REPORT This study type is classed as short-term. The standard test method for this study type ("General Study Plan" in OECD terminology) was reviewed for compliance once only on initial production. Inspection of the routine and repetitive procedures that constitute the study is carried out as a continuous process designed to encompass the major phases at or about the time this study was in progress. In addition, inspection of general facilities not specifically related to this study are done monthly or annually in accordance with QA Standard Procedure. This report has been audited by the Quality Assurance Unit, and is considered to be an accurate account ofthe data generated and ofthe procedures followed. In each case, the outcome of QA evaluation is reported to the Study Director and Management on the day of evaluation. Audits of study documentation, and process inspections appropriate to thetype and schedule ofthis study were as follows: 17 November 2008 Standard Test Method Compliance Audit 03 June 2009 Test Material Preparation 03 June 2009 Animal Preparation 03 June 2009 Dosing 05 June 2009 Assessment of Response 05 June 2009 Cell Harvest 05 June 2009 Staining/Slide Preparation 

### § 29 July 2009 Draft Report Audit 

### § Date of QA Signature Final ReportAudit 

## § Evaluation specific to this study 

## 04 AUG 

# 2009



# ...**M~** 

# ..**S0..~** 

# .............. DATE:
................................................ Forthe Quality Assurance Unit*

*Authorlsed QA Signatures: Manager, Quality Assurance: J G Riley SSe (Hons) MRQA Deputy Head of Department JM Crowther MIScT MRQA SeniorAudit Staff: GWren ONC MRQA


### 999PROJECT NUMBER: 014510219 PAGE 3 

### GLP COMPLIANCE STATEMENT The work. described was performed in compliance with UK GLP standards (Schedule 1. Good Laboratory Practice Regulations 1999 (SI 1999/3106 

### as amended by SI 2004/0994)}. These Regulations are in accordance with GLP standards published as OECD Principles on Good Laboratory Practice (revised 1997, ENVIMC/CHEM{98)17): and are in accordance with. and implement, the requirements of Directives 2004/9/EC and 2004/10/EC. This report fully and accurately reflects the procedures used and data generated.



## . 03 AUG 

# 2009 DATE
.................................................... L Flanders Study Director

This report may be presented In final form as a digital (pdf) document. Such documents are prepared byscanning the paperoriginal,

and are considered ofequivalent integrity and authenticityto versions produced by optical photocopy. However, In all cases the hand-slgned paper Original, held in secure archives. is the definitive document



### 1000PROJECT NUMBER: 0145/0219 PAGE 4


### CONTENTS QUALITY ASSURANCE REPORT 2 

### GLP COMPLIANCE STATEMENT 

## 3 CONTENTS 

### 4 SUMMARY 

### 5 1. INTRODUCTION 

### 7 2. PRINCIPLES OF INVESTIGATION 

### 7 3. TEST AND CONTROL MATERIALS AND EXPERIMENTAL PREPARATION 

### 8 3. 1 Test Material 

### 8 3.2 Positive Control Material 

### 8 3.3 Vehicle Control 

### 9 

## 4. METHODS 9 

### 4.1 Animals and Animal Husbandry 

### 9 4.2 Procedure 10 

## 5. ARCHIVES 

### 13 

## 6. RESULTS 

### 14 6.1 Range-finding Toxicity Test 14 6.2 Micronucleus Test 15 

## 7. CONCLUSION 

### 15 Table 1 Micronucleus Test - Summary of Group Mean Data 16 Table 2

.Table 

### 3

Table 4 Table 5 Table 6 Table 7 Table 8 Appendix 1 Historical Control Data from 45 Studies (2007 and 2008) 24 25 

### Appendix 2 Statement of GLP Compliance in Accordance with Directive 2004/9IEC 

### Micronucleus Test - Individual and Group Means and Standard Deviations: Vehicle Control (10 mllkg) 48-Hour Sampling Time 17 MicronucleusTest -Individual and Group Means and Standard Micronucleus Test -Individual and Group Means and Standard Micronucleus Test -Individual and Group Means and Standard Micronucleus Test - Individual and Group Means and Standard Micronucleus Test - Individual and Group Means and Standard MicronucleusTest -Individual and Group Means and Standard Deviations: Vehicle Control (10 mllkg) 24-Hour Sampling Time 

### 18 Deviations: Cyclophosphamide (50 mglkg) 24-Hour Sampling Time 

### 19 Deviations: Test Material (600 mglkg) 48-Hour Sampling Time 20 Deviations: Test Material (600 mglkg) 24-Hour Sampling Time 21 Deviations: Test Material (300 mglkg) 24-Hour Sampling Time 22 Deviations: Test Material (150 mg/kg) 24-Hour Sampling Time 23

1001PROJECT NUMBER: 0145/0219 PAGE 5


### Mixture ofPEMB and PE3MB: 

### MICRONUCLEUS TEST IN THE MOUSE SUMMARY Introduction. The study was performed to assess the potential of the test material to produce damage to chromosomes or aneuploidy when administered to mice. The method was designed to comply with the DECO Guidelines for Testing of Chemicals No.474 "Micronucleus Test", Method 812 of Commission Regulation (EC) No. 

### 44012008 of 30 May 2008, the USA EPA, TSCA and FIFRA guidelines and the Japanese METI/MHLW guidelines fortesting of new chemical substances. 

### Methods. A range-finding test was performed to find suitable dose levels of the test material, route of administration and to investigate to see if there was a marked difference in toxic response between the sexes. There was no marked difference in toxicity of the test material between the sexes; therefore the main test was performed using only male mice. The micronucleus test was conducted using the oral route in groups ofseven mice (males) at the maximum tolerated dose (MTD) 600 mglkg and with 300 and 150 mglkg as the two lower dose levels. Animals were killed 24 or 48 hours later, the bone marrow extracted, and smear preparations made and stained. Polychromatic (PCE) and normochromatic (NCE) erythrocytes were scored for the presence ofmicronuclei. Further groups, each of 7 mice, were given a single oral dose of arachis oil or dosed orally with cyclophosphamide (5 mice). to serve as vehicle and positive controls respectively. Vehicle control animals were killed 24 or 48 hours later, and positive control animals were killed after 24 hours. 

## Results. There were no premature deaths seen in any of the dose groups. Clinical signs were observed in animals dosed with the test material 

## at 600 mg/kg in both the 24 and 48-hour groups, these were as follows: Hunched posture, lethargy. ataxia and ptosis. No statistically significant decreases in the PCE/NCE ratio were observed in the 24 or 48-hour test material dose groups when compared to their concurrent control groups.

1002PROJECT NUMBER: 014510219 PAGES 

### However, the observation of clinical signs was taken to indicate that systemic absorption had occurred and exposure to the target tissue had been achieved. There was no evidence of a significant increase in the incidence of micronucleated polychromatic erythrocytes in animals dosedwith the test material when compared tothe concurrent vehicle control groups. The positive control group showed a marked increase in the incidence of micronucleated polychromatic erythrocytes hence confirming the sensitivity of the system to the known mutagenic activity ofcyclophosphamide under the conditions ofthe test. 

### Conclusion. Thetest material was considered to be non-genotoxic underthe conditions ofthe test.

1003PROJECT NUMBER: 0145/0219 PAGE 7 

### Mixture of PEMB and PE3MB: MICRONUCLEUS TEST IN THE MOUSE 1. INTRODUCTION The micronucleus test is a mammalian 

### in vivo test that detects damage to the chromosomes induced by chemicals. In addition, numerical changes due to chromosome loss during cell division can be detected in this test. The study was performed according to a method that was designed to comply with the 1997 OECD Guidelines for Testing 

### of Chemicals No.474 "Micronucleus Tesf', Method 812 of Commission Regulation (EC) No. 440/2008 of30 May 2008, the USA EPA, TSCA and FIFRA guidelines and the Japanese METIIMHLW guidelines for testing of new chemical substances. The results of the test are believed to be ofvalue in predicting the mutagenic potential of the test material 

## to man. The test system was chosen because the mouse has been shown to be a suitable model for this type of study and is recommended in the test method. The experimental phases of the study were performed between 13 May 2009 and 03 July 2009. 

### 2. PRINCIPLES OF INVESTIGATION In mitotic cells in which chromosome damage has been caused by the test material or its metabolites, fragments (centric or acentric) or whole chromosomes tend to lag behind in the anaphase stage of cell division. After telophase a large proportion ofthe fragments are not included in the nuclei ofthe daughter cells and hence form a single or multiple micronuclei (Howell-Jolly bodies) in the cytoplasm ofthese cells. These micronuclei are seen in a wide variety of cell types, but erythrocytes are chosen since micronuclei are easily detected in these cells. A few hours afterthe last mitosis is completed, erythrocytes expel their nuclei. Immature erythrocytes, less than 24 hours old, stain blue with May-GrOnwald/Giemsa due to the presence of minute fragments of nuclear material in the cytoplasm. This material is mainly ribonucleic acid (RNA), which gradually disappears so that more mature erythrocytes (normochromatic erythrocytes) stain pink with May-GrOnwald/Giemsa. The

1004PROJECT NUMBER: 014510219 PAGES 

### immature blue staining cells are known as polychromatic erythrocytes and mauve stained micronuclei are easily detected in this cell type. If scoring is restricted to polychromatic erythrocytes, all the chromosomal damage detected 

### will have been caused during the final cell cycle of the nucleated precursor cells. Thus by examining polychromatic cells at various periods after administration, the effect of the test material overthe previous 30 hours can be monitored. Any toxic effects of the test material on the immature nucleated cells may lead to a reduction in cell division and cell death. This in turn leads to a reduction in cell volume and to compensate forthis, peripheral blood is shunted into the bone marrow. Ifthe ratio of polychromatic to normochromatic erythrocytes is scored and found to be significantly lowerthan the control value, this is taken as being indicative of cytotoxicity. 

### 3. TEST AND CONTROL MATERIALS AND EXPERIMENTAL PREPARATION 3.1 Test Material Sponsor's identification Mixture of PEMB and PE3MB
w ••**_~** __ •• _ ••• ______ ••**~~** __ • , , , 

# . , , 

### Description , 

# . , 

# . 

# . Batch number 

# . 

# . ..**-~**

## ..

# -....

# -...**--.-.---~** 

### Date received 15 December 2008 Storage conditions Room temperature in the dark The integrity of supplied data relating to the identity, purity and stability of the test material is the responsibility ofthe Sponsor. For the purpose of this study the test material was freshly prepared as required as a solution atthe appropriate concentration in arachis oil. Detennination by analysis of the concentration, homogeneity and stability of the test material preparations was not appropriate because it was not specified in the Standard Test Method. 

### 3.2 Positive Control Material The positive control material was supplied by Acros Organics, as follows:

1005PROJECT NUMBER: 014510219 PAGES 

### Supplier's identification Cyclophosphamide Supplier's lot number A0164185 Date received 10 March 2009 Storage conditions Approximately 4°C in the dark For the purpose of this study the positive control material was freshly prepared as required as a solution at the appropriate concentration in distilled water (supplied by PAM Medical Supplies Ltd. batch no. 300522801). The concentration, homogeneity and stability of the positive control material and its preparation were not determined by analysis. 

### 3.3 Vehicle 

### Control The vehicle was supplied by Lab 3 Ltd, as follows: Supplier's identification Arachis Oil BP Supplier's lot number W72 Date received 05 February 2008 Description Pale straw coloured slightly viscous liquid Storage conditions Room temperature 

### 4. METHODS 

### 4.1 Animals and Animal Husbandry Sufficient albino Hsd: leR

### (CD-1~ strain mice were obtained from Harlan UK. At the start of the main test the male mice weighed 23 to 30g and were approximately five to eight weeks old. After a minimum acclimatisation period of five days the animals were selected at random and given a number unique within the study by tail marking and a numberwritten on a colour coded cage card. The animals were housed in groups of up to seven, by sex, in solid-floor polypropylene cages with wood-flake bedding. Free access to mains drinking water and food (Harlan Teklad 2014 Rodent Pelleted Diet) was allowed throughout the study.

1006PROJECT NUMBER: 014510219 PAGE 10 

### The temperature and relative humidity were set to achieve limits of 19 to 

## 25°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours light and twelve hours darkness. 

### 4.2 Procedure 4.2.1 Range-finding Toxicity Test A range-finding toxiCity test was performed to determine a suitable dose level and route ofadministration forthe micronucleus test. The dose level selected should ideally bethe maximum tolerated dose level or that which produces some evidence of toxicity up to a maximum recommended dose of 2000 

### mg/kg. The range-finding toxicity test was also used to determine ifthe main testwas to be performed using both sexes or males only. Groups 

### ofmice were dosed orally as follows: Dose Level Concentration DoseVofume Numberof Mice

(mg/kg) {mg/mO 

### (mllkg) Male Female 

### 2000 1000

800 

### 600 600 200 100

80 60 60 

### 10 10 10 10 10 

### 1 1 1 

### 1 2 1 

### 1 1 1 

### 0 All animals were dosed once only at the appropriate dose level by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its bodyweight at thetime 

### ofdosing. Animals were observed within the time periods of 

### '%, 1 and 2 hours after dosing and subsequently once daily for up to two days. Any deaths and evidence of overt toxicity were recorded at each observation. No necropsies were performed. 

### 4.2.2 Micronucleus Test Groups, each of seven mice, were dosed once only via the oral route with the test material at 600, 300 or 150 mg/kg. One group of mice from each dose level was killed

1007PROJECT NUMBER: 0145/0219 PAGE 11 

### by cervical dislocation 24 hours following treatment and a second group dosed with test material at600 

### mg/kg was killed after 48 hours. In addition, three further groups of mice were included in the test; two groups (each of seven mice) were dosed via the oral route with the vehicle alone (arachis oil) and a third group (five mice) was dosed orally with cyclophosphamide. Cyclophosphamide is a positive control material known to produce micronuclei under the conditions of the test. The vehicle controls were killed 24 or 48 hours fo.llowing dosing and positive control group animals were killed 24 hours following dosing. The experimental design is summarised as follows:
Dose Group Dose Level (mglkg) Concentration (mg/ml) Dose Volume (mVkg) Kill Time (Hours After Dosing) Animal Numbers 

### 1. Vehicle Control (Arachis oil) 0 0 10 48 1-7 2. Vehicle Control (Arachis oil) 0 0 10 24 8 -14 3. Positive Control (Cyclophosphamide) 50 5 10 24 15 -19 4. Mixture of PEMB and PE3MB 600 60 10 48 20 -26 5. Mixture of PEMB and PE3MB 600 60 10 24 27 -33 6. Mixture of PEMB and PE3MB 300 30 10 24 34-40 7. Mixture of PEMB and PE3MB 150 15 10 24 41-47 

### All animals were observed for signs ofovert toxicity and death one hour after dosing and then once daily as applicable and immediately priortotermination. 

### 4.2.3 Slide Preparation Immediately following termination (i.e. 24 or 48 hours following dosing), both femurs were dissected from each animal, aspirated with foetal calf serum and bone marrow smears prepared following centrifugation and re-suspension. The smears were air-dried, fIXed in absolute methanol, stained in May-GrOnwald/Giemsa, allowed to air-dry and a cover slip applied using mounting medium.

1008PROJECT NUMBER: 014510219 PAGE 12 

### 4.2.4 Slide Evaluation 

### Stained bone marrow smears were coded and examined blind using light microscopy at x1000 magnification. The incidence of micronucleated cells per 2000 polychromatic erythrocytes (PCE-blue stained immature cells) per animal was scored. Micronuclei are normally circular in shape. although occasionally they may be oval or half-moon shaped, and have a sharp contour with even staining. In addition, the number of normochromatic erythrocytes (NCE-pink stained mature cells) associated with 1000 erythrocytes was counted; these cells were also scored for incidence of micronuclei. The ratio of polychromatic to normochromatic erythrocytes was calculated together with appropriate group mean values and standard deviations. 

### 4.2.5 Interpretation of Results 

### A comparison was made between the number of micronucleated polychromatic erythrocytes occurring in each of the test material groups and the number occurring in the corresponding vehicle control group. A positive mutageniC response was demonstrated when a statistically Significant, doseresponsive, toxicologically relevant increase in the number of micronucleated polychromatic erythrocytes was observed for either the 24 or 48-hour kill times when compared totheir corresponding control group. If these criteria were not fulfilled, then the test material was considered to be nongenotoxic underthe conditions ofthe test. A positive response for bone marrow toxiCity was demonstrated when the dose group mean polychromatic to normochromatic ratio was shown to be statistically significantly lowerthan the concurrentvehicle control group. All data were statistically analysed using appropriate statistical methods as recommended by the UKEMS Sub-committee on Guidelines for Mutagenicity Testing Report. Part III (1989). The data was analysed following a .j(x+1) transformation using Student's t-test (two tailed) and any significant results were confirmed using the one way analysis ofvariance.

1009PROJECT NUMBER: 0145/0219 PAGE 13 

### 5. ARCHIVES Unless instructed otherwise by the Sponsor, all original data and the final report will be retained in the Harlan Laboratories Ltd, Shardlow, UK archives for five years, afterwhich instructions will 

### be soUght as to further retention or disposal.

1010

### 6.1 PROJECT NUMBER: 014510219 PAGE 14


### 6. RESULTS Range-finding Toxicity Test The mortality data are summarised as follows:­

Dose Level

(mg/kg) Sex Number of Animals Treated Route Deaths on Day Total Deaths 

### 0 1 

### 2 2000 

### 1000 Male 

### 1 oral oral 

### 1e 

# - - 212
012 

### Female

Male 

### 1 

### 1 1 

### 0 

# - 0 

# - 0 Female 

### 1 0 

## a 0 800 

### Male 

### 1 oral 

### 0 0 0 1/2 i 

### Female 

### 1 1 

# - - 600 Male 

### 1 oral 

### 0 0 

### 0 0/2 Female 

### 1 

## a 0 

## a 600 Male 

### 2 oral 

## a 0 0 0/2 Female 

### 0 

## - 

# - - In animals dosed with the test material via the oral route premature deaths occurred at 800 and 2000 

### mg/kg. and clinical signs were observed at and above 600 mg/kg as follows: Hunched posture. ptosis. ataxia, lethargy. pilo-erection, splayed gait, decreased respiratory rate. laboured respiration. elevated tail and tonic convulsions. The test material showed no marked difference in its 

### toxicity to male or female mice, it was therefore considered to be acceptable to use males only for the main test. Adequate evidence of test material toxicity was demonstrated via the oral route of administration, therefore, this was selected for use in the main test. The maximum tolerated dose (MTD) of the test material, 600 mg/kg, was selected for use in the main test, with 300 and 150 mg/kg as the lower dose levels.



### - = No data e

### = Killed in extremis



### 1011PROJECT NUMBER: 014510219 PAGE 15 

### 6.2 Micronucleus Test 6.2.1 Mortality Data and Clinical Observations There were no premature deaths seen in any of the dose groups. Clinical signs were observed in animals dosed with the test material at 600 mglkg in both the 24 and 48-hourgroups, these were as follows: Hunched posture, lethargy. ataxia and ptOSiS. 

### 6.2.2 Evaluation of Bone Marrow Slides A summary of the results of the micronucleus test is given in Table 1. Individual and group mean data are presented in Tables 2 to 8. There were no statistically significant decreases in the peE/NCE ratio in the 24 or 48-hour test material groups when compared to their concurrent vehicle control groups. However, the observation of clinical signs was taken to indicate that systemic absorption had occurred and exposure to the target tissue had been achieved. There were no statistically significant increases in the frequency of micronucleated PCE in any ofthe test material dose groups when compared to their concurrent vehicle control groups. The positive control group showed a marked increase in the incidence of micronucleated polychromatic erythrocytes hence confirming the sensitivity of the system to the known mutagenic activity of cyclophosphamide underthe conditions ofthe test. The test material was found not to produce a Significant increase in the frequency of micronuclei in polychromatic erythrocytes ofmice underthe conditions ofthetest. 

### 7. CONCLUSION Thetest materialwas considered to 

### be non-genotoxic underthe conditions ofthe test.

1012PROJECT NUMBER: 014510219 PAGE 16 Mixture of PEMB and PE3MB: MICRONUCLEUS TEST IN THE MOUSE 

### Table 1 MicronucleusTest- Summary ofGroup Mean Data
Treatment Group Number of PCE with Micronuclei per2000 PCE PCE/NCE Ratio i Group Mean SO Group Mean SO 1. Vehicle Control 10 mllkg 48-hour Sampling Time 0.4 0.5 1.02 0.18 2. Vehicle Control 10 mVkg 24-hour Sampling Time 0.7 0.8 0.78 0.16 3. Positive Control 50 mgJkg 24-hour Sampling Time 30.0-* 4.7 0.64 0.14 4. Mixture of PEMB and PE3MB 600 mglkg 48-hour Sampling Time 0.7 0.8 0.99 0.12 

### 5. Mixture of PEMB and PE3MB 600 mg/kg 24-hour Sampling Time 0.6 0.8 1.00 0.32 6. Mixture of PEMB and PE3MB 300 mg/kg 24-hour Sampling Time 1.6 1.5 0.81 0.15 

### 7. Mixture of PEMB and PE3MB 150 mglkg 24-hour Sampling Time 1.0 1.0 0.79 0.30

PCE 

### = Polychromatic erythrocytes NCE 

### = Nonnochromatic erythrocytes SO 

# =standard deviation 

## *.. 

# =P < 0.001



### 1013Mixture of PEMB and PE3MB: MICRONUCLEUS TEST IN THE MOUSE 

### Table 2 Micronucleus Test - Individual and Group Means and Standard Deviations: Vehicle Control (10 ml/kg)**48~Hour** 

### Sampling Time BODYWEIGHT POLYCHROMATIC ERYTHROCYTES NORMOCHROMATIC TREATMENT GROUP 

### ANIMAL (g) WHEN (PCE) ERYTHROCYTES (NCE) PCE/NCE NUMBER NUMBER NUMBER RATIO DOSED PCE+MN %PCE+MN NCE+MN SCORED SCORED 

### 1 26 2000 

## a 0.00 445 

## a 1.25



## ---­ -----­ 2 28 2000 0 0.00 446 0 1.24 -_. - ..**.-,-~** - . ­ 

### '­ ........ 

### -"**-~.--** , .­ ___ H • 3 27 2000 

### 1 0.05 482 0 1.07 

### 1. 4 27 2000 

### 1 0.05 498 0 1.01 

### VEHICLE CONTROL 5 23 2000 

### 1 0.05 544 0 0.84

10 mllkg 48-hour

sampling time 6 27 2000 0 0.00 530 1 0 0.89 7 

### 26 2000 0 0.00 552 1 0.81 Group Mean 26.3 2000 0.4 

# lu­ 0.02 500 0.1 1.02 !----­

----­ 

### SO 1.6 

## a 0.5 0.03 44 0.4 0.18

--­ j

--­ , --­



### o


### ...... .1/10. PROJECT NUMBER: 014510219 PAGE 17

### Mixture ofPEMB and PE3MB: MICRONUCLEUS TEST IN THE MOUSE 

### Table 3 Micronucleus Test - Individual and Group Means and Standard Deviations: Vehicle Control (10 ml/kg) 24-Hour Sampling Time BODVWEIGHT POLYCHROMATIC ERYTHROCYTES NORMOCHROMATIC TREATMENT GROUP ANIMAL (g) 

### WHEN (PCE) ERYTHROCYTES (NCE) PCE/NCE NUMBER NUMBER NUMBER RATIO DOSED PCE+ MN %PCE+ MN NCE+ MN SCORED SCORED 

### 8 

### 27 2000 0 0.00 594 2 0.68 

### 9 29 2000 1 0.05 486 0 1.06
, -<. __..._­ 

### -**----.~.--** ..

## __. - ---­ - - .

## __., -_..

## ­**~.~** ,-_...

## _­ - . ... - ._-, , -------,. 

### 10 25 2000 1 0.05 580 0 0.72

.. 

### 2. 11 26 2000 0 0.00 577 

### 0 0.73 VEHICLE CONTROL -------­



### 10 mllkg 24-hour 12 30 2000 0 0.00 619 

### 0 0.62

sampling time 13 

### 29 2000 2 0.10 588 0 0.70**~--** 

### 14 29 2000 1 0.05 521 

### 1 0.92 Group Mean 27.9 2000 0.7 0.04 566 0.4 0.78

----­ 

### SO 1.9 0 0.8 0.04 46 0.8 0.16



### o 

# .... c.n PROJECT NUMBER: 0145/0219 PAGE 18

### Mixture of PEMB and PE3MB: MICRONUCLEUS TEST IN THE MOUSE 

### Table 4 MicronucleusTest -Individual and Group Means and Standard Deviations: Cyclophosphamide (60 mg/kg) 24-Hour Sampling Time POLYCHROMATIC ERYTHROCYTES NORMOCHROMATIC ANIMAL BODYWEIGHT (PCE) ERYTHROCYTES (NCE) PCE/NCE TREATMENT GROUP (g)

### WHEN NUMBER DOSED NUMBER NUMBER RATIO SCORED PCE+MN °Ji,PCE + MN SCORED NCE+MN 

### 15 23 2000 32 1.60 703 0 0.42 15 23 2000 25 1.25 577 0 0.73

,.. ,._--.. - "­ '. --_._._-­**~-** .-.**~-"** -­ 1---,
..... -, ----- .. 

## ,­ .. ..**-~** 3. 

### 17 

### 24 2000 33 1.55 607 0 0.65 CYCLOPHOSPHAMIDE

- 50 mglkg 

### 18 28 2000 35 1.75 563 0 0.78 24-hour sampling time 

### 19 24 2000 25 1.25 625 0 0.50 Group Mean 

### 24.4 2000 30.0 1.50 615 0.0 0.64

..... 

# I SD 

### 2.1 0 4.7 0.23 55 

### 0.0 0.14

o en PROJECT NUMBER: 014510219 PAGE 19Mixture of PEMB and PE3MB: MICRONUCLEUS TEST IN THE MOUSE 

### Table 5 Micronucleus Test -Individual and Group Means and Standard Deviations: Test Material (600 mg/kg) 48-Hour Sampling Time
BODYWEIGHT POLYCHROMATIC ERYTHROCYTES (PCE) NORMOCHROMATIC TREATMENT GROUP ANIMAL (g) WHEN ERYTHROCYTES (NCE) PCE/NCE NUMBER DOSED NUMBER NUMBER RATIO SCORED PCE+ MN %PCE+MN SCORED NCE+MN 20 28 2000 1 0.05 

### 514 0 0.95

--­ 

# -­ 21 26 2000 0 0.00 485 0 1.06

---­ 22 

### 29 2000 1 0.05 506 0 0.98 4. Mixture of PEMB and 23 24 2000 1 0.05 454 0 1.20**--~** PE3MB 

### 24 23 2000 0 0.00 558 0 0.79 600 mg/kg ---­ --­ -­ --­ - 48-hour sampling time 25 27 2000 0 0.00 504 0 0.98 26 

### 25 2000 2 0.10 509 1 0.96 Group Mean 26.0 2000 0.7 0.04 504 0.1 0.99 SD 

### 2.2 0 0.8 0.04 31 0.4 0.12

-­



### o


### ...... ....., PROJECT NUMBER: 0145/0219 PAGE 20

### Mixture of PEMB and PE3MB: MICRONUCLEUS TEST IN THE MOUSE 

### Table 6 Micronucleus Test -Individual and Group Means and Standard Deviations: Test Material (600 mg/kg) 24-Hour Sampling Time
BODYWEIGHT POLYCHROMATIC ERYTHROCYTES (PCE) NORMOCHROMATIC TREATMENT GROUP ANIMAL (g) 

### WHEN ERYTHROCYTES (NCE) PCEINCE NUMBER DOSED NUMBER NUMBER RATIO SCORED PCE+MN %PCE+MN SCORED NCE+ MN 27 28 2000 1 0.05 508 0 0.97 28 28 2000 2 0.10 533 0 0.88

---­ 29 26 2000 0 0.00 377 0 1.65 

### 5.

--­ Mixture of PEMB and 30 27 2000 0 0.00 604 0 0.66 PE3MB 31 25 2000 1 0.05 519 0 0.93 600 mg/kg 32 24 2000 0 0.00 24-hour sampling 

### time 482 

## a 1.07**-~-** 33 29 2000 0 0.00 548 0 0.82 Group Mean 26.7 2000 0.6 0.03 510 0.0 1.00

--­ 

### SO 1.8 0 0.8 0.04 70 0.0 0.32

--­ 

# -

o 

# .... CIO PROJECT NUMBER: 0145/0219 PAGE 21Mixture of PEMB and PE3MB: MICRONUCLEUS TEST IN THE MOUSE 

### Table 7 MicronucleusTest - Individual and Group Means and Standard Deviations: Test Material (300 mg/kg) 24-Hour Sampling Time
BODYWEIGHT POLYCHROMATIC ERYTHROCYTES (PCE) NORMOCHROMATIC I TREATMENT GROUP ANIMAL (g) WHEN ERYTHROCYTES (NCE) PCE/NCE NUMBER DOSED NUMBER NUMBER RATIO SCORED PCE+MN O/OPCE + MN SCORED NCE+ MN 34 25 2000 1 0.05 598 0 0.67

--­ -­ -­ 35 24 I 2000 0 0.00 520 0 0.92 

### 36 25 2000 4 0.20 604 0 0.66 6. Mixture of PEMB and



## -­ 37 26 2000 1 0.05 525 

## a 0.90 PE3MB 

### 38 24 2000 0 0.00 501 0 1.00 300mglkg 24-hour sampling time 39 25 2000 

### 3 0.15 604 0

# o~ --­ --­ 40 25 2000 2 0.10 530 0 0.89 Group Mean 24.9 2000 1.6 0.08 555 0.0 0.81 

### SD 0.7 0 1.5 0.08 45 0.0 0.15



# -­**-~** 

# --­ I

o co PROJECT NUMBER: 0145/0219 PAGE 22Mixture of PEMB and PE3MB: MICRONUCLEUS TEST IN THE MOUSE 

### Table 8 Micronucleus Test -Individual and Group Means and Standard Deviations: Test Material (150 mg/kg)**24~our** 

### Sampling Time

BODYWEIGHT POLYCHROMATIC ERYTHROCYTES (PCE) NORMOCHROMATIC TREATMENT GROUP ANIMAL (g) WHEN ERYTHROCYTES (NCE) PCE/NeE NUMBER DOSED NUMBER NUMBER RATIO SCORED PCE+MN %PCE+MN SCORED NCE+MN 41 25 2000 0 0.00 705 0 0.42

-­ 42 24 2000 2 0.10 584 0 0.71

----. 43 24 2000 2 0.10 603 0 0.66 7. -1------­

--­ Mixture of PEMB and 44 26 2000 0 0.00 542 0 0.85

-­ PE3MB 45 26 2000 

### 1 0.05 603 0 0.66 150 mglkg --­ 24-hour sampling time 46 26 2000 0 0.00 

### 533 0 0.88 47 29 2000 2 0.10 420 

## a 1.38 Group Mean 25.7 2000 1.0 0.05 570 0.0 0.79 

### SO 1.7 0 

## I 1.0 0.05 87 0.0 0.30



### o N 

### o PROJECT NUMBER: 0145/0219 PAGE 23PROJECT NUMBER: PAGE 24 Mixture of PEMB and PE3MB : MICRONUCLEUS TEST IN THE MOUSE 

### Appendix 1 Historical Control Data from 45 Studies (2007 and 2008) 48-HourVehicle Control Group Mean Data

! PCE + MN Per 2000 PCE PCEINCE 1000 Erythrocytes Mean 0.90 1.09

SO 0.54 0.37 Minimum 0.00 0.62 Maximum 2.60 2.54 24-HourVehicle Control Group Mean Data PCE + MN Per2000 PCE PCElNCE 1000 Erythrocytes I Mean 0.99 1.05

SO 0.60 0.32 Minimum 0.10 0.60 Maximum 3.20 2.32 24·Hour Positive Control Group Mean Data PCE + MN Per2000 PCE PCEfNCE 1000 Erythrocytes Mean 42.76 1.17

SO 13.55 0.31 Minimum 17.60 0.72 Maximum 66.40 2.03

PCE 

# =Polychromatic erythrocytes NCE 

# =Normochromatic erythrocytes SO 

### = Standard deviation



### 1021PROJECT NUMBER: 014510219 PAGE 25 

### Appendix 2 Statement of GLP Compliance in Accordance with Directive 2004/9IEC



# ,DH') De.'partment
, of

## Health

THEDEPARTMENTOFREALTH OF

### THE GOVERNMENT 

## OFTIm

## UNITED KlNGDOM GOODLABOllATORYPRACTICE STATEMENTOFCOMPLIA.."iCE INACCORDANCEWlTflDJR.ECm1B2004J91EC 'T)';ST FACILrrv TES'fTYPE Harlan LaboratoriesLtd. Analytical/ClinkalChelJ!isby ShardlawBllSiness Park EnvironmentalFate .L&ndon Rood EnvironmentalToxicology Sliardlow Mutag'nicity Derby Pby&lCbem 

### DE72 2GD Toxicology

19thAugust: 2008**Agen~ral** 

### inspeco<m for compliance with the Principles ofGood LabQcatory Pracrice

was**c~** outa! the ftbove1:est facility as partoftbe

### UK. G.LPCompliancePrOgrnmme. At the**~rile** ofinspection DO deviations were fQuod 

### ofsufficient magnitude to affect the validity olnon-clinical slUdlesperfonned attitesefacilities.

Dr.AndrewJ. Gray Head, UK GLPMonitoringAuthorllJ



### 1022

### PAGE 1 OF 68 PAGES 

# harlannl 

# ....

Mixture of PEMB and PE3MB: DETERMINATION OF ABIOTIC DEGRADATION, HYDROLYSIS AS A FUNCTION OF pH PROJECT NUMBER: 014510218

AUTHORS: R E Butler D FWhite

STUDY SPONSOR: TEST FACILITY: Showa Denko K.K. Harlan Laboratories Ltd 13-9, Shiba Daimon 1-Chome Shardlow Business Park Minato-ku Shardlow TOKYO 105-8518 Derbyshire JAPAN DE722GD 

### UK Telephone: +44 

### (O) 1332792896 Facsimile: +44 (0) 1332 799018

1023PROJECT NUMBER: 014510218 PAGE 2 

### QUALITY ASSURANCE REPORT This study type is classed as short-tenn. Inspection of the routine and repetitive procedures that constitute the study is carried out as a continuous process designed to encompass the major phases at or about the time this study was in progress. In addition, inspection of general facilities not specifically related to this study are done monthly orannually in accordance with QA 

### Standard Procedure. This report has been audited by the Quality Assurance Unit, and is considered to be an accurate account ofthe data generated and ofthe procedures followed. In each case, the outcome of QA 

### evaluation is reported to the Study Director and Management on the day of evaluation. Audits of study documentation, and process inspections appropriate to the type and schedule of

### this study were as follows: 

### § 30 April 2009 Protocol Compliance Audit 03,06,09,10 July 2009 Abiotic Degradation 

### § 07 September 2009 Draft Report Audit 

### § Date of QA Signature Final Report Audit 

### § Evaluation specific to this study

\

'"Authorised QA Signatures: Manager, Quality Assurance: J G Riley SSe (Hons) MRQA Deputy Head of Department: JM Crowther MIScT MRQA SeniorAudit Staff: G Wren ONC MRQA

1024PROJECT NUMBER: 014610218 PAGE 3 

### GLP COMPLIANCE 

### STATEMENT The work described was performed in compliance with UK GLP standards (Schedule 1, Good Laboratory Practice Regulations 1999 (SI 1999/3106 

### as amended by SI 2004/0994»). 

### These Regulations are in accordance with GLP standards published as OECD Principles on Good Laboratory Practice (revised 1997, ENVIMC/CHEM(98}17): and are in accordance with, and implement, the requirements of Directives 2004/9/EC 

### and 2004/10/EC. 

### This report fully and accurately reflects the procedures used and data generated
. 

## . 2

# It SEP 

# 2009

................. ......................... DATE
................................................. R E Butler GRSC STUDY DIRECTOR

This report may be presented in final form as a digital (Pdf) document. Such documents .ue prepared by scanning the paperOriginal,

and are considered ofequivalent integrity and authenticitytoversions produced by optical photocopy. However, in all cases the hand-signed paper original, held in secure archives. Is the definitive document



### 1025PROJECT NUMBER: 0145/0218 PAGE 4 

### CONTENTS QUALITY ASSURANCE REPORT 2 GLP COMPLIANCE STATEMENT 3 CONTENTS 4 SUMMARY 5 1. INTRODUCTION 6 2. TEST MATERIAL 6 2.1 Description, Identification and Storage Conditions 6 2.2 Chemical Structure 7 3. ARCHIVES 7 4. HYDROLYSIS AS A FUNCTION OF pH 8 4.1 Method 8 4.2 Procedure 8 4.3 Calculation 15 4.4 Results 17 4.5 Validation 66 4.6 Discussion 66 4.7 Conclusion 67 Appendix 1 Statement ofGLP Compliance in accordance with Directive 2004l9/EC 68



### 1026PROJECT NUMBER: 0145/0218 PAGE 5


### Mixture of PEMB and PE3MB: DETERMINATION OF ABIOTIC DEGRADATION, HYDROLYSIS AS A FUNCTION OF pH SUMMARY Assessment of hydrolytic stability was carried out using Method C7 Abiotic Degradation, Hydrolysis as a Function of pH of Commission Regulation (EC) No 44012008 of 30 May 2008 and Method 111 ofthe OECD Guidelines for Testing of Chemicals, 13 April 2004. The results are as follows: pH Rate constant (S·1) Estimated half-life at 25"C PE3MB PEMB PE3MB PEMB 4 not applicable not applicable >1 year >1 year 7 not applicable not applicable >1 year >1 year 

### 9 2.07

### x 10-5 2.91 

### x 10.5 9.33 hours 6.61 hours 

### No definitive signs of hydrolysis at pH 4 or pH 7. Testing performed at various temperatures indicated that losses observed were not pseudo-first order and therefore most likely to be due other mechanisms or effects rather than hydrolysis. For further information refer to Discussion (Section 4.6).



### 1027

### 2.1 PROJECT NUMBER: 014510218 PAGE 6 

### Mixture ofPEMB and PE3MB: DETERMINATION OF ABIOTIC DEGRADATION, HYDROLYSIS AS A FUNCTION OF pH
1. INTRODUCTION The abiotic degradation. hydrolysis as a function of pH of the test material has been determined. The method employed complies with those specified in Commission Regulation (EC) No 440/2008 

### of 30 May 2008. Part C: Methods for the determination of ecotoxicity and the current OECD Guidelines for Testing ofChemicals. Testing was conducted between 01 May 2009 and 29 July 2009. 

### 2. TEST MATERIAL Description, Identification and Storage Conditions Sponsor's identification Mixture of PEMB and PE3MB 

### .-----------.-.-.. ------------ 

### ..**----~** 

### Description Purity Batch number 

# . Date received 

## ··-10·0ecEiiiioer-200S·········, Storage conditions room temperature in the dark The integrity of supplied data relating to the identity, purity and stability of the test material is the responsibility ofthe Sponsor.

1028

### 2.2 PROJECT NUMBER: 014510218 PAGE 7 

### Chemical Structure The Sponsor provided the**foll?~i.~~.c?~~.,,!!i.C?~I.~~~I:I~I:I!~.~9rJ~.~J~~trJ:I~~rj~L** 

### ...........

, .. ---- .......................................... --- ...... --............ f 

# · . · . · . · . · 

# . · . · 

# . ·

. : ................... __ ....................................... _ .............................. __ ........ _._ .. _ ............................... _._ ............................._ ................ _ ...... _ .. _ .. _t 

### 3. ARCHIVES Unless instructed otherwise by the Sponsor, all original data and the final report will be retained in the Harlan Laboratories Ltd, Shardlow, UK archives forfive years, after which instructionswill be sought as tofurther retention or disposal.

1029PROJECT NUMBER: 014510218 PAGE 8 

### 4. HYDROLYSIS AS A FUNCTION OF pH 4.1 Method The determination was carried out using Method C7 Abiotic Degradation, Hydrolysis as a Function of pH of Commission Regulation (EC) No 

## 44012008 of 30 May 2008 and Method 111 ofthe OECD Guidelines forTesting ofChemicals, 13 April 2004. 

### 4.2 Procedure 4.2.1 Specification of

### buffersolutions Table 4.1 Buffer solution (pH) Components Concentration (moldm-3) 

### 4 Citric acid Sodium chloride 

### 0.061 0.044
7 

### Disodium hydrogen orthophosphate (anhydrous) Potassium dihydrogen orthophosphate Sodium chloride 

### 0.03 0.02 0.02 

### 9 Disodium tetraborate Sodium chloride 

### 0.01 0.02 

### The buffer solutions were filtered through a 0.2 IJm membrane filter to ensure they were sterile before commencement of the test. Also these solutions were subjected to ultrasonication and degassing with nitrogen to minimise dissolved oxygen content. 

### 4.2.2 Preparation ofsamples Sample solutions were prepared in capped glass bottles at a nominal concentration of 3.7 x 10-4 gil in the three buffer solutions. A 1% co-solvent ofacetonitrile was used to aid solubility. The test solutions were split into individual vessels for each data point. The solutions were shielded from lightwhilst maintained at the testtemperature.

1030PROJECT NUMBER: 0145/0218 PAGE 9 

### 4.2.3 Preliminary testJTier 1 Sample solutions at pH 4, 7 and 9 were maintained at 50.0 

## ±O.soC. 

### 4.2.4 Tier 2 Results from the Preliminary testITier 1 showed it was necessary to undertake further testing at pH 4, pH 7 and pH 9. Testing atthe three pHs was performed as follows; pH 4 at 40, 50 and 60°C, pH 7 at 20, 30, 40, 50 and 60°C, and pH 9 at 20, 30 and 40°C. The time intervals atwhich hydrolysis were monitored are given in Tables 4.20 to 4.36. 

### 4.2.5 Analysis ofsample solutions The sample solutions were taken from the water baths at various times and the pH of each solution recorded. The concentration of the sample solution was determined by high performance liquid chromatography (HPLC). 

### Samples An aliquot (100 ml) of each sample was extracted with three portions (3 x 10 ml) of methyl tertiary butyl ether (MTBE). The combined extracts were evaporated to dryness and the residue redissolved in 1 ml ofacetonitrile: water (1:1 v/v). 

### Standards Duplicate standard solutions of test material were prepared in acetonitrile water (1: 1 v/v) at a nominal concentration of37 mg/l. 

### Matrixblanks An aliquot (100 ml) ofthe relevant buffer solution was extracted with three portions (3 x 10 ml) of MTBE. The combined extracts were evaporated to dryness and the residue redissolved in 1 ml ofacetonitrile: water (1:1 v/v).

1031PROJECT NUMBER: 0145/0218 PAGE 10 

### Analysis The standard conditions*: and sample solutions were analysed by HPLC using the following HPLC System Agilent Technologies 1100, incorporating autosampler and workstation Column Phenomenex 00S3 5lJm (250 x 4.6 mm id) Column tempe Mobile phase rature 40°C SolventA: acetonitrile (0.1% orthophosphoric acid) Solvent B: water (0.1% orthophosphoric acid) 

# , Time (mins) 

# o mins SolventA (%) 50 Solvent B (%) 50 25 mins 80 20 I 

### 26 mins 100 0 31 mins 100 0 Flow-rate 1.0 mllmin 

### UV detectorwavelength 200 nm Injection volume 100 

### IJI Retention time Component

## A: -12 mins Component B: - 22 mins

• Analysis of pH 4. 40°C samples at time pOints, initial, 48. 70.5 and 144 hours were analysed with the following amendments to the conditions: 1. Column: Phenomenex ODS3 5IJm (150 x 4.6 mm id) 2. Mobile Phase: gradient modified to 75% Solvent A. 25 % Solvent B at 25 minutes. 3. Retention times: Component A -9 mlns, Component B -19 mins


### 1032PROJECT NUMBER: 014510218 PAGE 11 

### Typical Chromatography Standard: 37.7 mgn
VWD1A. Wavelength=200 nm (PGT3221001-0101.0) mAU

175 150 125 100 75

.... 

### '" N SO <II 2S A

# ~Jl 0 

## J\

n**~** 

### 10 15



### Sample: pH 4, 50°C, 24 Hour 

# ---_..

# _-­ VW01 A. Wavelengtll=200 nm (PGT5S41007-0701.0) mAU**~**

200 175 150**~** 125**~** 100 75



# ... 50 

# ...**~** 25

10 15 2 I I 

# 20

1033PROJECT NUMBER: 0145/0218 PAGE 12 

### Typical Chromatography Matrix Blank: pH 4

mllU VW01 A. Wavelenglh=200 nm (PGT5941021-2102.0)

200 175 15D 125 100 75 50

I 25 0 

### ;; 

### \.. 1Q 15 20 

### 2S --./



### Sample: pH 7, 60°C, 43 Hour
VW01 A. Wavelenglh-200 lim (PGT48BIO07.o701.0) mAU

200 175 150 125 100 75 so 25 o



### 1034PROJECT NUMBER: 014510218 PAGE 13 

### Typical Chromatography Matrix Blank: pH 7

mAU VWOl A, Wavelengtlr-2OO om (PGT486\D()4..0401.0)

200 175 1!ill 125 100 75 50 26 

### o 

### .M .A**~** 

### \ v-. 

# lLJ-!

I) Ii HI :IS 2!l 211 '"



### Sample: pH 9, 30G

### C, 2 Hour
VW01 A. Wavelength=200 nm (PGT32211l11-1101.0) mAU

175 150 125 100 75 50

### ~ 25

# ~~~A~A~~ '"

________

# ~J~~---~

__**~QL-** ________**~5L-** ________**~1~Q** __________**'~5** ________**~2wO** __________**.~L-** ________**~m~!a**



### 1035150



# I PROJECT NUMBER: 014510218 PAGE 14 

### Typical Chromatography Matrix Blank: pH 9
VW01 A. Wawlanglh"'200 nm (PGT3221OD4-0401.D} mAU 

# 1

175

125 100 75

25

## ~~~~l,~.~.~ 

# __**~----------------~** 10



### 1036PROJECT NUMBER: 014510218 PAGE 15 

## Treatlnentofnesults Graphs of the common logarithm of the concentration (gil) versus time (hours) were plotted for each pH at each temperature (see Figures 4.1 to 4.22) and where applicable, the rate constants and half-lives calculated using Equation 4.2 and Equation 4.3 respectively. By plotting the natural logarithm of the rate constants against the reciprocal of the temperature (K), the rate constants and half-lives at 25°C were obtained by interpolation or extrapolation (see Figures 4.23 and 4.24). 

### 4.3 Calculation 4.3.1 Sample solution concentration The mean peak height or area* of each standard was corrected to a nominal concentration of37 mgll and the mean value taken. The concentration ofthe sample solutions (gil) 

### was calculated using Equation 4.1. 

### Equation 4.1 

### P

SpI 

### 1 xDx-­ CSPI 

### =-xC std 

### 1000 P

sld 

### where: Cspl 

# = sample concentration (g/l) Pspl 

# = mean peak height or area ofsample solution Pstd 

# = mean peak height or area ofstandard solution, corrected to nominal standard concentration Cstd 

### = nominal standard concentration (37 mg/l) D 

# = sample dilution factor (0.01)

.. Peak area was used for the pH 4 and 9 calculations and peak height was used for the pH 7 calculations (see Discussion, Section 4.6).


### 1037PROJECT NUMBER: 0145/0218 PAGE 16 

### 4.3.2 Estimation of half-life From the graph of log10 concentration 

### (gIl) versus time, the rate constant was calculated using Equation 4.2. 

### Equation 4.2 kobs =-slopex2.303 and the half-life was obtained from the rate constant using Equation 4.3. 

### Equation 4.3

where:
kObs 

## = rate constant (hours-') half-life (hours)

1038PROJECT NUMBER: 014510218 PAGE 17 

### 4.4 Results 4.4.1 Preliminary testITier 1 The mean peak areas relating to the pH 4 and pH 9 standard and sample solutions are shown in the following table:
Solution Standard 46.2 mgll Standard 46.7 mgll Initial Sample A. pH 4 Initial Sample B. pH 4 2.4 hour Sample 

### A. pH 4 2.4 hour Sample B. pH 4 4 hourSample A. pH 4 4 hour Sample B, pH 4 Standard 46.2 mgll Standard 46.7 mgll 24 hour Sample A. pH 4 24 hour Sample B. pH 4 Initial Sample A, pH 9 Initial Sample B. pH 9 2.4 hour Sample A. pH 9 2.4 hour Sample B, pH 9 24 hour Sample A, pH 9 24 hour Sample 8, pH 9 Standard 46.2 mglJ Standard 46.7 mgll 120 hour Sample A, pH 4 120 hour Sample B, pH 4 _I 

### ND - none detected Table 4.2 Component A Mean PeakArea 376.809 387.843 349.774 351.318 364.178 240.039 353.094 330.860 384.043 397.867 146.740 278.857 256.161 272.743 

### NO 44.970



### NO NO 360.395 354.935 65.561 92.852 Component B Mean Peak Area 2.570x 103 

### 2.587x 103 

### 2.672 x 103 

### 2.882 x 103 

### 2.852 x 10 3 1.607 x 103 

### 3.062 x 103 

### 2.725x 103 2.511x103 2.616 x 103 

### 1.412 x 103 

### 2.930 x 103 

### 1.330x 103 

### 1.463x 103 

### NO 76.761



### NO NO 2.490x 103 

### 2.496x 10'

479.563 860.987



### 1039PROJECT NUMBER: 014510218 PAGE 18 

### The mean peak heights relating to the pH 7 standard and sample solutions are shown in the following table: 

### Tabla 4.3 Solution Component B Mean Peak Height Standard 46.2 mg/l 234.921 Standard 46.7 mgll 248.334 Initial Sample A, pH 7 156.610 Initial Sample S, pH 7 145.797 2.4 hour Sample A, pH 7 18.970 2.4 hour Sample S, pH 7 41.456 50 hour Sample A, pH 7 

### NO 50 hour Sample B, pH 7 

### NO 96 hour Sample A, pH 7 

### NO 96 hour Sample S, pH 7 

### NO NO - none detected The test material concentrations at the given time points are shown in the following tables: 

### Table 4.4 

### pH 4 at 50.0

# ±O.SoC M 

### Component A Time (Hours) Concentration (gIl) Logio [concentration (gll)1 

### I %of mean initial concentration A B A 

### B A 

### S 0 4.25 X 10"" 4.27 X 10"" -3.37 -3.37 

# - 

# - 2.4 4.43 x 1.r 2.92 x 10"'" -3.35 -3.54 104 68.5 4 4.29 x 10"'" 4.02 X 10"" -3.37 -3.40 101 94.4 24 1.74x10"" 3.31 x 10"" -3.76 -3.48 40.9 77.8 120 8.51 x 10-5 1.12x 10"'" -4.07 -3.92 20.0 28.3 

### Result: Slope 

## = -4.99 x 

### 10-3 

### (see Figure 

### 4.1) 

## r2 

# = 0.850 

## kobs = 1.15 x 

### 10-2 

### hou(1, 

### 3.19 X 

### 10-6 second-1 

## t% 

# = 6004 hours, 2.52 days

1040PROJECT NUMBER: 0145/0218 PAGE 19 

### Table4.5 pH 4 at50.0 

# ±O.5°C

- ComponentB Time (Hours) Concentration (g/l) L0910 

### [concentration (gil)] % 

### ofmean initial concentration A 

### 8 A 

### 8 A 

### 8 0 4.81 X 10"" 5.19x10·4 -3.32 -3.29 

# - 2.4 5.14x10"" 2.90x 10"" -3.29 -3.54 103 57.9 

### 4 5.52 x 10"" 4.91 X 10"" -3.26 -3.31 110 98.1 24 2.56 x 10"" 5.31 X 10"" -3.59 -3.28 51.1 106 120 8.94 x 1005 1.60 X 10"" -4.05 -3.80 17.9 32.1 

### Result: Slope 

# = -5.00 x 

### 10-3 (see Figure 

### 4.2)

### ~ 

# = 0.794 1.15x 

### 10-2 

### hou(1, 

### 3.20 x 

### 10-6 second-1 

### 60.2 hours, 

### 2.51 days


### Table4.6 pH 7 at50.0 

# ±O.SOC • ComponentB Time (Hours) Concentration (gil) 

### Log 10 

### [concentration (gIl)] % 

### of mean initial concentration A 

### B A 

### B A 

### B Initial 3.01 2.80 -3.52 -3.55 

# - - 2.4 3.65 7.97 -4.44 -4.10 12.5 27.4 50 

# - - - 

# - - - 96 

# - 

# - - 

# - - - Result: Slope 

# = -0.305 (see Figure 

### 4.3)

### ~ 

# = 0.903 kobs 

## = 0.702 hour-1, 

### 1.95 x 10-4 second-1**t~** 

## = 0.988 hours, 

### 4.12 x 10-2 

### days

1041PROJECT NUMBER: 014510218 PAGE 20 

### Table 4.7 pH 9 at50.0 

## ±O.soC**~** 

### Component A
Time (Hours) Concentration (gil) Log 10 [concentration (gil)] 

### % ofmean initial concentration 

### A B A B A B Initial 3.04 x 10-4 3.24 X 10"" -3.52 -3.49 

# - - 2.4 

# - 5.34 x 10-5 

# - -4.27 

# - 17.0 24 

# - 

# - - - . - Result: Slope = 

### -0.321 

### (see Figure 4.4) 

# r2 

# = 1.00 0.738 

### hOUf1, 

### 2.05 x 10-4 

### second-1 

### 0.939 

### hours, 3.91 x 10.2 

### days
Table 4.8 pH 9 at 50.0 

# ±O.soC - Component B
Time (Hours) Concentration (gil) Log 10 [concentration (gil)) 

### % of mean initial concentration A 

### B A 

### B A 

### B Initial 2.41 X 10-4 2.65 x 10"" -3.62 -3.58 

# - 2.4 

# - 1.39 x 10-5 

## . -4.86 

## - 5.50 24 

# - - - - 

## . 

# - Result: Slope 

# = -0.525 

### (see Figure 4.5) 

# r2 

# = 1.00 kObl 

## = 1.21 

### hOU(l, 3.36 X 

### 10-4 

### second-1 

### 0.574 

### hours, 2.39 x10-2 

### days
For each pH, the extent of hydrolysis indicated that further tests (Tier 2). 

### conducted at three temperatures' were required to estimate the rate constants and half-lives.

* Testing at pH 7 was initially performed at three temperatures (20, 30 and 40°C). Due 

### to inconclusive data. further testing was pertormed at elevated temperatures of50 and 60°C plus some testing at25°C.


### 1042PROJECT NUMBER: 0145/0218 PAGE 21 

### Figure

### 4.1 pH 

### 4 at

### 50.0 

## ±O.soC - ComponentA Graph oflog10 Concentration (gil) versus Time (Hours) pH4\PreUmlnary Test at

## so·e**~-3.** 

# S c 

### ,8 

# i ·3, 

# § 

# £ Q

### ~-3.5 -3.S
-3.7 

# •

•

.3. 

# -4.0 -.0 4.)72

_**~'/O** l.4OO .uN 2.A4IO 4
... 4.00II
..... ,.DaD ..... 

# - ..... 2'- 4AIG 120JIIIG ....,.,



# •**-4.1~------------------------""'-------------""'-----** 

## o 20 40 

### 60 80 100 120 Ttme (hours)



### 1043

# • •



# • • PROJECT NUMBER: 014510218 PAGE 22 

### Figure 4.2 pH 4 at

## 50.0 

# ±0.5OC

- Component B Graph of IOg10 Concentration (gIl) versus TIme (Hours) pH4\PrelimlnaryTest

### at50'e**~-3.2** 

## S
:;:s 

# a g c: 

## 8 

# 1-3.4 0


### .....**~**
-3.6

-3. 

# •

-4. 

# •**-4.2~-------------------------------------------** 

## o 20 40 60 

### 80 100 120 Time (hours)

1044PROJECT NUMBER: 0145/0218 PAGE 23 

### Figure 4.3 pH 7 at

### SO.O 

# ±O.soC

- Component B Graph of 10g1o Concentration (gil) versus Time (Hours)

-3.8

-4.0

-4.2

-4.4 pHnPrelimlnary Test at SOOC



# •



# • -4.6'------------------...-..----.

0.0 0.5 1.0 1.5 

### 2.0 2.5 TIme (hours)



### 1045-3.8 PROJECT NUMBER: 014510218 PAGE 24 

### Figure 4.4 pH 9 at 50.0 :t: 

### 0.5°C - Component A Graph of 10910 

### Concentration (gil) versus Time (Hours) pH9\Preliminary Test at 50°C

......uo:s 

# ..--. 

# ..

-4.

-4.2**-4.4k-------------------------------~--------** 

### 0.0 

### 0.5 1.0 1.5 

### 2.0 2.5 Time (hours)



### 1046PROJECT NUMBER: 014510218 PAGE 25 

### Figure 4.5 pH 9 at

## SO.O ::I: 

### 0.5°C - Component B Graph of IOg10 Concentration (gil) versus Time (Hours) pH9\PreliminaryTest at

## so·e ::::::-3.2

### ~ c 

# i**~ ~.3.**  

# J

-4.0

-4.4

-4.8 

# -5.2'----------------------­

0.0 

### 0.5 1.0 1.5 

### 2.0 2.5 Time (hours)



### 1047PROJECT NUMBER: 014510218 PAGE 26 

## 4.4.2 Tier 2 The mean peak areas relating to the standard and sample solutions are shown in the following table: 

## Table 4.9

- pH 4, 40.0°C Solution Component A Mean Peak Area Component B Mean Peak Area Standard 36.5 mgll 363.676 2.425 x 103 Standard 38.4 mgll 384.687 2.571 x 103 Initial Sample A, pH 4, 40°C 326.388 2.012 x 103 Initial Sample B, pH 4, 40°C 306.091 1.896 x 103 Standard 35.5 mgll 349.483 2.340 x 10 3 Standard 35.4 mgll 347.767 2.329 x 103 48 hour Sample A, pH 4, 40°C 305.432 2.073 x 103 48 hour Sample B, pH 4, 40°C 319.634 1.965 x 103 Standard 39.0 mgll 396.670 2.680 x 103 Standard 37.8 mgll 369.230 2.474 x 103 70.5 hour Sample A, pH 4, 400C 305.548 1.975 x 103 70.5 hour Sample B, pH 4, 40°C 271.469 1.673 x 103 Standard 36.1 mgll 359.705 2.330 x 103 Standard 35.4 mglJ 356.530 2.313 x 103 144 hour Sample A, pH 4. 400C 307.226 1.775 x 103 144 hour Sample B. pH 4. 400C 306.714 1.753 x 103 Standard 36.4 mgll 283.989 2.026 x 103 Standard 35.1 mg/l 293.127 2.017 x 10 3 168 hour Sample

### A. pH 4, 40°C 148.711 1.338 x 103 168 hour Sample B, pH 4, 40°C 163.450 1.178 x 103 Standard 38.9 mgll 329.985 2.495 x 16' Standard 36.6 mg/l 309.613 2.138 x 103 192 hour Sample A. pH 4, 40°C 234.394 1.968 x 103 192 hour Sample B. pH 4, 40°C 199.665 1.675 x 103 216 hour Sample A. pH 4. 400c 272.301 1.832 x 103 216 hour Sample B. pH 4, 400C 276.868 1.999 x 103 240 hour Sample A. pH 4. 400C 251.460 1.920 x 103. 240 hour Sample B, pH 4, 400C 256.364 1.803 x 103



### 1048PROJECT NUMBER: 014510218 PAGE 27


### Table 4.10

- 

### pH 4, 50.0°C Solution eomponentA Mean Peak Area Component B Mean PeakArea Standard 36.1 mgll Standard 36.9 mg/l 284.882 304.104 2.001 x 10 3 2.096 x 103 Initial Sample A, pH 4, 50G

## e 260.503 1.250 x 103 Initial Sample B, pH 4. 50G 

## e 257.228 1.227 x 103 17.5 hour Sample A, pH 4, 50Ge 17.5 hour Sample B, pH 4, 50

## G e 257.282 205.585 1.004 x 103 994.525 24 hour Sample A, pH 4, 500e 212.452 1.238 x 103 24 hour Sample B, pH 4, 50G e 237.786 1.122 x 103 42 hour Sample A, pH 4, 500C 198.590 890.156 42 hour Sample B, pH 4, 50G

## e 176.134 934.834 72 hour Sample A, pH 4, 50G

# e 72 hour Sample B, pH 4, 

## sOGe 164.029 220.916 665.490 922.371 Standard 36.1 mgtl 280.907 1.948 x 103 Standard 36.9 mg/l 297.772 2.021 x 103 144 hour Sample A, pH 4, 50G

## e 201.211 800.869 144 hour Sample B, pH 4, 50G

# e 199.580 905.924 162 hour Sample A, pH 4, 50G

## e 208.545 813.875 162 hour Sample B, pH 4, 50G

## e 209 hour Sample A, pH 4, 50G 

# e 209 hour Sample B, pH 4, 5Q

## G e 221.548 223.379 236.429 i 

## I 994.144 909.384 983.451



### 1049PROJECT NUMBER: 014510218 PAGE 28 

### Table 4.11 - pH 4, 

### 60.DoC Solution Component A Mean Peak 

### Area ComponentB Mean PeakArea Standard 38.9 mgll 329.985 2.495 x 103 Standard 36.6 mgll 309.613 2.138 x 103 Initial Sample

### A. pH 4, 60°C 252.557 2.203 x 103 Initial Sample B, pH 4, 60°C 256.376 2.612 x 103 Standard 36.6 mgll 314.073 2.180 x 103 Standard 36.7 mgll 321.039 2.149 x 103 5.5 hour Sample A, pH 4, 60°C 217.485 1.455 x 103 5.5 hour Sample B, pH 4, 60°C 218.362 1.44S x 103 27 hour Sample 

### A. pH 4, 600C 22S.215 1.407 x 103 27 hour Sample B t pH 4, SooC 81.543 349.624 Standard 36.S mgll 307.341 2.029 x 103 Standard 36.7 mg/l 314.859 2.062 x 103 45.5 hour Sample A, pH 4, SooC 219.999 1.368 x 103 45.5 hour Sample B, pH 4, 60°C 207.938 1.388 x 103 52.5 hour Sample A, pH 4, eooe 218.841 1.210 x 103 52.5 hour Sample B. pH 4, 60°C 221.278 1.205 x 10 3 72 hour Sample

### A. pH 4, 60°C 200.475 926.899 72 hour Sample B, pH 4. 60°C 204.481 1.367 x 103 96 hour Sample A, pH 4, 600C 224.059 1.559 x 103 9S hour Sample B, pH 4, 60°C 240.450 2.S89 x 103 Standard 40.6 mg/l 330.393 2.222 x 103 Standard 43.0 mg/l 357.839 2.402 x 103 168 hour Sample A, pH 4, sooe 211.106 1.401 x 103 168 hour Sample B, pH 4, eo°c 254.353 1.184x 103



### 1050PROJECT NUMBER: 014510218 PAGE 29 

### The mean peak heights relating to the standard and sample solutions are shown in the following table: 

### Table4.12

- pH 

### 7, 20.0°C Solution Mean Peak Height Standard 36.7 mgll 205.480 Standard 35.3 mgn 185.033 Initial Sample A. pH 7. 20°C 98.889 Initial Sample S, pH 7, 20°C 146.413 2 Hour Sample A. pH 7, 20°C 54.478 2 Hour Sample S, pH 7, 20°C 71.160 4 Hour Sample A, pH 7, 20°C 78.544 4 Hour Sample B. pH 7, 20°C 123.681 24 Hour Sample A. pH 7, 20°C 105.604 24 Hour Sample B. pH 7, 20°C 51.597 Standard 34.0 mg/l 200.386 Standard 35.0 mg/l 193.892 96 Hour Sample A, pH 7, 20°C 154.810 96 Hour Sample B. pH 7, 20°C 207.335 Standard 36.5 mgJI 198.865 Standard 36.0 mgll 205.550 120 Hour Sample A, pH 7, 20°C .53.262 120 Hour Sample S, pH 7. 20°C 168.125 144 Hour Sample A, pH 7, 20°C 157.104 144 Hour Sample B. pH 7, 20°C 42.115



### 1051PROJECT NUMBER: 014510218 PAGE 30


### Table 

### 4.13

- pH 

### 7, 30.0°C Solution Mean Peak Height Standard 

### 39.2 mgll 

### 224.389 Standard 

### 39.3 mg/l 

### 201.859 Initial Sample A, pH 

### 7, 300

### e 230.982 Initial Sample B, pH 

### 7, 300

### e 241.923 0.5 Hour Sample A, pH 

### 7, 300e 177.151 0.5 Hour Sample B, pH 

### 7, 300e 178.177 1 Hour Sample A, pH 

### 7, 300G 217.271 1 Hour Sample B, pH 

### 7 I 

### 300

### e ND 2 Hour Sample A, pH 

### 7, 300

### e 174.125 2 Hour Sample B, pH 

### 7. 300

### e 173.772 3 Hour Sample A, pH 

### 7. 300

### e 239.311 3 Hour Sample B, pH 

### 7, 300e 204.052 4 Hour Sample A, pH 

### 7, 300

### e 187.011 4 Hour Sample B. pH 

### 7, 300

### e 214.148 6 Hour Sample A, pH 

### 7. 300

### e 83.174 6 Hour Sample B. pH 

### 7, 30e

### e 229.365 Standard 

### 39.2 mgll 

### 237.978 Standard 

### 39.3 mgil 

### 206.333 24 Hour Sample A, pH 

### 7, 30e

### e 111.432 24 Hour Sample B. pH 

### 7, 300

### e 239.600 30 Hour Sample A, pH 

### 7. 300G 221.399 30 Hour Sample B, pH 

### 7, 30e

### e 184.277 Standard 

### 36.7 mgil 

### 208.555 Standard 

### 35.3 mg/l 

### 184.920 48 Hour Sample 

### A. pH 

### 7, 300G 42.437 48 Hour Sample B, pH 

### 7. 30e

### e 79.174 Standard 

### 34.0 mgll 

### 200.386 Standard 

### 35.0 mg/l 

### 193.892 120 Hour Sample A, pH 

### 7, 300

### e 187.426 120 Hour Sample B, pH 

### 7, 300

### e 80.119 

### NO - none detected

1052PROJECT NUMBER: 014510218 PAGE 31 

### Table4.14

- pH 7, 40.0°C Solution Mean Peak Height Standard 37.1 mgll 209.086 Standard 36.5 mgll 190.380 Initial Sample A, pH 7, 40°C 173.506 Initial Sample B, pH 7 I 

### 40°C 208.041 Standard 37.6 mgll 208.951 Standard 37.5 mg/t 205.367 72 Hour Sample A, pH 7, 40°C 74.405 72 Hour Sample B, pH 7, 400C 166.715 Standard 40.7 mgll 219.627 Standard 36.5 mgll 182.629 96 Hour Sample A, pH 7, 40°C 109.314 96 Hour Sample B, pH 7, 40°C 115.875 Standard 36.5 mg/! 

### 206.654 Standard 38.4 mgl1 211.145 120 HourSample A, pH 7, 40°C 86.306 120 Hour Sample B. pH 7, 40°C 66.804 Standard 35.5 mg/I 198.470 Standard 35.4 mg/l 

### 195.271 120 Hour Sample A, pH 7, 40°C 139.362 120 Hour Sample B, pH 7, 40°C 

## NO Standard 39.0 mg/l 239.926 Standard 37.S mg/l 226.913 168 Hour Sample A, pH 7, 400C 90.951 168 Hour Sample B, pH 7. 40°C 73.880 Standard 39.0 mg/l 259.826 Standard 37.8 mg/I 233.015 240 Hour Sample A. pH 7. 40°C 45.363 240 Hour Sample B, pH 7. 40°C 76.631 Standard 36.4 mgll 189.465 Standard 35.1 mg/l 191.769 264 Hour Sample A, pH 7, 40°C 31.819 264 Hour Sample B. pH 7, 40°C 73.540 Standard 40.0 mg/l 226.175 Standard 39.3 mgll 217.131 288 Hour Sample A, pH 7, 40°C 34.121 288 Hour Sample B. pH 7. 40°C 118.684 312 Hour Sample A. pH 7, 40°C 84.052 312 Hour Sample B, pH 7, 40°C 41.059 Standard 37.1 mg/l 218.160 Standard 39.1 mg/I 214.240 336 Hour Sample A, pH 7, 40°C 7.965 336 HourSample B, pH 7, 400C 14.076 

### NO - none detected



### 1053PROJECT NUMBER: 014510218 PAGE 32 

### Table 

### 4.15

- pH 

### 7, 50.0o

# e Solution Mean Peak Height Standard 

### 34.0 mgll 

### 200.386 Standard 

### 35.0 mg/I 

### 193.892 Initial Sample A. pH 

### 7. 500

### e 175.853 Initial Sample B, pH 

### 7. 50G 

### e 140.206 2 Hour Sample 

### A. pH 

### 7. 50G 

### e 62.632 2 Hour Sample B, pH 

### 7. 500

### e 33.762 Standard 

### 34.0 mg/l 

### 213.735 Standard 

### 35.0 mg/l 

### 202.226 4 Hour Sample A, pH 

### 7, 500

### e 139.173 4 Hour Sample B, pH 

### 7, 50G

### e 97.991 6 Hour Sample A, pH 

### 7. 50·e 65.654 6 Hour Sample B. pH 

### 7, 500e 80.473 Standard 

### 36.5 mgtl 

### 188.231 Standard 

### 36.0 mg/l 

### 200.644 22.75 Hour Sample

### A. pH 

### 7. 50·e 47.585 22.75 Hour Sample B, pH 

### 7, 50G 

### e 50.283 28 Hour Sample A, pH 

### 7, 50G

### e 52.376 28 Hour Sample B, pH 

### 7. 50·e 50.177 46 Hour Sample A. pH 

### 7, 50G

### e 58.953 46 Hour Sample B. pH 

### 7, 500

### e 47.833 52 Hour Sample A, pH 

### 7. 50G

### e 43.774 52 Hour Sample B. pH 

### 7. 500

### e 41.472 Standard 

### 36.5 mgtl 

### 198.865 Standard 

### 36.0 mgll 

### 205.550 70.5 Hour Sample A. pH 

### 7, 500e 44.187 70.5 Hour Sample B. pH 

### 7, 500e 46.049 Standard 

### 37.1 mgtl 

### 209.086 Standard 

### 36.5 mgt! 

### 190.380 96 Hour Sample A, pH 

### 7. 50G

### e 49.737 96 Hour Sample B. pH 

### 7, 500

### e 53.893 Standard 

### 37.6 mg/l 

### 208.951 Standard 

### 37.5 mg/I 

### 205.367 168 Hour Sample 

### A. pH 

### 7, 500

### e 47.802 168 Hour Sample B, pH 

### 7, 500

### e 126.163



### 1054PROJECT NUMBER: 014510218 PAGE 33 

### Table 

### 4.16

- pH 

### 7, 60.0o

# e Solution Mean Peak Height Standard 

### 37.6 mgll 

### 208.951 Standard 

### 37.5 mg/I 

### 205.367 Initial Sample A, pH 

### 7, 

# aooc 214.411 Initial Sample B, pH 

### 7, BOoC 228.369 Standard 

### 40.7 mgJl 

### 219.627 Standard 

### 36.5 mgll 

### 182.629 18.75 Hour Sample A, pH 

### 7, 60°C 73.Sn 18.75 Hour Sample B, pH 

### 7, 60°C 58.289 Standard 

### 36.5 

### mgJI 206.654 Standard 

### 38.4 mgll 

### 211.145 24 Hour Sample A, pH 

### 7. 60°C 140.374 24 Hour Sample B. pH 

### 7, 60°C 135.720 43 Hour Sample A. pH 

### 7. 60°C 169.007 43 Hour Sample B, pH 

### 7. 60°C 157.198 48 Hour Sample A. pH 

### 7. 600c 9S.770 48 Hour Sample B, pH 

### 7, BOoC 41.722 Standard 

### 35.5 mg/l 

### 198.470 Standard 

### 35.4 mgJI 

### 195.271 67 Hour Sample A, pH 

### 7, 600C 30.025 67 Hour Sample B, pH 

### 7, 60°C 34.356 Standard 

### 39.0 mgll 

### 239.926 Standard 

### 37.S mgll 

### 226.913 72 Hour Sample A, pH 

### 7. 600c 120.256 72 Hour Sample B, pH 

### 7, 60°C 7.533 91 Hour Sample A, pH 

### 7, 60°C 50.857 91 Hour Sample B, pH 

### 7, 60°C 86.965 96 Hour Sample A, pH 

### 7. 600c 21.370 96 Hour Sample B. pH 

### 7, 60°C 14.264



### 1055PROJECT NUMBER: 0145/0218 PAGE 34 

### The mean peak areas relating to the standard and sample solutions are shown in the following table: Table

## 4.17

- pH 

## 9, 20.O°C Component A ComponentB Solution Mean PeakArea Mean PeakArea 306.851 2.028 x103 Standard 36.0 mgll 276.116 Standard 37.2 mgll 1.825 x103 Initial Sample A, pH 9, 20ClC 230.835 1.357 x103 217.788 Initial Sample B, pH 9, 20°C 1.390 x103 1 hour Sample A, pH 9, 20°C 51.504 605.362 1 hour Sample B, pH 9, 20°C 70.532 1.028x103 2 hour Sample A, pH 9, 20°C 249.740 1.386 x10a 2 hour Sample B, pH 9, 20°C 224.057 1.287 x103 4 hour Sample A, pH 9, 20°C 227.952 1.192 x103 4 hour Sample B, pH 9, 20ClC 191.379 1.025 x103 Standard 36.0 mgll 327.155 2.170 x103 Standard 37.2 mg/l 294.037 1.937 x103 22.5 hour Sample A, pH 9, 20°C 89.477 346.558 22.5 hour Sample B, pH 9, 20ClC 79.429 318.134 25 hour Sample A, pH 9, 20°C 61.524 254.378 25 hour Sample B, pH 9, 20°C 61.814 256.067 28 hour Sample A, pH 9, 20°C 60.499 317.926 28 hour Sample B, pH 9, 200C 

### NO NO 48 hour Sample A, pH 9, 20°C 

### NO 74.124 48 hour Sample B, pH 9, 200C 

### NO 31.385 50 hour Sample A, pH 9, 20°C 17.319 112.637 50 hour Sample B, pH 9, 200C 

### NO 147.497 

### ND - none detected

1056PROJECT NUMBER: 014510218 PAGE 35 

### Table 

### 4.18 - pH 

### 9, 30.0°C Solution Component A Mean Peak Area eomponentB Mean Peak Area Standard 37.7 mgll 296.928 2.040 x 103 Standard 35.3 mg/l 298.854 2.026 x 103 Initial Sample A, pH 9, 30De 216.380 1.676 x 103 Initial Sample B, pH 9, 30De 239.002 1.607 x 103 0.5 hour Sample A. pH 9, 30De 213.732 1.267 x 103 0.5 hour Sample B. pH 9, 30°C 218.453 1.308x 103 1 hour Sample A, pH 9, 30°C 230.713 1.250 x 103 1 hour Sample B, pH 9, 30°C 220.130 1.429 x 103 2 hour Sample A, pH 9, 30De 220.375 1.006 x 103 2 hourSample S, pH 9, 30De 210.096 983.161 3 hour Sample A, pH 9, 30°C 105.259 

### 493.0n 3 hour Sample B, pH 9, 30°C 221.040 933.354 4 hour Sample A, pH 9, 30°C 175.047 649.668 4 hour Sample S, pH 9, 30°C 145.732 569.211 6 hour Sample A, pH 9, 30De 135.529 496.333 6 hour Sample B, pH 9, 30°C 169.313 574.470 24 hour Sample A, pH 9, 30°C 

### NO NO 24 hour Sample B, pH 9, 30De 

### NO NO 27 hour Sample A, pH 9, 300e 

### NO NO 27 hour Sample B, pH 9, 30°C 

### NO NO 30 hour Sample A, pH 9, 30De 

### NO NO 30 hour Sample B, pH 9, 300e 

### NO NO NO - none detected

1057PROJECT NUMBER: 014510218 PAGE 36 

### Table4.19

- pH 9, 40.0°C Solution ComponentA Mean Peak Area ComponentB Mean Peak Area Standard 36.8 mg/l 305.932 2.020 x 103 Standard 34.8 mgll 285.237 1.837 x 103 Initial Sample A, pH 9, 40°C 230.879 1.343 x 103 Initial Sample B, pH 9, 40°C 206.530 1.237 x 103 0.5 hour Sample A, pH 9, 40°C 232.431 1.175 x 103 0.5 hour Sample B, pH 9, 40°C 254.164 1.339 x 103 1 hour Sample A, pH 9, 40°C 177.409 787.260 1 hour Sample B, pH 9, 400C 205.872 904.013 2 hour Sample A, pH 9, 40°C 173.851 598.211 2 hour Sample B, pH 9, 40°C 180.180 641.124 3 hour Sample A, pH 9, 40°C 12.819 124.355 3 hour Sample B, pH 9, 40°C 95.648 358.425 4 hour Sample A, pH 9, 40°C 28.042 153.363 4 hour Sample B, pH 9, 40°C 43.125 187.116 5 hour Sample A, pH 9. 40°C 

### NO 15.913 5 hour Sample B. pH 9. 40°C 12.487 85.739 6 hour Sample A, pH 9. 40°C 6 hour Sample B, pH 9, 40°C 

## I I 

### NO 

### NO NO 

### NO NO - none detected

1058PROJECT NUMBER: 0145/0218 PAGE 37 

### The test material concentrations at the given time points are shown in the following tables: Table 4.20 pH 4 at40.0 

## ±0.5°C • ComponentA Time (Hours) Concentration 

### (gIl) L0910 

### [concentration (gll)J % 

### of mean initial concentration A B A B A B 

### Initial 3.27x 10"'" 3.06x 10"'" -3.49 -3.51 

### - 

# -

48 3.11 x 10"'" 3.25 x 10"" -3.51 -3.49 98.1 103 70.5 3.07x 10"" 2.72x 10-4 -3.51 -3.57 96.8 86.0 144 3.07x 10-4 3.06x 10"" -3.51 -3.51 96.9 96.7 168 1.84x 10"'" 2.02 x 10"" I -3.74 -3.69 58.2 63.9 192 2.77 x 10-4 2.36 x 10"" -3.56 -3.63 87.4 74.5 216 3.21 x 10"'" 3.27 X 10"" -3.49 -3.49 102 103 240 2.97 x 10"'" 3.03 X 10"'" -3.53 -3.52 93.8 95.6 

### Result: No definitive signs 

### of hydrolysis. Half-life expected to be greater than 1yearat 25°C. Table 4.21 pH 4 at 40.0 t 

### 0.5°C - Component B Time (Hours) Concentration (g/l) L0910 

### [concentration (g/l)1 % 

### of mean initial concentration A B A 

### B A B 

### Initial 3.01 x 10"" 2.84 X 10"" -3.52 -3.55 

# - -

48 3.15 x 10"" 2.98 X 10"'" -3.50 -3.53 107 102 70.5 2.94 x 10"" 2.49 X 10"" -3.53 -3.60 100 85.1 144 2.73 x 10"" 2.70 X 10'" -3.56 -3.57 93.3 92.1 168 2.37 x 10"'" 2.08X 10-4 -3.63 -3.68 80.8 71.1 192 3.21 x 10"'" 2.73 X 10-4 -3.49 -3.56 110 93.3 216 2.99 x 10-4 3.26x 10"" -3.52 -3.49 102 111 240 3.13x10"" 2.94 x 10"" -3.50 -3.53 107 100 

### Result: No definitive signs of hydrolysis. Half-life expected to be greater than 1year at 25°C.

1059PROJECT NUMBER: 0145/0218 PAGE 38


### Table 4.22 pH 4 at50.0 

# ±0.5OC • ComponentA Time (Hours) Concentration (gil) LOQ10 

### [concentration (gil)} % 

### ofmean initial concentration 

### A B 

### A B 

### A B Initial 3.23 X 10-4 3.19 X 10-4 -3.49 -3.50 

# - 

# - 17.5 3.19 X 10-4 2.55 X 10-4 -3.50 -3.59 99.4 79.4 24 2.63x 10-4 2.95 X 10-4 -3.58 -3.53 82.1 91.9 42 2.46 x 10-4 2.18 X 10-4 -3.61 -3.66 76.7 68.0 

### 72 2.03 x 10"" 2.74 X 10-4 -3.69 -3.56 63.4 85.3 144 2.54 x 10-4 2.52 X 10-4 -3.60 -3.60 79.1 78.5 162 2.63 x 10-4 2.80 X 10-4 -3.58 -3.55 82.0 87.1 209 2.82 x 10-4 2.98 X 10-4 -3.55 -3.53 87.8 93.0 

### Result: No definitive signs of hydrolysis. Half-life expected to be greater than 1year at 25"C. Table 4.23 pH 4 at50.0 

## ±O.SoC • Component B Time (Hours) Concentration (gIl) LOQ10 

### (concentration (gil)] % 

### ofmean initial concentration 

### A B 

### A B 

### A B 

### Initial 2.23 x 10"" 2.19x 10-4 -3.65 -3.66 

# - - 17.5 1.79x10-4 1.77x 10-4 -3.75 -3.75 81.1 80.3 24 2.21 x 10-4 2.00X 10-4 -3.66 -3.70 99.9 90.6 42 1.59 x 10-4 1.67x10-4 -3.80 -3.78 71.9 75.5 72 1.19x10-4 1.64 x 10-4 -3.93 -3.78 53.7 74.5 144 1.47 X 10-4 1.67 x 10-4 -3.83 -3.78 66.7 75.5 162 1.50 x 10-4 1.83 X 10-4 -3.83 -3.74 67.8 82.8 209 1.67 x 10-4 1.81 X 10-4 -3.78 -3.74 75.8 81.9 

### Result: No definitive signs of hydrolysis. HalfRlife expected to be greater than 1 year at 25"C.

1060PROJECT NUMBER: 014510218 PAGE 39


### Table 4.24 pH 4 at 60.0 

## ±0.5°C - Component A Time (Hours) Concentration (g/l) Logl0 [concentration (gil)] % ofmean initial concentration A B A B A B Initial 2.98

### x 10-4 3.03 X 10-4 -3.53 -3.52 

## - 

# - 5.5 2.54

### x 10-4 2.55 X 10-4 -3.59 -3.59 84.7 85.0 27 2.65

### x 10-4 9.54 X 10.5 -3.58 -4.02 88.1 31.8 45.5 2.63

### x 10-4 2.48 X 10-4 -3.58 -3.61 87.5 82.7 52.5 2.61 

### x 10-4 2.64 X 10-4 -3.58 -3.58 87.0 88.0

72 2.39 

### x 10-4 2.44 X 10.4 -3.62 -3.61 79.7 81.3 96 2.68

### x 10-4 2.87 X 10-4 -3.57 -3.54 89.1 95.6 168 2.57

### x 10-4 3.09 X 10-4 -3.59 -3.51 85.4 103 

### Result: No definitive signs of hydrolysis. Half-life expected to be greater than 

## 1 year at 

## 25 Q

## C. Table 4.25 pH 4 at60.0 

## ±O.SoC - Component B

No definitive signs of hydrolysis. Half-life expected to be greater than 

## 1year at 

## 25 Q

### C. Time (Hours) 

# : Initial 5.5 27 45.5 52.5 72 96 168 

### Result: Concentration (gil) Log 10 [concentration 

### (glOJ % ofmean initial concentration A B A 

### B A B 3.60

### x 10-4 4.26 X 10-4 -3.44 -3.37 

## - 

# - 2.50 

### x 10-4 2.48 X 10-4 -3.60 -3.61 63.5 63.1 2.41 

### x 10-4 6.00 X 10-0 -3.62 -4.22 61.4 15.3 2.48

### x 10-4 2.52 X 10-4 -3.61 -3.60 63.2 64.2 2.20 

### x10-4 2.19 X 10-4 -3.66 -3.66 55.9 55.7 1.68

### x10-4 2.48 X 10-4 -3.77 -3.61 42.8 63.2 2.83

### x 10-4 4.88 X 10-4 -3.55 -3.31 72.0 124 2.53

### x 10-4 2.14 X 10.4 -3.60 -3.67 64.5 54.5



### 1061PROJECT NUMBER: 014510218 PAGE 40


### Table 4.26 pH 7 at 20.0 

## ±0.5°C M 

### Component B 

## I Time (Hours) • Concentration (gil) Log10 {concentration (gIl)] % 

### of mean initial concentration A B A B A B 

### Initial 

### 1.82 x 

### 10'" 2.70 X 

### 10'" -3.74 -3.57 

# - -

2 1.01 X 

### 10'" 1.31 X 

### 10'" -4.00 -3.88 44.4 58.0 4 1.45

### x 10'" 2.28 X 

### 10'" -3.84 -3.64 64.0 101 24 1.95

### x 10'" 9.52 X 

### 10.5 

### -3.71 -4.02 86.1 42.1 96 2.71 x 

### 10'" 3.63 X 

### 10'" -3.57 -3.44 120 160 120 9.55

### x 10-5 3.01 X 

### 10'" -4.02 -3.52 42.2 133 144 2.82 

### x 10'" 7.55 X 

### 10.5 

### -3.55 -4.12 124 33.4 

### Result: No definitive signs of hydrolysis. Half-life expected to be greater than 1 year at 25°C. Table 4.27 pH 7 at30.0 

## ±O.soC - Component B Time (Hours) Initial 

### 0.5

1 2 3 4 6 24 30 48 120 

### Result: Concentration (gil) L0910 [concentration (g/l)] % 

### of mean initial concentration A B A B A B 

### 4.25 

### x 10'" 4.46 X 

### 10'" -3.37 -3.35 

# - - 3.26

### x 10'" 3.28 X 

### 10'" -3.49 -3.48 74.9 75.4 4.00 

### x 10'" 

# - -3.40 

# - 91.9 

# - 3.21 X 

### 10'" 3.20 X 

### 10'" -3.49 -3.50 73.6 73.5 4.41 

### x 10'" 3.76 X 

### 10'" -3.36 -3.43 101 86.3 3.44

### x 10'" 3.94 X 

### 10'" -3.46 -3.40 79.1 90.6 1.53

### x 10'" 4.22 X 

### 10'" -3.82 -3.37 35.2 97.0 1.97

### x 10'" 4.23 X 

### 10'" -3.71 -3.37 45.2 97.2 3.91 

### x 10'" 3.26 X 

### 10'" -3.41 -3.49 89.8 74.8 7.77 

### x 10-4 1.45 X 

### 10'" -4.11 -3.84 17.8 33.3 3.28 

### x 10'" 1.40 X 

### 10'" -3.48 -3.85 75.3 32.2 

### No definitive signs of hydrolysis. Half-life expected to be greater than 1 year at 25°C.

106272 PROJECT NUMBER: 014510218 PAGE 41


### Table 4.28 pH 7 at40.0 

## ±O.SOC - Component B



### Result: Time (Hours) Initial

96 120 144 168 240 264 288 312 336 

### Concentration (gIl) L0910 

### [concentration (gIl)] 

## I % 

### of mean initial concentration A 

### B A 

### B A B 3.20

### x 10-4 3.83 X 10-4 -3.50 -3.42 

# - - 1.35

### x 10-4 3.02 X 10-4 -3.87 -3.52 38.4 85.9 2.10

### x 10-4 2.23

### x 10-4 -3.68 -3.65 59.8 63.4 1.55

### x 10-4 1.20

### x 10-4 -3.81 -3.92 44.0 34.0 2.51 

### x 10-4 

# - -3.60 

# - 71.7 

# - 1.50

### x 10-4 1.22

### x 10-4 -3.83 -3.92 42.6 34.6 7.07

### x 10-6 1.20 X 10-4 -4.15 -3.92 20.1 34.0 5.97

### x 10-5 1.38

### x 10...( -4.22 -3.86 17.0 39.2 6.10 X 10-6 2.12 

### x 10...( -4.21 -3.67 17.4 60.4 1.50

### x 10-4 7.35 X 10-5 -3.82 -4.13 42.8 20.9 1.40

### x 10-5 2.48 X 10.5 -4.85 -4.61 3.99 7.05 

### No definitive signs of hydrolysis. Half-life expected to be greater than 1 year at 25°C. Table 4.29 pH 7 at50.0 

## ±O.soC - Component B 

## I

Time (Hours) Concentration (gil) LOQ10 

### [concentration (gIl)) % 

### of mean initial concentration A B 

### A B 

### A B 

### Initial 3.08 

### x 10.4 2.45 X 10-4 -3.51 -3.61 

# - 

# -

2 1.10X 10-4 5.91 X 10-5 -3.96 -4.23 39.6 21.4 4 2.31 

### x 10...( 1.62 X 10-4 -3.64 -3.79 83.5 58.8 6 1.09

### x 10-4 1.33 X 10-4 -3.96 -3.88 39.4 48.3 22.75 8.87

### x 10-6 9.37

### x 10-6 -4.05 -4.03 32.1 33.9

28 9.76

### x 10-5 9.35

### x 10-6 -4.01 -4.03 35.3 33.8 46 1.10

### x 10-4 8.92

### x 10-6 -3.96 -4.05 39.7 32.3 52 8.16

### x 10-5 7.73 X 10.5 -4.09 -4.11 29.5 28.0 70.5 7.92

### x 10-6 8.25

### x 10-6 -4.10 -4.08 28.7 29.9 96 9.17

### x 10.5 9.93

### x 10.5 -4.04 -4.00 33.2 35.9 168 8.67

### x 10-5 2.29 X 10-4 -4.06 -3.64 31.3 82.7 

### Result: No definitive signs of hydrolysis. Half-life expected to be greater than 1year at25°C.

1063PROJECT NUMBER: 0145/0218 PAGE 42


### Table 4.30 pH 7 at 60.0 

## ± 0.5°C - Component B Time (Hours) Concentration (g/l) L0910 

### [concentration (gil)} % 

### of mean initial concentration A 8 A 8 A 8 

### Initial 3.89 x 10-4 4.14 X 10.4 -3.41 -3.38 

# - - 18.75 1.42 x 10-4 1.12 X 10-4 -3.85 -3.95 35.4 27.9

24 2.52 x 10-4 2.43 X 10"" -3.60 -3.61 62.7 60.6 43 3.03 x 10-4 2.82 X 10-4 -3.52 -3.55 75.5 70.2 48 1.77 x 10-4 7.48 X 10.5 -3.75 -4.12 44.1 18.6 67 5.41 x 10-5 6.19x10·s -4.26 -4.21 13.5 15.4 72 1.98 x 10"" 1.24 x 10-5 -3.70 -4.91 49.3 3.09 91 8.37 x 10.5 1.43 X 10"" -4.08 -3.84 20.9 35.7 

### 96 3.52 x 10-5 2.35 X 10-5 -4.45 -4.63 8.76 5.85 

### Result: No definitive signs of hydrolysis. Half-life expected to be greater than 1year at 25°C.

1064PROJECT NUMBER: 0145/0218 PAGE 43


### Table 4.31 pH 

### 9 at

### 20.0 

## :t O.SOC • Component

### A Time (Hours) Concentration (gil) Log 10 [concentration (911)] % of mean initial concentration 

### A B 

### A B 

### A B Initial 2.90 x 10-4 2.73 X 10-4 ·3.54 -3.56 

# - -

1* 6.46 X 10-5 8.85 X 10-6 4.19 -4.05 23.0 31.4 2 3.13x10-4 2.81 X 10-4 -3.50 -3.55 111 99.9 4 2.86 x 10-4 2.40 X 10-4 -3.54 -3.62 102 85.3 22.5 1.05 x 10-4 9.35 X 10-6 -3.98 -4.03 37.4 33.2 25 7.24x 10.5 7.28 x 10-6 4.14 -4.14 25.7 25.9 28 7.12 x 10.5


# - 4.14 

# - 25.3 

### . 48 

# - 

# - - - - 

# - 50 2.04 X 10.5



# - -4.69 

# - 7.25 

# - Result: Slope 

## = -2.36 X 

### 10-2 

### (see Figure 

### 4.17) 

## f = 0.988 

# kobs 

# = 5.43 x 

### 10-2 

### hOU(1, 

### 1.51 x 

### 10-5 second-1 

### t% = 

### 12.8 hours, 

### 0.532 days Table4.32 pH 

### 9 at 

### 20.0 

# ±O.SoC - Component

### B TIme (Hours) Initial

1 2 4 22.5 25 28 48 50 Concentration (gil) L0910 [concentration (gil)] A 2.58 x 10-4 1.15 X 10"" 2.63x 10-4 2.26 x 10-4 6.17 X 10-fi 4.53 x 10-6 5.66 x 10-5 1.32 x 10.5 2.01 x 10.5 

### B 

### A B 2.63 X 10"" 3.59 -3.58 1.95 X 10-4 -3.94 -3.71 2.44 X 10-4 -3.58 -3.61 1.95 X 10-4 -3.65 -3.71 5.66 x 10-6 4.21 4.25 4.56 X 10-6 -4.34 -4.34



# - 4.25 

# - 5.59 X 10-6 4.88 -5.25 2.63x 10.5 4.70 4.58 

### -2.49 X 

### 10.2 

### (see Figure 

### 4.18) 0.897 5.73 x 

### 10-2 

### hOUf1. 

### 1.59 X 

### 10-5 

### second-1 

### 12.1 hours, 

### 0.504 days % of mean initial concentration 

### A B



# - 

# - 44.1 74.9 101 93.7 86.8 74.6 23.7 21.7 17.4 17.5 21.7 

# - 5.06 2.14 7.69 10.1 

### Result: Slope = 

## f 

# = kobs 

# = t% =

.. 1 hourtime pOint considered to be an outlier and not used in the calculations.


### 1065PROJECT NUMBER: 0145/0218 PAGE 44


### Table 4.33 pH 9 at30.0 

### ± O.SoC • Component A

Result: Slope 

## = r2 

# = kobs 

### = Concentration (gil) Log 10 [concentration (g/l)1 % of mean initial Time (Hours) concentration 

### A B 

### A B 

### A B Initial 2.65 x 10-4 2.93 X 10-4 -3.58 -3.53 

## - 

# - J 0.5

1 2 3 4 6 2.62 x 10-4 2.82 X 10-4 2.70 X 10-4 1.29 x 10-4 2.14 x 10-4 1.66 X 10-4 2.67 X 10-4 -3.58 -3.57 2.69 X 10-4 -3.55 -3.57 2.57 X 10-4 -3.57 -3.59 2.71 X 10-4 -3.89* -3.57 1.78 X 10-4 -3.67 -3.75 2.07 X 10'" -3.78 -3.68 

### -3.18 X 

### 10- 2 

### (see Figure 4.19) 0.731 7.32 

### x 10-2 

### hour1, 

### 2.034 

### x 10-5 

### second-1 

### 9.47 

### hours, 0.394 

### days 93.9 95.9 101 96.7 96.8 92.3 46.2 97.1 76.9 64.0 59.5 74.4 I
I



### Table 4.34 pH 9 at 30.0 

### ± O.SOC - Component B
Time (Hours) I
! Concentration (g/l)* 

### A 

### B Log 10 [concentration (gIl)] 

### A· I B % of mean initial concentration 

### A 

### B Initial 3.01 x 10-4 2.88 X 10'" -3.52 -3.54 

# - - 0.5 2.27 x 10-4 2.34 X 10-4 -3.64 -3.63 77.2 79.7

1 2 

### 3 2.24 x 10'" 1.81 x 10'" 8.85 x 10.5 2.56 X 10-4 1.76 X 10-4 1.67 X 10'" -3.65 -3.74 -4.05* -3.59 -3.75 -3.78 76.2 61.3 30.0 87.0 59.9 56.9 4 6 1.17 x 10-4 8.90 x 10.5 1.02x10'" 1.03 X 10'" -3.93 -4.05 -3.99 -3.99 39.6 30.2 34.7 35.0 

### Result: Slope 

# = -8.26 X 

### 10-2 

### (see Figure 4.20) 

## r2 

## = 0.935 kobs 

# = 0.190 

### hour\ 5.28 

### x 10.5 

### second-1**t~** 

# = 3.65 

### hours, 0.152 

### days

* Components A and B. 3 hour time points, replicate A, considered to be outliers and not used in the calculations.


### 1066PROJECT NUMBER: 0145/0218 PAGE 45


### Table 4.35 pH 9 at40.0 

# ±0.5°C • ComponentA
Time (Hours) Concentration (gil) Log 10 [concentration (g/l)1 

### % of mean initial concentration 

### A 

### B A 

### B A 

### B Initial 2.80 x 10-4 2.50 X 10-4 -3.55 -3.60 

# - - 0.5 2.82 x 10-4 3.08 X 10-4 -3.55 -3.51 106 116

1 2.15 x 10-4 2.49 x 10'" -3.67 -3.60 81.1 94.1 2 2.11 x 10-4 2.18 X 10-4 -3.68 -3.66 79.5 82.4 3 1.55 x 10-5 1.16x10-5 -4.81* -3.94 5.86 43.7 4 3.24 x 10-5 4.99 X 10.5 -4.49 -4.30 12.2 18.8 5 

# - 1.44 X 10-5



# - -4.84 

# - 5.45 

### Result: Slope 

## = -0.238 (see Figure 

### 4.21) 

## f 

# = 0.872 0.549 hou(1, 

### 1.53 x 

### 10-4 second-1 

## !cobs 

# = t% 

# = 1.26 hours, 

### 5.26x 

### 10-2 

### days 

### Table 4.36 pH 9 at40.0 

# ±O.5°C - Component B
Time (Hours) Concentration (g/l)* Log 10 [concentration (gIl)] % ofmean initial concentration 

### A B 

### A B 

### A B Initial 2.50 x 10-4 2.30 X 10-4 -3.60 -3.64 

# - 

# - 0.5 2.18x10-4 2.49 x 10-4 -3.66 -3.60 91.1 104

1 1.46 x 10-4 1.68 X 10-4 -3.84 -3.78 61.0 70.1 2 1.11 x 10-4 1.19x10'" -3.95 -3.92 46.4 49.7 3 2.31 x 10.5 6.66 X 10-5 

### -4.64t -4.18 9.64 27.8 4 2.69 x 10-5 3.28 X 10-5 -4.57 -4.48 11.2 13.7 5 2.79 x 10-6 1.51 X 10.5 -5.55t -4.82 1.17 6.28 

### Result: Slope 

# = -0.240 (see Figure 

### 4.22) 

## f = 

### 0.972 kobs 

## = 0.551 houf1, 

### 1.53

## x 10-4 seconcf1 

### 1.26 hours, 

### 5.24

## x 10-2 

### days

.. Component

### A. 3 hourtime point, replicate 

### A. considered to be an outlier and not used in the calculations. t Component B, 3 and 5 hour time points, replicate 

### A. considered to be outliers and not used In the calculations.


### 1067PROJECT NUMBER: 014510218 PAGE 46 

### Figure 4.6 pH 4 at40.0 

# ±O.soC - ComponentA Graph of

### 10g1o Concentration 

### (gil) versus Time (Hours)**~** o.CIOIE40 

# - 

# - 'IUGII 

# - 144.C1111 

# - ,_ 

# - - 21U11O 

# - 21U11O 

# -

•**-3.7·5'--~----------------------** 

## o 50 

### 100 150 200 250 TIme (hours)

1068

# -- • 

# • PROJECT NUMBER: 0145/0218 PAGE 47 

### Figure 4.7 pH 4 at

### 40.0 ::t 

### O.soC - Component B Graph of log10 Concentration (gil) versus Time (Hours) 

# • • 

# • 

# • !:=::-3.48 0:::: S Co 

# • 0 :.1:1 

# •**~** 53 

# 1-3• 

# • 0 

# • ClII 

# - .S! 

# _to 4.121 4,I4C .ua2 Q,OQIII!"



# - 4.. oIl1111 oUIt 

# - 7O.IIDI 

# 01_ 144_**~** t.._ 

# ,.­ 4_ t._ 1
.._ ••1 

# 1­ .3._ tlUGO 

# ... .uIl 

# 21"_ ItuaO .3.4111 

# :

....4,I4C 

# 1-..-..**.f~** -3.56 

# •

-3.60 

# • 

# • -3.64

-3.68 

# •

-3.72 0 50 

### 100 150 200 250 

### Time (hours)



### 1069

# • • PROJECT NUMBER: 0145/0218 PAGE 48 

### Figure 4.8 pH 4 at

### 50.0

# ±O.5°C- ComponentA Graph oflog10 Concentration (gIl) versus Time (Hours) 

# a_**~-3.48** 

# ! i 

# • 

# g-3.62 

# •**~** d 

# •

..... CD ..!2 

# • 

# • -3.58 

# •

• -3.60 

# • • 

# •

-3.84 

# • -3.68 

# •
-3.72 a-.o 11_ 

# 17_



# - - - 

# - T.tOIIO 11_ 

# ,

# ..

# ­ I
.... 

# - 1
__ 

# = 4AM .;tMI 4AtII .UN 4Jl7I 4.QO .s.tCIII -1.111 

# - - .:a_ 

# - 4.­ 

# - = A• .:aJIM 

# ':1:

0 

### 40 

### 80 120 

### 160 200 240 Time (hours)



### 1070

# -- PROJECT NUMBER: 0145/0218 PAGE 49 

### Figure 4.9 pH 4 at SO.O 

## :t O.soC- Component B Graph of 

### 10910 Concentration (gIl) versus Time (Hours)



# • 

# -3.915'----------------------­ o 40 80 

### 120 160 

### 200 240 Time (hours)**~-3.6** 

# i 

# • 

# L7 •**~** .... 

# r • • .,.**~** 0.-..0 4'­ 

# 17_ 17_ 4:1"


# - 4.11'



# - - 4 .• of•• 4_ .ani 1'lD -3.121 1'lD -UN 

# .... .....

# ­**;~** 4.11'1 4._ 182.GOO l_

...m 

# - A-4.m 

# . ....

# - oll_

1071

### Figure

### 4.10 pH 

### 4 at

### 60.0 1: 

### O.soC- ComponentA Graph of 10g1o Concentration (gn) versus Time (Hours) PROJECT NUMBER: 014510218 PAGE 50



# ..**~..a.** 

# • 

# - C 

# 1 • • • g -3. 

# • I

# ~ .... I -3.7

-3.8 

# _ 0.-..

IJ,.$GO UCiO 21_ %1I/l10 

# ... .u. IUGII IaJII1II**~** 

# ... 

# ... '''0IIII <UIII 

## ".It, "J84 

# "

# ... .u71 ""-ClIO 4M1 

# ,,­ 4._ .u71 4
..' .un ..un .ua 4MI**A.~** 

# ...

•**~.1~--------------------------------------------** 

### o 80 120 160 200 TIme (hours)



### 1072

### --3.7 PROJECT NUMBER: 014510218 PAGE 51 

### Figure

### 4.11 pH 

### 4 at

### 60.0 

## ±O.S°C- Component B Graph of log10 Concentration 

### (gil) versus Time (Hours)
2;:-3. 

# • S 

# i 8 I::: 

# J,w3.4



### .....**~** 

# D_
-II,""**~** -2.:1'10



# - .. .. ..­ 

## .­ 

# .... ..­ 11'_ "flY .uos 

# - .uN IUCII 4.l1li. 

## .­ 4MO


# - 4.774**~** n­ 

# .... 4_ IUD 4:at1 

# -".;&JIIt .uta



# ..........



# • •

• ·3.8'-----------------------
..... o 40 

### 80 120 160 200 nme(hours}



### 1073PROJECT NUMBER: 014510218 PAGE 52 

### Figure 4.12 pH 7 at20.0 

## :t 0.5°C- Component B Graph ofIOg10 

### Concentration (gIl) 

### versus Time (Hours)**~-3.4** 

# - i 

# 8 

# i -3.5 C· 

## .§. C 

# ... ..S'-3.6 

# • •
• 

# • •

-3.7 

# •



# - -3.8 

# • -3.9

# •

-4.0

# • • 

# •
-4.1 

# •
-4.2 

### 0 40 

### 80 .120 160 Time (hours)**~** 1IJIIIIII.a 2.GOO 2.GOO .a.ooo 4.Il00 <iNJIIIt :wIlD 

# -­ 

# -­ 120.Il00 

# - :: 4..". 4MI 4_ 4_ 4.m 4.1Nl 4.7tII -4J1i11 4.H7 4...cI "'-"20 4_**~**

...4.7111 ••3.......

• -li.1D4



### 1074

# -- PROJECT NUMBER: 014510218 PAGE 53

4.m 4:18' 4MI 4MI ..u. 4MI <IMt!I 4.:l1li 4Aa .:JAG 4_ ':'.l1S 4.114



### ....

# ­ ".37:1**~** -',417 

# "". 4MI 

# ""­ Figure

### 4.13 pH 7 at 

### 30.0 

## ±O.S°C-Component B Graph oflog1D Concentration (gil) versus Time (Hours) 

# 0._ !I.IIOIIEtG o.faO o.faO 

## ,.­ 

# 2._ UGO 3.0IIII**~** 4JIIIG 1.000



# - uoo 24.1100 

# .... 

# - .... 

# - -A-4A11 

# ..**~**



## ,

# .

• •



# •**-42.~-----------------------------------------** 

## o 20 40 60 80 

### 100 120 Time (hours)**~-3.2**


# -­ i .c 

# 8 

# • 

# 1-3.4 •

.... 

# I

83.**~.8** 

# •



# -4. • • 

# •

•

1075

# --

-4.4 PROJECT NUMBER: 0145/0218 PAGE 54 

### Figure 

### 4.14 pH 7 at

### 40.0 

## :t O.SOC- Component B Graph of log10 Concentration (gil) versus Time (Hours)**~-3.2** c:

# L~ • • 0 

# I ..­



### -4. 

# 0_

4.
...**~tO ~AIt**  n.ooo 4.1111 <IJI2II n.ooo oUTI 4M2 

# ,_ 

# ­ 4.1\1 

# 1_ 1_ 

# ­ 4_ 4AOO 1M_ 4.111!1 1_ 4.115 -4.tI!II _OlIO 4.123 

# - 2M_ -4.ZM -1M! ..uu 

# - .1m JIZ..GIJII 

## ...­ 

# - :n:I.GIIO -4.IM -4.153 

# - A
......«II 

# ...**~**



# •
• 

# -5.2'-------------------------' o 100 200 300 400 Time (hours)



### 1076

# • •

# • • • 

# --

-4.1 PROJECT NUMBER: 014510218 PAGE 55 

### Figure 

### 4.15 pH 7 at

### 50.0 

## ±O.soC- Component B Graph of 10g1o Concentration (g/l) versus Time (Hours)**~** 4.11l 4.l1G o.!ICIIIIM 

# - ­ 2.lIIIO 4JIIII 

# .... Z.QlII 

# f.
4.IS7 4JIIIO 4.711 4.1113 UIII 

# .... 4.m



# .. -4

# -

• lUOII lUOII 

# • 

# ..­ ..unG 3
... 2&lIIIO 4_ 

# .... .... 

# .... 

# - .... 

# - -4.1t:/ 

# - ".101 ",au 

# ... 

# - ..­ ".GO! 

## 1:: 

# =: "'-4.121 a....?'77II.f

o4.f!1l!



# • •

-4.2**-4.3.~-------------------------------------------** 

## o 40 80 120 160 200 TIme (hours) 

# •

1077

## 6 PROJECT NUMBER: 0145/0218 PAGE 56 

### Figure 

### 4.16 pH 7 at 

### 60.0:t0.6OC- Component B Graph of log10 Concentration (gil) versus Time (Hours)**~-3.2**

### ~ 

# J E: 

## B r:

### ~-3.


### ..... 

# F



# • • -4.4

-4.8 

# •**-5.2~l-------,----------------** ..-.0 

## G_'" ,a.TiIQ lilJ110 IN.IIGO U.llGO**~lGCIG** GJIGO 8.11CO 

# ...., 

# .,­ .,,­ ?2.DIIO 

# ,,_ 1l.OOO fI.IIGO 

# .... 4.41& .ut:!

.....7 

# ...... 4_ 4.1tl 

# .:1_ 4.$11

...

# .,., 

# ..... .......,. "-* 

## -4._

.....1111 .un' 4.144 

## "'
.....
•• "IMI)

.....a1
...



# .

o 20 40 

### 60 80 100 Time (hours)



### 1078PROJECT NUMBER: 014510218 PAGE 57 

### Figure 

### 4.17 pH 9 at

### 20.0 :t 

### O.SOC- ComponentA Graph of log10 Concentration (gIl) versus Time (Hours)
::;::-3.4 c:::: 

### .9

## ~ 

# • 

# i 

# i-3

.

# a
0 

# .... 

# B' -3.8 

# 0_ 0.-.. -UIII



# - - .".... 

# - uoo


# -**~** 

# - ZJIlI) -UII'**~** .".... UOII -uN 22.5CD


### ....

# ­ - 111,000 "',1.

..... Q 

# - -

... "--IJIIII'4.1.



# .**~**

-4.0

-4.2

-4.4

-4.6

### 4.8:~----------------------------------------- 

## o 10 

### 20 30 40 50 Time (hours)



### 1079

# --- PROJECT NUMBER: 014510218 PAGE 58 

### Figure 4.18 pH 9 at 20.0 

## ±O.S°C- Component B Graph of 10910

### Concentration (g/l) versus Time (Hours)
:;::-3.2 

# i S 

# ! t:: 

# § 8 --3. 

### a'


# .... j -4.

-4.

-5.2 

# •

-5
..

# 6'----------------------­ 

# . 

# _



# - 1_



# ..

....... 

# - 4.II1II 

### 1._ "L7tG 2JIOII 

# ..... _I 2JIOII**~.oao** 4.
... 4.(11l0 41f' 

# 11_ 2UOII -4.no -urr**~~ ~M1**  

# - &ClIO ..c.a41 

# -

...... ".I11III .a.2D 

# - - A-4AMO 

# ..**~** 

## ,. 7



## o 10 

### 20 30 40 50 TIme (hours)



### 1080PROJECT NUMBER: 014510218 PAGE 59 

### Figure 4.19 pH 9 at 30.0 

## t 0.6°C- Component A Graph of 10910 

### Concentration (gil) versus Time (Hours)**~-3.5** 1I.CCCE<o 4.177 

### :§ 1I.CCCE<o 4.Q1**~** 

# ! c; 4.112 4IMI)**~** 1.oao 4Mt ,.oao**~** 2.lDI -aMI c; 2.lIIIO ''''Il10

## ~ -3.55 

# • UCG ..AlII 

# - UCG 

# - 4Mt 

## .§. 

# • 4.748**~.oao** 0 .1.710 

## .... 

# • 

# -A·4.511/

### ~ .'·UIGM 

# .

-3.7



# , 

# • -3.8 

# •



# •

0 2 

### 3 4 

### 5 6 Time (hours)



### 1081

# • 

# • PROJECT NUMBER: 014510218 PAGE 60 

### Figure 4.20 pH 9 at30.0 :t

### 0.5°C- Component B Graph of 10910 

### Concentration (gn) versus Time (Hours) 

# 0_ lI.IlOIIIEtO

o.soo o.soo \.000 UIIIO 2.000 2.000 

# - 1.000 "-000 _.IICO UDIl 4A2'Z oU4C .".dO .a.­ ."
... 03.111 4.744 .1.110& 

# - 4.771 -uu 03,1It\

........ -3.7 

# • -3.8



### -3.9 

# -4. -4.1'----------------------­ o 1 2 3 4 

### 5 6 Time (hours)



### 1082PROJECT NUMBER: 014510218 PAGE 61 

### Figure 4.21 pH 9 at40.0 

# ±O.S°C- Component A Graph of log'lo Concentration (gIl) versus Time (Hours)**~-3.2**

### ~ 

# I 8 

# 1-3. 0 

# - J

-4.



### -4.8 CI.OOGI;+O 

# _ .. IUIIQ IUIIQ 1.@ 1.000 2.000 2.000 

# - UGe ..coo ..coo 

# •

..-.uot 

### .--G.13I 

# . •



# • .I&.AA 4.
_ 4Ma 4.612**.~** 4.ICII 4.f11 4,1111 

# - 03'­



### ...

# ­ o4JI«I


### ...**-5.2:1--------------~-------** 

# ...... o 1 

### 2 3 4 5 Time (hours)



### 1083-4.2 PROJECT NUMBER: 014510218 PAGE 62 

### Figure 4.22 pH 9 at

### 40.0 

## ±0.5°C- Component B Graph of log10 Concentration (gIl) versus Time (Hours)

II.IIDaEtO 4.11i11 II.DCOI<O**~** Q.$III -1./111 0JlCIII 4.101 1.0011 4.as 1_ 4175 .LIIIIO 4.114 2.CIIIII 4.n4 

# - ­ 3.tIIlU "",177 tJIIO
....170 

# .­

...

# ­ - A-4M8

# ­ ".0.240 

# .

•



# • • -4.


# •

•.

### ~-----------------------------------------



## o 1 2 3 4 5 Time (hours)

1084PROJECT NUMBER: 014510218 PAGE 63 

### The Arrhenius plots were constructed using the data shown in the following tables: 

### Table 4.37 pH 9 Arrhenius Data - Component A T (0C) T (K) 1 T(K) kobS (h(l) 

### Inkob$ 20 293 3.41 

### x 10-3 5.43 X 10-2**~2.91** 30 303 3.30

### x 10-3 7.32 X 10-2 -2.61 40 313 3.19 

### x 10-3 0.549 -0.599 

### From the graph (Figure 

### 4.23) of the above data, the rate constant and half-life at 

### 25'-'C have been estimated to be as follows:
kObS 

## = 7.43 X 

### 10.2 

### hou(l, 

### 2.07 x 

### 10-5 

### second-1**t~** 

# = 9.33 hours, 

### 0.389 days 

### Table 4.38 pH 9 Arrhenius Data - Component B T(OC) T (K) 1 T(K} 

### kobs (hf1) 

### In kobs 20 293 3.41 

### x 10-3 5.73X 10-2 -2.86 30 303 3.30

### x 10-3 0.190 -1.66 40 313 3.19

### x 10-3 0.551 -0.595 

### From the graph (Figure 

### 4.24) of the above data, the rate constant and half-life at 

### 25°C have been estimated to be as follows: 

### 0.105 hou(1, 

### 2.91 x 

### 10-5 second-1 

### 6.61 hours, 

### 0.275 days

1085PROJECT NUMBER: 014510218 PAGE 64 

### Figure 4.23 pH 9 - ComponentA

Graph ofIn.kobs versus 11T (K)



# •

-3

0.00316 0.00320 0.00324 0.00328 0.00332 0.00336 0.00340 0.00344 1I[Temperature{K}}



### 1086PROJECT NUMBER: 014510218 PAGE 65 

### Figure 4.24 pH 9 - Component B

Graph of In.kobs versus 

## 11T (K)

--1 

# I I

-2



### 0.00316 0.00820 0.00324 0.00328 0.00332 0.00336 0.00340 0.00344 1/[Temperature(K)}



### 1087PROJECT NUMBER: 0145f0218 PAGE 66 

### 4.5 Validation The linearity of the detector response with respect to concentration was assessed over the nominal concentration range of 0 to 50 mgt!. This was satisfactory with a correlation coefficient of 1.00 being obtained for Components A and B. Recovery of analysis of the sample procedure was assessed and proved adequate for the test, with the exception ofComponent A in pH 7 buffer. Recovery data is shown in the following table: 

### Table 4.39 Buffer Nominal concentration (mgll) ! I Recovery range (%)

Component A Component B Mean recovery (%) Component A Component B pH4 0.37 87.3 to 92.7 75.8 to 82.3 90.8 78.4 pH 7 0.37 0 62.0 to 74.1 0 66.2 pH9 0.37 62.9 to 80.3 78.2 to 84.7 72.7 

### 82.0 

### Concentrations have not been corrected for recovery ofanalysis. 

### 4.6 Discussion Initial experiments demonstrated poor recoveries of analyte in buffer solutions, but acceptable recoveries in pH adjusted water. Therefore, preliminary testing was performed in reverse osmosis water adjusted to pH 

### 4. 7 and 9 using 0.1 M hydrochloric acid or 0.1 M sodium hydroxide. However, due to the absence of buffering, the pH of these solutions was unstable. Further investigation revealed that acceptable recoveries could be achieved in the buffers specified in Section 4.2.1, with the exception of pH 7 phosphate buffer in which no recovery of Component A could be achieved. This anomaly could not be readily explained since the pH 7 matrix blank did not demonstrate interfering peaks and the analytical procedure was shown to be successful for both analytes in pH 4 and pH 9 buffers. Therefore, no data for Component A at pH 7 could be generated. Tier 2 testing at pH 7 demonstrated a significant degree of variation in the analytical results for duplicate samples and across the time points over the period of the test. EVen though this test was performed at five different temperatures plus some limited testing at 25°C, consistent data could not be obtained. The variation in analytical data was not considered to be due to solubility issues. 

### It was concluded that there was no evidence of hydrolysis 

## at pH 7, since losses observed were not of a pseudo-first order kinetic nature and were considered to be due to other mechanisms or effects.

1088PROJECT NUMBER: 014510218 PAGE 67 

### For additional information, an estimation ofthe hydrolytic stability ofthe test material was performed using the specialised predictive software, HYDROWIN v 

### 2.00 (September 

### 2008), 

### © 2000 US Environmental Protection Agency. The estimated half-lives at 

### 25°C are shown in the following table: Component pH7 pHS A (PE3MB) 13.1 years 1.31 years B (PEMB) 9.85 years 360 days 

### For calculation of the test material concentration, peak area was used throughout the pH 4 and pH 9 tests, whereas peak heightwas the pH 7 tests. The use ofpeak height in the pH 7 calculations gave initial concentrations consistent with the fortified concentrations. The kinetics of the study for pH 9 has been detennined to be consistent with that of a pseudo-first order reaction as the graphs of 

### 10910 concentration versus time are straight lines. As the test material was determined to be hydrolytically stable under acidic conditions**(t~** 

### > 1 year at 

### 25°C). no additional testing was performed at pH 

### 1.2, 37.0 

## ±O.5°C. 

### 4.7 Conclusion The rate constants and estimated half-lives at 

### 25°C ofthe test material are shown in the following table: pH 

## I I 

### Rate constant (S·1) 

### PE3MB PEMB Estimated half-life 

### at 25°C PE3MB PEMB 

### 4 not applicable not applicable >1 year >1 year 7 9 

### not applicable 2.07 x 10.5 

### not applicable 2.91 X 

### 10-6 >1 year 9.33 hours >1 year 6.61 hours 

### No definitive signs of hydrolysis at pH 4 or pH 7. Testing performed at various temperatures indicated that losses observed were not pseudo-first order and therefore most likely to be due other mechanisms or effects ratherthan hydrolysis.

1089PROJECT NUMBER: 0145/0218 PAGE 68 

### Appendix 1 Statement ofGLP Compliance in accordance with Directive 2004/9/EC


# ,DH) Department

## ~ ofHealth

THE DEPARTMENTOFHEALTH OFTHE GOVERNMENT OFTHE UNITED KINGDOM GOODLABORATORYPRACTICE STATEMENTOFCOMPLIANCE INACCORDANCEWlTIfDJRECTI\'E2004191EC
TESTFACIL1TV TE!>'TTYI'E Karlun LnboratoriesLtd. Analytical/CUnical Cbemlstry Shal'dJow BusinessPurl{ EnvironmontalFate London Road EDl'iroDmcnfalToxicology Shardlol\' Mutagenicity Derby PbyslCbem DE7l2GD Toxicology

DATE OFINSPECTION 19thAugust 2008

Ageneral inspection for compliance with the Principles ofGood Laboratory Practice was curried out atthe abovetestfacility as partofthe UK GLPComplianceProgramme. At the time ofinspection no deyiations were found of sufficient magnitude to affect the validity ofnon-clinical studies perfunned atthesefacilities
.

Dr.AndrewJ.Gray Head, UKGLPMOllitoringAuthority 

# •

1090[KarenzMT PEl] [SHOWA DENKO K.K.J [SCA-1279] [02/10/2009] [1/6]



### SHOWADENKO KK 13-9, ShibaDaimon l-Chome 

# unA Minato-Ku, Tokyo 105-8518, Japan 

## OEln Date ofpreparation : March 31, 2006 Date ofrevision October 2, 2009 

# MATERIAL SAFETYDATA SHEET 1. 

### PRODUCTAND COMPANY IDENTIFICATION Product name KarenzMTTM PE1 Company name SHOWA DENKO K.K. Address 5-1, Ogimachi, Kawasaki-Ku, Kawasaki-shi, Kanagawa 210-0867 Japan Section Chemicals Division, Chemicals Sector Phone number +81-44-329-0726 Facsimile number +81-44-329-0782 Productcode PEl Emergency phone number : +81-90-7239-0335(cell phone) Recommended use of the chemical and restrictions on use Industrial Purpose Only MSDS number : SCA-1279 

### 2. HAZARDS IDENTIFICATION GHS classification

Physical hazards Any of"classification notpossible" and "Notclassified" Health hazards Sensitization -Skin :Hazard category 1 Other Hazard Class : Any of "classification not possible" and "Not classified" Environmental hazards Hazard to the Aquatic Environment-acute hazard :Hazard category 1 Hazard to the Aquatic Environment-chronic hazard: Not classified GHS label elements

Pictograms (Symbols)
Signal words Hazard statements Precautionary statements

Main symotoms Emergency overview Warning May causes an allergic skin reaction Very toxic to aquatic life [Prevention]

Avoid breathingdust/fumelgaslmist/vaporslspmy. Contaminated work clothing should notbe allowed out of the workplace. Wearprotective gloves. [Response]

IF ON SKIN: Wash with plenty ofsoap and water. IF Skin irritation orrash occurs: Getmedical advice/attention. Wash contaminated clothing before reuse. [Disposal]

Dispose of contents/container to licensed waste disposal site in accordance with 10cal/regional/national/intemationalregulation. No information available No information available
1091

### [KarenzMT PEl] [SHOWA DENKO K.K.J [SCA-1279J [02/10/2009J 

### [2/6J 3.COMPOSITION/INFORMATIONONINGREDIENTS Single substance ormixture : Mixture**-~-** 

# --- ..-.-.-.----------

## ....

# -..

# -.--...

# -.....

# -... ....-.-----.-

## ..

# -...

# --.. ..

# -...... Common chemical name

(generic name) Synonym(s) Chemical formula "



### CAS number Content Publicationnumberin Chemical Substances Control Law: Low production volume chemical

Japanese official gazette substances Industrial Safety and HealthLaw: 2-(6)-1770 4. FIRST-AIDMEASURES Inhalation Move to a well-ventilated space to get fresh air and immediately obtain medical aidregardless ofpatient's sYmptoms. Skin contact Remove contaminated clothing, and wash affected area with plenty of water or lukewarm water using soap. If there is the change in the appearance or irritation persists, obtain medical aid. Eye contact Immediately flush with plenty offresh water for at least 15 minutes, and immediately obtain medical aid. Ingestion Immediately obtain medical aid. Briefdescription ofthe most Not specified.

important symptoms Protection offlTst-aiders Remove polluted clothes. Weargloves andbe careful notto touch the toxic substance. Special notes to aphysician Ifthe victim has a medical wound, after having removed apollutant, treat as anormal burn allowance. 5.FIRE-FIGHTINGMEASURES Extinguishing media Powder, carbon dioxide, halides, foam Inappropriate extinguishing Not specified.

media Specific hazards with regard Besides the gases such as carbon monoxide etc, sulfur compounds may be

to fire-fighting measures included inthe combustion gas 

### ofthe product. Specific methods offire­ Stop supply ofsource offire to the burning spot and put out the fire using

fighting and special an extinguishing medium. The fire-fighting operation should be carried out equipment from the upwind. Protection offirefighters Wear the protective cloth, goggles for chemicals and gas 

### mask, to prevent from contact and inhalation ofthe vapor and harmful gases. 6. ACCIDENTALRELEASE MEASURES

1092[KarenzMT PElJ [SHOWA DENKO K.K.J [SCA-1279J [02110/2009J [3/6J Personal precautions,

protective equipment and emergency procedures Environmental precautions Methods for cleaning up
Prevention ofsecondary

hazards 

### 7. HANDLINGAND STORAGE Handling

Technical measures Local exhaust ventilation! general ventilation Precautions Storage

Appropriate storage

conditions Safe packaging materials Wear appropriate protective equipment during operations to prevent from contactofsplashed product andthe like with the skin. Do not allow concentrated effluent to flow into public water conduits or rivers. For small spills, recover the spills with saw dust or the like and incinerate them. In case of large spills, recover as much ofthe spills as possible and be careful NOTto flow into public water or rivers. No infonnation available

Take measures against static electricity and wear conductive clothes and shoes. Handle in the local exhaust ventilation or at a place with total ventilation facilities. Handle the productwhere adequate local exhaustventilation is provided. Store the product in a dry, cool, and dark place. Do not allow high temperature objects, sparks or flame in the vicinity ofthe product. Not specified. 8. EXPOSURE CONTROLS/PERSONALPROTECTION Engineering measures to reduce exposure Provide local exhaustventilation equipment. Administrative control level : Notestablished. Exposure guidelines

Japan Society for Occupational Health (2008) Notestablished. ACGIH (2009) Not established. OSHA (2004) Not established. Personal protective equipment Respiratory protection Gas mask for organic gas. Airrespirator Hand protection Rubber gloves Eye protection Protective goggles Skin and body protection Apron and boots to avoid contactto the skin. Specific hygiene measures Do not eator smoke while working. 9. PHYSICALAND CHEMICALPROPERTIES Physical state Appearance Color "

### -----------------------, Odor (odor threshold) : Slightly sulfur odor pH : No data available 

### .-------------------------­ Boiling point 

## .. :**·~-------------------** ______ I Initial boiling point and No data available

boiling range Melting point/freezing point Decompositiontemperature FJashpoint Auto-ignition temperature

1093[KarenzMT PElJ [SHOWA DENKO K.K.J [SCA-l279J [02110/2009J [4/6J Upperllower flammability or No data available

explosion limits Vaporpressure Vapor density Evaporation rate Relative density Solubility

Water .' ., , , , , , Other solvents ., n-octanollwaterpartition

coefficient , ,**~**

### ..........**~**

## -....._

### ........_

### .......... _

### ..-......_ 

### ................................................_ ...... .._' 

### 10. STABILITYAND REACTIVITY Stability Stable

### in usual handling. Possibility ofhazardous Reacts with oxidizingcompounds, and forms disulfide compounds
..

reactions Causes addition reactions to ethylene-type double bonds Conditions to avoid Contactwith oxidizing agents. Incompatible materials No information available Hazardous decomposition Oxidizing agents

products 

### 11. TOXICOWGICALINFORMATION Acutetoxicity Oral RatLD50 >2000mg!kg 3) Dermal RatLD50 >2000mg!kg 4) Skin corrosion/irritation Non-Irritanttorabbit skin (Draize classification scheme) No corrosive effects were noted. P.l.L 0.0 5) Serious eye damage/irritation Minimal irritant to eyes of rabbits. (Kay and Calandra Classification scheme). Mean scores were 8.0. 6) Respiratory or skin Positive in the local lymph node assay (LLNA) in mice. (OECD T0429) 7)

sensitization Oerm cell mutagenicity 'Negative in the Ames test for Salmonella typhimurium TA98, TAIoo, TA 1535, TA 1537 and Escherichiacoli WP2uvrAwith and without metabolic activation. 8) •Positive in the Chromosome aberration test for Chinese hamster lung fibroblasts with and withoutmetabolic activation. 14) •Negative

### in the Micronucleustestfor mice. (OECD T0474) 15) Carcinogenicity Nodataavailable Reproductivetoxicity Nodata available Specifictarget organ toxicity No data available -single exposure Specifictarget organ toxicity No data available -repeatedexposure Aspiration hazard No dataavailable 

### 12. ECOLOGICALINFORMATION Eco-toxicity

Fish toxicity MedakaLC50 (96hr) 0.16mgIL (Semi-static system) 9) Others DaphiniamagnaEC50 (48hr) 9.0mgIL (Semi-static system) 10) Algae EC50 (12hr) OAOmgIL III Persistence/degradability Readily biodegradation under the condition of OECD T0301B, CO2 evolution test (70% degradation after 28 days) 12)

1094[KarenzMT PEIJ [SHOWA DENKO K.K.J [SCA-1279J [02/10/2009J [5/6J Bioaccumulativepotential Bioconcentration potential (after 60 days) using Carp was low. 13) High exposure level {2.51lg/L):BCF 70 High exposure level (IIlg/L):BCF 170 Mobility in soil No data available 

### 13. DISPOSALCONSIDERATIONS Because this product contains a sulfur compound, please bum up in an appropriate incinerator or dispose of contents/container to licensed waste disposal site in accordance with locallregionallnationallintemational regulation. Note: When disposing ofthe product outside Japan, conform to applied laws and regulations in that country orterritory. 

### 14. TRANSPORT INFORMATION International regulations for transport

UNhazard class Not applicable UN number Notapplicable UN Proper ShippingName Not applicable Packing group Notapplicable Marine pollutant Notapplicable Additional regulations for Notapplicable

transport Specific precautionary transport measures and conditions When transporting the product, inspect the containers for leakage and load then securely to prevent from topping, failing, or breakage, and take preventive measures against collapsing ofcontainers. Emergency Response Not applicable

Guidebook number Note: When transporting the product outside Japan, conform to applied laws and regulations in that country orterritory. 

### 15. REGULATORY INFORMATION Laws and regulations applied in Japan: The Fire Service Law: Designated inflarnmables{Flammable liquids) Note: When using the product outside Japan, it must be handled in accordance with applied laws and regulations in that country orterritory. 

### 16. OTHERINFORMATION ContentofPRTRLawchemicals : Notcontained TSCA Inventory Not included EINECS number Not included References 1) ShowaDenko K.K. test report 014510193 (2009) 2) ShowaDenko K.K. testreport 1000855956 (2009) 3) ShowaDenko K.K. testreport 014510194 (2009) 4) ShowaDenkoK.K. test report 014510195 (2009) 5) Showa DenkoK.K. testreport 014510198 (2009) 6) ShowaDenkoK.K. testreport 014510199 (2009) 7) Showa Denko K.K. testreport 014510200 (2009) 8) ShowaDenko K.K. testreport KO 1-4229 (2009) 9) ShowaDenko K.K. testreport 94746 (2009) 10) Showa Denko K.K. testreport94745 (2009) 11) ShowaDenko K.K. testreport 94744 (2009) 12) ShowaDenkoK.K. testreport 014510215 (2009) 13) ShowaDenko K.K. testreport 44929 (2008) 14) ShowaDenko K.K. testreport K06-1279 (2009)
1095[KarenzMT PEl] [SHOWA DENKO K.KJ [SCA-1279] [02/10/2009J [6/6J 

### 15) Showa Denko K.K. testreport 014510219 (2009) 

### Forfurther information. please contact Chemicals Division. Chemicals Sector. ShowaDenko K.K. Telephone number +81-44-329-0726 Facsimile number +81-44-329-0782 The information in this MSDS was obtained from sources which we believe are reliable, but no warranty or representation as to its accuracy or completeness is hereby given. Users should consider the information herein only as a supplement to 

### other information gathered by them and must make independentdeterminations ofsuitability and completeness ofinformation from all sources to assure proper use and disposal, the safety and health ofemployees and customers and the protection ofthe environment. This is atranslation oforiginal Material Safety Data Sheetprepared in Japanese.

1096